Up-to-date information on hearth health, respiratory & COVID-19.
Post–COVID 2021Conditions Among Adult COVID-19 Survivors Aged 18–64 and ≥65 Years — United States, March 2020–November
MMWR CDD | May 27, 2022
As more persons are exposed to and infected by SARS-CoV-2, reports of patients who experience persistent symptoms or organ dysfunction after acute COVID-19 and develop post-COVID conditions have increased. COVID-19 survivors have twice the risk for developing pulmonary embolism or respiratory conditions; one in five COVID-19 survivors aged 18–64 years and one in four survivors aged ≥65 years experienced at least one incident condition that might be attributable to previous COVID-19. Implementation of COVID-19 prevention strategies, as well as routine assessment for post-COVID conditions among persons who survive COVID-19, is critical to reducing the incidence and impact of post-COVID conditions, particularly among adults aged ≥65 years.
Disentangling a Thorny Issue: Myocarditis and Pericarditis Post COVID-19 and Following mRNA COVID-19 Vaccines
Pharmaceuticals, April 25, 2022
Considering the clinical significance for myocarditis and pericarditis after immunization with mRNA COVID-19 vaccines, the present pharmacovigilance study aimed to describe these events reported with mRNA COVID-19 vaccines in the Vaccine Adverse Events Reporting System (VAERS). From 1990 to July 2021, the mRNA vaccines were the most common suspected vaccines related to suspected cases of myocarditis and/or pericarditis (myocarditis: N = 1,165; 64.0%; pericarditis: N = 743; 55.1%), followed by smallpox vaccines (myocarditis: N = 222; 12.2%; pericarditis: N = 200; 14.8%). We assessed all suspected cases through the case definition and classification of the Brighton Collaboration Group, and only definitive, probable, and possible cases were included in the analysis. Our findings suggested that myocarditis and pericarditis mostly involve young male, especially after the second dose with a brief time to onset. Nevertheless, this risk is lower (0.38/100,000 vaccinated people; 95% CI 0.36–0.40) than the risk of developing myocarditis after SARS-CoV-2 infection (1000–4000 per 100,000 people) and the risk of developing “common” viral myocarditis (1–10 per 100,000 people/year). Comparing with the smallpox vaccine, for which is already well known the association with myocarditis and pericarditis, our analysis showed a lower probability of reporting myocarditis (ROR 0.12, 95% CI 0.10–0.14) and pericarditis (ROR 0.06, 95% CI 0.05–0.08) following immunization with mRNA COVID-19 vaccines.
ACC Guidance on the cardiovascular impact of COVID-19 and post-acute sequelae of SARS-CoV-2
Cardiovascular Business, April 21, 2022
[Video] Ty Gluckman, MD, MHA, medical director, Center for Cardiovascular Analytics, Research, and Data Science (CARDS) at Providence St. Joseph Health in Portland, Oregon, explains the main points of the American College of Cardiology (ACC) expert consensus on the cardiovascular consequences stemming from a COVID-19 infection. Gluckman was the co-chair of the expert consensus decision pathway that can be used for the evaluation and management of adults with cardiovascular consequences from a COVID-19 infection. This includes cardiac issues by long-COVID. These ACC guidelines were designed to help clinicians learn how to manage COVID patients with cardiovascular involvement during both the acute infection and long-COVID. The post-acute phase symptoms are referred to in the document by the official clinical designation of long-COVID as post-acute sequelae of SARS-CoV-2 infection (PASC).
Cardiovascular Manifestations in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19 According to Age
Children, April 20, 2022
Cardiac involvement in multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus-19 disease is often observed with a high risk of heart failure. The aim is to describe cardiovascular involvement, management and early outcome in MIS-C by comparing cardiovascular manifestations in children younger and older than 6 years old. This retrospective observational study included 25 children with MIS-C, admitted to a single pediatric center between March 2020 and September 2021. The median age was 5 years (13 patients under 6 years and 12 over 6 years); coronary artery abnormalities were observed in 77% of preschoolers, with small and medium aneurysms in half of the cases and two cases of mild ventricular dysfunction. School-age children presented myopericardial involvement with mild to moderate ventricular dysfunction in 67% of cases, and two cases of transient coronary dilatation. There was a significant NT-pro-BNP and inflammatory markers increase in 25 of the patients, and mild elevation of troponin 1 in 9. All patients were treated with intravenous immunoglobulin and corticosteroids, and 8 with anakinra. None of the patients needed inotropes or intensive care unit admission. Our study shows the frequent cardiovascular involvement in MIS-C with a peculiar distribution, according to different age group: coronary artery anomalies were more frequent in the younger group, and myopericardial disease in the older one. A prompt multi-target, anti-inflammatory therapy could probably contribute to a favorable outcome.
How delivering cardiopulmonary resuscitation and basic life support skills training through places of worship can help save lives and address health inequalities
European Heart Journal, April 20, 2022
Early delivery of high-quality cardiopulmonary resuscitation (CPR) and rapid defibrillation strengthen the initial links of the chain of survival and can help improve out-of-hospital cardiac arrest (OHCA) outcomes. However, health inequalities exist in OHCA survival at regional and global levels, which reduces the chances of survival, with disproportionately lower CPR delivery rates seen in areas of socio-economic deprivation and ethnic minority groups. In the United Kingdom for example, the British Muslim and South Asian communities also have higher levels of health disparities in cardiovascular disease, diabetes, and physical activity, which can predispose them to poorer outcomes from OHCA. Thus, when developing and delivering training for the public, it is important to ensure that there is equitable access.
SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study of 23 Million Residents
JAMA Cardiology, April 20, 2022
Reports of myocarditis after SARS-CoV-2 messenger RNA (mRNA) vaccination have emerged. To evaluate the risks of myocarditis and pericarditis following SARS-CoV-2 vaccination by vaccine product, vaccination dose number, sex, and age. Four cohort studies were conducted according to a common protocol, and the results were combined using meta-analysis. Participants were 23 122 522 residents aged 12 years or older. They were followed up from December 27, 2020, until incident myocarditis or pericarditis, censoring, or study end (October 5, 2021). Data on SARS-CoV-2 vaccinations, hospital diagnoses of myocarditis or pericarditis, and covariates for the participants were obtained from linked nationwide health registers in Denmark, Finland, Norway, and Sweden. The 28-day risk periods after administration date of the first and second doses of a SARS-CoV-2 vaccine, including BNT162b2, mRNA-1273, and AZD1222 or combinations thereof. A homologous schedule was defined as receiving the same vaccine type for doses 1 and 2. Incident outcome events were defined as the date of first inpatient hospital admission based on primary or secondary discharge diagnosis for myocarditis or pericarditis from December 27, 2020, onward. Secondary outcome was myocarditis or pericarditis combined from either inpatient or outpatient hospital care. Poisson regression yielded adjusted incidence rate ratios (IRRs) and excess rates with 95% CIs, comparing rates of myocarditis or pericarditis in the 28-day period following vaccination with rates among unvaccinated individuals. Among 23 122 522 Nordic residents (81% vaccinated by study end; 50.2% female), 1077 incident myocarditis events and 1149 incident pericarditis events were identified. Within the 28-day period, for males and females 12 years or older combined who received a homologous schedule, the second dose was associated with higher risk of myocarditis, with adjusted IRRs of 1.75 (95% CI, 1.43-2.14) for BNT162b2 and 6.57 (95% CI, 4.64-9.28) for mRNA-1273. Among males 16 to 24 years of age, adjusted IRRs were 5.31 (95% CI, 3.68-7.68) for a second dose of BNT162b2 and 13.83 (95% CI, 8.08-23.68) for a second dose of mRNA-1273, and numbers of excess events were 5.55 (95% CI, 3.70-7.39) events per 100 000 vaccines after the second dose of BNT162b2 and 18.39 (9.05-27.72) events per 100 000 vaccines after the second dose of mRNA-1273. Estimates for pericarditis were similar.
Right Ventricular Abnormality in Patients Hospitalized With COVID-19 Infection During Omicron Variant Surge
American Journal of Cardiology, April 19, 2022
Echocardiographic changes in the acute phase of COVID-19 infection have been extensively reported during the COVID-19 pandemic. Measures of right ventricular (RV) performance during acute infection have been associated with mortality. We aimed at studying the association of in-hospital mortality with echocardiographic measures of RV performance during the COVID-19 infection surge in New York City attributed to the spread of the Omicron variant. In this retrospective study, we enrolled consecutive patients hospitalized with COVID-19 infection who underwent clinically indicated echocardiograms from December 15, 2021, to January 26, 2022. Omicron became the predominant strain in the United States in December 2021 and accounted for >99% of COVID-19 cases. Echocardiograms were performed adhering to a focused, time-efficient protocol with appropriate use of personal protective equipment and limited viral exposure time. Portable ultrasound machines were used: CX50 (Philips Medical Systems, Bothell, Washington) and Vivid S70 (GE Healthcare Systems, Milwaukee, Wisconsin). Echocardiographic studies were interpreted by experienced echocardiography attending physicians. RV abnormality was defined as basal RV diastolic diameter >4.1 cm in the RV-focused apical view and/or tricuspid annular plane systolic excursion <1.7 cm from the apical 4-chamber view. The primary end point was in-hospital mortality. Kaplan-Meier curves and Cox regression analysis were used to explore the associations of clinical and echocardiographic predictors with in-hospital mortality.
Coronavirus 2019 (COVID-19) venovenous extracorporeal oxygenation: Single community hospital results and insights
Journal of Cardiac Surgery, April 19, 2022
The role of extracorporeal membrane oxygenation (ECMO) for patients with refractory respiratory failure due to coronavirus 2019 (COVID-19) is still unclear even now over a year into the pandemic. ECMO is becoming more commonplace even at smaller community hospitals. While the advantages of venovenous (VV) ECMO in acute respiratory distress syndrome (ARDS) from COVID-19 have not been fully determined, we believe the benefits outweighed the risks in our patient population. Here we describe all patients who underwent VV ECMO at our center. All patients placed on ECMO at our center since the beginning of the pandemic, May 5, 2020, until February 20, 2021 were included in our study. All patients placed on ECMO during the time period described above were followed until discharge or death. The primary endpoint was in-hospital death. Secondary outcomes included discharge disposition, that is, whether patients were sent to a long-term acute care center (LTAC), inpatient rehabilitation, or went directly home. A total of 41 patients were placed on VV ECMO for refractory acute respiratory failure. Survival to discharge, the primary end point, was 63.4% (26/41). Inpatient mortality was 36.6% (15/41). We show here that a successful high-volume VV ECMO program for ARDS is achievable at even a medium-size community hospital. We think our success can be replicated by most small- and medium-size community hospitals with cardiothoracic surgery programs and intensivist teams.
Characterization of COVID-19-associated cardiac injury: evidence for a multifactorial disease in an autopsy cohort
Laboratory Investigation, April 18, 2022
As the coronavirus disease 2019 (COVID-19) pandemic evolves, much evidence implicates the heart as a critical target of injury in patients. The mechanism(s) of cardiac involvement has not been fully elucidated, although evidence of direct virus-mediated injury, thromboembolism with ischemic complications, and cytokine storm has been reported. We examined suggested mechanisms of COVID-19-associated heart failure in 21 COVID-19-positive decedents, obtained through standard autopsy procedure, compared to clinically matched controls and patients with various etiologies of viral myocarditis. We developed a custom tissue microarray using regions of pathological interest and interrogated tissues via immunohistochemistry and in situ hybridization. Severe acute respiratory syndrome coronavirus 2 was detected in 16/21 patients, in cardiomyocytes, the endothelium, interstitial spaces, and percolating adipocytes within the myocardium. Virus detection typically corresponded with troponin depletion and increased cleaved caspase-3. Indirect mechanisms of injury—venous and arterial thromboses with associated vasculitis including a mixed inflammatory infiltrate—were also observed. Neutrophil extracellular traps (NETs) were present in the myocardium of all COVID-19 patients, regardless of injury degree. Borderline myocarditis (inflammation without associated myocyte injury) was observed in 19/21 patients, characterized by a predominantly mononuclear inflammatory infiltrate. Edema, inflammation of percolating adipocytes, lymphocytic aggregates, and large septal masses of inflammatory cells and platelets were observed as defining features, and myofibrillar damage was evident in all patients. Collectively, COVID-19-associated cardiac injury was multifactorial, with elevated levels of NETs and von Willebrand factor as defining features of direct and indirect viral injury.
The Impact of Cardiovascular Risk Factors on the Course of COVID-19
Journal of Clinical Medicine, April 18, 2022
The aim of our review is to indicate and discuss the impact of cardiovascular risk factors, such as obesity, diabetes, lipid profile, hypertension and smoking on the course and mortality of COVID-19 infection. The coronavirus disease 2019 (COVID-19) pandemic is spreading around the world and becoming a major public health crisis. All coronaviruses are known to affect the cardiovascular system. There is a strong correlation between cardiovascular risk factors and severe clinical complications, including death in COVID-19 patients. All the above-mentioned risk factors are widespread and constitute a significant worldwide health problem. Some of them are modifiable and the awareness of their connection with the COVID-19 progress may have a crucial impact on the current and possible upcoming infection. We searched for research papers describing the impact of selected cardiovascular risk factors on the course, severity, complications and mortality of COVID-19 infection form PubMed and Google Scholar databases. Using terms, for example: “COVID-19 cardiovascular disease mortality”, “COVID-19 hypertension/diabetes mellitus/obesity/dyslipidemia”, “cardiovascular risk factors COVID-19 mortality” and other related terms listed in each subtitle. The publications were selected according to the time of their publications between January 2020 and December 2021. From the PubMed database we obtain 1552 results. Further studies were sought by manually searching reference lists of the relevant articles. Relevant articles were selected based on their title, abstract or full text. Articles were excluded if they were clearly related to another subject matter or were not published in English. The types of articles are mainly randomized controlled trial and systematic review. An additional criterion used by researchers was co-morbidities and age of patients in study groups. From a review of the publications, 105 of them were selected for this work with all subheadings included. The intention of this review was to summarize current knowledge about comorbidities and development of COVID-19 infection. We tried to focus on the course and mortality of the abovementioned virus disease in patients with concomitant CV risk factors. Unfortunately, we were unable to assess the quality of data in screened papers and studies we choose because of the heterogenicity of the groups. The conducted studies had different endpoints and included different groups of patients in terms of nationality, age, race and clinical status. We decide to divide the main subjects of the research into separately described subtitles such as obesity, lipid profile, hypertension, diabetes, smoking. We believe that the studies we included and gathered are very interesting and show modern and present-day clinical data and approaches to COVID-19 infection in specific divisions of patients.
Coronary Microvascular Dysfunction is Common in Patients Hospitalized with COVID-19 Infection
Microcirculation, April 18, 2022
Microvascular disease is considered as one of the main drivers of morbidity and mortality in severe COVID-19, and microvascular dysfunction has been demonstrated in the subcutaneous and sublingual tissues in COVID-19 patients. The presence of coronary microvascular dysfunction (CMD) has also been hypothesized, but direct evidence demonstrating CMD in COVID-19 patients is missing. In the present study, we aimed to investigate CMD in patients hospitalized with COVID-19, and to understand whether there is a relationship between biomarkers of myocardial injury, myocardial strain and inflammation and CMD. Thirty-nine patients that were hospitalized with COVID-19 and 40 control subjects were included to the present study. Biomarkers for myocardial injury, myocardial strain, inflammation and fibrin turnover were obtained at admission. A comprehensive echocardiographic examination, including measurement of coronary flow velocity reserve (CFVR), were done after the patient was stabilized. Patients with COVID-19 infection had a significantly lower hyperemic coronary flow velocity, resulting in a significantly lower CFVR (2.0±0.3 vs. 2.4±0.5,p<0.001). Patients with severe COVID-19 had a lower CFVR compared to those with moderate COVID-19 (1.8±0.2 vs. 2.2±0.2, p<0.001) driven by a trend towards higher basal flow velocity. CFVR correlated with troponin (p=0.003,r:-0.470), B-type natriuretic peptide (p<0.001,r:-0.580), C-reactive protein (p<0.001,r:-0.369), interleukin-6 (p<0.001,r:-0.597) and d-dimer (p<0.001,r:-0.561), with the three latter biomarkers having the highest areas-under-curve for predicting CMD. CMD is common in patients with COVID-19, and is related with the severity of the infection. CMD may also explain the “cryptic” myocardial injury seen in patients with severe COVID-19 infection.
How rare is heart inflammation in COVID-19 patients?
Nature Italy, April 15, 2022
Acute myocarditis, inflammation of the heart muscle that can compromise its ability to pump blood, is a rare but serious complication of SARS-CoV-2 infection. Italian researchers at Niguarda Hospital in Milan and Brescia University have led an international, multicentre study to estimate its frequency and consequences1. They found that acute myocarditis affected 2.4 per 1,000 hospitalised COVID-19 patients, who had an average age of 38 years. One in five died or needed temporary mechanical circulatory support, but patients who recover do not usually have permanent cardiac damage. The authors looked at data from patients admitted to 23 hospitals in Europe and the United States from February 2020 to April 2021 to evaluate the frequency, clinical features and outcomes of acute myocarditis. “Amid widespread concerns about cardiac involvement and long-term consequences of SARS-CoV-2 infection, it is important to precisely define the disease,” says Enrico Ammirati, cardiologist at De Gasperis Cardio Center and Transplant Center Niguarda Hospital and co-author of the study. The scientists considered acute myocarditis diagnosed in hospitalised patients using cardiac muscle biopsy or magnetic resonance imaging plus increased levels of troponin, a blood biomarker of heart injury. “That’s why our reported prevalence is lower compared with studies involving large numbers of COVID-19 convalescents submitted to magnetic resonance alone,” Ammirati explains. Those studies found rates of 50% or higher of symptomatic or asymptomatic cardiac injury, including but not limited to myocarditis.
The Incidence of Myocarditis and Pericarditis in Post COVID-19 Unvaccinated Patients—A Large Population-Based Study
Journal of Clinical Medicine, April 15, 2022
Myocarditis and pericarditis are potential post-acute cardiac sequelae of COVID-19 infection, arising from adaptive immune responses. We aimed to study the incidence of post-acute COVID-19 myocarditis and pericarditis. Retrospective cohort study of 196,992 adults after COVID-19 infection in Clalit Health Services members in Israel between March 2020 and January 2021. Inpatient myocarditis and pericarditis diagnoses were retrieved from day 10 after positive PCR. Follow-up was censored on 28 February 2021, with minimum observation of 18 days. The control cohort of 590,976 adults with at least one negative PCR and no positive PCR were age- and sex-matched. Since the Israeli vaccination program was initiated on 20 December 2020, the time-period matching of the control cohort was calculated backward from 15 December 2020. Nine post-COVID-19 patients developed myocarditis (0.0046%), and eleven patients were diagnosed with pericarditis (0.0056%). In the control cohort, 27 patients had myocarditis (0.0046%) and 52 had pericarditis (0.0088%). Age (adjusted hazard ratio [aHR] 0.96, 95% confidence interval [CI]; 0.93 to 1.00) and male sex (aHR 4.42; 95% CI, 1.64 to 11.96) were associated with myocarditis. Male sex (aHR 1.93; 95% CI 1.09 to 3.41) and peripheral vascular disease (aHR 4.20; 95% CI 1.50 to 11.72) were associated with pericarditis. Post COVID-19 infection was not associated with either myocarditis (aHR 1.08; 95% CI 0.45 to 2.56) or pericarditis (aHR 0.53; 95% CI 0.25 to 1.13). We did not observe an increased incidence of neither pericarditis nor myocarditis in adult patients recovering from COVID-19 infection.
Cerebrovascular Complications of COVID-19 and COVID-19 Vaccination
Circulation Research, April 14, 2022
The risk of stroke and cerebrovascular disease complicating infection with SARS-CoV-2 has been extensively reported since the onset of the pandemic. The striking efforts of many scientists in cooperation with regulators and governments worldwide have rapidly brought the development of a large landscape of vaccines against SARS-CoV-2. The novel DNA and mRNA vaccines have offered great flexibility in terms of antigen production and led to an unprecedented rapidity in effective and safe vaccine production. However, as mass vaccination has progressed, rare but catastrophic cases of thrombosis have occurred in association with thrombocytopenia and antibodies against PF4 (platelet factor 4). This catastrophic syndrome has been named vaccine-induced immune thrombotic thrombocytopenia. Rarely, ischemic stroke can be the symptom onset of vaccine-induced immune thrombotic thrombocytopenia or can complicate the course of the disease. In this review, we provide an overview of stroke and cerebrovascular disease as a complication of the SARS-CoV-2 infection and outline the main clinical and radiological characteristics of cerebrovascular complications of vaccinations, with a focus on vaccine-induced immune thrombotic thrombocytopenia. Based on the available data from the literature and from our experience, we propose a therapeutic protocol to manage this challenging condition. Finally, we highlight the overlapping pathophysiologic mechanisms of SARS-CoV-2 infection and vaccination leading to thrombosis.
Disparity in Obesity and Hypertension Risks Observed Between Pacific Islander and Asian American Health Fair Attendees in Los Angeles, 2011–2019
Journal of Racial and Ethnic Health Disparities, April 14, 2022
The Pacific Islander American population is understudied due to being aggregated with Asian Americans. In this study, we conduct a comparative analysis of directly measured body mass index (BMI), body fat percentage (%BF), and blood pressure (BP) between Pacific Islander Americans and Asian Americans from health screenings in Los Angeles, California. We hope to reveal intra-APIA health disparities masked by this data aggregation. We analyzed BMI, %BF, and BP that were objectively measured by trained personnel at health screenings in Los Angeles between January 2011 and December 2019. We performed multivariable multinomial logistic regression models with obesity and hypertensive categories as outcome variables and ethnicity as the primary independent variable of interest. Models controlled for year of visit, participant age, sex, income, education level, years living in the USA, employment status, English proficiency, regular doctor access, and health insurance status. A total of 4,832 individuals were included in the analysis. Multivariable analyses revealed that Pacific Islander participants were at significantly higher risks for being classified as obese compared with all Asian American subgroups studied, including Chinese, Korean, Thai, Vietnamese, Filipino, and Japanese. Pacific Islanders also exhibited significantly lower predicted probability of having a normal blood pressure compared with Chinese and Thai participants. Some variation between Asian subgroups were also observed. Pacific Islander participants had higher risk of several sentinel health problems compared to Asian American participants. Disaggregation of PI Americans from the APIA umbrella category in future studies is necessary to unmask the critical needs of this important community.
Lockdown surgery: the impact of coronavirus disease 2019 measures on cardiac cases
Interactive Cardiovascular and Thoracic Surgery, April 13, 2022
The need to ration medical equipment and interventions during the coronavirus disease 2019 pandemic translated to an ever-lengthening wait list for surgical care. Retrospective analysis of lockdowns is of high importance to learn from the current situation for future pandemics. This monocentric study assessed the impact of lockdown periods on cardiac surgery cases and outcomes. The single-centre cross-sectional descriptive observational study was conducted to investigate the first lockdown period and the following post-lockdown period in comparison to the same periods during the previous 3 years at the Department of Cardiac Surgery at the Medical University of Innsbruck. Data were prospectively collected and retrospectively analysed from the department-specific quality management system. The primary objective was to compare the number of open-heart procedures between the pre-lockdown and the lockdown period. The secondary objectives were to analyse the characteristics and the outcomes of open-heart procedures. There were no differences in patient demographics. A significant decrease of 29% in weekly surgical procedures was observed during the lockdown period. The surgical case-mix was unaffected: The numbers of aortic valve replacements, coronary artery bypass grafts, mitral valve repair or replacement procedures and others remained stable. The urgency of cases increased significantly, and the general health conditions of patients appeared to be worse. However, outcomes were unchanged.
Clevidipine and COVID 19: From Hypertension to Inflammatory Response
Dovepress, April 13, 2022
Globally, more than 4 million have died from COVID-19, World Health Organization (WHO) to declare COVID-19 a pandemic. The COVID 19 pathology, produced by SARS-COV2, a virus from the coronavirus family, emerged at the end of 2019. The majority of cases usually have a mild or moderate form, characterized by fever, cough, intense asthenia and multiple symptoms derived from the initial replicative effect and subsequent hyperimmune effect. Severe cases present with Acute Respiratory Distress Syndrome (ARDS), due to pneumonia with bilateral involvement, which lead to hospital admission of patients and the need for admission to intensive care units (ICU) of approximately 10‒20%. According to the different series; the mortality of the condition once the patient is admitted to the ICU is close to 35‒45%. Currently, more than 4 million people have died in the world due to this pathology. The volume of infections generated the declaration by the World Health Organization (WHO) of the pandemic situation. Factors associated with a higher risk of progression into severe disease include age and comorbidities, especially systemic arterial hypertension due to its high incidence in the general population. Clevidipine can be rapidly and effectively adjusted to the clinical status of the patient, since it can be withdrawn and its effects reversed in just a few minutes, and contains high concentrations of lipids, and it could reduce the inflammatory response induced by SARS-COV2, which is key to progression into severe disease. However, its application in pro-inflammatory settings has not yet been explored, although it must play a key role in inflammation as a scavenger molecule.
Fourth Dose of BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting
New England Journal of Medicine, April 13, 2022
With large waves of infection driven by the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), alongside evidence of waning immunity after the booster dose of coronavirus disease 2019 (Covid-19) vaccine, several countries have begun giving at-risk persons a fourth vaccine dose. To evaluate the early effectiveness of a fourth dose of the BNT162b2 vaccine for the prevention of Covid-19–related outcomes, we analyzed data recorded by the largest health care organization in Israel from January 3 to February 18, 2022. We evaluated the relative effectiveness of a fourth vaccine dose as compared with that of a third dose given at least 4 months earlier among persons 60 years of age or older. We compared outcomes in persons who had received a fourth dose with those in persons who had not, individually matching persons from these two groups with respect to multiple sociodemographic and clinical variables. A sensitivity analysis was performed with the use of parametric Poisson regression. The primary analysis included 182,122 matched pairs. Relative vaccine effectiveness in days 7 to 30 after the fourth dose was estimated to be 45% (95% confidence interval [CI], 44 to 47) against polymerase-chain-reaction–confirmed SARS-CoV-2 infection, 55% (95% CI, 53 to 58) against symptomatic Covid-19, 68% (95% CI, 59 to 74) against Covid-19–related hospitalization, 62% (95% CI, 50 to 74) against severe Covid-19, and 74% (95% CI, 50 to 90) against Covid-19–related death. The corresponding estimates in days 14 to 30 after the fourth dose were 52% (95% CI, 49 to 54), 61% (95% CI, 58 to 64), 72% (95% CI, 63 to 79), 64% (95% CI, 48 to 77), and 76% (95% CI, 48 to 91). In days 7 to 30 after a fourth vaccine dose, the difference in the absolute risk (three doses vs. four doses) was 180.1 cases per 100,000 persons (95% CI, 142.8 to 211.9) for Covid-19–related hospitalization and 68.8 cases per 100,000 persons (95% CI, 48.5 to 91.9) for severe Covid-19. In sensitivity analyses, estimates of relative effectiveness against documented infection were similar to those in the primary analysis. A fourth dose of the BNT162b2 vaccine was effective in reducing the short-term risk of Covid-19–related outcomes among persons who had received a third dose at least 4 months earlier.
What is the association of renin–angiotensin–aldosterone system inhibitors with COVID-19 outcomes: retrospective study of racially diverse patients?
British Medical Journal, April 12, 2022
The objective of this study was to describe the clinical outcomes of COVID-19 in a racially diverse sample from the US Southeast and examine the association of renin–angiotensin–aldosterone system (RAAS) inhibitor use with COVID-19 outcome. This study is a retrospective cohort of 1024 patients with reverse-transcriptase PCR-confirmed COVID-19 infection, admitted to a 1242-bed teaching hospital in Alabama. Data on RAAS inhibitors use, demographics and comorbidities were extracted from hospital medical records. In-hospital mortality, a need of intensive care unit, respiratory failure, defined as invasive mechanical ventilation (iMV) and 90-day same-hospital readmissions. Among 1024 patients (mean (SD) age, 57 (18.8) years), 532 (52.0%) were African Americans, 514 (50.2%) male, 493 (48.1%) had hypertension, 365 (36%) were taking RAAS inhibitors. During index hospitalisation (median length of stay of 7 (IQR (4–15) days) 137 (13.4%) patients died; 170 (19.2%) of survivors were readmitted. RAAS inhibitor use was associated with lower in-hospital mortality (adjusted HR, 95% CI (0.56, (0.36 to 0.88), p=0.01) and no effect modification by race was observed (p for interaction=0.81). Among patients with hypertension, baseline RAAS use was associated with reduced risk of iMV, adjusted OR, 95% CI (aOR 0.58, 95% CI 0.36 to 0.95, p=0.03). Patients with heart failure were twice as likely to die from COVID-19, compared with patients without heart failure. In this retrospective study of racially diverse patients, hospitalised with COVID-19, prehospitalisation use of RAAS inhibitors was associated with 40% reduction in mortality irrespective of race.
Rate of acute myocarditis low in hospitalized patients with COVID-19
Healio | Cardiology Today, April 12, 2022
The prevalence of acute myocarditis was low in hospitalized patients with COVID-19 during the first 14 months of the pandemic, researchers reported in Circulation. The researchers conducted a retrospective cohort study of 56,963 hospitalized patients with COVID-19 from 23 centers in the United States and Europe from February 2020 to April 2021. “While COVID-19 is a virus that predominantly leads to acute respiratory illness, there has been a small group of individuals who also experience cardiac complications,” Enrico Ammirati, MD, PhD, a cardiologist at De Gasperis Cardio Center and Transplant Center at Niguarda Hospital in Milan, said in a press release. “A small study previously indicated acute myocarditis is a rare occurrence in people infected with COVID-19. Our analysis of international data offers better insight to the occurrence of acute myocarditis during COVID-19 hospitalization, particularly before the COVID-19 vaccines were widely available.” The researchers suspected 112 patients of having acute myocarditis and identified 97 as having possible acute myocarditis. Of those, 54 patients (median age, 38 years; 39% women) were identified has having definite or probable acute myocarditis after cardiac MRI and/or endomyocardial biopsy. The prevalence of definite or probable acute myocarditis was 2.4 per 1,000 COVID-19 hospitalizations and the prevalence of possible acute myocarditis was 4.1 per 1,000 COVID-19 hospitalizations, Ammirati and colleagues found. Among those with definite or probable acute myocarditis, the most common symptoms were chest pain (55.5%) and dyspnea (53.7%), according to the researchers.
Clinical Practice Changes in Monitoring Hypertension early in the COVID-19 Pandemic
American Journal of Hypertension, April 11, 2022
Clinical practices can use telemedicine and other strategies (e.g., self-measured blood pressure [SMBP]) for remote monitoring of hypertension to promote control while decreasing risk of exposure to SARS-CoV-2, the virus that causes COVID-19. The DocStyles survey collected data from primary care providers (PCPs), obstetricians-gynecologists (OB/GYNs), and nurse practitioners/physician assistants (NP/PAs) in fall 2020 (n=1,502). We investigated clinical practice changes for monitoring hypertension that were implemented early in the COVID-19 pandemic and examined differences by clinician and practice characteristics (p<0.05). Overall, 369 (24.6%) of clinicians reported their clinical practices made no changes in monitoring hypertension early in the pandemic, 884 (58.9%) advised patients to monitor blood pressure at home or a pharmacy, 699 (46.5%) implemented or increased use of telemedicine for blood pressure monitoring visits, and 545 (36.3%) reduced the frequency of office visits for blood pressure monitoring. Compared with NP/PAs, PCPs were more likely to advise SMBP monitoring (adjusted prevalence ratios (aPR) 1.28, 95% confidence intervals (CI) 1.11-1.47), implement or increase use of telemedicine (aPR 1.23, 95% CI 1.04-1.46) and reduce the frequency of office visits (aPR 1.37, 95% CI 1.11-1.70) for blood pressure monitoring, and less likely to report making no practice changes (aPR 0.63, 95% CI 0.51-0.77).
Myopericarditis following COVID-19 vaccination and non-COVID-19 vaccination: a systematic review and meta-analysis
The Lancet | Respiratory Medicine, April 11, 2022
Myopericarditis is a rare complication of vaccination. However, there have been increasing reports of myopericarditis following COVID-19 vaccination, especially among adolescents and young adults. We aimed to characterise the incidence of myopericarditis following COVID-19 vaccination, and compare this with non-COVID-19 vaccination. We did a systematic review and meta-analysis, searching four international databases from Jan 1, 1947, to Dec 31, 2021, for studies in English reporting on the incidence of myopericarditis following vaccination (the primary outcome). We included studies reporting on people in the general population who had myopericarditis in temporal relation to receiving vaccines, and excluded studies on a specific subpopulation of patients, non-human studies, and studies in which the number of doses was not reported. Random-effects meta-analyses were conducted, and the intra-study risk of bias and certainty of evidence were assessed. We analysed the difference in incidence of myopericarditis among subpopulations, stratifying by the type of vaccine (COVID-19 vs non-COVID-19) and age group (adult vs paediatric). Among COVID-19 vaccinations, we examined the effect of the type of vaccine (mRNA or non-mRNA), sex, age, and dose on the incidence of myopericarditis. The overall incidence of myopericarditis from 22 studies (405 272 721 vaccine doses) was 33·3 cases (95% CI 15·3–72·6) per million vaccine doses, and did not differ significantly between people who received COVID-19 vaccines (18·2 [10·9–30·3], 11 studies [395 361 933 doses], high certainty) and those who received non-COVID-19 vaccines (56·0 [10·7–293·7], 11 studies [9 910 788 doses], moderate certainty, p=0·20). Compared with COVID-19 vaccination, the incidence of myopericarditis was significantly higher following smallpox vaccinations (132·1 [81·3–214·6], p<0·0001) but was not significantly different after influenza vaccinations (1·3 [0·0–884·1], p=0·43) or in studies reporting on various other non-smallpox vaccinations (57·0 [1·1–3036·6], p=0·58). Among people who received COVID-19 vaccines, the incidence of myopericarditis was significantly higher in males (vs females), in people younger than 30 years (vs 30 years or older), after receiving an mRNA vaccine (vs non-mRNA vaccine), and after a second dose of vaccine (vs a first or third dose).
SARS-CoV-2 Infection and Associated Cardiovascular Manifestations and Complications in Children and Young Adults: A Scientific Statement From the American Heart Association
Circulation, April 11, 2022
Coronavirus disease 2019 (COVID-19) resulted in a global pandemic and has overwhelmed health care systems worldwide. In this scientific statement, we describe the epidemiology, pathophysiology, clinical presentations, treatment, and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome in children and young adults with a focus on cardiovascular manifestations and complications. We review current knowledge about the health consequences of this illness in children and young adults with congenital and acquired heart disease, the public health burden and health disparities of this infection in these populations, and vaccine-associated myocarditis.
Patients with allergic disorders have greater risk of high blood pressure and coronary heart disease
News Medical, April 11, 2022
Data from the National Health Interview Survey demonstrated adults with a history of allergic disorders have an increased risk of high blood pressure and coronary heart disease, with the highest risk seen in Black male adults. The study is being presented at ACC Asia 2022 Together with the Korean Society of Cardiology Spring Conference on April 15-16, 2022. Previous studies reported an association between allergic disorders and cardiovascular disease, which remain controversial findings, Guo said. The current study aimed to determine whether adults with allergic disorders have increased cardiovascular risk. The study used 2012 data from the National Health Interview Survey (NHIS), which is a cross-sectional survey of the United States population. The allergic group included adults with at least one allergic disorder, including asthma, respiratory allergy, digestive allergy, skin allergy and other allergy. Overall, the study included 34,417 adults, over half of whom were women and averaged 48.5 years old. The allergic group included 10,045 adults. The researchers adjusted for age, sex, race, smoking, alcohol drinking and body mass index; they also examined subgroups stratified by demographic factors. The researchers found a history of allergic disorders was associated with increased risk of developing high blood pressure and coronary heart disease. In further analyses, individuals with a history of allergic disorders between ages 18 and 57 had a higher risk of high blood pressure. A higher risk of coronary heart disease was seen in study participants who were between ages 39-57, male and Black/African American. Asthma contributed most to the risk of high blood pressure and coronary heart disease.
New-Onset Atrial Fibrillation in COVID-19 Infection: A Case Report and Review of Literature
Cureus, April 7, 2022
Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many cases of arrhythmias have been reported in patients with COVID-19 infection. We present the case of a 66-year-old female with no known cardiovascular history who presented with worsening shortness of breath and productive cough and tested positive for COVID-19 infection in the ED. The patient had a recent hospitalization for COVID-19 infection during which she was treated with dexamethasone and remdesivir therapy and her course remained uncomplicated at that time. Following this, she developed worsening shortness of breath at home for which she presented to the ED. During this hospitalization, she was treated with dexamethasone, remdesivir, and supplemental oxygen. On day six of hospitalization, the patient became tachycardic and had palpitations. Cardiac monitor and EKG showed evidence of new-onset atrial fibrillation (NOAF). Initially patient received metoprolol and diltiazem, both of which failed to achieve adequate rate control. Following this, the patient was started on carvedilol 30 mg every six hours, which attained good rate control. Her CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74, and sex category) score was 4 for which she was started on apixaban 5mg twice daily. The patient was discharged on the same medications. Despite increasing reported incidences of NOAF in COVID-19 infection, only little is known about the optimal management strategies and possible etiopathology. The aim of our review is to highlight the possible mechanisms triggering atrial fibrillation in COVID-19 infection and go over the management strategies while reviewing the available literature.
Severe COVID linked to RAAS and hyperlipidemia associated metabolic syndrome conditions
News Medical, April 6, 2022
A recent study posted to the medRxiv preprint server investigated the association of renin-angiotensin-aldosterone system (RAAS)-mediated hypertension (HT) with coronavirus disease 2019 (COVID-19). Various studies have reported the role of angiotensin-converting enzyme-2 (ACE-2) receptors as the point of entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This information makes the ACE-2 receptors a critical focus in the assessment of RAAS-mediated hypertension and COVID-19 severity. In the present study, researchers explored the physiology of risk factors related to the impact of COVID-19 on RAAS-targeted HT drugs and the interactions of hyperlipidemia (HL) with other risk factors associated with severe COVID-19. The team collected data from electronic health records obtained from emergency and clinical health services and insurance records. The extracted records were classified into different sets based on several measures. The study results showed that among the two sample sets extracted, the random cohort comprised 997,140 individuals, the COVID-19-infected cohort comprised 269,536 patients, and the control group comprised 269,987 individuals. The team found a strong association between HT and severe COVID-19. Additionally, distinctive metabolic syndrome features were observed among the study populations, including susceptibility to HT drugs, type 2 diabetes, and subsequent kidney failure. In these populations, calcium channel blockers were the primary choice of medicines for HT treatment, whereas RAAS drugs were not used often by severe COVID-19 patients. The study findings showed that the RAAS complex played an important role in the exacerbation of chronic kidney disease in severe COVID-19 patients. The team also noted a trend that indicated that RAAS drugs suppressed the correlation of hypertension with severe COVID-19 more significantly than non-RAAS drugs.
ECG can pinpoint hospitalized COVID-19 patients at high risk of mortality
News Medical, April 4, 2022
A simple electrocardiogram (ECG) can pinpoint hospitalized COVID-19 patients at high risk of death who might need intensive management. That’s the finding of a study presented at EHRA 2022, a scientific congress of the European Society of Cardiology (ESC). Specifically, the research showed that a prolonged QT interval on the ECG was an independent risk factor for both myocardial injury and one-year mortality. An ECG records electrical activity as it travels through the heart. The information is displayed as a graph, which is divided into sections according to the location in the heart. The QT interval refers to the electrical signal from the moment the ventricles of the heart contract until they finish relaxing and is measured in milliseconds. Patients with a prolonged QT interval are at increased risk for life-threatening arrhythmias (heart rhythm disorders) and cardiac arrest. This study examined the association between QT prolongation and long-term mortality in patients hospitalized with COVID-19. It also evaluated the relationship between prolonged QT interval and myocardial injury, a condition in which cells in the heart die. A total of 335 consecutive patients hospitalized with COVID-19 were prospectively studied. All patients had an ECG upon admission. Patients were deemed to have myocardial injury if they showed reduced function on an echocardiogram, which is an ultrasound of the heart, and/or had troponin in the bloodstream. Troponin is a protein found only in heart cells. When the heart is damaged, for example in myocardial injury, troponin is released into the bloodstream. At one year, 41% of patients in the prolonged QT interval group had died compared to 17% in the normal QT interval group. QT prolongation was associated with a 1.85-fold increased risk of dying within a year after adjusting for age, co-existing conditions and severity of COVID-19. When patients were divided into four groups according to the presence of myocardial injury (yes/no) and QT prolongation (yes/no), those with both conditions had a 6.6-fold higher likelihood of one-year mortality compared to patients without QT prolongation and no myocardial injury.
How to use digital devices to detect and manage arrhythmias: an EHRA practical guide
EP Europace, April 3, 2022
The recent advances in technology combined with the need to manage patients remotely during the coronavirus disease-19 (COVID-19) pandemic, have led to a rapid adaptation of the use of digital devices in clinical practice. The term digital devices for heart rhythm monitoring in this paper encompasses many of the novel devices, such as patches, various wearable devices, and handheld devices that have been approved by regulatory authorities for medical purposes. Cardiac implantable electronic devices (CIEDs), devices that can deliver therapy (such as life vests) and Holter monitors fall outside the scope of this paper. Although many perceive the potential benefits from digital workflow, recent surveys show disparities in management with concerns from healthcare professionals of data overload and unsolicited registrations from unfamiliar digital devices. The aim of the document is to provide up-to-date practical guidance on the use of digital devices for arrhythmias, from early detection through management and implementation, using the categories of consensus.
The impact of pre-existing hypertension and its treatment on outcomes in patients admitted to hospital with COVID-19
Hypertension Research, March 29, 2022
The impact of pre-existing hypertension on outcomes in patients with the novel corona virus (SARS-CoV-2) remains controversial. To address this, we examined the impact of pre-existing hypertension and its treatment on in-hospital mortality in patients admitted to hospital with Covid-19. Using the CAPACITY-COVID patient registry we examined the impact of pre-existing hypertension and guideline-recommended treatments for hypertension on in-hospital mortality in unadjusted and multi-variate-adjusted analyses using logistic regression. Data from 9197 hospitalised patients with Covid-19 (median age 69 [IQR 57–78] years, 60.6% male, n = 5573) was analysed. Of these, 48.3% (n = 4443) had documented pre-existing hypertension. Patients with pre-existing hypertension were older (73 vs. 62 years, p < 0.001) and had twice the occurrence of any cardiac disease (49.3 vs. 21.8%; p < 0.001) when compared to patients without hypertension. The most documented class of anti-hypertensive drugs were angiotensin receptor blockers (ARB) or angiotensin converting enzyme inhibitors (ACEi) (n = 2499, 27.2%). In-hospital mortality occurred in (n = 2020, 22.0%), with more deaths occurring in those with pre-existing hypertension (26.0 vs. 18.2%, p < 0.001). Pre-existing hypertension was associated with in-hospital mortality in unadjusted analyses (OR 1.57, 95% CI 1.42,1.74), no significant association was found following multivariable adjustment for age and other hypertension-related covariates (OR 0.97, 95% CI 0.87,1.10). Use of ACEi or ARB tended to have a protective effect for in-hospital mortality in fully adjusted models (OR 0.88, 95% CI 0.78,0.99). After appropriate adjustment for confounding, pre-existing hypertension, or treatment for hypertension, does not independently confer an increased risk of in-hospital mortality patients hospitalized with Covid-19.
Vascular Dysfunction of COVID-19 Is Partially Reverted in the Long-Term
Circulation Research, March 29, 2022
COVID-19 is characterized by severe inflammation during the acute phase and increased aortic stiffness in the early postacute phase. In other models, aortic stiffness is improved after the reduction of inflammation. We aimed to evaluate the mid- and long-term effects of COVID-19 on vascular and cardiac autonomic function. The primary outcome was aortic pulse wave velocity (aPWV). The cross-sectional Study-1 included 90 individuals with a history of COVID-19 and 180 matched controls. The longitudinal Study-2 included 41 patients with COVID-19 randomly selected from Study-1 who were followed-up for 27 weeks. Study-1: Compared with controls, patients with COVID-19 had higher aPWV and brachial PWV 12 to 24 (but not 25–48) weeks after COVID-19 onset, and they had higher carotid Young’s elastic modulus and lower distensibility 12 to 48 weeks after COVID-19 onset. In partial least squares structural equation modeling, the higher the hs-CRP (high-sensitivity C-reactive protein) at hospitalization was, the higher the aPWV 12 to 48 weeks from COVID-19 onset (path coefficient: 0.184; P=0.04). Moreover, aPWV (path coefficient: −0.186; P=0.003) decreased with time. Study-2: mean blood pressure and carotid intima-media thickness were comparable at the end of follow-up, whereas aPWV (−9%; P=0.01), incremental Young’s elastic modulus (−17%; P=0.03), baroreflex sensitivity (+28%; P=0.049), heart rate variability triangular index (+15%; P=0.01), and subendocardial viability ratio (+12%; P=0.01×10−4) were significantly improved. There was a trend toward improvement in brachial PWV (−6%; P=0.14) and carotid distensibility (+18%; P=0.05). Finally, at the end of follow-up (48 weeks after the onset of COVID-19) aPWV (+6%; P=0.04) remained significantly higher in patients with COVID-19 than in control subjects.
FDA authorizes second COVID-19 booster shot for adults aged 50 years or older
Healio | Infectious Disease, March 29, 2022
The FDA on Tuesday authorized a second booster dose of COVID-19 vaccine for people aged 50 years or older and certain immunocompromised patients, citing evidence that it improves protection against severe disease. The authorization applies to the messenger RNA vaccines made by Pfizer-BioNTech and Moderna. The FDA previously authorized a booster shot for older adults in September. They are now eligible for a fourth shot. Immunocompromised adults who received a recommended three-dose primary series of either vaccine have been eligible for a fourth dose since October and may now receive a fifth dose. Following the authorization, the CDC updated its recommendations to include an additional dose for these populations, adding that adults who received a primary vaccine and booster dose of Johnson & Johnson’s vaccine at least 4 months ago may now receive a second booster dose of an mRNA vaccine. The FDA specified that a second booster dose of either mRNA vaccine may be administered to people aged 50 years or older at least 4 months after they received their first booster dose of any authorized or approved COVID-19 vaccine.
Inflammatory cytokines and cardiac arrhythmias: the lesson from COVID-19
Nature Reviews Immunology, March 28, 2022
Although inflammatory cytokines are implicated in the pathogenesis of cardiac arrhythmias, inflammation is still largely overlooked in the current management of heart rhythm disorders. Now, COVID-19, a systemic inflammatory disease, causes an unexpectedly high prevalence of arrhythmic events, emphasizing the relevance of inflammation in the pathogenesis of cardiac arrhythmias. Cardiac arrhythmias are a leading cause of morbidity and mortality in Western countries, but the underlying mechanisms are still ill-defined. Over the past decade, systemic inflammation has been shown to promote a wide spectrum of cardiac arrhythmias, particularly atrial fibrillation, long-QT syndrome and Torsades de Pointes and atrioventricular blocks. Moreover, inflammatory cytokines also seem to be involved in arrhythmogenic cardiomyopathy and other arrhythmogenic syndromes. Nevertheless, inflammation is still largely overlooked in the management of arrhythmias, and as yet, agents that target the immune-inflammatory system have not become standard treatments as antiarrhythmics. There is increasing evidence that these medications may be effective in the clinic; however, large randomized placebo controlled trials are yet to be carried out. The unexpectedly high prevalence of arrhythmic events after COVID-19 has caused a marked increase in interest in this topic. Suddenly, millions of patients share the same, repetitive and well-defined cause of systemic inflammation along with frequent cardiac arrhythmias.
Post-COVID-19 assessment may be needed in some high-hazard workers before return to work
Healio | Cardiology Today, March 26, 2022
The Aviation and Occupational Cardiology Task Force of the European Association of Preventive Cardiology issued a statement on the post-COVID-19 infection evaluation of high-hazard workers prior to return to dangerous work. The task force defined high-hazard workers as pilot and non-pilot aircrews, drivers of heavy goods vehicles, train drivers, professional taxi services, fire crew, police, divers, military, mountaineers, polar workers, offshore workers, and astronauts and space workers. Published in the European Journal of Preventive Cardiology, the position statement includes a decision pathway for cardiopulmonary assessment for occupationally informed physicians based on high-hazard worker COVID-19 symptom severity as well as recommendations for testing modalities. “The challenge in assessing patients with ongoing symptoms following COVID-19 infection is the requirement to discriminate symptoms caused by organ pathology, from those caused by a more typical post-viral syndrome, documented in many well-characterized viral diseases,” Rienk Rienks, MD, PhD, cardiologist at the Central Military Hospital, University Hospital Utrecht, the Netherlands, and colleagues wrote. “This challenge is often compounded by health anxiety, which is particularly pertinent to employees undertaking high-hazard work due to additional concerns regarding future employment. Whilst the overall likelihood of significant pathology in this cohort may be low, employers need to be able to sign off an employee to undertake their high-hazard (and high risk) employment, and to ensure risk is mitigated. Even those who are asymptomatic may need investigation, given that subclinical disease may be occupationally significant.” The position statement included a COVID-19 assessment tool, a flow chart to assist clinical risk triage based on COVID-19 symptoms, hypoxia and ECG findings.
Stroke ‘exceedingly rare’ after COVID-19 vaccination
Healio | Neurology, March 24, 2022
Strokes were reported to be a rare adverse event following the administration of a COVID-19 vaccine, according to a study in Neurology. Using data provided by the Mexican Ministry of Health, Diego Lopez-Mena, MD, of the National Institute of Neurology and Neurosurgery in Mexico City, and colleagues conducted a nationwide retrospective, descriptive study that analyzed stroke incidence per million COVID-19 vaccine doses administered in hospitalized adults from December 2020 to August 2021. Strokes were reported only if they were confirmed within the first 30 days after vaccination. During the study, 79,399,446 doses of six different COVID-19 vaccines from Pfizer/BioNTech, AstraZeneca, Sinovac Biotech, CanSino Biologics, Johnson & Johnson and Sputnik V were administered. A total of 28,646 adverse events occurred within the first 30 days. Of those, 27,968 (98%) were classified as non-serious, and 56 were confirmed as stroke (8.2% of serious adverse events; 55.5% women; median age, 65 years). Overall, stroke incidence was 0.71 cases per 1,000,000 administered doses (95% CI, 0.54-0.92), and the median time from vaccination to stroke was 2 days (interquartile range = 1-5 days). Further, the most frequent type of stroke was acute ischemic stroke, which occurred in 43 of the 56 patients (75%; incidence rate = 0.54 per 1,000,000; 95% CI, 0.40-0.73); nine strokes were intracerebral hemorrhages (16.1%; IR – 0.11 per 1,000,000; 95% CI, 0.06-0.22). The most common risk factors were hypertension (58.9%) and diabetes mellitus (39.3%).
Long COVID and cardiovascular disease: a learning health system approach
Nature Reviews Cardiology, March 24, 2022
Cardiovascular disease is both a risk factor and potential outcome of the direct, indirect and long-term effects of COVID-19. A recent analysis in >150,000 survivors of COVID-19 demonstrates an increased 1-year risk of numerous cardiovascular diseases. Preventing and managing this new disease burden presents challenges to health systems and requires a learning health system approach. Xie and colleagues systematically assessed the incidence of numerous CVD subtypes in 153,760 individuals with COVID-19 from the US Department of Veterans Affairs national database who survived beyond 30 days, comparing them with control groups from the same database from before and during the pandemic and with no evidence of SARS-CoV-2 infection. The investigators found an increased risk and excess burden of incident CVDs among all subgroup of patients with COVID-19 (non-hospitalized, hospitalized and those admitted to the intensive care unit) compared with the control groups. These diseases included atrial fibrillation (HR 1.71, 95% CI 1.64–1.79), ischaemic heart disease (HR 1.72, 95% CI 1.56–1.90), pericarditis (HR 1.85, 95% CI 1.61–2.13), myocarditis (HR 5.38, 95% CI 3.80–7.59), heart failure (HR 1.72, 95% CI 1.65–1.80) and thromboembolic disease (HR 2.93, 95% CI 2.73–3.15). To summarize, bidirectional relationships exist between CVD and COVID-19. Multimorbidity and CVD are key considerations in patients with long COVID, who require multidisciplinary and integrated care. Long COVID, including cardiovascular complications, has potentially far-reaching implications for health system resources, including staffing, infrastructure and funding.
Rise in heart disease, stroke deaths seen during first year of pandemic
Healio | Cardiology Today, March 23, 2022
CDC data show heart disease and stroke deaths increased during the first year of the COVID-19 pandemic due to factors other than an aging population, reversing prior trends and widening race disparities. From 2019 to 2020, researchers also found Black adults had both the greatest increase and the highest overall rate of heart disease and stroke deaths compared with adults from other races and ethnicities. “We had been making progress in reducing deaths from heart disease and stroke, primarily due to preventive measures and timely interventions,” Stephen Sidney, MD, MPH, director of research clinics and senior research scientist with Kaiser Permanente Northern California Division of Research, told Healio. “Our study showed the pandemic didn’t just stop these gains, it reversed them, with Black, Latino and Asian adults hit hardest. This tells us we are not doing enough nationwide to make health care equally accessible to all and to optimize the preventive measures we know can improve CV health.” Sidney and colleagues analyzed CDC data collected from 2011 to 2020 to assess age-adjusted mortality rates for heart disease and stroke, age-specific numbers of deaths and population estimates, using the WONDER database. Researchers estimated year-to-year change in age-associated deaths by multiplying the age-specific death rate for 1 year by the age-specific population of the next year. Risk-associated mortality was calculated as change in total deaths minus age-associated change in deaths, representing deaths associated with underlying changes in disease risk. During the first year of the COVID-19 pandemic, heart disease and stroke deaths increased by 5.8% and 6.8%, respectively. However, the age-associated increases were 1.6% and 1.7% for heart disease and stroke, respectively, whereas risk-associated increases were 4.1% for heart disease and 5.2% for stroke.
In Conversation: Long COVID’s cardiovascular implications
Medical News Today, March 22, 2022
Millions of people worldwide live with long COVID, a condition characterized by symptoms of COVID-19 and other syndromes months after the initial illness has subsided. One aspect of particular concern is its cardiovascular implications, including a rise in postural orthostatic tachycardia syndrome (POTS) and increased cardiovascular disease risk. Our latest In Conversation episode delves into this topic. It is unclear how many people around the world live with long COVID. However, one study that is yet to undergo peer review estimates that as of August 2021, about 43% of people who tested positive for COVID-19, and more than half of those who received hospitalized care for this disease, ended up developing long COVID.
Closed Loop Medicine announces completion of precision medicine clinical trial for patients with high blood pressure
News Medical, March 22, 2022
Closed Loop Medicine Ltd, a leader in the development of single prescription drug plus digital therapy (DTx) combination products to enable precision dosing and care, announced today that the last patient has completed participation in a clinical trial investigating the Company’s integrated precision care product solution for patients with hypertension. Closed Loop Medicine is developing drug and digital therapeutic combination products centred around dose optimization, to improve outcomes for patients, support clinicians, and enable a move towards a value-based medicine proposition for health systems by delivering precision care at a population health scale. The clinical trial, called PERSONAL COVID BP, aimed to investigate whether a combination product that links a drug to a smart phone app can enable patients to personalize and optimise their therapy regimen to treat hypertension. Importantly, the technology in the study allowed patients shielding from COVID-19 to report COVID-19 infection related symptoms as well as control their blood pressure remotely, on a daily basis, from home. The Company rapidly evolved its approach to continue studies through the COVID-19 lockdown, by re-designing studies to run remotely and through technology development, including using the uMED decentralised clinical trial platform. The interventional arm of the study exceeded its recruitment target of 200 patients, with patients receiving drug therapy while using an app to monitor blood pressure and any potential side effects. The data from this study is being used to drive the development of the Company’s highly innovative product that will deliver precision control of blood pressure at population health scale. The product will save lives by addressing the number one killer in the western world, high blood pressure – which, even in the pre-vaccination year of COVID-19 in 2020, killed more people than cancer or COVID-19.
Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial
Journal of the American Medical Association, March 22, 2022
The efficacy of antiplatelet therap
Anticoagulation in Patient
y in critically ill patients with COVID-19 is uncertain. Our objective was to determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days. Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. The primary endpoint was organ support–free days (days alive and free of intensive care unit–based respiratory or cardiovascular organ support) within 21 days, ranging from −1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support–free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support–free days was 7 (IQR, −1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, −0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support–free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm).
Pericardial Involvement in Patients Hospitalized With COVID‐19: Prevalence, Associates, and Clinical Implications
Journal of the American Heart Association, March 21, 2022
The scope of pericardial involvement in COVID‐19 infection is unknown. We aimed to evaluate the prevalence, associates, and clinical impact of pericardial involvement in hospitalized patients with COVID‐19. Consecutive patients with COVID‐19 underwent clinical and echocardiographic examination, irrespective of clinical indication, within 48 hours as part of a prospective predefined protocol. Protocol included clinical symptoms and signs suggestive of pericarditis, calculation of modified early warning score, ECG and echocardiographic assessment for pericardial effusion, left and right ventricular systolic and diastolic function, and hemodynamics. We identified predictors of mortality and assessed the adjunctive value of pericardial effusion on top of clinical and echocardiographic parameters. The study included 530 patients. Pericardial effusion was found in 75 (14%), but only 17 patients (3.2%) fulfilled the criteria for acute pericarditis. Pericardial effusion was independently associated with modified early warning score, brain natriuretic peptide, and right ventricular function. It was associated with excess mortality (hazard ratio [HR], 2.44; P=0.0005) in nonadjusted analysis. In multivariate analysis adjusted for modified early warning score and echocardiographic and hemodynamic parameters, it was marginally associated with mortality (HR, 1.86; P=0.06) and improvement in the model fit (P=0.07). Combined assessment for pericardial effusion with modified early warning score, left ventricular ejection fraction, and tricuspid annular plane systolic excursion was an independent predictor of outcome (HR, 1.86; P=0.02) and improved model fit (P=0.02). In hospitalized patients with COVID‐19, pericardial effusion is prevalent, but rarely attributable to acute pericarditis. It is associated with myocardial dysfunction and mortality. A limited echocardiographic examination, including left ventricular ejection fraction, tricuspid annular plane systolic excursion, and assessment for pericardial effusion, can contribute to outcome prediction.
Association of Amlodipine with the Risk of In-Hospital Death in Patients with COVID-19 and Hypertension: A Reanalysis on 184 COVID-19 Patients with Hypertension
Pharmaceuticals, March 21, 2022
Association between calcium channel blockers (CCBs) or functional inhibitors of acid sphingomyelinase (FIASMAs) use and decreased mortality in people with COVID-19 has been reported in recent studies. Since amlodipine is both a CCB and a FIASMA, the aim of this study was to investigate the association between chronic amlodipine use and the survival of people with hypertension infected with COVID-19. This retrospective cohort study used data extracted from the medical records of adult inpatients with hypertension and laboratory-confirmed COVID-19. We re-analyzed the data of the retrospective cohort study using only the 184 patients (103 males, 81 females) with a mean age of 69.54 years (SD = 14.6) with hypertension. The fifty-five participants (29.9%) receiving a chronic prescription of amlodipine were compared with the 129 patients who did not receive a chronic prescription of amlodipine. Univariate and multivariate logistic regressions were used to explore the relationships between mortality and sex, age, comorbidities, smoking, and amlodipine status. Out of the 184 participants, 132 (71.7%) survived and 52 (28.3%) died. The mortality rates were, respectively, 12.73% (n = 7) and 34.88% (n = 45) for the amlodipine and non-amlodipine groups. Multivariate logistic regression was significant (Chi square (5) = 29.11; p < 0.0001). Chronic kidney disease and malignant neoplasm were significant predictors as well as amlodipine status. For chronic kidney disease and malignant neoplasm, the odds ratio with 95% confidence interval (95% CI) were, respectively, 2.16 (95% CI: 1.04–4.5; p = 0.039) and 2.46 (95% CI: 1.01–6.01; p = 0.047). For amlodipine status the odds ratio was 0.29 (95% CI: 0.11–0.74; p = 0.009). The result of the present study suggests that amlodipine may be associated with reduced mortality in people with hypertension infected with COVID-19. Further research and randomized clinical trials are needed to confirm the potential protective effect of amlodipine in people with hypertension infected with COVID-19.
Fulminant Giant Cell Myocarditis following Heterologous Vaccination of ChAdOx1 nCoV-19 and Pfizer-BioNTech COVID-19
Medicina, March 20, 2022
The global spread of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has resulted in countless deaths. To prevent this, several COVID-19 vaccines have been used worldwide. The ChAdOx1 nCoV-19 (or AZD1222) vaccine is an adenoviral vector-based vaccine and its design was based on the vaccine for the previous Middle East Respiratory Syndrome Coronavirus. Pfizer-BioNTech COVID-19, using mRNA, encodes a pre-fusion membrane-bound stabilized full-length S-2P encapsulated with lipid nanoparticles. Vaccination is crucial in controlling the spread of COVID-19 and decreasing the COVID-19 morbidity and mortality rates. The development of myocarditis and inflammatory myocardial cellular infiltrates have been reported after vaccination, especially after the smallpox vaccine. Witberg et al. reported association between the development of myocarditis and the receipt of messenger RNA (mRNA) vaccines against COVID-19. The estimated incidence of myocarditis was 2.13 cases per 100,000 persons. Most cases of myocarditis were mild or moderate in severity. Two previous studies on myocarditis, following COVID-19 mRNA vaccination, reported cardiac biopsy results, which showed no evidence of myocarditis. Almost all patients had resolution of symptoms and signs, and improvement in clinical markers and imaging with or without treatment. In our case, the patient presents a rapid deterioration of cardiac function, following heterologous ChAdOx1 nCoV-19 and Pfizer-BioNTech COVID-19 vaccination and cardiac transplantation. We present a case of fulminant giant cell myocarditis (GCM) following heterologous vaccination with the ChAdOx1 nCoV-19 and Pfizer-BioNTech COVID-19 vaccines and discuss its clinicopathologic findings.
Does Losartan reduce the severity of COVID-19 in hypertensive patients?
BMC Cardiovascular Disorders, March 19, 2022
One of the global problems is to control the coronavirus epidemic, and the role of different medicines is still unknown to policymakers. This study was conducted to evaluate the effects of losartan on the mortality rate of COVID-19 in hypertensive patients. The research sample of analytical study included 1458 patients presenting to COVID-19 diagnostic centers in Yazd that were examined in the first six months of 2020. Data were analyzed using descriptive statistics as well as chi-square, Fisher’s exact test, t test, and logistic regression. Of 1458 subjects that were studied, 280 were hypertensive of whom 179 tested positive for SARS-CoV-2 PCR. The results showed a lower chance of death by more than 5 times in hypertensive patients who used losartan (P = 0.003). Moreover, regarding the effect of losartan on the prevention of COVID-19 in hypertensive patients, it was found that this medicine played a protective role although this relationship was not statistically significant (P = 0.86). The results showed that losartan reduced the chance of mortality in hypertensive patients. It is recommended that the effect of losartan and other blood pressure medicines on COVID-19 patients be investigated in larger studies as well as laboratory investigations.
Significant association between ischemic heart disease and elevated risk for COVID-19 mortality: A meta-analysis
The American Journal of Emergency Medicine, March 18, 2022
A number of previous papers have examined the association between ischemic heart disease (IHD) and the risk for mortality among patients with coronavirus disease 2019 (COVID-19), but there have been inconsistent findings across studies. For example, a few studies have found that there was a significant association between IHD and an elevated risk for COVID-19 mortality, but some other studies have concluded that IHD was not significantly associated with the risk for COVID-19 mortality. Therefore, we performed this quantitative meta-analysis to determine whether there was a significant association between IHD and COVID-19 mortality or not. Gender, age and several comorbidities have been documented to affect the clinical outcomes of COVID-19 patients, indicating that those variables might affect the relationship between IHD and the risk for COVID-19 mortality. Taken together, the pooled effect on the relationship between IHD and COVID-19 mortality was estimated on the basis of adjusted effects in this meta-analysis. We searched PubMed, Web of Science and EMBASE using the following keywords: (“SARS-CoV-2” or “COVID-19” or “2019-nCoV”) and (“ischemic heart disease”) and (“death” or “mortality” or “fatality” or “deceased” or “non-survivor”). A total of 36 studies (335, 720 cases) were included in this meta-analysis. Our meta-analysis demonstrated that there was a significant association between IHD and an elevated risk of COVID-19 mortality (pooled effect size = 1.27, 95% confidence interval (CI) [1.17–1.38]). In summary, our meta-analysis showed that IHD was significantly associated with an increased risk for death among COVID-19 patients. Further well-designed studies with large sample sizes are required to verify the findings of our present study.
Multisystem inflammatory syndrome-related refractory cardiogenic shock in adults after COVID-19 infection: a case series
European Heart Journal Case Reports, March 18, 2022
A novel multisystem inflammatory syndrome in children (MIS-C) temporally associated with the coronavirus disease 2019 (COVID-19) infection has been reported, arising weeks after the peak incidence of COVID-19 infection in adults. Patients with MIS-C have been reported to have cardiac involvement and clinical features overlapping with other acute inflammatory syndromes such as Kawasaki-Disease, toxic shock syndrome, and macrophage activation syndrome. MIS-C may follow Covid-19 infection, most of the time after its asymptomatic form, even though it can lead to serious and life-threatening illness. In this case series, we discuss two cases of young adults with no former medical history who fit with the criteria defined in MIS-C. They both developed a refractory cardiogenic shock and required intensive care treatment including mechanical circulatory support, specifically the use of venous-arterial extracorporeal membrane oxygenation (VA-ECMO). They were both treated early with intravenous immune globulin and adjunctive high-dose steroids. They recovered ad integrum in less than two weeks. MIS-C occurs 2 to 4 weeks after infection with SARS-CoV-2. Patients with MIS-C should ideally be managed in an intensive care environment since rapid clinical deterioration may occur. It would be preferable to have a multi-disciplinary care to improve outcomes. Patients should be monitored for shock. Elucidating the mechanism of this new entity may have importance for understanding COVID-19 far beyond the patients who have had MIS-C to date. The pathogenesis seems to involve post-infectious immune dysregulation so early administration intravenous immune globulin associated to corticosteroids appears appropriate. It implies early recognition of the syndrome even in young adults.
ACC Issues Playbook for Long COVID With Cardiac Involvement
MedPage Today, March 16, 2022
People with long COVID and cardiovascular symptoms may now follow a prescribed path for evaluation and treatment recommended by the American College of Cardiology (ACC). According to the new guidance, people with post-acute sequelae of SARS-CoV-2 infection (PASC) should undergo evaluation with laboratory tests, electrocardiograms (ECGs), echocardiography, ambulatory rhythm monitoring, and/or additional pulmonary testing depending on the clinical presentation, according to Ty Gluckman, MD, MHA, of Providence St. Joseph Health in Tigard, Oregon, and colleagues of the writing group. Abnormal test results would merit cardiology consultation and further evaluation, Gluckman’s team said in a new ACC expert consensus decision pathway, published online in the Journal of the American College of Cardiology. The statement suggests that PASC patients should be split into two groups—those with outright, documented cardiovascular disease; and those with “cardiovascular syndrome,” a heterogeneous disorder that includes a wide range of cardiovascular symptoms that cannot be explained by testing. In the case of PASC-cardiovascular syndrome, the predominant symptom should drive evaluation and management. People with unexplained tachycardia and exercise intolerance, for example, should avoid cardiovascular deconditioning and maintain physical activity by means of seated exercises (e.g., rowing, swimming or cycling). They can transition back to upright exercise as symptoms improve.
Myocardial performance index increases at long-term follow-up in patients with mild to moderate COVID-19
Echocardiography, March 16, 2022
The long-term cardiovascular effects of Coronavirus disease-2019 (COVID-19) are not yet well known. Myocardial performance index (MPI) is a non-invasive, inexpensive and reproducible echocardiographic parameter that reflects systolic and diastolic cardiac functions. The aim of the study was to compare MPI with a healthy control group in patients with mild or moderate COVID-19 infection who subsequently had unexplained cardiac symptoms. The study included 200 patients aged 18–70 years who were diagnosed with COVID-19 infection at least 2 months ago and defined cardiac symptoms in their follow-up. Patients with mild or moderate symptoms, no history of hospitalization, and no other pathology that could explain cardiac symptoms were included in the study. As the control group, 182 healthy volunteers without COVID-19 were evaluated. Echocardiographic examination was performed on the entire study group. Isovolumetric contraction time (IVCT), isovolumetric relaxation time (IVRT), and ejection time (ET) were measured by tissue Doppler imaging. MPI was calculated with the IVCT+IVRT/ET formula. The mean age of the study group was 44.24 ± 13.49 years. In the patient group the MPI was significantly higher (.50 ± .11 vs .46 ± .07, p < .001), IVRT was longer (69.67 ± 15.43 vs 65.94 ± 12.03 ms, p = .008), and ET was shorter (271.09 ± 36.61 vs 271.09 ± 36.61 ms, p = .028). IVCT was similar between groups (63.87 ± 13.66 vs. 63.21 ± 10.77 ms, p = .66). Mitral E and mitral A wave, E’, A’, and E/A were similar in both groups.
Cardiac involvement in coronavirus disease 2019 assessed by cardiac magnetic resonance imaging: a meta-analysis
Heart and Vessels, March 16, 2022
In this systematic review and meta-analysis, we sought to evaluate the prevalence of cardiac involvement in patients with COVID-19 using cardiac magnetic resonance imaging. A literature review was performed to investigate the left ventricular (LV) and right ventricular (RV) ejection fraction (EF), the prevalence of LV late gadolinium enhancement (LGE), pericardial enhancement, abnormality on T1 mapping, and T2 mapping/T2-weighted imaging (T2WI), and myocarditis (defined by modified Lake Louis criteria). Pooled mean differences (MD) between COVID-19 patients and controls for LVEF and RVEF were estimated using random-effects models. We included data from 10.462 patients with COVID-19, comprising 1.010 non-athletes and 9.452 athletes from 29 eligible studies. The meta-analysis showed a significant difference between COVID-19 patients and controls in terms of LVEF [MD = − 2.84, 95% confidence interval (CI) − 5.11 to − 0.56, p < 0.001] and RVEF (MD = − 2.69%, 95% CI − 4.41 to − 1.27, p < 0.001). However, in athletes, no significant difference was identified in LVEF (MD = − 0.74%, 95% CI − 2.41 to − 0.93, p = 0.39) or RVEF (MD = − 1.88%, 95% CI − 5.21 to 1.46, p = 0.27). In non-athletes, the prevalence of LV LGE abnormalities, pericardial enhancement, T1 mapping, T2 mapping/T2WI, myocarditis were 27.5% (95%CI 17.4–37.6%), 11.9% (95%CI 4.1–19.6%), 39.5% (95%CI 16.2–62.8%), 38.1% (95%CI 19.0–57.1%) and 17.6% (95%CI 6.3–28.9%), respectively. In athletes, these values were 10.8% (95%CI 2.3–19.4%), 35.4% (95%CI − 3.2 to 73.9%), 5.7% (95%CI − 2.9 to 14.2%), 1.9% (95%CI 1.1–2.7%), 0.9% (0.3–1.6%), respectively. Both LVEF and RVEF were significantly impaired in COVID-19 patients compared to controls, but not in athletes. In addition, the prevalence of myocardial involvement is not negligible in patients with COVID-19.
Epicardial adipose tissue in contemporary cardiology
Nature Reviews | Cardiology, March 16, 2022
Interest in epicardial adipose tissue (EAT) is growing rapidly, and research in this area appeals to a broad, multidisciplinary audience. EAT is unique in its anatomy and unobstructed proximity to the heart and has a transcriptome and secretome very different from that of other fat depots. EAT has physiological and pathological properties that vary depending on its location. It can be highly protective for the adjacent myocardium through dynamic brown fat-like thermogenic function and harmful via paracrine or vasocrine secretion of pro-inflammatory and profibrotic cytokines. EAT is a modifiable risk factor that can be assessed with traditional and novel imaging techniques. Coronary and left atrial EAT are involved in the pathogenesis of coronary artery disease and atrial fibrillation, respectively, and it also contributes to the development and progression of heart failure. In addition, EAT might have a role in coronavirus disease 2019 (COVID-19)-related cardiac syndrome. EAT is a reliable potential therapeutic target for drugs with cardiovascular benefits such as glucagon-like peptide 1 receptor agonists and sodium–glucose co-transporter 2 inhibitors. This Review provides a comprehensive and up-to-date overview of the role of EAT in cardiovascular disease and highlights the translational nature of EAT research and its applications in contemporary cardiology.
Impact of the COVID‐19 Pandemic on Patients Without COVID‐19 With Acute Myocardial Infarction and Heart Failure
Journal of the American Heart Association, March 15, 2022
Excess mortality from cardiovascular disease during the COVID‐19 pandemic has been reported. The mechanism is unclear but may include delay or deferral of care, or differential treatment during hospitalization because of strains on hospital capacity. We used emergency department and inpatient data from a 12‐hospital health system to examine changes in volume, patient age and comorbidities, treatment (right‐ and left‐heart catheterization), and outcomes for patients with acute myocardial infarction (AMI) and heart failure (HF) during the COVID‐19 pandemic compared with pre‐COVID‐19 (2018 and 2019), controlling for seasonal variation. We analyzed 27 427 emergency department visits or hospitalizations. Patient volume decreased during COVID‐19 for both HF and AMI, but age, race, sex, and medical comorbidities were similar before and during COVID‐19 for both groups. Acuity increased for AMI as measured by the proportion of patients with ST‐segment elevation. There were no differences in right‐heart catheterization for patients with HF or in left heart catheterization for patients with AMI. In‐hospital mortality increased for AMI during COVID‐19 (odds ratio [OR], 1.46; 95% CI, 1.21–1.76), particularly among the ST‐segment–elevation myocardial infarction subgroup (OR, 2.57; 95% CI, 2.24–2.96), but was unchanged for HF (OR, 1.02; 95% CI, 0.89–1.16). Cardiovascular volume decreased during COVID‐19. Despite similar patient age and comorbidities and in‐hospital treatments during COVID‐19, mortality increased for patients with AMI but not patients with HF. Given that AMI is a time‐sensitive condition, delay or deferral of care rather than changes in hospital care delivery may have led to worse cardiovascular outcomes during COVID‐19.
Left ventricular thrombus of unknown etiology in a patient with COVID-19 disease with no significant medical history
Cardiovascular Revascularization Medicine, March 12, 2022
The incidence of left ventricular thrombus is relatively low. Ventricular thrombi typically manifest in patients with reduced ejection fraction and post myocardial infarction. The impact of COVID-19’s hypercoagulability state is presented here. A 44-year-old male who contracted COVID-19, progressed to moderate disease requiring inpatient treatment with supplemental oxygen. During the course of the hospital stay, while receiving National Institutes of Health guideline directed thromboembolism prophylaxis for COVID-19 infected patients, the patient developed a left ventricular thrombus, which consequently embolized and occluded the left anterior descending and left circumflex coronary arteries requiring rheolytic thrombectomy.
Anticoagulation in Patients With COVID-19: JACC Review Topic of the Week
Journal of the American College of Cardiology, March 8, 2022
Clinical, laboratory, and autopsy findings support an association between coronavirus disease-2019 (COVID-19) and thromboembolic disease. Acute COVID-19 infection is characterized by mononuclear cell reactivity and pan-endothelialitis, contributing to a high incidence of thrombosis in large and small blood vessels, both arterial and venous. Observational studies and randomized trials have investigated whether full-dose anticoagulation may improve outcomes compared with prophylactic dose heparin. Although no benefit for therapeutic heparin has been found in patients who are critically ill hospitalized with COVID-19, some studies support a possible role for therapeutic anticoagulation in patients not yet requiring intensive care unit support. We summarize the pathology, rationale, and current evidence for use of anticoagulation in patients with COVID-19 and describe the main design elements of the ongoing FREEDOM COVID-19 Anticoagulation trial, in which 3,600 hospitalized patients with COVID-19 not requiring intensive care unit level of care are being randomized to prophylactic-dose enoxaparin vs therapeutic-dose enoxaparin vs therapeutic-dose apixaban.
Critical Illness Among Patients Hospitalized With Acute COVID-19 With and Without Congenital Heart Defects
Circulation, March 7, 2022
[Research Letter] Given the increased risk for severe COVID-19 ill-ness in individuals with cardiac disease, individuals with congenital heart defects (CHDs) might have increased risk of severe illness from COVID-19 as well. Most publications on CHD and COVID-19 illness have been restricted to patients at congenital cardiology centers, limiting generalizability, because many individuals with CHD do not receive specialized cardiology care. Furthermore, the studies did not include comparison groups without CHD or adjust for difference in established risk factors for critical COVID-19, and comparisons to general population estimates may be confounded. We compared the period prevalence of critical COVID-19 illness (intensive care unit [ICU] admission invasive mechanical ventilation [IMV], or death) among hospitalized patients with COVID-19 with and without CHD. Among patients with CHD, we examined characteristics associated with critical COVID-19 illness. We used data on inpatient encounters from March 2020 through January 2021 from the Premier Health-care Database Special COVID-19 Release, an all-payor database representing ≈20% of US hospital admissions. The current analyses compared period prevalence of critical COVID-19 between patients with and without CHD at the same hospitals, adjusted for and stratified by established high-risk factors for severe COVID-19 infection, and found up to 2 times higher adjusted prevalence of critical COVID-19 among patients with CHD, although results are specific to hospitalized patients.
Evaluation of the Knowledge, Attitude, and Practice of COVID-19 Prevention Methods Among Hypertensive Patients in North Shoa, Ethiopia
https://www.dovepress.com/evaluation-of-the-knowledge-attitude-and-practice-of-covid-19-preventi-peer-reviewed-fulltext-article-RMHP
Risk Management and Healthcare Policy, March 4, 2022
The occurrence of coronavirus diseases 2019 (COVID-19) has affected more than 247 million populations around the world. People with comorbidities such as hypertension, diabetes mellitus, congestive heart failure, kidney disease, elderly people, and people with weak immunity develop severe types of COVID-19 if exposed to the disease. Therefore, this study aimed to assess knowledge, attitude, and practice of COVID-19 prevention methods among hypertensive patients in North Shoa, Oromia region, Ethiopia. Data were collected using a structured questionnaire and study participants were recruited using a simple random sampling technique. A total of 360 (97.0%) hypertension patients responded. This study revealed that 210 (58.3%) study participants had good knowledge of COVID-19 prevention methods, 199 (55.3%) had a favorable attitude towards COVID-19 prevention methods, and 210 (58.3%) hypertension patients at follow-up practiced COVID-19 prevention methods. Respondents who received less than two thousand Ethiopian birrs monthly and respondents who followed electronic news media were significantly associated with the use of sanitizer, respondents who had a favorable attitude towards the COVID-19 prevention method were significantly associated with mask-wearing, and respondents who received less than two thousand Ethiopian birrs monthly were significantly associated with maintaining a physical distance. Generally, this study finding revealed that the level of knowledge, attitude, and practice towards COVID-19 prevention among hypertension patients was low. Therefore, increasing knowledge, attitude, and practice on COVID-19 among hypertension patients requires a coordinated effort from the government, non-government, and health professionals.
Myocarditis post SARS-CoV-2 vaccination: a systematic review
QJM: An International Journal of Medicine, March 3, 2022
Variable clinical criteria taken by medical professionals across the world for myocarditis following COVID-19 vaccination along with wide variation in treatment necessitates understanding and reviewing the same. A systematic review was conducted to elucidate the clinical findings, laboratory parameters, treatment and outcomes of individuals with Myocarditis after COVID-19 vaccination after registering with PROSPERO. Electronic databases including MEDLINE, EMBASE, PubMed, LitCovid, Scopus, ScienceDirect, Cochrane Library, Google Scholar, Web of Science were searched. A total of 85 articles encompassing 2184 patients were analysed. It was a predominantly male (73.4%) and young population (Mean age 25.5 ± 14.2 years) with most having taken an mRNA-based vaccines (99.4%). The mean duration from vaccination to symptom onset was 4.01 ± 6.99 days. Chest pain (90.1%), dyspnoea (25.7%) and fever (11.9%) were the most common symptoms. Only 2.3% had comorbidities. CRP was elevated in 83.3% and cardiac troponin in 97.6% patients. An abnormal ECG was reported in 979/1313 (74.6%) patients with ST-segment elevation being most common (34.9%). Echocardiographic data was available for 1243 patients (56.9%) of whom 288 (23.2%) had reduced left ventricular ejection fraction. NSAIDS (76.5%), steroids (14.1%) followed by colchicine (7.3%) were used for treatment. Only 6 patients died among 1317 of whom data was available. Myocarditis following COVID-19 vaccination is often mild, seen more commonly in young healthy males and is followed by rapid recovery with conservative treatment.
Association of COVID-19 Infection With Survival After In-Hospital Cardiac Arrest Among US Adults
JAMA Network Open, March 2, 2022
[Research Letter] Early on in the COVID-19 pandemic, investigators reported poor survival rates (<3%) after in-hospital cardiac arrest (IHCA) among patients with COVID-19 infection in the US and China. These findings have prompted discussions regarding universal do-not-resuscitate orders for patients with COVID-19. However, these results were from single-center studies that comprised only 295 patients with COVID-19 in hospitals that were overwhelmed early during the pandemic. Whether the poor IHCA survival rate reported in earlier studies is broadly representative of patients with COVID-19 in US hospitals remains unknown. This study examined the association of COVID-19 infection with survival outcomes of US adults after IHCA. The study used data from the American Heart Association Get With the Guidelines–Resuscitation (GWTG-R) registry, which contains detailed information on patients who experience cardiac arrest at participating hospitals in the United States. Within the GWTG-R registry, we identified all adults (aged ≥18 years) who developed IHCA during March to December 2020. Race and ethnicity were self-reported by the study patients, and these data were collected in the GWTG-R registry to examine disparities in care and outcomes of IHCA patients. This study included 24 915 patients with IHCA from 286 hospitals who had a mean (SD) age of 64.7 (15.2) years. There were 9848 women (39.5%) and 15 066 men (60.5%), with sex missing for 1 patient. In terms of race and ethnicity, 6170 patients (24.8%) were Black, 15 223 (61.1%) were White, 949 (3.8%) were of other race or ethnicity (American Indian or Alaska Native, Asian or Pacific Islander, and other races and ethnicities), and 2573 (10.3%) were of unkown race or ethnicity. A suspected or confirmed COVID-19 infection was present in 5916 patients (23.7%). Patients with COVID-19 were younger, more frequently men and of Black race, and more likely to have an initial nonshockable rhythm, pneumonia, respiratory insufficiency, or sepsis and be receiving mechanical ventilation and vasopressors at the time of IHCA. Patients with COVID-19 and IHCA had lower rates of survival to discharge (11.9% vs 23.5%; adjusted RR, 0.65 [95% CI, 0.60-0.71]; P < .001) and ROSC (53.7% vs 63.6%; adjusted RR, 0.86 [95% CI, 0.83-0.90]; P < .001). They were also more likely to have received delayed defibrillation (27.7% vs 36.6%; RR, 1.30 [95% CI, 1.09-1.55]; P = .003) but not delayed epinephrine treatment. The association between COVID-19 infection and worse survival outcomes was consistent for patients with nonsurgical diagnoses, patients in the intensive care unit (ICU), and patients who had received timely defibrillation or epinephrine treatment.
The COVID Heart—One Year After SARS-CoV-2 Infection, Patients Have an Array of Increased Cardiovascular Risks
Journal of the American Medical Association, March 2, 2022
An analysis of data from nearly 154 000 US veterans with SARS-CoV-2 infection provides a grim preliminary answer to the question: What are COVID-19’s long-term cardiovascular outcomes? The study, published in Nature Medicine by researchers at the Veterans Affairs (VA) St Louis Health Care System, found that in the year after recovering from the illness’s acute phase, patients had increased risks of an array of cardiovascular problems, including abnormal heart rhythms, heart muscle inflammation, blood clots, strokes, myocardial infarction, and heart failure. What’s more, the heightened risks were evident even among those who weren’t hospitalized with acute COVID-19. The new analysis in Nature Medicine examined a comprehensive, prespecified set of cardiovascular outcomes among patients in the US Veterans Health Administration (VHA) system who survived the first 30 days of COVID-19. The researchers estimated the risks and excess burden of cardiovascular outcomes per 1000 persons 12 months after COVID-19 using electronic medical record data from 3 large cohorts. The cohorts largely comprised older White male patients. The COVID-19 cohort, which averaged 61 years old, included 89% males and about 71% White individuals. But, because the study was large, it also included almost 17 000 female patients; about 37 000 Black patients; and almost 8000 Latino, Asian, American Indian, Native Hawaiian, and patients of other races with COVID-19. The increased risks were most pronounced for heart failure and atrial fibrillation, but the breadth of cardiovascular disease involvement was “eye opening,” according to study senior author Ziyad Al-Aly, MD, chief of research and development at the VA St Louis Health Care System and a clinical epidemiologist at Washington University in St Louis. The researchers also were surprised to see elevated risks for people who were not hospitalized for COVID-19 during the acute phase—the segment that represents the majority of people with SARS-CoV-2 infection. However, the study did not analyze symptomatic vs asymptomatic infections, a potential area for further research.
An insight into the mechanisms of COVID-19, SARS-CoV2 infection severity concerning β-cell survival and cardiovascular conditions in diabetic patients
Molecular and Cellular Biochemistry, March 2, 2022
A significantly high percentage of hospitalized COVID-19 patients with diabetes mellitus (DM) had severe conditions and were admitted to ICU. In this review, we have delineated the plausible molecular mechanisms that could explain why there are increased clinical complications in patients with DM that become critically ill when infected with SARS-CoV2. RNA viruses have been classically implicated in manifestation of new onset diabetes. SARS-CoV2 infection through cytokine storm leads to elevated levels of pro-inflammatory cytokines creating an imbalance in the functioning of T helper cells affecting multiple organs. Inflammation and Th1/Th2 cell imbalance along with Th17 have been associated with DM, which can exacerbate SARS-CoV2 infection severity. ACE-2-Ang-(1–7)-Mas axis positively modulates β-cell and cardiac tissue function and survival. However, ACE-2 receptors dock SARS-CoV2, which internalize and deplete ACE-2 and activate Renin-angiotensin system (RAS) pathway. This induces inflammation promoting insulin resistance that has positive effect on RAS pathway, causes β-cell dysfunction, promotes inflammation and increases the risk of cardiovascular complications. Further, hyperglycemic state could upregulate ACE-2 receptors for viral infection thereby increasing the severity of the diabetic condition. SARS-CoV2 infection in diabetic patients with heart conditions are linked to worse outcomes. SARS-CoV2 can directly affect cardiac tissue or inflammatory response during diabetic condition and worsen the underlying heart conditions.
Enhanced External Counterpulsation Eases ‘Long COVID’
Medical Professionals Reference, March 1, 2022
In a living systematic review and updated article published online March 1 in the Annals of Internal Medicine, final practice points are presented for use of remdesivir for hospitalized patients with COVID-19. Anjum S. Kaka, MD, from the University of Minnesota School of Medicine in Minneapolis, and colleagues updated the living review of remdesivir for adults hospitalized with COVID-19. The authors note that 1 new randomized controlled trial (RCT) and one new subtrial comparing a 10-day course of remdesivir with control (placebo or standard care) were identified since the last update. Based on the evidence from 5 RCTs, the researchers found that the updated results confirm a 10-day course of remdesivir probably results in little to no reduction in mortality compared with control. Amir Qaseem, MD, PhD, from the American College of Physicians in Philadelphia, and colleagues updated the living, rapid practice points for the use of remdesivir as a COVID-19 treatment. The authors note that five days of remdesivir should be considered for hospitalized patients with COVID-19 who do not require invasive ventilation or extracorporeal membrane oxygenation (ECMO). Extending remdesivir to 10 days should be considered for patients who develop the need for invasive ventilation or ECMO within a 5-day course. Initiation of remdesivir should be avoided for hospitalized patients with COVID-19 who are already on invasive ventilation or ECMO.
TEA Clinical Profile of Infective Endocarditis in Patients with Recent COVID-19: A Systematic Review
American Journal of the Medical Sciences, February 27, 2022
Coronavirus disease 2019 (COVID-19) can progress to cardiovascular complications which are linked to higher in-hospital mortality rates. Infective endocarditis (IE) can develop in patients with recent COVID-19 infections, however, characterization of IE following COVID-19 infection has been lacking. To better characterize this disease, we performed a systematic review with descriptive analysis of the clinical features and outcomes of these patients. Our search was conducted in 8 libraries for all published reports of probable or definite IE in patients with a prior COVID-19 confirmed diagnosis. After ensuring an appropriate inclusion of the articles, we extracted data related to clinical characteristics, modified duke criteria, microbiology, outcomes, and procedures. Searches generated a total of 323 published reports, and 20 articles met our inclusion criteria. The mean age of patients was 52.2 ± 16.9 years and 76.2% were males. Staphylococcus aureus was isolated in 8 (38.1%) patients, Enterococcus faecalis in 3 patients (14.3%) and Streptococcus mitis/oralis in 2 (9.5%) patients. The mean time interval between COVID-19 and IE diagnoses was 16.7 ± 15 days. Six (28.6%) patients required critical care due to IE, 7 patients (33.3%) underwent IE-related cardiac surgery and 5 patients (23.8%) died during their IE hospitalization. Our systematic review provides a profile of clinical features and outcomes of patients with a prior COVID-19 infection diagnosis who subsequently developed IE. Due to the ongoing COVID-19 pandemic, it is essential that clinicians appreciate the possibility of IE as a unique complication of COVID-19 infection.
Serial Assessment of Myocardial Injury Markers in Mechanically Ventilated Patients With SARS-CoV-2 (from the Prospective MaastrICCht Cohort)
American Journal of Cardiology, February 24, 2022
Myocardial injury in COVID-19 is associated with in-hospital mortality. However, the development of myocardial injury over time and whether myocardial injury in patients with COVID-19 at the intensive care unit is associated with outcome is unclear. This study prospectively investigates myocardial injury with serial measurements over the full course of intensive care unit admission in mechanically ventilated patients with COVID-19. As part of the prospective Maastricht Intensive Care COVID cohort, predefined myocardial injury markers, including high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and electrocardiographic characteristics were serially collected in mechanically ventilated patients with COVID-19. Linear mixed-effects regression was used to compare survivors with nonsurvivors, adjusting for gender, age, APACHE-II score, daily creatinine concentration, hypertension, diabetes mellitus, and obesity. In 90 patients, 57 (63%) were survivors and 33 (37%) nonsurvivors, and a total of 628 serial electrocardiograms, 1,565 hs-cTnT, and 1,559 NT-proBNP concentrations were assessed. Log-hs-cTnT was lower in survivors compared with nonsurvivors at day 1 (β −0.93 [−1.37; −0.49], p <0.001) and did not change over time. Log-NT-proBNP did not differ at day 1 between both groups but decreased over time in the survivor group (β −0.08 [−0.11; −0.04] p <0.001) compared with nonsurvivors. Many electrocardiographic abnormalities were present in the whole population, without significant differences between both groups. In conclusion, baseline hs-cTnT and change in NT-proBNP were strongly associated with mortality. Two-thirds of patients with COVID-19 showed electrocardiographic abnormalities. Our serial assessment suggests that myocardial injury is common in mechanically ventilated patients with COVID-19 and is associated with outcome.
Persistent cardiac injury—An important component of long COVID-19 syndrome
eBioMedicine, February 24, 2022
[Commentary] As the COVID-19 pandemic goes on, we continue to identify the long-term complications or symptoms among patients who recovered from this infection, be it mild or severe.1 These complications are collectively recognized as “COVID-19 long-hauler syndrome”. It is crucial to understand the factors leading to the development of these long-term sequelae to identify, prevent and manage them using appropriate interventions. Acute cardiac injury (ACI), marked by elevation of troponin levels in the blood over the 99th percentile, is an important phenomenon shown to occur in nearly 30% of patients admitted to the hospital with COVID19 infection.2 ACI has been shown to be associated with an elevated risk of critical illness, increased duration of hospital stay and mortality. Multiple processes, both ischaemic and non-ischaemic, have been shown to contribute to the development of ACI in COVID-19 patients. The most important among them is the direct myocardial injury caused by SARS-CoV-2.4 Tavazzi et al. demonstrated direct viral infection in the interstitial cells of the myocardium on endomyocardial biopsy, accompanied by low-grade inflammation. But to date, there has been no demonstration of COVID-19 genome in the cardiac tissue in patients with clinical myocarditis. Other mechanisms postulated to increase myocardial injury include systemic inflammation, vascular endothelial damage, cardiomyocyte apoptosis, abnormal myocardial strain, microthrombi formation and supplydemand mismatch. The precise mechanisms of myocardial injury in patients with COVID-19 are still unclear. It is also unknown if the myocardial injury is a direct effect of the virus or a response to systemic inflammation or both. As we continue to obtain long-term data on COVID19 survivors, it is imperative to look at how the patients with troponin elevation during their hospital admission fair after discharge.
Long COVID: post-acute sequelae of COVID-19 with a cardiovascular focus
European Heart Journal, February 18, 2022
Emerging as a new epidemic, long COVID or post-acute sequelae of coronavirus disease 2019 (COVID-19), a condition characterized by the persistence of COVID-19 symptoms beyond 3 months, is anticipated to substantially alter the lives of millions of people globally. Cardiopulmonary symptoms including chest pain, shortness of breath, fatigue, and autonomic manifestations such as postural orthostatic tachycardia are common and associated with significant disability, heightened anxiety, and public awareness. A range of cardiovascular (CV) abnormalities has been reported among patients beyond the acute phase and include myocardial inflammation, myocardial infarction, right ventricular dysfunction, and arrhythmias. Pathophysiological mechanisms for delayed complications are still poorly understood, with a dissociation seen between ongoing symptoms and objective measures of cardiopulmonary health. COVID-19 is anticipated to alter the long-term trajectory of many chronic cardiac diseases which are abundant in those at risk of severe disease. In this review, we discuss the definition of long COVID and its epidemiology, with an emphasis on cardiopulmonary symptoms. We further review the pathophysiological mechanisms underlying acute and chronic CV injury, the range of post-acute CV sequelae, and impact of COVID-19 on multiorgan health. We propose a possible model for referral of post-COVID-19 patients to cardiac services and discuss future directions including research priorities and clinical trials that are currently underway to evaluate the efficacy of treatment strategies for long COVID and associated CV sequelae.
Major cardiovascular risk factors common yet undertreated in patients with COPD
Healio | Pulmonology, February 17, 2022
Among patients with COPD, major cardiovascular risk factors were common but inadequately monitored, treated and controlled, researchers reported in the Annals of the American Thoracic Society. “COPD inherently conveys high cardiovascular risk due to cumulative smoking burden, advanced population age and clustering of additional risk factors, intertwined with socioeconomic deprivation, impaired health literacy and reduced physical activity,” Nathaniel M. Hawkins, MD, MPH, assistant professor in the division of cardiology at the University of British Columbia, Vancouver, and colleagues wrote. “Risk factors were very common in our cohort, with one-quarter having diabetes, > 50% hypertension, > 60% dyslipidemia, > 70% overweight and > 80% smoking history.” The cross-sectional analysis evaluated medical records of 32,695 patients with COPD (mean age, 68.4 years; 50.7% women) in the Canadian Primary Care Sentinel Surveillance Network from 2013 to 2018. These patients were matched for age, sex and rural residence with 32,638 control participants (mean age, 68.4 years; 50.7% women). Researchers identified five CV risk factors in the cohort: hypertension, dyslipidemia, diabetes, obesity and smoking. The mean Framingham Risk Score was 20.6% among patients with COPD compared with 18.6% among controls. Nearly 54% of patients with COPD were categorized as having high CV risk. All five CVD risk factors were more common among patients with COPD compared with controls: hypertension (52.3% vs. 44.9%); dyslipidemia (62% vs. 57.8%); diabetes (25% vs. 20.2%); obesity (40.8% vs. 36.8%); and smoking (40.9% vs. 11.4%). In addition, CV therapies were underutilized in patients with COPD. Angiotensin-converting enzyme inhibitors were used in 69%, statins in 69% and smoking-cessation therapies in 27%.
Myocardial Injury Pattern at MRI in COVID-19 Vaccine–associated Myocarditis
Radiology, February 15, 2022
There is limited data on the pattern and severity of myocardial injury in patients with COVID-19 vaccination associated myocarditis. The objective is to describe myocardial injury following COVID-19 vaccination and to compare these findings to other causes of myocarditis. In this retrospective cohort study, consecutive adult patients with myocarditis with at least one T1-based and at least one T2-based abnormality on cardiac MRI performed at a tertiary referral hospital between 2019-2021 were included. Patients were classified into one of three groups: myocarditis following COVID-19 vaccination, myocarditis following COVID-19 illness, and other myocarditis not associated COVID-19 vaccination or illness. Of the 92 included patients, 21 (22%) had myocarditis following COVID-19 vaccination (mean age 31 years ±14 [standard deviation]; 17 men; mRNA-1273 in 12 [57%] and BNT162b2 in 9 [43%]). Ten patients (11%) had myocarditis following COVID-19 illness (mean age 51 years ±14; 3 men), and 61 (66%) had other myocarditis (mean age 44 years ±18; 36 men). MRI findings in vaccine associated myocarditis included late gadolinium enhancement (LGE) in 17 (81%) and left ventricular dysfunction in 6 (29%). Compared with other causes of myocarditis, patients with vaccine-associated myocarditis had higher left ventricular ejection fraction and less extensive LGE, even after controlling for age, sex, and duration between symptom onset and MRI. The most frequent location of LGE in all groups was subepicardial at the basal inferolateral wall, although septal involvement was less common in vaccine associated myocarditis. At short-term follow-up (median 22 [IQR 7-48] days), all patients with vaccine associated myocarditis were asymptomatic with no adverse events.
In older adults with COVID-19, stroke risk highest in first 3 days after diagnosis
Healio | Cardiology Today, February 13, 2022
In older adults with COVID-19, ischemic stroke risk was much higher in the first 3 days after diagnosis than at points thereafter, researchers reported at the International Stroke Conference. “Stroke following the diagnosis of COVID-19 is a possible complication of COVID-19 that patients and clinicians should be aware of,” Quanhe Yang, PhD, senior scientist in the CDC’s Division for Heart Disease and Stroke Prevention, said in a press release. “Vaccination and other preventive measures for COVID-19 are important to reduce the risk of infection and complications including stroke.” Yang and colleagues analyzed 37,379 Medicare beneficiaries aged 65 years or older (median age, 80 years; 57% women) diagnosed with COVID-19 from April 2020 to February 2021 and hospitalized for acute ischemic stroke from January 2019 to February 2021. The study employed a self-controlled case series design and compared stroke risk in risk periods up to 28 days after COVID-19 diagnosis and other (control) periods. According to the researchers, ischemic stroke risk was more than 10-fold higher in the first 3 days after COVID-19 diagnosis compared with control periods (incidence rate ratio [IRR] = 10.3; 95% CI, 9.86-10.8). When day 0 was excluded, the increase in risk was attenuated but remained significant (IRR = 1.77; 95% CI, 1.57-2.01). Ischemic stroke risk was also elevated at 4 to 7 days (IRR = 1.61; 95% CI, 1.44-1.8), at 8 to 14 days (IRR = 1.44; 95% CI, 1.32-1.57) and 15 to 28 days (IRR = 1.09; 95% CI, 1.02-1.18), after COVID-19 diagnosis compared with control periods, Yang and colleagues found.
COVID-19 and Moral Injury: a Mental Health Pandemic for Frontline Health Care Workers
Pulmonology Advisor, February 11, 2022
More than 2 years ago, the alarm and first warnings of a global pandemic sounded. Now with over 830,000 deaths caused by COVID-19 in the US, there looms on the horizon a second underlying curve with equally serious long-term consequences: a mental health pandemic. The mental health fallout from the COVID-19 pandemic demands recognition, intervention, and mitigation strategies. Among the many at-risk populations are frontline health care workers who have been at the epicenter of the global pandemic, working long shifts with at times a tenuous safety net and limited support, and caring for COVID-19 patients with limited resources, mixed messaging, and uncertainty with regards to an end to the crisis. The psychological effects in some health care providers are akin to the moral trauma or moral injury that is recognized in combat veterans with post-traumatic stress disorder (PTSD). Mental health professionals and other health care providers caring for frontline health care workers who present with insomnia, depression, anxiety, panic attacks, PTSD, and suicidal thoughts should recognize and validate their experiences and moral injury. Intervention strategies including health promotion, resilience training, and ongoing multilevel support will play an important role in flattening the moral injury curve. Leaders in health care have the opportunity to create and foster a culture of open, nonjudgmental communication. In the face of unpredictable events such as the COVID-19 pandemic, natural disasters, and social and political unrest that impact health care delivery, strategies are available to promote mental health recovery and return to stability and wellness among frontline health care workers.
Heart-disease risk soars after COVID — even with a mild case
Nature, February 10, 2022
Massive study shows a long-term, substantial rise in risk of cardiovascular disease, including heart attack and stroke, after a SARS-CoV-2 infection. Even a mild case of COVID-19 can increase a person’s risk of cardiovascular problems for at least a year after diagnosis, a new study shows. Researchers found that rates of many conditions, such as heart failure and stroke, were substantially higher in people who had recovered from COVID-19 than in similar people who hadn’t had the disease. What’s more, the risk was elevated even for those who were under 65 years of age and lacked risk factors, such as obesity or diabetes. “It doesn’t matter if you are young or old, it doesn’t matter if you smoked, or you didn’t,” says study co-author Ziyad Al-Aly at Washington University in St. Louis, Missouri, and the chief of research and development for the Veterans Affairs (VA) St. Louis Health Care System. “The risk was there.” Al-Aly and his colleagues based their research on an extensive health-record database curated by the United States Department of Veterans Affairs. The researchers compared more than 150,000 veterans who survived for at least 30 days after contracting COVID-19 with two groups of uninfected people: a group of more than five million people who used the VA medical system during the pandemic, and a similarly sized group that used the system in 2017, before SARS-CoV-2 was circulating. People who had recovered from COVID-19 showed stark increases in 20 cardiovascular problems over the year after infection. For example, they were 52% more likely to have had a stroke than the contemporary control group, meaning that, out of every 1,000 people studied, there were around 4 more people in the COVID-19 group than in the control group who experienced stroke. The risk of heart failure increased by 72%, or around 12 more people in the COVID-19 group per 1,000 studied. Hospitalization increased the likelihood of future cardiovascular complications, but even people who avoided hospitalization were at higher risk for many conditions.
In survivors of acute COVID-19, CV risk, burden ‘substantial’
Healio | Cardiology Today, February 9, 2022
Compared with controls, survivors of acute COVID-19 have elevated CV risks and burdens at 1 year, even if they were not hospitalized for COVID-19, researchers reported in Nature Medicine. “Our results provide evidence that the risk and 1-year burden of cardiovascular disease in survivors of acute COVID-19 are substantial,” Yan Xie, MPH, biostatistician in the Clinical Epidemiology Center at the VA St. Louis Health Care System, and colleagues wrote. Xie and colleagues used Veterans Affairs databases to create three cohorts: 153,760 veterans who survived the first 30 days of COVID-19, a contemporary control group of 5,637,647 veterans who had no evidence of COVID-19 and a historical control group of 5,859,411 veterans from 2017 who did not have COVID-19. Participants were followed for approximately 1 year, corresponding to 12,095,836 person-years of follow-up, for incidence of various CV outcomes. The COVID-19 cohort was stratified into three groups representing disease severity: not hospitalized, hospitalized and admitted to the ICU. “Care strategies of people who survived the acute episode of COVID-19 should include attention to cardiovascular health and disease,” Xie and colleagues wrote. “Our study shows that the risk of incident cardiovascular disease extends well beyond the acute phase of COVID-19.” Read about the CV outcomes at 1 year of this COVID-19 cohort.
COVID-19 impact ‘substantial’ on outcomes for in-hospital cardiac arrest
Healio | Cardiology, February 8, 2022
The rate of survival after in-hospital cardiac arrest was lower during the initial surge of COVID-19 compared with prior years, even among patients hospitalized without confirmed COVID-19, researchers reported. According to data published in Circulation: Cardiovascular Quality and Outcomes, resuscitation times for in-hospital cardiac arrests were shorter during the initial surge of the pandemic and delayed epinephrine treatment was more prevalent compared with years before the pandemic. Chan and colleagues conducted a retrospective study to compare survival of in-hospital cardiac arrest during the COVID-19 pre-surge (Jan. 1-Feb. 29, 2020), surge (March 1-May 15, 2020) and immediate post-surge (May 16-June 30, 2020) compared with survival in 2015 through 2019. Researchers identified 61,586 in-hospital cardiac arrests that occurred from 2015 to 2020. During the pre-surge period, 24.2% of patients who experienced in-hospital cardiac arrest survived to discharge compared with 24.7% from 2015 to 2019 (adjusted OR = 1.12; 95% CI, 1.02-1.22). However, researchers observed lower survival during the surge period, with 19.6% surviving to discharge compared with 26% from 2015 to 2019 (aOR = 0.81; 95% CI, 0.75-0.88). Lower survival rate was most pronounced in counties with higher monthly COVID-19 mortality rates, with 28% lower survival in high COVID-19 mortality areas and 42% lower survival in very high COVID-19 mortality areas (P for interaction < .001), according to the researchers. During the post-surge period, survival to discharge rates were not different compared with the rates from 2015 to 2019 (22.3% vs. 25.8%; aOR = 0.93; 95% CI, 0.83-1.04), and also no longer differed in communities with higher COVID-19 mortality rates compared with communities with low COVID-19 mortality rates (P for interaction = .16)
Remote-delivered cardiac rehabilitation during COVID-19: a prospective cohort comparison of health-related quality of life outcomes and patient experiences
European Journal of Cardiovascular Nursing, February 8, 2022
Enforced suspension and reduction of in-person cardiac rehabilitation (CR) services during the coronavirus disease-19 (COVID-19) pandemic restrictions required rapid implementation of remote delivery methods, thus enabling a cohort comparison of in-person vs. remote-delivered CR participants. This study aimed to examine the health-related quality of life (HRQL) outcomes and patient experiences comparing these delivery modes. Participants across four metropolitan CR sites receiving in-person (December 2019 to March 2020) or remote-delivered (April to October 2020) programmes were assessed for HRQL (Short Form-12) at CR entry and completion. A General Linear Model was used to adjust for baseline group differences and qualitative interviews to explore patient experiences. Participants (n = 194) had a mean age of 65.94 (SD 10.45) years, 80.9% males. Diagnoses included elective percutaneous coronary intervention (40.2%), myocardial infarction (33.5%), and coronary artery bypass grafting (26.3%). Remote-delivered CR wait times were shorter than in-person [median 14 (interquartile range, IQR 10–21) vs. 25 (IQR 16–38) days, P < 0.001], but participation by ethnic minorities was lower (13.6% vs. 35.2%, P < 0.001). Remote-delivered CR participants had equivalent benefits to in-person in all HRQL domains but more improvements than in-person in Mental Health, both domain [mean difference (MD) 3.56, 95% confidence interval (CI) 1.28, 5.82] and composite (MD 2.37, 95% CI 0.15, 4.58). From qualitative interviews (n = 16), patients valued in-person CR for direct exercise supervision and group interactions, and remote-delivered for convenience and flexibility (negotiable contact times). Remote-delivered CR implemented during COVID-19 had equivalent, sometimes better, HRQL outcomes than in-person, and shorter wait times. Participation by minority groups in remote-delivered modes are lower. Further research is needed to evaluate other patient outcomes.
Long-term cardiovascular outcomes of COVID-19
Nature Medicine, February 7, 2022
The cardiovascular complications of acute coronavirus disease 2019 (COVID-19) are well described, but the post-acute cardiovascular manifestations of COVID-19 have not yet been comprehensively characterized. Here we used national healthcare databases from the US Department of Veterans Affairs to build a cohort of 153,760 individuals with COVID-19, as well as two sets of control cohorts with 5,637,647 (contemporary controls) and 5,859,411 (historical controls) individuals, to estimate risks and 1-year burdens of a set of pre-specified incident cardiovascular outcomes. We show that, beyond the first 30 d after infection, individuals with COVID-19 are at increased risk of incident cardiovascular disease spanning several categories, including cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure and thromboembolic disease. These risks and burdens were evident even among individuals who were not hospitalized during the acute phase of the infection and increased in a graded fashion according to the care setting during the acute phase (non-hospitalized, hospitalized and admitted to intensive care). Our results provide evidence that the risk and 1-year burden of cardiovascular disease in survivors of acute COVID-19 are substantial. Care pathways of those surviving the acute episode of COVID-19 should include attention to cardiovascular health and disease.
Clinical predictors of acute cardiac injury and normalization of troponin after hospital discharge from COVID-19
eBioMedicine, February 7, 2022
Although acute cardiac injury (ACI) is a known COVID-19 complication, whether ACI acquired during COVID-19 recovers is unknown. This study investigated the incidence of persistent ACI and identified clinical predictors of ACI recovery in hospitalized patients with COVID-19 2.5 months post-discharge. This retrospective study consisted of 10,696 hospitalized COVID-19 patients from March 11, 2020 to June 3, 2021. Demographics, comorbidities, and laboratory tests were collected at ACI onset, hospital discharge, and 2.5 months post-discharge. ACI was defined as serum troponin-T (TNT) level >99th-percentile upper reference limit (0.014ng/mL) during hospitalization, and recovery was defined as TNT below this threshold 2.5 months post-discharge. Four models were used to predict ACI recovery status. There were 4,248 (39.7%) COVID-19 patients with ACI, with most (93%) developed ACI on or within a day after admission. In-hospital mortality odds ratio of ACI patients was 4.45 [95%CI: 3.92, 5.05, p<0.001] compared to non-ACI patients. Of the 2,880 ACI survivors, 1,114 (38.7%) returned to our hospitals 2.5 months on average post-discharge, of which only 302 (44.9%) out of 673 patients recovered from ACI. There were no significant differences in demographics, race, ethnicity, major commodities, and length of hospital stay between groups. Prediction of ACI recovery post-discharge using the top predictors (troponin, creatinine, lymphocyte, sodium, lactate dehydrogenase, lymphocytes and hematocrit) at discharge yielded 63.73%-75.73% accuracy. Persistent cardiac injury is common among COVID-19 survivors. Readily available patient data accurately predict ACI recovery post-discharge. Early identification of at-risk patients could help prevent long-term cardiovascular complications.
Description of cardiovascular imaging abnormalities among hospitalized COVID-19 patients with elevated cardiac biomarkers
European Heart Journal – Cardiovascular Imaging, February 4, 2022
Myocardial injury is commonly encountered among severely-ill COVID-19 patients. Underlying mechanisms, however, remain incompletely understood. Describing cardiovascular imaging (CVI) abnormalities in this population will provide additional insight into mechanisms of myocardial injury with COVID-19 and may potentially guide management for these patients. Therefore, we aimed to describe CVI abnormalities in COVID-19 patients with elevated high-sensitivity cardiac troponin (hs-cTn). Consecutive hospitalized COVID-19 patients (n = 694) between February and July 2020 were retrospectively identified, including 409 patients with available hs-cTn (≥14 ng/dL was considered abnormal) Abnormality with any CVI—including transthoracic echocardiography (TTE), cardiac CT angiography, cardiac MR or invasive coronary angiography (ICA)—were identified through review of electronic records. Hospitalized COVID-19 patients with abnormal hs-cTn (107/409; 26.2%) had more frequent utilization of CVI compared with those with normal hs-cTn (61.7% vs. 30.5%, OR:3.7, 95%CI [2.3,5.8]) or those without available hs-cTn data (61.7% vs. 29.9%, OR:3.8, 95%CI [2.4,6]). Most utilized CVI modalities were TTE (63/107; 58.9%) followed by ICA (6/107; 5.6%). Echocardiographic abnormalities detected include right or left ventricular systolic dysfunction (22%), pericardial effusion (11%), while coronary artery disease was identified in 83.3% of patients who underwent ICA. In this single center experience, cardiac biomarker elevation in hospitalized COVID-19 patients was associated with a 3-fold increase in the likelihood of CVI utilization, most commonly TTE. Ventricular systolic dysfunction and severe coronary artery disease were commonly encountered in patients with abnormal hs-cTn. However, these results need to be interpreted in the context of inconsistent use of CVI in patients with elevated cardiac biomarkers, which may preclude arrival at definitive conclusions. Prospective studies with standardized use of CVI in high-risk COVID-19 patients are warranted to advance our understanding of cardiac toxicity with COVID-19.
Comparison of left heart echocardiographic parameters including strain in patients with COVID-19 pneumonia three months and one year after discharge
European Heart Journal – Cardiovascular Imaging, February 4, 2022
The long-term effect of a complicated course of COVID-19 on echocardiography (EchoCG) parameters, in particular on left heart, has not been sufficiently studied. To compare EchoCG parameters of left heart in patients with proven COVID-19 pneumonia 3 months and one year after discharge. The patients were identified according to the data of the medical information system of the monohospital from April 2020 to July 2021 within the framework of “One-year Cardiac Follow-up of COVID-19 Pneumonia”. A total of 116 men and women were included, mean age 49 ± 14.4 years, females 49.6%. During hospitalization, chest computed tomography detected mild lesions in 31.3%, moderate lesions in 33.3%, severe lesions in 29.3% and critical lesions in 6.1%. All patients underwent clinical examination including transthoracic EchoCG with 3 months ± 2 weeks and one year ± 3 weeks after discharge. All images were digitally stored and analyzed using off-line post processing with TomTec (Philips). The LV global and segmental longitudinal strain (LS) were studied in 100 individuals with satisfactory visualization quality 3 month after discharge and in 81 individuals one year after discharge. During the observation, the average body mass index of the subjects increased (28.7 ± 5.8 kg/m2 3 months after discharge vs 29.4 ± 6.1% one year after discharge, p < 0.001), as well as the rate of cardiovascular diseases (67% 3 months after discharge versus 79% one year after discharge, p = 0.008). Significant dynamics of mean left heart EchoCG parameters were observed. The mean index of left atrium (LA) maximal volume decreased (26.0 ± 7.2 vs 25.3 ± 7.4, p = 0.015), index of LA minimal volume increased (9.9 ± 5.4 vs 10.8 ± 5.6 ml/m2, p = 0.011). Left ventricular (LV) end-diastolic, end-systolic and stroke volume indexes decreased (49.3 ± 11.3 vs 46.9 ± 9.9 ml/m2, p = 0.008; 16.0 ± 5.6 vs 14.4 ± 4.1 ml/m2, p = 0.001; 36.7 ± 12.8 vs 30.8 ± 8.1 ml/m2, p < 0,001, respectively). The LV myocardial mass index increased (70.0 [60.8–84.0] vs 75.4 [68.2–84.9] g/m², p = 0.024). LV ejection fraction increased (68.1 ± 5.3 vs 69.7 ± 4.6%, p = 0.013). The LV global LS (-20.3 ± 2.2 vs -19.4 ± 2.7%, p = 0.001) and the LV segmental LS worsened: in mid segments (antero-septal -21.1 ± 3.3 vs -20.4 ± 4.1%, p = 0.039; inferior -21.0 ± 2.7 vs -20.0 ± 2.9%, p = 0.039; lateral -18.4 ± 3.7 vs -17.6 ± 4.4%, p = 0.021), and in apical segments (anterior -22.3 ± 5.0 vs -20.8 ± 5.2%, p = 0.006; inferior -24.6 ± 4.9 vs -22.7 ± 4.6, p = 0.003; lateral -22.7 ± 4.5 vs -20.4 ± 4.8%, p < 0.001; septal -25.3 ± 4.2 vs -23.1 ± 4,4%, p < 0.001; apical -23.7 ± 4.1 vs -21.8 ± 4.1%, p < 0.001). Compared to 3 month after discharge, in patients one year after COVID-19 pneumonia the LA maximal volume, LV end-diastolic, end-systolic and stroke volumes decrease, and the LV ejection fraction increased.
Right Ventricular Dysfunction in Critically Ill Patients With COVID-19
American Journal of Cardiology, January 25, 2022
Right ventricular (RV) dysfunction is a common complication in patients with acute respiratory distress syndrome (ARDS) occurring in 22% to 50% of patients. RV dysfunction in the context of ARDS is attributed to increased pulmonary vascular resistance and is associated with increased mortality in patients with ARDS even when lung protective ventilation strategies are employed. Severe COVID-19 is characterized by ARDS and respiratory failure of varying severity. In patients with COVID-19, RV dysfunction was found in 39% of 100 consecutively hospitalized patients on echocardiograms performed within 24 hours of hospital admission. Although RV dysfunction is reportedly common in patients with COVID-19, whether it is associated with worse outcomes is unknown. We reviewed medical records of patients admitted to the intensive care unit for COVID-19 at 2 hospitals. We identified 282 patients who required mechanical ventilation and had an echocardiogram performed during their hospitalization. Data abstracted from echocardiogram reports included the summary description of RV size and systolic function, tricuspid annular plane systolic excursion, and estimated RV systolic pressure in addition to left ventricular ejection fraction. We compared clinical characteristics and outcomes between patients with and without evidence of RV dysfunction using the t test or Mann–Whitney U test for continuous variables and the chi-square or Fischer’s exact test for categoric variables. Two-tailed p ≤0.05 were considered statistically significant. Overall, the mean age of the cohort was 62 (SD 13) and included 183 men (64.9%). Of the 282 hospitalized patients for COVID-19 who were mechanically ventilated and had an echocardiogram, 61 had evidence of at least mild RV dysfunction (21.6%). Only 6 patients (2.1%) showed signs of severe RV dysfunction. Patients with signs of RV dysfunction were more likely to have a history of congestive heart failure (16.4% vs 3.6%, p <0.001) and have a lower body mass index but otherwise had no significant differences in clinical characteristics compared with patients without RV dysfunction. There was no statistically significant difference in the incidence of acute kidney injury requiring renal replacement therapy in patients with RV dysfunction (6.6%) compared with those without RV dysfunction (9.5%, p = 0.47). Most importantly, in-hospital mortality was similar between patients with and without RV dysfunction (62.3% compared with 59.7%, respectively; p = 0.72). Among patients with abnormal RV function who died (n = 38), only 4 (10.5%) had severe RV dysfunction.
Myocarditis low after COVID-19 vaccination, but odds elevated in male teens, young adults
Healio | Cardiology Today, January 25, 2022
Despite low absolute rates, researchers observed elevated odds of cardiac injury among male adolescents and young adults after messenger RNA-based COVID-19 vaccination in a large U.S. study, as well as a smaller study in Hong Kong. Among 192.4 million vaccinated adolescents and young adults in the U.S., researchers observed 1,991 cases of myocarditis after at least one dose. According to the analysis published in JAMA, there were no confirmed cases of myocarditis among individuals younger than 30 years who died after receipt of a messenger RNA (mRNA)-based COVID-19 vaccination without another identifiable cause. “Onset of myocarditis typically follows an inciting process, often a viral illness; however, no antecedent cause is identified in many cases,” Matthew E. Oster, MD, pediatric cardiologist at Children’s Healthcare of Atlanta, and colleagues wrote. “It has been hypothesized that vaccination can serve as a trigger for myocarditis; however, only the smallpox vaccine has previously been causally associated with myocarditis based on reports among U.S. military personnel, with cases typically occurring 7 to 12 days after vaccination.” A total of 1,626 reports met the CDC’s definition of probable or confirmed myocarditis. Seventy-three percent of these individuals were younger than 30 years while 33% were younger than 18 years (median age, 21 years). The researchers reported that among cases for which dosage information was reported, 82% occurred after the second vaccination dose, and that among cases for which dosage information and time to symptom onset were reported, 74% occurred within 7 days. Abnormal ECG findings were present in 72% of myocarditis cases and among patients who received a cardiac MRI, abnormal findings consistent with myocarditis were present in 72%. Among the 721 patients who received an echocardiogram, 12% had reduced left ventricular ejection fraction. Researchers found no cases of myocarditis that required heart transplant, extracorporeal membrane oxygenation or a ventricular assist device.
Anxiety, home blood pressure monitoring, and cardiovascular events among older hypertension patients during the COVID-19 pandemic
Hypertension Research, January 21, 2022
The global coronavirus disease 2019 (COVID-19) pandemic has led to a health crisis. It remains unclear how anxiety affects blood pressure (BP) and cardiovascular risk among older patients with hypertension. In this study, we extracted longitudinal data on home BP monitored via a smartphone-based application in 3724 elderly patients with hypertension from a clinical trial (60–80 years; 240 in Wuhan and 3484 in non-Wuhan areas) to examine changes in morning BP during the COVID-19 outbreak in China. Anxiety was evaluated using Generalized Anxiety Disorder-7 item scores. Changes in morning systolic BP (SBP) were analyzed for five 30-day periods during the pandemic (October 21, 2019 to March 21, 2020), including the pre-epidemic, incubation, developing, outbreak, and plateau periods. Data on cardiovascular events were prospectively collected for one year. A total of 262 individuals (7.0%) reported an increased level of anxiety, and 3462 individuals (93.0%) did not. Patients with anxiety showed higher morning SBP than patients without anxiety, and the between-group differences in SBP change were +1.2 mmHg and +1.7 mmHg during the outbreak and plateau periods (P < 0.05), respectively. The seasonal BP variation in winter among patients with anxiety was suppressed during the pandemic. Anxious patients had higher rates of uncontrolled BP. During the 1-year follow-up period, patients with anxiety had an increased risk of cardiovascular events with a hazard ratio of 2.47 (95% confidence interval, 1.10–5.58; P = 0.03). In summary, COVID-19-related anxiety was associated with a short-term increase in morning SBP among older patients and led to a greater risk of cardiovascular events.
Cardiac Dysfunction and Arrhythmias 3 Months After Hospitalization for COVID‐19
Journal of the American Heart Association, January 20, 2022
The extent of cardiac dysfunction post‐COVID‐19 varies, and there is a lack of data on arrhythmic burden. This was a combined multicenter prospective cohort study and cross‐sectional case‐control study. Cardiac function assessed by echocardiography in patients with COVID‐19 3 to 4 months after hospital discharge was compared with matched controls. The 24‐hour ECGs were recorded in patients with COVID‐19. A total of 204 patients with COVID‐19 consented to participate (mean age, 58.5 years; 44% women), and 204 controls were included (mean age, 58.4 years; 44% women). Patients with COVID‐19 had worse right ventricle free wall longitudinal strain (adjusted estimated mean difference, 1.5 percentage points; 95% CI, −2.6 to −0.5; P=0.005) and lower tricuspid annular plane systolic excursion (−0.10 cm; 95% CI, −0.14 to −0.05; P<0.001) and cardiac index (−0.26 L/min per m2; 95% CI, −0.40 to −0.12; P<0.001), but slightly better left ventricle global strain (−0.8 percentage points; 95% CI, 0.2–1.3; P=0.008) compared with controls. Reduced diastolic function was twice as common compared with controls (60 [30%] versus 29 [15%], respectively; odds ratio, 2.4; P=0.001). Having dyspnea or fatigue were not associated with cardiac function. Right ventricle free wall longitudinal strain was worse after intensive care treatment. Arrhythmias were found in 27% of the patients, mainly premature ventricular contractions and nonsustained ventricular tachycardia (18% and 5%, respectively). At 3 months after hospital discharge with COVID‐19, right ventricular function was mildly impaired, and diastolic dysfunction was twice as common compared with controls. There was little evidence for an association between cardiac function and intensive care treatment, dyspnea, or fatigue. Ventricular arrhythmias were common, but the clinical importance is unknown.
One-year outcomes of invasively managed acute coronary syndrome patients with COVID-19
Heart & Lung, January 20, 2022
There is a limited data about the one-year outcomes of patients diagnosed with acute coronary syndrome (ACS) and coronavirus disease 2019 (COVID-19). The objective was to assess one-year mortality of invasively managed patients with ACS and COVID-19 compared to ACS patients without COVID-19. In our investigation, we defined the study time period as April 30 through September 1, 2020. The control groups consisted of ACS patients without COVID-19 at the same time period and ACS patients prior to the pandemic, within the same months as those of the study. COVID-19 infection was confirmed in all participants utilizing real-time polymerase chain reaction testing. This investigation examined 721 ACS participants in total. Among the participants, 119 patients were diagnosed with ACS and COVID-19, while 149 were diagnosed with ACS and without COVID-19. The other 453 ACS participants were diagnosed before the outbreak of the pandemic, within the same months as those of the study. One-year mortality rates were higher in the ACS participants with COVID-19 than in the ACS participants without COVID-19 and the pre-COVID-19 ACS participants (21.3% vs. 6.5% vs. 6.9%, respectively). An ACS along with COVID-19 was the only independent predictor of one-year mortality (HR=2.902, 95%CI=1.211–6.824, P = 0.018). According to the Kaplan-Meier survival curves, patients with ACS and COVID-19 had a lower chance of survival in the short-term and one-year periods. This is believed to be the first study to report that ACS patients with COVID-19 had higher one-year risk of mortality compared to ACS patients without COVID-19.
Constrictive pericarditis after SARS-CoV-2 vaccination: A case report
International Journal of Infectious Diseases, January 19, 2022
Coronavirus disease 2019 (COVID-19) and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with cardiovascular complications. We report a case of right-sided heart failure due to constrictive pericarditis that developed after administration of messenger ribonucleic acid (mRNA) vaccines against SARS-CoV-2. A 70-year-old woman presented with body weight gain, peripheral edema, and dyspnea on effort, which developed over a period of one week after the second vaccine injection. The jugular venous pressure was high with a prominent y descent (Friedreich’s sign) and paradoxical increase on inspiration (Kussmaul’s sign). The results of IgM and IgG testing specific to SARS-CoV-2 spike and nucleocapsid proteins were consistent with mRNA vaccine-induced antibody, not COVID-19 infection. Echocardiography demonstrated pericardial thickening and septal bounce of the interventricular septum. Computed tomography also revealed pericardial thickening compared with the previous examination four months earlier. A diagnosis of right-sided heart failure due to constrictive pericarditis was confirmed based on pressure analysis during cardiac catheterization.
Combined Role of Troponin and Natriuretic Peptides Measurements in Patients With Covid-19 (from the Cardio-COVID-Italy Multicenter Study)
American Journal of Cardiology, January 19, 2022
Data concerning the combined prognostic role of natriuretic peptide (NP) and troponin in patients with COVID-19 are lacking. The aim of the study is to evaluate the combined prognostic value of NPs and troponin in hospitalized COVID-19 patients. From March 1, 2020 to April 9, 2020, consecutive patients with COVID-19 and available data on cardiac biomarkers at admission were recruited. Patients admitted for acute coronary syndrome were excluded. Troponin levels were defined as elevated when greater than the 99th percentile of normal values. NPs were considered elevated if above the limit for ruling in acute heart failure (HF). A total of 341 patients were included in this study, mean age 68 § 13 years, 72% were men. During a median follow-up period of 14 days, 81 patients (24%) died. In the Cox regression analysis, patients with elevated both NPs and troponin levels had higher risk of death compared with those with normal levels of both (hazard ratio 2.94; 95% confidence interval 1.31 to 6.64; p = 0.009), and this remained significant after adjustment for age, gender, oxygen saturation, HF history, and chronic kidney disease. Interestingly, NPs provided risk stratification also in patients with normal troponin values (hazard ratio 2.86; 95% confidence interval 1.21 to 6.72; p = 0.016 with high NPs levels). These data show the combined prognostic role of troponin and NPs in COVID-19 patients. NPs value may be helpful in identifying patients with a worse prognosis among those with normal troponin values. Further, NPs’ cut-point used for diagnosis of acute HF has a predictive role in patients with COVID-19.
Longitudinal Assessment of Cardiac Outcomes of Multisystem Inflammatory Syndrome in Children Associated With COVID‐19 Infections
Journal of the American Heart Association, January 19, 2022
In multisystem inflammatory syndrome in children, there is paucity of longitudinal data on cardiac outcomes. We analyzed cardiac outcomes 3 to 4 months after initial presentation using echocardiography and cardiac magnetic resonance imaging. We included 60 controls and 60 cases of multisystem inflammatory syndrome in children. Conventional echocardiograms and deformation parameters were analyzed at 4 time points: (1) acute phase (n=60), (2) subacute phase (n=50; median, 3 days after initial echocardiography), (3) 1‐month follow‐up (n=39; median, 22 days), and (4) 3‐ to 4‐month follow‐up (n=25; median, 91 days). Fourteen consecutive cardiac magnetic resonance imaging studies were reviewed for myocardial edema or fibrosis during subacute (n=5) and follow‐up (n=9) stages. In acute phase, myocardial injury was defined as troponin‐I level ≥0.09 ng/mL (>3 times normal) or brain‐type natriuretic peptide >800 pg/mL. All deformation parameters, including left ventricular global longitudinal strain, peak left atrial strain, longitudinal early diastolic strain rate, and right ventricular free wall strain, recovered quickly within the first week, followed by continued improvement and complete normalization by 3 months. Median time to normalization of both global longitudinal strain and left atrial strain was 6 days (95% CI, 3–9 days). Myocardial injury at presentation (70% of multisystem inflammatory syndrome in children cases) did not affect short‐term outcomes. Four patients (7%) had small coronary aneurysms at presentation, all of which resolved. Only 1 of 9 patients had residual edema but no fibrosis by cardiac magnetic resonance imaging. Our short‐term study suggests that functional recovery and coronary outcomes are good in multisystem inflammatory syndrome in children. Use of sensitive deformation parameters provides further reassurance that there is no persistent subclinical dysfunction after 3 months.
Even mild COVID-19 cases can result in lingering heart issues
Cardiovascular Business, January 17, 2022
Mild and moderate COVID-19 infections can cause lingering changes to a patient’s heart and cardiovascular system, according to a new analysis published in European Heart Journal. “Autopsy studies indicate that SARS-CoV-2 affects multiple organs beyond the respiratory tract, including the heart, brain, and kidneys,” wrote lead author Elina Larissa Petersen, a cardiology specialist at the University Heart and Vascular Center in Hamburg, Germany, and colleagues. “Some patients continue to suffer from heterogeneous symptoms after the acute phase of critical illness. These conditions are described as ‘post-COVID-19 syndrome’ or—if symptoms continue longer than six months—as ‘long COVID-19 syndrome’. Clinical, imaging, or laboratory findings should accompany the diagnosis of post- or long COVID-19.” Petersen et al. reviewed data from more than 400 patients with a prior COVID-19 infection and more than 1,300 matched controls. Female patients made up 52.6% of the COVID-19 group and 54.1% of the control group. The median age was 55 years old for the COVID-19 group and 57 years old for the control group. Of the COVID-19 patients included in this study, 3.2% never experienced symptoms, 58.4% presented with mild symptoms and 31.2% presented with moderate symptoms. The median time between initial diagnosis and follow-up for this study was 9.6 months. All patients from the COVID-19 and control groups underwent the same assessment, which included body plethysmography, transthoracic echocardiography, cardiac MRI, compression ultrasound and routine laboratory work. Overall, a prior COVID-19 infection was associated with consistent subclinical changes, including lower measures of left and right ventricular function and a higher concentration of certain cardiac biomarkers. Even these slight changes in ventricular function, over time, can increase a patient’s risk of mortality. Cardiac MRI results were similar between the two patient groups, the authors added, but signs of deep venous thrombosis were much more common among patients with a history of COVID-19. Changes in total lung volume and airway resistance were also observed, and glomerular filtration rates revealed an effect on kidney function.
Pandemic-Associated Delays in Myocardial Infarction Presentation in Predominantly Rural Counties With Low COVID-19 Prevalence
American Journal of Cardiology, January 16, 2022
Fewer ST-elevation myocardial infarctions (STEMIs) presentations and increased delays in care occurred during the COVID-19 pandemic in urban areas. Whether these associations occurred in a more rural population has not been previously reported. Our objective was to evaluate the impact of COVID-19 on time-to-presentation for STEMI in rural locations. Patients presenting to a large STEMI network spanning 27 facilities and 13 predominantly rural counties between January 1, 2016 and April 30, 2020 were included. Presentation delays, defined as time from symptom onset to arrival at the first medical facility, classified as ≥12 and ≥24 hours from symptom onset were compared among patients in the pre–COVID-19 and the early COVID-19 eras. To account for patient-level differences, 2:1 propensity score matching was performed using binary logistic regression. Among 1,286 patients with STEMI, 1,245 patients presented in the pre–COVID-19 era and 41 presented during the early COVID-19 era. Presentation delays ≥12 hours (19.5% vs 4.0%) and ≥24 hours (14.6% and 0.2%) were more common in COVID-19 than pre–COVID-19 cohorts (p <0.001 for both), despite a low COVID-19 prevalence. Similar results were seen in propensity-matched comparisons (≥12 hours: 19.5% vs 2.4%, p = 0.002; ≥24 hours 14.6% vs 0.0%, p = 0.001). In a predominantly rural STEMI population, delays in seeking medical care after symptom onset were markedly more frequent during the COVID-19 era, despite low COVID-19 prevalence. Considering delays in reperfusion have multiple adverse downstream consequences, these findings may have important implications in rural communities during future pandemic resurgences.
Myocardial injury during COVID-19 hospitalization tied to mortality, long-term symptoms
Healio | Cardiology Today, January 13, 2022
Among patients hospitalized with COVID-19, myocardial injury as determined by high-sensitivity cardiac troponin T was linked to mortality and ongoing COVID-19 symptoms, researchers reported. Brittany Weber, MD, PhD, cardiologist at Brigham and Women’s Hospital and instructor in medicine at Harvard Medical School, and colleagues conducted a prospective analysis of 483 patients (median age, 63 years; 51% women) who were admitted to Brigham and Women’s Hospital for COVID-19 and had high-sensitivity cardiac troponin T measured at admission from March to May 2020. During the index hospitalization, 18.8% of patients died, 14.4% had thrombotic complications and 25.6% had CV complications, whereas at 1 year, 22.2% died, Weber and colleagues found. Cardiac injury, defined as high-sensitivity cardiac troponin T of at least 14 ng/L, occurred in 62.3% of the cohort during index hospitalization, according to the researchers. Patients with cardiac injury had higher rates of mortality at index hospitalization (28.6%) compared with those with low-level positive troponin (4.1%) and those with undetectable troponin (0%), Weber and colleagues wrote. Similar mortality rates were observed at 6 months (cardiac injury, 32.2%; low-level positive troponin, 4.9%; undetectable troponin, 0%) and at 12 months (cardiac injury, 33.2%; low-level positive troponin, 4.9%; undetectable troponin, 0%), according to the researchers. After adjustment for age, sex, CAD, hypertension, hyperlipidemia, HF and diabetes, cardiac injury was associated with elevated risk for mortality compared with undetectable troponin (HR = 13.76; 95% CI, 1.85-102.3; P = .01), but there was no difference in mortality risk between low-level positive troponin and undetectable troponin (HR = 2.31; 95% CI, 0.27-19.48; P = .44). Among the 211 patients who were alive at 6 months and had a detailed clinical assessment at that time, 37% had ongoing COVID-19-related symptoms, 16.1% had neurocognitive decline, 3.8% required increased supplemental oxygen and 19.9% had worsening functional status, according to the researchers.
Perceptions of changes in practice patterns and patient care among heart failure nurses during the COVID-19 pandemic
Heart & Lung, January 13, 2022
The Coronavirus (COVID-19) had a profound impact on the delivery of care in both hospital and outpatient settings across the United States. Patients with heart failure (HF) and healthcare providers had to abruptly adapt. Our objective was to describe how the COVID-19 pandemic affected practice patterns of HF nurses. Practicing HF nurses completed a cross-sectional, anonymous, web-based survey of perceptions of HF practice. Analyses involved descriptive and comparative statistics. Of 171 nurses who completed surveys, outpatient HF visits decreased and 63.2% added telehealth visits. Despite spending about 29 min educating patients during visits, 27.5% of nurses perceived that the pandemic decreased patients’ abilities to provide optimal self-care. Nurses reported decreased ability to collect objective data (62.4%; n = 78), although subjective assessment stayed the same (41.6%; n = 52). Conclusion: Nurses’ practice patterns provided insight into patient care changes made during COVID-19. Most core components of HF management were retained, but methods of delivery during the pandemic differed.
Usefulness of Combined Renin-Angiotensin System Inhibitors and Diuretic Treatment In Patients Hospitalized with COVID-19
American Journal of Cardiology, January 10, 2022
Antecedent use of renin-angiotensin system inhibitors (RASi) prevents clinical deterioration and protects against cardiovascular/thrombotic complications of COVID-19, for indicated patients. Uncertainty exists regarding treatment continuation throughout infection and doing so with concomitant medications. Hence, the purpose of this study is to evaluate the differential effect of RASi continuation in patients hospitalized with COVID-19 according to diuretic use. We used the Coracle registry, which contains data of hospitalized patients with COVID-19 from 4 regions of Italy. We used Firth logistic regression for adult (>50 years) cases with admission on/after February 22, 2020, with a known discharge status as of April 1, 2020. There were 286 patients in this analysis; 100 patients (35.0%) continued RASi and 186 (65%) discontinued. There were 98 patients treated with a diuretic; 51 (52%) of those continued RASi. The in-hospital mortality rates in patients treated with a diuretic and continued versus discontinued RASi were 8% versus 26% (p = 0.0179). There were 188 patients not treated with a diuretic; 49 (26%) of those continued RASi. The in-hospital mortality rates in patients not treated with a diuretic and continued versus discontinued RASi were 16% versus 9% (p = 0.1827). After accounting for age, cardiovascular disease, and laboratory values, continuing RASi decreased the risk of mortality by approximately 77% (odds ratio 0.23, 95% confidence interval 0.06 to 0.95, p = 0.0419) for patients treated with diuretics, but did not alter the risk in patients treated with RASi alone. Continuing RASi in patients concomitantly treated with diuretics was associated with reduced in-hospital mortality.
Systematic identification of ACE2 expression modulators reveals cardiomyopathy as a risk factor for mortality in COVID-19 patients
Genome Biology, January 10, 2022
Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for SARS-CoV-2. It plays critical roles in both the transmission and the pathogenesis of COVID-19. Comprehensive profiling of ACE2 expression patterns could reveal risk factors of severe COVID-19 illness. While the expression of ACE2 in healthy human tissues has been well characterized, it is not known which diseases and drugs might be associated with ACE2 expression. We develop GENEVA (GENe Expression Variance Analysis), a semi-automated framework for exploring massive amounts of RNA-seq datasets. We apply GENEVA to 286,650 publicly available RNA-seq samples to identify any previously studied experimental conditions that could be directly or indirectly associated with ACE2 expression. We identify multiple drugs, genetic perturbations, and diseases that are associated with the expression of ACE2, including cardiomyopathy, HNF1A overexpression, and drug treatments with RAD140 and itraconazole. Our joint analysis of seven datasets confirms ACE2 upregulation in all cardiomyopathy categories. Using electronic health records data from 3936 COVID-19 patients, we demonstrate that patients with pre-existing cardiomyopathy have an increased mortality risk than age-matched patients with other cardiovascular conditions. This study identifies multiple diseases and drugs that are associated with the expression of ACE2. The effect of these conditions should be carefully studied in COVID-19 patients. In particular, our analysis identifies cardiomyopathy patients as a high-risk group, with increased ACE2 expression in the heart and increased mortality after SARS-COV-2 infection.
Inappropriate sinus tachycardia in post-COVID-19 syndrome
Scientific Reports, January 7, 2022
Inappropriate sinus tachycardia (IST) is a common observation in patients with post-COVID-19 syndrome (PCS) but has not yet been fully described to date. To investigate the prevalence and the mechanisms underlying IST in a prospective population of PCS patients. Consecutive patients admitted to the PCS Unit between June and December 2020 with a resting sinus rhythm rate ≥ 100 bpm were prospectively enrolled in this study and further examined by an orthostatic test, 2D echocardiography, 24-h ECG monitoring (heart rate variability was a surrogate for cardiac autonomic activity), quality-of-life and exercise capacity testing, and blood sampling. To assess cardiac autonomic function, a 2:1:1 comparative sub-analysis was conducted against both fully recovered patients with previous SARS-CoV-2 infection and individuals without prior SARS-CoV-2 infection. Among 200 PCS patients, 40 (20%) fulfilled the diagnostic criteria for IST (average age of 40.1 ± 10 years, 85% women, 83% mild COVID-19). No underlying structural heart disease, pro-inflammatory state, myocyte injury, or hypoxia were identified. IST was accompanied by a decrease in most heart rate variability parameters, especially those related to cardiovagal tone: pNN50 (cases 3.2 ± 3 vs. recovered 10.5 ± 8 vs. non-infected 17.3 ± 10; p < 0.001) and HF band (246 ± 179 vs. 463 ± 295 vs. 1048 ± 570, respectively; p < 0.001). IST is prevalent condition among PCS patients. Cardiac autonomic nervous system imbalance with decreased parasympathetic activity may explain this phenomenon.
Some Patients With COVID-19 First Present With Arterial Thrombosis
Cardiology Advisor, January 6, 2022
A retrospective analysis found that some patients with COVID-19 present with arterial thrombosis as the first symptom. The study findings were published in the journal Vascular. The arterial thrombosis in COVID-19 (ARTICO-19) was an interventional registry comprising 21 centers in 9 countries in Latin America and Spain. Inpatients (N=81) with confirmed SARS-CoV-2 and arterial thrombotic complications between December 2019 and August 2020 were assessed for risk factors and outcomes. Patients had a mean age of 64.8±14.1 years; 67.9% were men; 50.0% had hypertension; 36.0% were on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers; 26.6% had diabetes; 24.4% dyslipidemia; 24.1% had a history of smoking; and 14.8% were active smokers. Over a third of patients (38.3%) first presented with ischemia-related symptoms and most patients had acute limb ischemia (97.5%). The thrombus occurred above the knee (45.0%), aorta and lower limb (14.8%), upper limb (14.8%), below the knee (13.8%), abdominal aorta (5.0%), above and below the knee (3.8%), visceral above the knee (1.3%) visceral below the knee (1.3%), and thoracic aorta (1.3%). Over a third of patients (36.5%) developed acute distress respiratory syndrome, 25.7% developed pneumonia, 12.2% had mild symptoms, and 25.7% were asymptomatic. Fewer patients with severe disease received surgical interventions (11.1% vs 88.9%; P =.004). More patients with severe disease were admitted to the intensive care unit (P =.001) and died (P =.015). Overall, the study found that some patients with COVID-19 presented with arterial thrombosis, particularly acute limb ischemia before respiratory symptoms.
Q&A: How will omicron affect long COVID?
Healio | Infectious Disease, January 6, 2022
The omicron variant of SARS-CoV-2 now accounts for 95% of COVID-19 cases in the United States, CDC Director Rochelle P. Walensky, MD, MPH, said during a White House briefing on Wednesday. If omicron causes less severe disease than the delta variant, could any lasting effects of COVID-19 also be less serious? We asked Ziyad Al-Aly, MD, FASN, a physician at the VA St. Louis Health Care System who studies long COVID, to answer this and other lingering questions about the variant.
LV global longitudinal strain may predict poor outcomes in COVID-19
Healio | Cardiology Today, January 5, 2022
Left ventricular global longitudinal strain predicted death and respiratory failure in patients hospitalized with COVID-19, researchers reported in the American Journal of Cardiology. Michele Bevilacqua, MD, internal medicine resident at University Hospital of Verona, Italy, and colleagues analyzed 87 patients with COVID-19 admitted to University Hospital of Verona who had a complete echocardiography examination within 72 hours of admission. The primary outcome, mechanical ventilation by orotracheal intubation and/or mortality, occurred in 14 patients, whereas the secondary outcome, severe acute respiratory distress syndrome, defined as worsening respiratory function as indicated by a partial pressure of oxygen to fraction of inspired oxygen ratio of less than 100, occurred in 24 patients, the researchers wrote. After the researchers adjusted for risk factors and considered LV global longitudinal strain as a continuous variable, they found LV global longitudinal strain was associated with the secondary outcome (adjusted HR = 1.48; 95% CI, 1.18-1.88; P = .001) and the primary outcome (aHR = 1.63; 95% CI, 1.13-2.38; P = .012). Having LV global longitudinal strain of at least –16.1% was independently associated with risk for severe acute respiratory distress syndrome (HR = 4; 95% CI, 1.4-11.1; P = .008) and death or orotracheal intubation (HR = 7.3; 95% CI, 1.6-34.1; P = .024), according to the researchers. “LV global longitudinal strain measured at the moment of admission was a strong predictor of respiratory failure and mortality,” Bevilacqua and colleagues wrote. “Although troponin is a good biomarker of myocardial injury, in our study troponin was not a predictor of mortality.
Cardiopulmonary Exercise Testing Provides Insights on Long-Haul COVID Symptoms
Pulmonology Advisor, January 5, 2022
Patients with post-acute sequelae of SARS-CoV-2 infection (PASC), informally referred to as “long-haul COVID,” were found to have circulatory impairment, abnormal ventilatory pattern, and/or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), according to results of a prospective study published in JACC: Heart Failure. For the analysis, researchers enrolled individuals (N=41) who developed dyspnea, or new and persistent shortness of breath, for over 3 months after recovering from a COVID-19 infection. Study participants received cardiopulmonary exercise testing (CPET) and were evaluated for ME/CFS symptoms. The participants had a mean age of 45.2±12.5 years; 23 were women; 18 were men; body mass index (BMI) was 28.3±6.4; hemoglobin was 14.0±1.3 g/dL; 9 participants had hypertension; 4 had diabetes; 2 had postural orthostatic tachycardia; 1 had prior atrial fibrillation ablation; and 1 had a history of colon cancer. During the CPET, peak oxygen consumption was 77%±21% of the predicted value. Oxygen consumption less than 80% of predicted value was observed among 24 patients who had low oxygen consumption (n=12), low oxygen consumption pulse (n=22), and/or elevated slope of minute ventilation to carbon dioxide production (n=23). Patients (41%) who had oxygen consumption greater than or equal to 80% of predicted value were considered to have normal exercise capacity but with reduced oxygen consumption pulse (n=2), respiratory rate greater than 55 breaths/min (n=3), and/or abnormal ventilatory patterns (n=12). Dysfunctional breathing was observed among 63% of study participants. The dysfunctional and normal breathers did not differ for oxygen consumption, resting end tidal pressure of carbon dioxide, maximum minute ventilation, respiratory rate, or respiratory exchange ratio. Thirty-two patients met the 1994 diagnostic criteria for ME/CFS. Excluding patients with confounding comorbidities, 46% were considered to have ME/CFS. Nearly half of this cohort (42%) also had dysfunctional breathing.
Both symptomatic and asymptomatic COVID-19 associated with increased risk of cardiovascular events
News Medical, January 4, 2022
Myocardial injury can be caused by direct injury to cardiac myocytes due to COVID-19 and as a result of secondary effects from the systemic inflammation and hypercoagulable state seen in acute infection. Therefore, COVID-19 patients with known cardiovascular disease (CVD) and other risk factors like age, hypertension, diabetes, obesity, kidney disease, and respiratory system disorders are more likely to require critical care and have a higher mortality rate. Long COVID, which is also known as post-acute COVID, is the persistence of symptoms or complications after the end of the acute phase of infection. However, the long-term impacts of COVID-19 on cardiovascular outcomes remain unknown. Furthermore, the causal role of asymptomatic and symptomatic SARS-CoV-2 infections in precipitating cardiovascular events has yet to be clarified. The objective of a recent retrospective double-cohort study was conducted at the Oregon Health & Science University (OHSU). The study was approved by the OHSU Institutional Review Board (IRB) and all results were reported using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. The primary outcome was a composite of cardiovascular death, acute HF, acute coronary syndrome (ACS) including ST-Segment Elevation Myocardial Infarction (STEMI), non-STEMI (NSTEMI), or unstable angina, as well as incident stroke or transient ischemic attack, another acute or new cardiovascular outcome prompting healthcare utilization. During the study period, 99,711 COVID-19 tests were performed for 65,585 individuals. Notably, COVID-19 positive (+) patients were often younger and more likely to be non-white or Hispanic. Additionally, a higher number of COVID-19(+) patients had a history of liver disease and/or diabetes mellitus than those who tested COVID-19 negative (-), while there was no difference in CVD history between the two cohorts. The results of the study suggest that both symptomatic and asymptomatic SARS-CoV-2 infections are associated with an increased risk of late cardiovascular outcomes and have a causal effect on all-cause mortality. These findings underscore the importance of COVID-19 prevention and emphasize careful follow-up for all patients who encounter SARS-CoV-2, regardless of whether they are symptomatic or asymptomatic, to monitor for late cardiovascular events.
Arrhythmias and Intraventricular Conduction Disturbances in Patients Hospitalized With Coronavirus Disease 2019
American Journal of Cardiology, January 1, 2022
Cardiac arrhythmias have been observed in patients hospitalized with coronavirus disease (COVID-19). Most analyses of rhythm disturbances to date include cases of sinus tachycardia, which may not accurately reflect true cardiac dysfunction. Furthermore, limited data exist regarding the development of conduction disturbances in patients hospitalized with COVID-19. Hence, we performed a retrospective review and compared characteristics and outcomes for patients with versus without incident arrhythmia, excluding sinus tachycardia, as well as between those with versus without incident conduction disturbances. There were 27 of 173 patients (16%) hospitalized with COVID-19 who developed a new arrhythmia. Incident arrhythmias were associated with an increased risk of intensive care unit admission (59% vs 31%, p = 0.0045), intubation (56% vs 20%, p <0.0001), and inpatient death (41% vs 10%, p = 0.0002) without an associated increase in risk of decompensated heart failure or other cardiac issues. New conduction disturbances were found in 13 patients (8%). Incident arrhythmias in patients hospitalized with COVID-19 are associated with an increased risk of mortality, likely reflective of underlying COVID-19 disease severity more than intrinsic cardiac dysfunction. Conduction disturbances occurred less commonly and were not associated with adverse patient outcomes.
Impact of serum lactate dehydrogenase on the short-term prognosis of COVID-19 with pre-existing cardiovascular diseases
Journal of Cardiology, December 27, 2021
Patients with coronavirus disease 2019 (COVID-19) and underlying cardiovascular comorbidities have poor prognoses. Our aim was to identify the impact of serum lactate dehydrogenase (LDH), which is associated with mortality in acute respiratory distress syndrome, on the prognoses of patients with COVID-19 and underlying cardiovascular comorbidities. Among 1518 patients hospitalized with COVID-19 enrolled in the CLAVIS-COVID (Clinical Outcomes of COVID-19 Infection in Hospitalized Patients with Cardiovascular Diseases and/or Risk Factors study), 515 patients with cardiovascular comorbidities were analyzed. Patients were divided into tertiles based on LDH levels at admission [tertile 1 (T1), < 0.001]. Multivariable analysis adjusted for age, comorbidities, vital signs, and laboratory data including D-dimer and high-sensitivity troponin showed T3 was associated with an increased risk of in-hospital mortality (adjusted hazard ratio, 3.04; 95% confidence interval, 1.50–6.13; p = 0.002). High serum LDH levels at the time of admission are associated with an increased risk of in-hospital death in patients with COVID-19 and known cardiovascular disease and may aid in triage of these patients.
Antiplatelet therapy and outcome in COVID-19: the Health Outcome Predictive Evaluation Registry
BMJ Journals | Heart, December 22, 2021
Standard therapy for COVID-19 is continuously evolving. Autopsy studies showed high prevalence of platelet-fibrin-rich microthrombi in several organs. The aim of the study was therefore to evaluate the safety and efficacy of antiplatelet therapy (APT) in hospitalised patients with COVID-19 and its impact on survival. 7824 consecutive patients with COVID-19 were enrolled in a multicentre international prospective registry (Health Outcome Predictive Evaluation-COVID-19 Registry). Clinical data and in-hospital complications were recorded. Data on APT, including aspirin and other antiplatelet drugs, were obtained for each patient. During hospitalisation, 730 (9%) patients received single APT (93%, n=680) or dual APT (7%, n=50). Patients treated with APT were older (74±12 years vs 63±17 years, p<0.01), more frequently male (68% vs 57%, p<0.01) and had higher prevalence of diabetes (39% vs 16%, p<0.01). Patients treated with APT showed no differences in terms of in-hospital mortality (18% vs 19%, p=0.64), need for invasive ventilation (8.7% vs 8.5%, p=0.88), embolic events (2.9% vs 2.5% p=0.34) and bleeding (2.1% vs 2.4%, p=0.43), but had shorter duration of mechanical ventilation (8±5 days vs 11±7 days, p=0.01); however, when comparing patients with APT versus no APT and no anticoagulation therapy, APT was associated with lower mortality rates (log-rank p<0.01, relative risk 0.79, 95% CI 0.70 to 0.94). On multivariable analysis, in-hospital APT was associated with lower mortality risk (relative risk 0.39, 95% CI 0.32 to 0.48, p<0.01). APT during hospitalisation for COVID-19 could be associated with lower mortality risk and shorter duration of mechanical ventilation, without increased risk of bleeding.
The association of statins use with survival of patients with COVID-19
Journal of Cardiology, December 21, 2021
Statins are frequently prescribed for patients with dyslipidemia and diabetes mellitus. These comorbidities are highly prevalent in coronavirus disease 2019 (COVID-19) patients. Statin’s beneficial effect on mortality in COVID-19 infection has been reported in several studies. However, these findings are still inconclusive. We conducted a retrospective observational study among 6,095 patients with laboratory confirmed COVID-19 hospitalized in Mount Sinai Health System between March 1st 2020 and May 7th 2020. Patients were stratified into two groups: statin use prior to or during hospitalization (N = 2,423) versus no statins (N = 3,672). We evaluated in-hospital mortality as a primary outcome using propensity score matching and inverse probability treatment weighted (IPTW) analysis. In additional analysis, we compared continuous use of statins (N = 1,108) with no statins, continuous use of statins with discontinuation of statins (N = 644), and discontinuation of statins with no statins. Among 6,095 COVID-19 patients, statin use prior to or during hospitalization group were older (70.8 ± 12.7 years versus 59.2 ± 18.2 years, p<0.001) and had more comorbidities compared to no statins group. After matching by propensity score (1,790 pairs), there were no significant differences in-hospital mortality between patients with statins and those without [28.9% versus 31.0%, p = 0.19, odds ratio (OR) 95% confidence interval (CI): 0.91 (0.79–1.05)]. This result was confirmed by IPTW analysis [OR (95% CI): 0.96 (0.81–1.12), p = 0.53]. In the additional analysis comparing continuous use of statins with no statins group, in-hospital mortality was significantly lower in continuous use of statins compared to no statins group [26.3% versus 34.5%, p<0.001, OR (95% CI): 0.68 (0.55–0.82)] after matching by propensity score (944 pairs), as well as IPTW analysis [OR (95% CI): 0.77 (0.64–0.94), p = 0.009]. Finally, comparison of continuous use of statins with discontinuation of statins showed lower in-hospital mortality in continuous use of statins group [27.9% versus 42.1%, p<0.001, OR (95% CI): 0.53 (0.41–0.68)]. Use of statins prior to or during hospitalization was not associated with a decreased risk of in-hospital mortality; however, continuous use of statins was associated with lower in-hospital mortality compared to no statin use and discontinuation of statins.
Bradyarrhythmia in COVID-19 Patients
Cureus, December 21, 2021
The emergence of coronavirus disease 2019 (COVID-19) in 2019 has rapidly become a global health emergency. COVID-19 develops from a severe acute respiratory syndrome coronavirus (SARS-CoV) infection, which directly impacts the cardiovascular system by disrupting angiotensin-converting enzyme-2 receptors in the tissues. This leads to severe complications that cause major morbidity and mortality. Several cardiovascular complications have been reported during the pandemic, including myocardial infarction, stroke, pulmonary embolism, myocarditis, and tachyarrhythmias. Although bradyarrhythmia is another cardiac event associated with COVID-19, it has been reported in only a few cases in the medical literature. Here, we report two cases of young adult patients who were admitted because of a positive reverse transcriptase-polymerase chain reaction test of SARS-CoV-2 and presented with bradycardia detected on electrocardiogram but had an otherwise normal health condition with no history of cardiovascular illness.
AHA to fund research on long-term impact of COVID-19 on heart, brain health
Healio | Cardiology Today, December 19, 2021
The American Heart Association announced a $10 million initiative to fund studies of long-term effects of COVID-19 on heart and brain health. The grants will fund projects studying the basic mechanisms underlying cardiac, vascular and cerebrovascular complications in patients with COVID-19, as well as why some people experience effects of COVID-19 beyond the standard recovery time, according to a press release from the association. “While COVID-19 was initially thought to be a disease only of the respiratory system, it quickly became evident that its effects were not limited to any one system of the body. Cardiovascular complications in aggregate have commonly been reported among COVID-19 patients and most often include blood clots, heart inflammation known as myocarditis, disruption of the heart rhythm, heart failure and heart attacks,” Svati H. Shah, MD, MS, MHS, FAHA, professor of medicine and associate dean for genomics in the division of cardiology at Duke University School of Medicine, said in the release. “Frequently reported symptoms in patients who have effects long after their initial COVID infection have cardiovascular-related aspects including fatigue, chest pain and shortness of breath. The patients also report effects on the central nervous system, including both psychological effects such as anxiety and depression, as well as cognitive effects such as confusion and deficits of memory and concentration. But we have a lot still to learn through rigorous research to understand long COVID.” Applications are due by Feb. 1, and awards will be announced in March. Information on how to apply can be found at professional.heart.org/en/research-programs/strategically-focused-research/long-covid-cv-consequences-grant.
AHA, ADA: Diabetes harder to manage during holidays, so keep health goals on track
Healio | Cardiology Today, December 18, 2021
Nearly half of people with type 2 diabetes said it is more difficult to manage their condition during the holiday season than at other times, according to a survey from the American Heart Association and American Diabetes Association. The survey conducted on behalf of the associations’ joint initiative, Know Diabetes by Heart, included more than 1,000 U.S. adults 45 and older. Around 28% of the participants said their main concern is staying on top of their health goals during the holiday season, while 15% were concerned about finances and 14% were concerned about safe gatherings during the COVID-19 pandemic. “The holidays provide challenges to staying heart healthy for many people, but especially for those managing conditions closely tied to daily nutrition, like type 2 diabetes,” Robert Eckel, MD, FAHA, immediate past president of medicine and science for the American Diabetes Association, past president of the American Heart Association, and an endocrinologist at the University of Colorado School of Medicine, said in a press release. “Even if you don’t have diabetes yourself, it’s important to create healthy environments for our friends and family members who do,” Eckel said in the release.
Health care provider recommendation key to COVID-19 vaccine uptake
Healio, December 16, 2021
Adults who said a health care provider recommended that they receive a COVID-19 vaccine were more likely to get one, data published in MMWR show. Kimberly H. Nguyen, DrPH, a member of CDC’s COVID-19 Vaccine Task Force, and colleagues analyzed data from 340,543 U.S. adults who completed a phone survey during one of four different time periods between April 22 and Sept. 25. About 51% of the survey respondents were women, most (24.5%) were aged 50 to 64 years and 62.1% were white. The researchers reported that proportion of adults who received a provider recommendation for COVID-19 vaccination increased from 34.6% to 40.5% during the survey period. Respondents who said a health care provider recommended COVID-19 vaccination were more likely to have received at least one dose of the vaccine than those who did not receive a recommendation (77.6% vs. 61.9%, adjusted prevalence ratio [aPR] = 1.12). A COVID-19 vaccination recommendation was also associated with a respondent’s concern about COVID-19 (aPR = 1.31), thinking COVID-19 vaccines were “important to protect oneself” (aPR = 1.15), thinking COVID-19 vaccination “was very or completely safe” (aPR = 1.17) and that “many or all of their family and friends had received COVID-19 vaccination” (aPR = 1.19). The researchers noted that the survey response rate was low, and it did not measure the number of health care provider visits. The study’s cross-sectional design was also a limitation, according to Nguyen and colleagues. However, they emphasized that “provider recommendation will continue to serve an important role in motivating individual patient vaccination acceptance and completion.”
Vision and hearing impairments increase risks for poor CV outcomes in type 2 diabetes
Healio | Endocrinology, December 15, 2021
People with type 2 diabetes and a hearing or vision impairment have an elevated risk for myocardial infarction, stroke and all-cause mortality, according to study findings published in the Journal of Diabetes Investigation. “Patients with both vision and hearing impairments had the highest risk for MI and mortality,” Jung Il Moon, MD, PhD, an ophthalmologist at Yeouido St. Mary’s Hospital, The Catholic University of Korea College of Medicine in Seoul, South Korea, and colleagues wrote. “Those with only vision impairment showed higher cardiovascular risk and mortality compared with those with only hearing impairment. The present findings suggest that vision and hearing impairments are independently and synergistically important risk factors for adverse cardiovascular events and mortality in patients with type 2 diabetes.” Researchers conducted a population-based cohort study of 771,128 adults with type 2 diabetes in the Korean National Health Information Database. All patients who underwent a National Health Screening Program exam in 2009 were included in the study and followed until Dec. 31, 2018. Visual impairment was defined as having any grade of visual disability or visual acuity worse than 20/40 in both eyes. Hearing impairment was having any grade of hearing disability or having impaired hearing on pure-tone audiometric testing in at least one ear. The endpoints were any new diagnosis of MI, stroke or all-cause mortality. Participants with both a visual and hearing impairment had the highest risks for MI (adjusted HR = 1.36; 95% CI, 1.25-1.48) and all-cause mortality (aHR = 1.59; 95% CI, 1.53-1.65) and the second-highest risk for stroke (aHR = 1.29; 95% CI, 1.2-1.38) of the three impairment groups. Adults with a vision impairment had the highest risk for stroke of the three groups (aHR = 1.32; 95% CI, 1.28-1.36) and second-highest risks for MI (aHR = 1.32; 95% CI, 1.28-1.38) and all-cause mortality (aHR = 1.42; 95% CI, 1.39-1.45). Those with only a hearing impairment had lower risks for all three outcomes compared with the vision impairment only and vision impairment plus hearing impairment groups, but still had a higher risk for MI (aHR = 1.12; 95% CI, 1.07-1.17), stroke (aHR = 1.13; 95% CI, 1.09-1.18) and all-cause mortality (aHR = 1.16; 95% CI, 1.14-1.19) than those with no impairment.
Patients with long COVID-19 may have cardiac complications due to dyspnea after 1 year
Healio | Cardiology Today, December 13, 2021
Patients who were hospitalized with COVID-19 may have developed cardiac complications as they continued presenting with dyspnea 1 year after hospital discharge, according to a small study presented at EuroEcho 2021. “Our study shows that more than a third of COVID-19 patients with no history of heart or lung disease had persistent dyspnea on effort a year after discharge from hospital,” Maria-Luiza Luchian, MD, PhD student at the University Hospital Brussels, said in a press release. “When looking in detail at heart function by cardiac ultrasound, we observed subtle abnormalities that might explain the continued breathlessness.” Researchers enrolled 66 patients who were hospitalized with COVID-19 (mean age, 50 years; 67% men) from March to April 2020 at the University Hospital Brussels. All patients had no previous heart or lung disease. Participants had their lung function and possible COVID-19 sequelae assessed through spirometry and chest CT 1 year after discharge. Researchers performed transthoracic echocardiography and used myocardial work, a new imaging technique, to provide more accurate information on heart function. At 1 year after hospital discharge, 35% of patients had dyspnea during physical activity. When examining the association between cardiac imaging measures and dyspnea on year post-discharge after adjusting for age and sex, researchers observed an independent and significant association between abnormal heart function and persistent dyspnea. These associations were observed among both the global constructive work (OR = 0.998; 95% CI, 0.996-1; P = .038) and the global work index (OR = 0.998; 95% CI, 0.996-1; P = .042).
Rate of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Use and the Number of COVID-19–Confirmed Cases and Deaths
American Journal of Cardiology, December 11, 2021
The novel coronavirus SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor as an entry point to the cell. Cardiovascular disease (CVD) is a risk factor for COVID-19 with poor outcomes. We tested the hypothesis that the rate of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) use is associated with the rate of COVID-19–confirmed cases and deaths. We conducted a geospatial, ecological study using publicly available county-level data. The Medicare ACEI and ARB prescription rate was exposure. The COVID-19–confirmed case and death rates were outcomes. Spatial autoregression models were adjusted for the rate of births and deaths; Group Quarters population; percentage of female; percentage of Native American, Pacific Islander, Hispanic, and Black; percentage of children and older (>65 years) adults; percentage of uninsured; percentage of those living in poverty; percentage of those who are obese, smoking, admitting insufficient sleep, and those with at least some college degree; median household income; air quality index; CVD hospitalization rate in Medicare beneficiaries; and CVD death rate in a total county population. After adjustment for confounders, the ACEI use rate did not associate with COVID-19–confirmed case rate (direct county-own effect + 0.027%; 95% confidence interval [CI] −1.080 to 1.134; p = 0.962; indirect spillover effect + 0.26%; 95% CI −70.0 to 70.5; p = 0.994). Similarly, the ARB use rate was not associated with COVID-19–confirmed case rate (direct effect + 0.029%; 95% CI −0.803 to 0.862; p = 0.945; indirect effect + 0.19%; 95% CI −52.8 to 53.2; p = 0.994). In both unadjusted and adjusted Bayesian zero inflation Poisson analysis, neither ACEI nor ARB use rates were associated with COVID-19 death rates. In conclusion, ACEI and ARB use rates were not associated with COVID-19 infectivity and death rate in this ecological study.
Global Longitudinal Strain to Predict Respiratory Failure and Death in Patients Admitted for COVID-19–Related Disease
American Journal of Cardiology, December 9, 2021
Evidence of the involvement of the cardiovascular system in patients with COVID-19 is increasing. The evaluation of the subclinical cardiac involvement is crucial for risk stratification at admission, and left ventricular global longitudinal strain (LVGLS) may be useful for this purpose. A total of 87 consecutive patients admitted to the COVID Center were enrolled from December 2020 to April 2021. A complete echocardiography examination was performed within 72 hours from admission. The main outcome was the need for mechanical ventilation by way of orotracheal intubation (OTI) and mortality, and the secondary outcome was the worsening of the respiratory function during hospitalization, interpreted as a decrease of the ratio between the partial pressure of oxygen and the fraction of inspired oxygen (P/F) <100. Of 87 patients, 14 had severe disease leading to OTI or death, whereas 24 had a P/F <100. LVGLS was significantly impaired in patients with severe disease. After adjustment for risk factors, by considering LVGLS as continuous variable, the latter remained significantly associated with severe acute respiratory distress syndrome (P/F <100) (hazard ratio [HR] 1.48, 95% confidence interval [CI] 1.18 to 1.88, p = 0.001) and OTI/death (HR 1.63, 95% CI 1.13 to 2.38, p = 0.012). When using an LVGLS cutoff of −16.1%, LVGLS ≥ −16.1% was independently associated with a higher risk of severe acute respiratory distress syndrome (HR 4.0, 95% CI 1.4 to 11.1, p= 0.008) and OTI/death (HR 7.3, 95% CI 1.6 to 34.1, p = 0.024). LVGLS can detect high-risk patients at the admission, which can help to guide in starting early treatment of the admitted patients.
Blood pressure levels in US adults rose during COVID-19 pandemic
Healio | Cardiology Today, December 6, 2021
BP levels in U.S. adults increased during the COVID-19 pandemic compared with prior years, a finding that is not attributable to weight gain during lockdown, researchers reported in Circulation. Average monthly increases in BP ranged from 1.1 mm Hg to 2.5 mm Hg during the pandemic, according to the research letter. According to Luke J. Laffin, MD, co-director of the Center for Blood Pressure Disorders at Cleveland Clinic, and colleagues, “the increase in systolic BP among U.S. adults during the COVID-19 pandemic could signal a forthcoming increase in incident cardiovascular disease mortality. Reasons for pandemic-associated BP elevations are likely multifactorial, and although weight gain was not the reason, other possible reasons could include increased alcohol consumption, less physical activity, emotional stress and less ongoing medical care (including reduced medication adherence).” To assess changes in BP before and during the COVID-19 pandemic, the researchers conducted a longitudinal analysis utilizing data from an annual employer-sponsored wellness program operated by Quest Diagnostics. For the program, employees had annual BP measurements taken by trained personnel from 2018 to 2020. The present analysis included 464,585 participants (53.5% women; mean age, 45 years). Researchers observed no significant changes in BP measurements during the pre-pandemic period (2019 and January-March 2020). Changes from the preceding year in both systolic and diastolic BP showed no differences between 2019 and January to March 2020 (P for systolic = .8; P for diastolic BP = .3); however, annual BP increase was higher during the pandemic (April to December 2020) compared with pre-pandemic (P < .0001). During the pandemic period, monthly increases in BP averaged 1.1 mm Hg to 2.5 mm Hg for systolic BP and 0.14 mm Hg to 0.53 mm Hg for diastolic BP, compared with the previous year (P < .0001).
Symptoms of vaccine-related myocarditis in young people rare, mild, resolve quickly
Healio | Cardiology Today, December 6, 2021
Most young people under the age of 21 years with suspected myocarditis following COVID-19 vaccination had mild symptoms that resolved quickly, according to data published in Circulation. Most cases of suspected COVID-19 vaccine myocarditis occurred in white males and followed a messenger RNA (mRNA) vaccine, the researchers reported. “The highest rates of myocarditis following COVID-19 vaccination have been reported among adolescent and young adult males. Past research shows this rare side effect to be associated with some other vaccines, most notably the smallpox vaccine,” Jane W. Newburger, MD, MPH, FAHA, associate chair of academic affairs in the department of cardiology at Boston Children’s Hospital, the Commonwealth Professor of Pediatrics at Harvard Medical School, and member of the American Heart Association Council on Lifelong Congenital Heart Disease and Heart Health in the Young, said in a press release issued by the AHA. “While current data on symptoms, case severity and short-term outcomes is limited, we set out to examine a large group of suspected cases of this heart condition as it relates to the COVID-19 vaccine in teens and adults younger than 21 in North America.” The retrospective analysis included 139 adolescents and young adults aged younger than 21 years with 140 episodes of suspected myocarditis within 30 days of COVID-19 vaccination who presented to 26 U.S. centers before July 4, 2021. Myocarditis was classified as confirmed (n = 49) or probable (n = 91) based on CDC definitions. “It is important for health care professionals and the public to have information about early signs, symptoms and the time course of recovery of myocarditis, particularly as these vaccines become more widely available to children,” Truong said. “Studies to determine long-term outcomes in those who have had myocarditis after COVID-19 vaccination are also planned.”
Cardiopulmonary exercise testing valuable to assess unexplained dyspnea post-COVID-19
Healio | Cardiology Today, November 30, 2021
In a small study, cardiopulmonary exercise testing identified significant abnormalities, including dysfunctional breathing, resting hypocapnia and chronic fatigue syndrome, associated with post-acute sequelae of severe SARS-CoV-2 infection. “The current clinical guidelines do not recommend cardiopulmonary exercise testing out of concern that this test could worsen the patients’ [long COVID] symptoms,” Donna M. Mancini, MD, advanced heart failure and transplant specialist at the Icahn School of Medicine at Mount Sinai, told Healio. “However, we found that cardiopulmonary exercise was able to identify reduced exercise capacity in about 46% of patients. This reduced functional capacity was from a circulatory abnormality. This may include changes involving the pulmonary or peripheral vasculature. We also found that nearly 90% of patients had ventilatory abnormalities during exercise.” Mancini and colleagues aimed to assess the utility of cardiopulmonary exercise test to define unexplained dyspnea in patients with post-acute sequelae of SARS-CoV-2 (PASC) and also assessed patients for criteria to diagnose myalgic encephalomyelitis/chronic fatigue syndrome. The researchers enrolled 41 patients with long COVID symptoms at a median of 8.9 months after infection. Of those, 18 were men and the mean age was 45 years. According to Mancini, participants in this study developed COVID-19 before vaccines were widely available. Mean left ventricular ejection fraction was 59%. In the entire cohort, average peak VO2 was 20.3 mL/kg/min, mean slope of minute ventilation to CO2 production (VE/VCO2) was 30 and average end-tidal pressure of CO2 (PetCO2) at rest was 33.5 mm Hg. Researchers reported that 58.5% of participants had a peak VO2 of less than 80% of the predicted value, all of whom experienced circulatory limitation to exercise. Among 17 patients with normal peak VO2, 15 had ventilatory abnormalities, which included a peak respiratory rate greater than 55 or dysfunctional breathing, according to the results. Eighty-eight percent of participants had ventilatory abnormalities with dysfunctional breathing, elevated VE/VCO2 and/or PetCO2 less than 35 mm Hg.
Incidence of Myopericarditis and Myocardial Injury in Coronavirus Disease 2019 Vaccinated Subjects
American Journal of Cardiology, November 28, 2021
Several recent publications have described myopericarditis cases after the coronavirus disease 2019 (COVID-19) vaccination. However, it is uncertain if these cases occurred secondary to the vaccination or more common etiologies of myopericarditis. To help determine whether a correlation exists between COVID-19 vaccination and myopericarditis, the present study compared the gender-specific cumulative incidence of myopericarditis and myocardial injury in a cohort of COVID-19 vaccinated patients at a tertiary care center in 2021 with the cumulative incidence of these conditions in the same subjects exactly 2 years earlier. We found that the age-adjusted incidence rate of myopericarditis in men was higher in the vaccinated than the control population, rate ratio 9.7 (p = 0.04). However, the age-adjusted incidence rate of myopericarditis in women was no different between the vaccinated and control populations, rate ratio 1.28 (p = 0.71). We further found that the rate of myocardial injury was higher in both men and women in 2021 than in 2019 both before and after vaccination, suggesting that some of the apparent increase in the diagnosis of myopericarditis after vaccination may be attributable to factors unrelated to the COVID-19 vaccinations. In conclusion, our study reaffirms the apparent increase in the diagnosis of myopericarditis after COVID-19 vaccination in men but not in women, although this finding may be confounded by increased rates of myocardial injury in 2021. The benefits of COVID-19 vaccination to individual and public health clearly outweigh the small potential increased risk of myopericarditis after vaccination.
Stress level up, mood and physical activity down during COVID-19 lockdown
Helio | Cardiology Today, November 22, 2021
The COVID-19 pandemic may have reduced overall mood and physical activity among study participants and increased their levels of self-reported stress, a speaker reported. According to results of the COVID-19 Health Evaluation and Cardiovascular Complications (CHECC) study presented at the American Heart Association Scientific Sessions, the changes in mood, stress and physical activity during the pandemic lockdown in Michigan may also vary by age and race. “Michigan has been one of the hardest COVID-19 hit states, with over 1.3 million cases and approximately 24,000 deaths as of November, this month,” Nirav Shah, MD, associate professor in the department of anesthesiology at the University of Michigan, said during a presentation. “We know that heart disease, hypertension and diabetes can lead to more severe disease. Also, stress, social distancing and unemployment may disrupt non-COVID-19 treatment and healthy lifestyles. With that context, [CHECC] consisted of two components.” This first component was a retrospective analysis derived from the MIPACT study that enrolled approximately 7,000 participants with wearable sensor data, including step count, activity data and ambulatory BP, combined with electronic health record and survey data (45% men; 63% white; 48% untreated hypertensive; 27% normal BMI). The second component, for which results will be presented at a later date, was a prospective analysis that enrolled student athletes and included an arm of participants with a recent COVID-19 diagnosis. Twenty-three percent of the cohort was younger than 40 years; 43% was aged 40 to 60 years; and 35% was older than 60 years. According to the presentation, the researchers observed large dips in mood scores and large spikes in stress scores in the weeks immediately following the pandemic lockdown in Michigan. These fluctuations were consistent, regardless of age group. Following the initial fluctuations, Shah reported persistent declines in mood score and increases in stress score within all age groups. After stratification by race, the changes in mood and stress were less dramatic, according to the presentation; however, Black participants’ self-reported mood scores were, on average, higher compared with other races.
Getting to the heart of COVID-19-related cardiac injury
Helio | Cardiology Today, November 19, 2021
The ability of COVID-19 to cause cardiac injury and myocarditis has been well documented since the pandemic began, and data continue to accumulate. “We certainly know that COVID-19 has a long-term effect, or ‘long COVID’, which is the systemic disease that even patients with mild COVID-19 can develop,” Howard J. Eisen, MD, senior advanced heart failure specialist at Penn State Medical Center, told Cardiology Today. “They can be fatigued, have a shortness of breath, drops in blood pressure, elevated heart rates. And a lot of that is thought to maybe be due to autoimmune phenomena and enhanced inflammation. But one thing we know is that myocarditis can, in some patients, develop into heart failure. A lot of these patients who we see who have what we call idiopathic dilated cardiomyopathy … we suspect that they have myocarditis.” As research continues and new information evolves, Cardiology Today spoke with experts in the field about COVID-19-related outcomes on the heart, the risks for myocardial injury as a result of COVID-19 and with vaccination, based on the current knowledge base, and more. In a study published in the European Heart Journal in May, myocardial injury was detected in more than half of patients hospitalized with severe COVID-19, and elevated cardiac troponin persisted months after hospital discharge. “Troponin levels are easy to obtain. While an elevated level indicates cardiac injury, it does not necessarily equate to myocarditis,” Kemna told Cardiology Today. “Myocarditis can present in many different ways. For COVID-19, cardiac inflammation may be part of a multi-organ inflammatory response or there may be endotheliitis leading to cardiac injury, and it can be challenging to distinguish between those and true myocarditis.”
Association of cardiac injury with hypertension in hospitalized patients with COVID-19 in Chin
Scientific Reports, November 17, 2021
Outbreak of global pandemic Coronavirus disease 2019 (COVID-19) has so far caused countless morbidity and mortality. However, a detailed report on the impact of COVID-19 on hypertension (HTN) and ensuing cardiac injury is unknown. Herein, we have evaluated the association between HTN and cardiac injury in 388 COVID-19 (47.5 ± 15.2 years) including 75 HTN and 313 normotension. Demographic data, cardiac injury markers, other laboratory findings, and comorbidity details were collected and analyzed. Compared to patients without HTN, hypertensive-COVID-19 patients were older, exhibited higher C-reactive protein (CRP), erythrocyte sedimentation rate, and comorbidities such as diabetes, coronary heart disease, cerebrovascular disease and chronic kidney disease. Further, these hypertensive-COVID-19 patients presented more severe disease with longer hospitalization time, and a concomitant higher rate of bilateral pneumonia, electrolyte disorder, hypoproteinemia and acute respiratory distress syndrome. In addition, cardiac injury markers such as creatine kinase (CK), myoglobin, lactic dehydrogenase (LDH), and N-terminal pro brain natriuretic peptide were significantly increased in these patients. Correlation analysis revealed that systolic blood pressure correlated significantly with the levels of CK, and LDH. Further, HTN was associated with increased LDH and CK-MB in COVID- 19 after adjusting essential variables. We also noticed that patients with elevated either high sensitivity-CRP or CRP demonstrated a significant high level of LDH along with a moderate increase in CK (p = 0.07) and CK-MB (p = 0.09). Our investigation suggested that hypertensive patients presented higher risk of cardiac injury and severe disease phenotype in COVID-19, effectively control blood pressure in HTN patients might improve the prognosis of COVID-19 patients.
Cardiac biomarker-guided corticosteroid dosing feasible, safe in COVID-19 pneumonia
Helio | Cardiology Today, November 16, 2021
An individualized, biomarker-guided approach to corticosteroid dosing utilizing C-reactive protein for COVID-19-related pneumonia reduced patients’ cumulative steroid exposure and increased the number of hospital- and oxygen-free days. This novel approach for treating pneumonia and hypoxemic respiratory failure was quickly and successfully adapted at the onset of the COVID-19 pandemic and was also safe in this population, according to Yewande Odeyemi, MD, assistant professor in the division of pulmonary and critical care at Mayo Clinic in Rochester, Minnesota. “Prior to COVID-19, corticosteroid use in community-acquired pneumonia was both controversial and undefined,” Odeyemi said during a presentation at the American Heart Association Scientific Sessions. “Our goal was to assess the feasibility and safety of an individualized, biomarker-guided corticosteroid-dosing approach utilizing C-reactive protein compared to usual care in patients with community-acquired pneumonia and acute hypoxemic respiratory failure. Our secondary goal was to assess any potential preliminary efficacy of this strategy on noncardiovascular outcomes. This was quickly adapted to include COVID-19 pneumonia at the beginning of the pandemic with the addition of cardiovascular outcomes.” The trial included patients hospitalized with community-acquired pneumonia including COVID-19 and acute hypoxemic respiratory failure (n = 44). Methylprednisolone was administered daily and dosed based on CRP levels or patients were treated with usual care. “Usual care did change as the standard of care for COVID-19 infection evolved,” Odeyemi said. “Prior to July 2020, steroids were contraindicated in COVID-19 infection. After the publication of the results of the RECOVERY trial, steroids became standard of care in a fixed-dose regimen.” The primary outcome was feasibility. Secondary noncardiovascular outcomes included cumulative steroid exposure, hospital-free days, oxygen-free days, in-hospital mortality, advanced respiratory support, hyperglycemia and delirium. Secondary CV outcomes included requirement for vasopressor therapy, new-onset or worsening arrhythmia, myocardial injury as measured by troponin or LV dysfunction, or new diagnosis of right ventricular dysfunction.
Potent Antiplatelet Not a Good Idea for Moderate COVID-19
MedPage Today, November 16, 2021
P2Y12 inhibitors did not improve outcomes for non-critically ill patients hospitalized with COVID-19, an ACTIV-4a platform trial showed.
Patients randomized to receive a potent antiplatelet, typically atop therapeutic anticoagulation with heparin, actually had numerically fewer organ support-free days through day 21 than those who received usual care without a P2Y12 inhibitor (adjusted OR 0.83, 95% CI 0.55-1.25), reported Jeffrey Berger, MD, of NYU Grossman School of Medicine in New York City, during the virtual American Heart Association meeting. In a Bayesian analysis, there was a 96% chance of futility and an 81% likelihood that P2Y12 inhibitors were worse than placebo, which prompted early termination of that portion of the trial after enrollment of 562 patients. And for the composite of death or need for organ support, the P2Y12 inhibitor also trended in the wrong direction (26% vs 22%; HR 1.19, 95% CI 0.84-1.68). “The data that you’ve seen does not support the use of these agents in context, but it will be important to address the similar question in higher-risk populations,” said study discussant Amy Towfighi, MD, of the University of Southern California in Los Angeles, at the late-breaking clinical trial session. The trial included a population with confirmed SARS-CoV-2 with at least one higher-risk criterion—elevated D-dimer, ages 60 to 84, need for more than 2 L/min oxygen, hypertension, diabetes, impaired kidney function, cardiovascular disease, or obesity—but was still a fairly low-risk group, she noted. ACTIV-4a, together with the REMAP-CAP and ATTACC multi-platform trials, had shown a relative 27% increase in organ support-free days in patients with moderate COVID-19 given therapeutic-dose levels of heparin, but no advantage in critically ill patients. Thus, nearly 90% of patients in both arms of the P2Y12 portion of ACTIV-4a received therapeutic-dose heparin.
Women with long COVID may need rehab to improve physical activit
Helio | Women’s Health & OB/GYN, November 16, 2021
Women with long COVID experience heart-rate irregularities after physical exertion, which could constrain their exercise tolerance and their free-living physical activity, according to a study published in Experimental Physiology. Since there is a greater prevalence of age-related physical disability among women than among men, these findings illustrate the need for targeted rehabilitation programs that manage persistent heart and lung problems in women with long COVID, the researchers said. “Consistent with other universities during the spring of 2020, our usual research activities involving exercise training and postmenopausal women were temporarily halted amid the emerging pandemic,” author Stephen J. Carter, MS, PhD, assistant professor in the department of kinesiology at the Indiana University School of Public Health – Bloomington, told Healio. “Since our lab has a history of studying the acute and chronic effects of exercise in women, we thought it sensible to pivot our research efforts accordingly. We felt this to be especially important, given that women are largely underrepresented in clinical work, and thus offering us a unique opportunity to explore the effects of SARS-CoV-2 on cardiopulmonary health,” Carter said. The researchers recruited 45 women for the case-controlled study. According to the researchers, 29 women (age, 54 ± 10 years; BMI, 25.6 ± 5.4 kg/m2) had a positive laboratory test for mild to moderate SARS-CoV-2 infection 4 weeks before enrolling in the study or earlier, while the control group included 16 women (age, 58 ± 11 years; BMI, 26.7 ± 4.8 kg/m2) who never tested positive. The participants with a history of SARS-CoV-2 infection had reduced total lung capacity (84% ± 8% vs. 93% ± 13%; P = .006), vital capacity (87% ± 10% vs. 93% ± 10%; P = .04), functional residual capacity (75% ± 16% vs. 88% ± 16%; P = .006) and residual volume (76% ± 18% vs. 93% ± 22%; P = .001) compared with controls.
Stemi mimicking post COVID: a case of focal myopericarditis post COVID infectio
Journal of Community Hospital of Internal Medicine Perspectives, November 15, 2021
[Case Report] Since the beginning of the coronavirus disease 2019 (COVID19) pandemic, several cases of myocarditis related to COVID-19 infection have been reported. These cases range from asymptomatic disease to fulminant heart failure or sudden cardiac death. Cardiac injury has also been found in asymptomatic patients and patients who recovered from the disease. Data regarding cardiovascular involvement due to COVID-19 infection are still limited, and the actual prevalence of myocarditis due to COVID-19 infection is still unknown. We present a case of focal myopericarditis in a patient recently recovered from COVID-19 pneumonia with electrocardiogram showing ST elevation in inferior and lateral leads. This case highlights the need for studying the long-term cardiovascular complications of COVID-19 and reinforces the use of cardiac magnetic resonance (CMR) and cardiac biomarkers in the diagnosis of COVID-19-related myocarditis.
Blood pressure control ‘decreased substantially’ during COVID-19 pandemi
Helio | Cardiology Today, November 14, 2021
BP control declined among U.S. adults in 2020 compared with 2019, due to the COVID-19 pandemic, according to a study of 24 health systems presented at the American Heart Association Scientific Sessions. “We observed large variability across health systems in blood pressure control metrics,” Alanna M. Chamberlain, PhD, MPH, FAHA, associate professor of epidemiology in the departments of cardiovascular medicine and quantitative health sciences at Mayo Clinic in Rochester, Minnesota, said during a presentation. “Our results showed suboptimal blood pressure control even before the COVID-19 pandemic, and show substantial opportunity for improvement. Blood pressure control decreased substantially during the COVID-19 pandemic, accompanied by a reduction in follow-up health care visits among persons with hypertension. Blood pressure control has not rebounded to pre-pandemic levels.” The BP Track study analyzed trends in BP control in the year before the COVID-19 pandemic and during the pandemic in patients with hypertension from 24 health systems participating in the National Patient-Centered Clinical Research Network (PCORnet). According to Chamberlain, this study “is the first use of PCORnet for national surveillance of blood pressure control and related process metrics.” She noted that “each health system transforms their data to a common data model, which is updated on a quarterly basis.” The declines in BP control and repeat visits occurred in all races and ethnicities, and BP control remained lowest in Black patients, Chamberlain said. BP control at the end of 2020 had not rebounded to 2019 levels, Chamberlain said.
Hypertension and its management in COVID-19 patients
International Journal of Cardiology Cardiovascular Risk and Prevention, November 13, 2021
Coronavirus disease 2019 (COVID-19) is suspected to mainly be more deleterious in patients with underlying cardiovascular diseases (CVD). There is a strong association between hypertension and COVID-19 severity. The binding of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) leads to deregulation of the renin-angiotensin-aldosterone system (RAAS) through down-regulation of ACE2 with subsequent increment of the harmful Ang II serum levels and reduction of the protective Ang-(1–7). Both angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) are commonly used to manage hypertension. Objective was to illustrate the potential link between hypertension and COVID-19 regarding the role of angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) in hypertensive patients with COVID-19. We carried out comprehensive databases search from late December 2019 to early January 2021 by using online engines of Web of Science, Research gate, Scopus, Google Scholar, and PubMed for published and preprinted articles. The present study’s findings showed that hypertension is regarded as an independent risk factor for COVID-19 severity. Both ACEIs and ARBs are beneficial in managing hypertensive patients. This study concluded that hypertension increases COVID-19 severity due to underlying endothelial dysfunctions and coagulopathy. COVID-19 might augment the hypertensive complications due to down-regulation of ACE2. The use of ACEIs or ARBs might be beneficial in the management of hypertensive patients with COVID-19.
Common cardiac medications potently inhibit ACE2 binding to the SARS-CoV-2 Spike, and block virus penetration and infectivity in human lung cells
Scientific Reports, November 12, 2021
To initiate SARS-CoV-2 infection, the Receptor Binding Domain (RBD) on the viral spike protein must first bind to the host receptor ACE2 protein on pulmonary and other ACE2-expressing cells. We hypothesized that cardiac glycoside drugs might block the binding reaction between ACE2 and the Spike (S) protein, and thus block viral penetration into target cells. To test this hypothesis we developed a biochemical assay for ACE2:Spike binding, and tested cardiac glycosides as inhibitors of binding. Here we report that ouabain, digitoxin, and digoxin, as well as sugar-free derivatives digitoxigenin and digoxigenin, are high-affinity competitive inhibitors of ACE2 binding to the Original [D614] S1 and the α/β/γ [D614G] S1 proteins. These drugs also inhibit ACE2 binding to the Original RBD, as well as to RBD proteins containing the β [E484K], Mink [Y453F] and α/β/γ [N501Y] mutations. As hypothesized, we also found that ouabain, digitoxin and digoxin blocked penetration by SARS-CoV-2 Spike-pseudotyped virus into human lung cells, and infectivity by native SARS-CoV-2. These data indicate that cardiac glycosides may block viral penetration into the target cell by first inhibiting ACE2:RBD binding. Clinical concentrations of ouabain and digitoxin are relatively safe for short term use for subjects with normal hearts. It has therefore not escaped our attention that these common cardiac medications could be deployed worldwide as inexpensive repurposed drugs for anti-COVID-19 therapy.
COVID-19 diagnosis in patients with STEMI tied to elevated in-hospital mortality
Helio | Cardiology Today, November 9, 2021
In a cohort of patients with STEMI, a COVID-19 diagnosis significantly increased the rates of in-hospital mortality compared with patients without a COVID-19 diagnosis from the past year, according to new data. Marwan Saad, MD, PhD, FACC, FSCAI, FESC, assistant professor of medicine and director of interventional structural heart research at the Warren Alpert Medical School of Brown University, and colleagues conducted the retrospective cohort study. They included 80,449 consecutive adult patients admitted between January 2019 and December 2020 with out-of-hospital or in-hospital STEMI at 509 U.S. centers in the Vizient Clinical Database. In-hospital mortality served as the primary outcome measure. Researchers propensity-matched patients based on the likelihood of COVID-19 diagnosis, and compared patients with COVID-19 with those without COVID-19 during the previous calendar year. Overall, the out-of-hospital STEMI arm featured 76,434 patients (64% aged 51 to 74 years; 70% men), while the in-hospital STEMI arm featured 4,015 patients (58% aged 51 to 74 years; 61% men). After propensity matching, there were 551 patients with COVID-19 and 2,755 patients without COVID-19 in the out-of-hospital STEMI group, and 252 patients with COVID-19 and 756 patients without COVID-19 in the in-hospital STEMI group. Results indicated that COVID-19 status did not significantly impact the likelihood of patients with out-of-hospital STEMI receiving primary PCI. However, patients with in-hospital STEMI and COVID-19 demonstrated a significantly decreased likelihood of receiving invasive diagnostic or therapeutic coronary procedures than those without COVID-19.
Clinical outcomes of hypertensive patients with COVID-19 receiving calcium channel blockers: a systematic review and meta-analysis
Hypertension Research, November 9, 2021
We aimed to perform a systematic review and meta-analysis to determine the overall effect of the preadmission/prediagnosis use of calcium channel blockers (CCBs) on the clinical outcomes in hypertensive patients with COVID-19. A systematic literature search with no language restriction was conducted in electronic databases in July 2021 to identify eligible studies. A random-effects model was used to estimate the pooled summary measure for outcomes of interest with the preadmission/prediagnosis use of CCBs relative to the nonuse of CCBs at 95% confidence intervals (CIs). The meta-analysis revealed a significant reduction in the odds of all-cause mortality with the preadmission/prediagnosis use of CCBs relative to the nonuse of CCBs (pooled OR = 0.65; 95% CI 0.49–0.86) and a significant reduction in the odds of severe illness with preadmission/prediagnosis use of CCBs relative to the nonuse of CCBs (pooled OR = 0.61; 95% CI 0.44–0.84), and is associated with adequate evidence to reject the model hypothesis of ‘no significant difference’ at the current sample size. The potential protective effects offered by CCBs in hypertensive patients with COVID-19 merit large-scale prospective investigations.
Helio | Cardiology Today, November 8, 2021
The COVID-19 pandemic continues to challenge our health care system to deliver essential inpatient and outpatient care to infected patients while continuing to treat patients with non-COVID-19-related illnesses. All of this is occurring in a challenging environment intended to minimize spread of this virulent virus. The telehealth techniques that have proliferated to address this increased demand for medical care will have lasting and profound effects on the future practice of cardiology. Telehealth is not a new concept. Cardiologists have long made use of transtelephonic monitoring of pacemakers, and more recently use other biometric devices and cardiac imaging procedures for both live and asynchronous data transmission to our offices and hospitals for interpretation and management recommendations. With COVID-19, we quickly recognized the convenience and value of person-to-person tele-video communication with our patients outside the hospital and office settings, especially for those patients needing post-acute care or experiencing chronic illnesses such as HF and hypertension. Properly applied, televideo can improve our efficiency and deliver more and better care than many routine in-person office visits. Televideo is especially effective in providing education and individualized support, increasing patients’ compliance with both medical and lifestyle interventions, which in turn improve patients’ quality of life while avoiding the expense and inconvenience of nonessential office visits, unnecessary urgent care and avoidable hospitalization. The stress the COVID-19 pandemic has placed on our health care system has exposed deep-rooted inequities in health care delivery in our country. Socioeconomic, racial and geographic disparities extend far beyond COVID-19. The acute, chronic and worsening shortage of physicians has heightened recognition of the power of televideo communication to supplement in-person care and appreciation of the essential role nonphysician members of the health care team play in expanding productivity to bring high quality care to more patients with CVD than otherwise possible.
Clinical presentation, disease course, and outcome of COVID-19 in hospitalized patients with and without pre-existing cardiac disease: a cohort study across 18 countries
European Heart Journal, November 4, 2021
Patients with cardiac disease are considered high risk for poor outcomes following hospitalization with COVID-19. The primary aim of this study was to evaluate heterogeneity in associations between various heart disease subtypes and in-hospital mortality. We used data from the CAPACITY-COVID registry and LEOSS study. Multivariable Poisson regression models were fitted to assess the association between different types of pre-existing heart disease and in-hospital mortality. A total of 16 511 patients with COVID-19 were included (21.1% aged 66–75 years; 40.2% female) and 31.5% had a history of heart disease. Patients with heart disease were older, predominantly male, and often had other comorbid conditions when compared with those without. Mortality was higher in patients with cardiac disease (29.7%; n = 1545 vs. 15.9%; n = 1797). However, following multivariable adjustment, this difference was not significant [adjusted risk ratio (aRR) 1.08, 95% confidence interval (CI) 1.02–1.15; P = 0.12 (corrected for multiple testing)]. Associations with in-hospital mortality by heart disease subtypes differed considerably, with the strongest association for heart failure (aRR 1.19, 95% CI 1.10–1.30; P < 0.018) particularly for severe (New York Heart Association class III/IV) heart failure (aRR 1.41, 95% CI 1.20–1.64; P < 0.018). None of the other heart disease subtypes, including ischaemic heart disease, remained significant after multivariable adjustment. Serious cardiac complications were diagnosed in <1% of patients. Considerable heterogeneity exists in the strength of association between heart disease subtypes and in-hospital mortality. Of all patients with heart disease, those with heart failure are at greatest risk of death when hospitalized with COVID-19. Serious cardiac complications are rare during hospitalization.
Takotsubo cardiomyopathy after vaccination for coronavirus disease 2019 in a patient on maintenance hemodialysis
CEN Case Reports, November 3, 2021
Coronavirus disease-2019 (COVID-19) has affected more than 220 million individuals since the global pandemic began. There is an urgent need for safe and effective vaccines, and vaccinations, such as mRNA vaccines, have been initiated worldwide. However, the adverse effects of these vaccines remain unclear. We herein present a case of an 80-year-old female on maintenance hemodialysis who developed Takotsubo cardiomyopathy 4 days after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine. There was no obvious trigger for the onset of Takotsubo cardiomyopathy other than the COVID-19 vaccination, which was the most significant event preceding her presentation. Echocardiograms obtained during her admission allowed us to monitor and show the recovery of left ventricular wall motion. We confirmed the diagnosis of Takotsubo cardiomyopathy based on the findings, including transient left ventricular dysfunction, electrocardiographic abnormalities, an elevated troponin level, and the absence of occlusive coronary artery disease. In the present case, the vaccination may have triggered emotional or physical stress. Although difficulties are associated with proving the causal relationship in the present case, the temporal relationship between the vaccination and the onset of Takotsubo cardiomyopathy is highly suggestive. The adverse effects associated with the vaccine are typical of COVID-19 vaccines administered to date, most of which are acceptable. Therefore, despite our experience of the present case, we still recommend the vaccination for COVID-19 because Takotsubo cardiomyopathy induced by the COVID-19 vaccine is extremely rare and the prognosis of the patient was good. We herein present the first case of a patient on hemodialysis who developed Takotsubo cardiomyopathy after receiving COVID-19 vaccination.
Incidence of Atrioventricular Blocks and its Association with In-Hospital Mortality and Morbidity in Patients with Coronavirus Disease 2019
Journal of Cardiology, November 1, 2021
Cardiovascular sequelae of coronavirus disease 2019 (COVID-19) infection have been explored by clinicians and researchers all over the world. The purpose of this study was to evaluate the incidence of atrioventricular block (AV) in patients hospitalized for COVID-19 and its association between in-hospital morbidity and mortality. In-hospital electrocardiograms (ECGs) of 438 patients were compared with their prior or baseline ECGs to ascertain the development of new onset AV block. Patients who developed new AV blocks were then followed at 30 and 90 days post-discharge to check for resolution of AV block. Demographic characteristics, clinical characteristics, and complications during their hospital stay were evaluated. Major complications including respiratory failure requiring oxygen supplementation and mechanical ventilation, sepsis, deep vein thrombosis, elevated troponins, hospital and intensive care unit (ICU) length of stay, as well as death were compared between those who developed new onset AV blocks and those who did not. Based on our single center study, the incidence of new onset AV blocks among patients admitted for COVID-19 during the study period was 5.5 cases per 100 patients. New onset AV blocks were not associated with longer hospital and ICU length of stay, increased intubation rates, or increased mortality. Although the development of a new onset AV block is most likely multifactorial and not solely due to COVID-19, it is still important for clinicians to be mindful about the possibility of developing symptomatic bradycardia and life-threatening arrhythmias in patients admitted for COVID-19. This can be achieved by appropriate rhythm monitoring in-patient but the need for a cardiac event monitor upon discharge is unlikely to be necessary. Careful history taking, including family and drug use history is also of great importance as emerging drug therapies for COVID-19 have potential arrhythmogenic effects.
Mild COVID Not Linked to Long-Term Cardiac Damage
MedPage Today, November 1, 2021
Cardiac parameters suggestive of myocarditis were no more common at 6 months after mild or asymptomatic COVID-19 than among people who never had the infection, a prospective case-control study found. Compared with seronegative healthcare workers, those who had generally mild SARS-CoV-2 had no differences in cardiac structure, function, MRI markers of myocarditis, or cardiac injury biomarkers 6 months later, James Moon, MD, of St. Bartholomew’s Hospital in London, and colleagues reported in JACC: Cardiovascular Imaging. The maximum prevalence of myocarditis in the type of healthcare worker population they studied may be less than 4% at 6 months, the analysis suggested. “Thus, screening in asymptomatic patients following nonhospitalized COVID-19 is currently not indicated,” the group concluded, pointing to it as yet more evidence counteracting an early but alarming finding that 78% of COVID survivors had lingering myocardial inflammation and other cardiac MRI abnormalities. Colin Berry, PhD, and Kenneth Mangion, PhD, both of the University of Glasgow, agreed in an accompanying editorial, calling the findings welcome reassurance for healthy individuals. “This is a reasonably reassuring result drawn from a healthy population,” the editorialists wrote, “however, the sample size limits the precision of this estimate, and the prevalence of cardiovascular abnormalities (e.g., myocardial scar) would be expectedly higher in an unbiased community population including individuals from less-advantaged socioeconomic circumstances (e.g., unemployed) and with pre-existing health problems.”
Evaluating Factors of Greater Patient Satisfaction with Outpatient Cardiology Telehealth Visits During the COVID-19 Pandemic
Cardiovascular Digital Health Journal, October 29, 2021
The impact of telehealth on cardiovascular care during the COVID-19 pandemic on patient satisfaction and factors associated with satisfaction are not well characterized. We conducted a non-randomized, prospective cross-sectional survey study for outpatient telehealth cardiovascular visits over a 169-day period utilizing a validated telehealth usability questionnaire. For each variable, patients were divided into two groups – one with scores above the median labeled “greater satisfaction” and the other with scores below the median labeled “less satisfaction”. 13913 outpatient telehealth encounters were successfully completed during the study period. 7327 unique patients were identified and received a survey invitation. 5993 (81.8%) patients opened the invitation, and 1034 (14.1%) patients consented and completed the survey. Overall mean and median scores were 3.15 (SD 0.74) and 3.37 (IQR 2.73–3.68) (maximum score 4.00). Greater satisfaction was noted among younger patients (mean age 63.3±14.0 years, p=0.005), female gender (46.3%, p=0.007), non-white ethnicity (24.2%, p=0.006), self-identified early adopters and innovators of new technology (49.8%, p<0.001), one-way travel time greater than 1 hour (22.3%, p<0.001), one-way travel distance greater than 10 miles (49.0%, p<0.001), patients needing child care arrangement (16.4%, p<0.001), and history of orthotopic heart transplant (OHT) (5.1%, p=0.04). Patients reported overall satisfaction with telehealth during the COVID-19 pandemic. Factors associated with patient convenience, along with female gender, younger age and non-white ethnicity correlated with greater satisfaction. Cardiovascular comorbidities did not correlate with greater satisfaction except for OHT.
Patient delay prior to care-seeking in acute myocardial infarction during the outbreak of the coronavirus SARS-CoV2 pandemic
European Journal of Cardiovascular Nursing, October 29, 2021
Our objective was to examine patient delay in seeking medical care when afflicted by an acute myocardial infarction during March–June 2020. This was a cross-sectional study in a region in Sweden during the first wave of the COVID-19 pandemic examining patients selected from the national registry (SWEDEHEART). Eligible patients were those with acute myocardial infarction, and a total of 602 patients were invited. A self-administered psychometric evaluated questionnaire, ‘Patients’ appraisal, emotions, and action tendencies preceding care-seeking in acute myocardial infarction’ (AMI), was sent to the patients, and questions regarding COVID-19 were added. A total of 326 patients answered the questionnaire. Of these, 19% hesitated to seek medical care because of the pandemic, which was related to a fear that the healthcare services were already overcrowded with patients with COVID-19, followed by a fear of becoming infected with COVID-19 in hospital. Characteristics of this cohort were significantly higher prevalences of women, immigrants, smokers, and patients with type 2 diabetes. During the outbreak and first wave of the COVID-19 pandemic, women and immigrants delayed seeking medical care for AMI because of fears about overcrowded hospitals and about becoming infected themselves. Therefore, during the COVID-19 pandemic, it is especially important to convey information about how and when to seek medical care. A collaboration involving the healthcare professionals, patient organizations, and the media would be desirable.
Hypertension and COVID-19: Potential use of beta-blockers and a call for randomized evidence
Indian Heart Journal, October 27, 2021
[Opinion Paper] Hypertension is one of the most common morbidities in COVID-19. Previous studies demonstrated that hypertension increases composite poor outcomes in patients with COVID-19. Beta-blockers is widely used as one of the most common antihypertensive agents. Beta-blockers may hold potential benefits in COVID-19 treatment, with current evidence of the potential mechanism of beta-blockers remains scarce. However, several mechanisms were suggested, including decreasing RAAS pathway activity and lowering the ACE2 levels, reducing cytokine storms, and may be beneficial in reducing mortality in ARDS related COVID-19. Further large-scale randomized clinical trials should be conducted before a definite recommendation can be drawn.
Covid-19 and Heart Damage
News Medical, October 27, 2021
The coronavirus disease 2019 (COVID-19) pandemic led to well over 200 million infections, with a fatal outcome in over 4.5 million cases. In the survivors, most recovered completely but some showed long-haul symptoms – now often called Long COVID. One important potentially long-term clinical consequence of COVID-19 seems to be heart damage. This has been recognized as far back as the Wuhan, China, outbreak. Several patients hospitalized with the disease at that time had high levels of cardiac troponin, which is a molecular biomarker of myocardial injury. Echocardiographic evaluation of these patients showed the presence of functional deficits in the heart. The obvious conclusion was that COVID-19 severity was correlated with the presence of myocardial injury. It was quite clear that people that came into the hospital sick that had heart injury were the ones that were at greatest risk of requiring mechanical ventilation and, ultimately, at the greatest risk of dying,” says Aaron Baggish, of Massachusetts General Hospital. However, the large number of asymptomatic cases coupled with a lack of focused research means that the question of how common this complication is, remains unanswered. It is also not clear whether the damage to the heart muscle is due to the systemic inflammatory reaction in COVID-19 or because of myocarditis. Most importantly, the chances of long-term injury are also unclear at this point, though it is a very significant one, considering the huge number of infections that have occurred so far.
Implantation of Cardiac Electronic Devices in Active COVID-19 Patients. Results from an International Survey
Heart Rhythm, October 26, 2021
Cardiac implantable electronic device (CIED) implantation rates, as well as the clinical and procedural characteristics and outcomes in patients with known active COVID-19 are unknown. To gather information regarding CIED procedures during active COVID-19, performed with personal protective equipment, based on an international survey. Fifty-three centers from 13 countries across 4 continents provided information on 166 patients with known active COVID-19 who underwent a CIED procedure. CIED procedure rate in 133,655 hospitalized COVID-19 patients ranged from 0 to 16.2 per 1000 patients (p<0.001). Most devices were implanted due to high degree / complete AV block (112, 67.5%) or sick sinus syndrome (31, 18.7%). Of the166 patients surveyed, the 30-day complication rate was 13.9% and the 180-day mortality rate was 9.6%. One patient had a lethal outcome as a direct result of the procedure. Differences in patient and procedural characteristics and outcomes were found between Europe and North America. An older population (76.6 vs. 66 years, p<0.001) with a non-significant higher complication rate (16.5% vs. 7.7%, p=0.2) were observed in Europe, while a higher rate of critically ill patients (3.3% vs. 33.3%, p<0.001) and mortality (5% vs. 26.9%, p=0.002) were observed in North America. CIED procedure rates during known active COVID-19 disease varied greatly from 0 to 16.2 per 1000 hospitalized COVID-19 patients worldwide. Patients with active COVID-19 infection who underwent CIED implantation had high complication and mortality rates. Operators should take into consideration these risks prior to proceeding with CIED implantation in active COVID-19 patients.
Cardiac involvement in the long-term implications of COVID-19
Nature Reviews | Cardiology, October 22, 2021
Throughout 2021, the medical and scientific communities have focused on managing the acute morbidity and mortality caused by the coronavirus disease 2019 (COVID-19) pandemic. With the approval of multiple vaccines, there is a light at the end of this dark tunnel and an opportunity to focus on the future, including managing the long-term sequelae in patients who have survived acute COVID-19. In this Perspectives article, we highlight what is known about the cardiovascular sequelae in survivors of COVID-19 and discuss important questions that need to be addressed in prospective studies to understand and mitigate these lasting cardiovascular consequences, including in post-acute COVID-19 syndrome. To provide the greatest benefit to these survivors, prospective studies should begin now, with resources made available to monitor and study this population in the coming years.
Management Strategies for COVID-19 in the General Ward of Cardiovascular Surgery: Experience From a Single Tertiary Hospital in China
The Heart Surgery Forum, October 21, 2021
Coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease that threatens global health. During the pandemic period of COVID-19, the task for prevention in the general ward of cardiovascular surgery is fairly arduous. The present study intends to summarize our experience with infection control, including ward setting, admission procedures, personnel management, health education, and so on, to provide references for clinical management.
Symptom Persistence Despite Improvement in Cardiopulmonary Health – Insights from longitudinal CMR, CPET and lung function testing post-COVID-19
EClinicalMedicine, October 20, 2021
The longitudinal trajectories of cardiopulmonary abnormalities and symptoms following infection with coronavirus disease (COVID-19) are unclear. We sought to describe their natural history in previously hospitalised patients, compare this with controls, and assess the relationship between symptoms and cardiopulmonary impairment at 6 months post-COVID-19. Fifty-eight patients and thirty matched controls (single visit), underwent symptom-questionnaires, cardiac and lung magnetic resonance imaging (CMR), cardiopulmonary exercise test (CPET), and spirometry at 3 months following COVID-19. Of them, forty-six patients returned for follow-up assessments at 6 months. At 2-3 months, 83% of patients had at least one cardiopulmonary symptom versus 33% of controls. Patients and controls had comparable biventricular volumes and function. Native cardiac T1 (marker of fibroinflammation) and late gadolinium enhancement (LGE, marker of focal fibrosis) were increased in patients at 2-3 months. Sixty percent of patients had lung parenchymal abnormalities on CMR and 55% had reduced peak oxygen consumption (pV̇O2) on CPET. By 6 months, 52% of patients remained symptomatic. On CMR, indexed right ventricular (RV) end-diastolic volume (-4·3 mls/m2, P=0·005) decreased and RV ejection fraction (+3·2%, P=0·0003) increased. Native T1 and LGE improved and was comparable to controls. Lung parenchymal abnormalities and peak V̇O2, although better, were abnormal in patients versus controls. 31% had reduced pV̇O2 secondary to symptomatic limitation and muscular impairment. Cardiopulmonary symptoms in patients did not associate with CMR, lung function, or CPET measures. In patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health.
Study of 1 million people finds lower risk of death from COVID-19 in statin users
Medical News Today, October 20, 2021
Statins are a group of drugs used to reduce levels of low-density lipoprotein (LDL) cholesterol in the blood, also known as “bad” cholesterol. Having high LDL cholesterol levels can lead to the hardening and narrowing of arteries and cardiovascular disease. Around 40 million people in the United States use statins to manage their cholesterol levels. Cardiovascular disease and high cholesterol levels have been linked to worsened COVID-19 outcomes. Meanwhile, other research has suggested that statins may have antiviral, anti-inflammatory, and anti-clotting effects that may be beneficial against COVID-19. This spring, a study that included 648 patients hospitalized with COVID-19 found that participants who took statins before developing COVID-19 were around 50% less likely to die in the hospital than those who did not. Until now, there has been little research on how statin use affects COVID-19 outcomes outside of hospital settings. Recently, researchers from Sweden and Australia conducted a large population study of almost 1 million people, exploring the relationship between statins and COVID-19 mortality. They found that statin use was associated with a slightly lower risk of dying from the disease. “The results were in line with our hypothesis, and some previous observational studies have shown similar results,” Rita Bergqvist, co-first author of the study and a medical student at the Karolinska Institutet, in Solna, Sweden, told Medical News Today.
Cardiac SARS-CoV-2 infection is associated with pro-inflammatory transcriptomic alterations within the heart
Cardiovascular Research, October 14, 2021
Cardiac involvement in COVID-19 is associated with adverse outcome. However, it is unclear whether cell specific consequences are associated with cardiac SARS-CoV-2 infection. Therefore, we investigated heart tissue utilizing in situ hybridization, immunohistochemistry and RNA-sequencing in consecutive autopsy cases to quantify virus load and characterize cardiac involvement in COVID-19. In this study, 95 SARS-CoV-2-positive autopsy cases were included. A relevant SARS-CoV-2 virus load in the cardiac tissue was detected in 41/95 deceased (43%). MACE-RNA-sequencing was performed to identify molecular pathomechanisms caused by the infection of the heart. A signature matrix was generated based on the single-cell dataset “Heart Cell Atlas” and used for digital cytometry on the MACE-RNA-sequencing data. Thus, immune cell fractions were estimated and revealed no difference in immune cell numbers in cases with and without cardiac infection. This result was confirmed by quantitative immunohistological diagnosis. MACE-RNA-sequencing revealed 19 differentially expressed genes (DEGs) with a q-value <0.05 (e.g. up: IFI44L, IFT3, TRIM25; down: NPPB, MB, MYPN). The upregulated DEGs were linked to interferon pathways and originate predominantly from endothelial cells. In contrast, the downregulated DEGs originate predominately from cardiomyocytes. Immunofluorescent staining showed viral protein in cells positive for the endothelial marker ICAM1 but rarely in cardiomyocytes. The GO term analysis revealed that downregulated GO terms were linked to cardiomyocyte structure, whereas upregulated GO terms were linked to anti-virus immune response. This study reveals that cardiac infection induced transcriptomic alterations mainly linked to immune response and destruction of cardiomyocytes. While endothelial cells are primarily targeted by the virus, we suggest cardiomyocyte-destruction by paracrine effects. Increased pro-inflammatory gene expression was detected in SARS-CoV-2-infected cardiac tissue but no increased SARS-CoV-2 associated immune cell infiltration was observed.
Vaccination for Respiratory Infections in Patients with Heart Failure
Journal of Clinical Medicine, September 22, 2021
Bronchopulmonary infections are a major trigger of cardiac decompensation and are frequently associated with hospitalizations in patients with heart failure (HF). Adverse cardiac effects associated with respiratory infections, more specifically Streptococcus pneumoniae and influenza infections, are the consequence of inflammatory processes and thrombotic events. For both influenza and pneumococcal vaccinations, large multicenter randomized clinical trials are needed to evaluate their efficacy in preventing cardiovascular events, especially in HF patients. No study to date has evaluated the protective effect of the COVID-19 vaccine in patients with HF. Different guidelines recommend annual influenza vaccination for patients with established cardiovascular disease and also recommend pneumococcal vaccination in patients with HF. The Heart Failure group of the French Society of Cardiology recently strongly recommended vaccination against COVID-19 in HF patients. Nevertheless, the implementation of vaccination recommendations against respiratory infections in HF patients remains suboptimal. This suggests that a national health policy is needed to improve vaccination coverage, involving not only the general practitioner, but also other health providers, such as cardiologists, nurses, and pharmacists. This review first summarizes the pathophysiology of the interrelationships between inflammation, infection, and HF. Then, we describe the current clinical knowledge concerning the protective effect of vaccines against respiratory diseases (influenza, pneumococcal infection, and COVID-19) in patients with HF and finally we propose how vaccination coverage could be improved in these patients.
COVID-19 and the Cardiovascular System: Insights into Effects and Treatments
Canadian Journal of Physiology and Pharmacology, September 21, 2021
Coronavirus disease 2019 (COVID-19), an acute and highly transmissible infectious disease has reached a pandemic level since March 11, 2020 and continues to challenge the healthcare system worldwide. The pathogenesis of COVID-19 is a complex process involving mechanisms that suppress the host antiviral and innate immune response, while triggering marked activation of coagulation and hyperinflammation leading to cytokine storm in severe COVID-19. This review summarizes current evidence related to COVID-19-associated cardiovascular severe illness and mortality, which encompasses life-threatening clinical manifestations, including myocardial injury, fulminant myocarditis, cardiac arrhythmia and ischemic stroke. The onset of hypercoagulable state is consistent with increased venous thromboembolism including deep vein thrombosis and pulmonary embolism. Thromboembolic manifestations include arterial thrombotic events such as stroke, myocardial infarction, and limb ischemia. Several treatment strategies have been investigated to mitigate COVID-19-associated cardiovascular clinical manifestations. The prevalence of thrombo-inflammatory syndrome and subsequent cardiovascular dysfunction prompted the implementation of antithrombotic therapy and strategies targeting major proinflammatory cytokines involved in COVID-19 cytokine storm. The development of new guidelines for effective treatment strategies requires concerted efforts to refine our understanding of the mechanisms underlying cardiovascular disease and large-scale clinical trials to reduce the burden of COVID-19 hospitalization and mortality.
COVID Deaths Surpass 1918 Flu Deaths
MedPage Today, September 21, 2021
U.S. COVID-19 deaths have now surpassed the 675,000 estimated deaths that occurred during the H1N1 influenza pandemic of 1918, but SARS-CoV-2 hasn’t exacted as heavy a toll as that pandemic. With a national population of around 103 million people at that time — about a third of the current total of 330 million Americans — the 1918 pandemic killed roughly 1 in 150 people in the U.S.; COVID has killed 1 in 500 Americans. Globally, the 1918 flu wrought more havoc than COVID, too, infecting about 500 million people, or a third of the world’s population at that time. It killed about 50 million people globally, according to CDC estimates. SARS-CoV-2 has infected nearly 230 million people around the world and killed some 4.7 million of them. There are many reasons for the differences in infection and mortality. The 1918 pandemic hit while the world was enmeshed in World War I and international travel was frequent; hospitals didn’t have the same medicines and technology at their disposal to treat patients; the cause of the illness was unidentifiable and therefore a test, targeted treatment, or vaccine was impossible. During the COVID-19 pandemic, global travel came to a halt and public health measures such as social distancing and masking were implemented relatively rapidly, vaccines were produced in record time, and treatments were investigated in real-time with a few proving helpful (with more still in development). Still, misinformation and disinformation campaigns stymied the effectiveness of some of those approaches in the U.S., and the virus threw humanity a curveball with the far more transmissible Delta variant.
Predictors of mortality in thrombotic thrombocytopenia after adenoviral COVID-19 vaccination: the FAPIC score
European Heart Journal, September 21, 2021
The clinical manifestation and outcomes of thrombosis with thrombocytopenia syndrome (TTS) after adenoviral COVID-19 vaccine administration are largely unknown due to the rare nature of the disease. We aimed to analyse the clinical presentation, treatment modalities, outcomes, and prognostic factors of adenoviral TTS, as well as identify predictors for mortality. PubMed, Scopus, Embase, and Web of Science databases were searched and the resulting articles were reviewed. A total of 6 case series and 13 case reports (64 patients) of TTS after ChAdOx1 nCoV-19 vaccination were included. We performed a pooled analysis and developed a novel scoring system to predict mortality. The overall mortality of TTS after ChAdOx1 nCoV-19 vaccination was 35.9% (23/64). In our analysis, age ≤60 years, platelet count <25 × 103/µL, fibrinogen <150 mg/dL, the presence of intracerebral haemorrhage (ICH), and the presence of cerebral venous thrombosis (CVT) were significantly associated with death and were selected as predictors for mortality (1 point each). We named this novel scoring system FAPIC (fibrinogen, age, platelet count, ICH, and CVT), and the C-statistic for the FAPIC score was 0.837 (95% CI 0.732–0.942). Expected mortality increased with each point increase in the FAPIC score, at 2.08, 6.66, 19.31, 44.54, 72.94, and 90.05% with FAPIC scores 0, 1, 2, 3, 4, and 5, respectively. The FAPIC scoring model was internally validated through cross-validation and bootstrapping, then externally validated on a panel of TTS patients after Ad26.COV2.S administration. Fibrinogen levels, age, platelet count, and the presence of ICH and CVT were significantly associated with mortality in patients with TTS, and the FAPIC score comprising these risk factors could predict mortality. The FAPIC score could be used in the clinical setting to recognize TTS patients at high risk of adverse outcomes and provide early intensive interventions including intravenous immunoglobulins and non-heparin anticoagulants.
The Myocardial and Neuronal Infectivity of SARS-CoV-2 and Detrimental Outcomes
Canadian Journal of Physiology and Pharmacology, September 21, 2021
The epidemiological outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), alias COVID-19, began in Wuhan, Hubei, China, in late December and eventually turned into a pandemic that has led to 3.71+ million deaths and 173+ million infected cases worldwide. In addition to respiratory manifestations, COVID-19 patients with neurological and myocardial dysfunctions exhibit a higher risk of in-hospital mortality. The immune function tends to be affected by cardiovascular risk factors and is thus indirectly related to the prognosis of COVID-19 patients. Many neurological symptoms and manifestations have been reported in COVID-19 patients. However, detailed descriptions of the prevalence and characteristic features of these symptoms are restricted due to insufficient data. It is thus advisable for clinicians to be vigilant for both cardiovascular and neurological manifestations in order to detect them at an early stage to avoid inappropriate management of COVID-19 and to address the manifestations adequately. Patients with severe COVID-19 are notably more susceptible to developing cardiovascular and neurological complications than non-severe COVID-19 patients. This review focuses on the consequential outcomes of COVID-19 on cardiovascular and neuronal functions, including other influencing factors.
Pre-medication with oral anticoagulants is associated with better outcomes in a large multinational COVID-19 cohort with cardiovascular comorbidities
Clinical Research in Cardiology, September 21, 2021
Coagulopathy and venous thromboembolism are common findings in coronavirus disease 2019 (COVID-19) and are associated with poor outcome. Timely initiation of anticoagulation after hospital admission was shown to be beneficial. In this study we aim to examine the association of pre-existing oral anticoagulation (OAC) with outcome among a cohort of SARS-CoV-2 infected patients. We analysed the data from the large multi-national Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) from March to August 2020. Patients with SARS-CoV-2 infection were eligible for inclusion. We retrospectively analysed the association of pre-existing OAC with all-cause mortality. Secondary outcome measures included COVID-19-related mortality, recovery and composite endpoints combining death and/or thrombotic event and death and/or bleeding event. We restricted bleeding events to intracerebral bleeding in this analysis to ensure clinical relevance and to limit reporting errors. A total of 1 433 SARS-CoV-2 infected patients were analysed, while 334 patients (23.3%) had an existing premedication with OAC and 1 099 patients (79.7%) had no OAC. After risk adjustment for comorbidities, pre-existing OAC showed a protective influence on the endpoint death (OR 0.62, P = 0.013) as well as the secondary endpoints COVID-19-related death (OR 0.64, P = 0.023) and non-recovery (OR 0.66, P = 0.014). The combined endpoint death or thrombotic event tended to be less frequent in patients on OAC (OR 0.71, P = 0.056). Pre-existing OAC is protective in COVID-19, irrespective of anticoagulation regime during hospital stay and independent of the stage and course of disease.
Fear of COVID-19 in Patients with Acute Myocardial Infarction
International Journal of Environmental Research and Public Health, September 18, 2021
A marked decline in myocardial infarction (AMI) hospitalizations was observed worldwide during the COVID-19 outbreak. The pandemic may have generated fear and adverse psychological consequences in these patients, delaying hospital access. The main objective of the study was to assess COVID fear through the FCV-19S questionnaire (a self-report measure of seven items) in 69 AMI patients (65 ± 11 years, mean ± SD; 59 males). Females presented higher values of each FCV-19S item than males. Older subjects (>57 years, 25th percentile) showed a higher total score with respect to those in the first quartile. The percentage of patients who responded “agree” and “strongly agree” in item 4 (“I am afraid of losing my life because of the coronavirus”) and 3 (“My hands become clammy when I think about the coronavirus”) was significantly greater in the elderly than in younger patients. When cardiovascular (CV) patients were compared to a previously published general Italian population, patients with CV disease exhibited higher values for items 3 and 4. Measures should be put in place to assist vulnerable and high CV risk patients, possibly adding psychologists to the cardiology team.
Continuous Remote Patient Monitoring Shows Early Cardiovascular Changes in COVID-19 Patients
Journal of Clinical Medicine, September 17, 2021
COVID-19 exerts deleterious cardiopulmonary effects, leading to a worse prognosis in the most affected. This retrospective multi-center observational cohort study aimed to analyze the trajectories of key vitals amongst hospitalized COVID-19 patients using a chest-patch wearable providing continuous remote patient monitoring of numerous vital signs. The study was conducted in five COVID-19 isolation units. A total of 492 COVID-19 patients were included in the final analysis. Physiological parameters were measured every 15 min. More than 3 million measurements were collected including heart rate, systolic and diastolic blood pressure, cardiac output, cardiac index, systemic vascular resistance, respiratory rate, blood oxygen saturation, and body temperature. Cardiovascular deterioration appeared early after admission and in parallel with changes in the respiratory parameters, showing a significant difference in trajectories within sub-populations at high risk. Early detection of cardiovascular deterioration of COVID-19 patients is achievable when using frequent remote patient monitoring.
Sex defining factors influence expression of ACE2 and other SARS-CoV-2 machinery
News Medical, September 17, 2021
The angiotensin-converting enzyme 2 (ACE2) has been identified as the major functional site facilitating binding and host-cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The evidence of multiple risk factors for the severity of coronavirus disease 2019 (COVID-19) has been described earlier, with consistent data on male sex and its association with increased hospitalizations, ICU admissions, and deaths. A possible hypothesis for why males are disproportionally affected by COVID-19 could be the location of the ACE2 gene. The ACE2 gene is located on the X chromosome. This gene has been demonstrated to be under the influence of sex hormone regulation. Several studies indicate the positive effects of estrogen to stimulate ACE2 gene transcription and its role in regulating the Renin-Angiotensin System (RAS). The activation of RAS is known to cause hypertension, kidney and cardiovascular disorders. Hence there may be a link between the sex of an individual to the severity and post-infection sequelae in COVID-19 patients. …results from this study provided evidence for the hypothesis that sex defining factors, including sex hormones and sex chromosome complement, influence the expression of ACE2 and other SARS CoV-2 machinery (ADAM17, TMPRSS2) to favor a higher residual level of cACE2 and lower local RAS activity in females than males exposed to SARS-CoV-2 S protein. This is a significant indicator that males with risk factors like diabetes, obesity, hypertension, and cardiovascular diseases will always be at a greater risk of having severe COVID-19 infection sequelae.
Left atrial appendage orifice area and morphology is closely associated with flow velocity in patients with nonvalvular atrial fibrillation
BMC Cardiovascular Disorders, September 16, 2021
Thromboembolic events are the most serious complication of atrial fibrillation (AF), and the left atrial appendage (LAA) is the most important site of thrombosis in patients with AF. During the period of COVID-19, a non-invasive left atrial appendage detection method is particularly important in order to reduce the exposure of the virus. This study used CT three-dimensional reconstruction methods to explore the relationship between LAA morphology, LAA orifice area and its mechanical function in patients with non-valvular atrial fibrillation (NVAF). A total of 81 consecutive patients with NVAF (36 cases of paroxysmal atrial fibrillation and 45 cases of persistent atrial fibrillation) who were planned to undergo catheter radiofrequency ablation were enrolled. All patients were examined by transthoracic echocardiography (TTE), TEE, and computed tomography angiography (CTA) before surgery. The LAA orifice area was obtained according to the images of CTA. According to the left atrial appendage morphology, it was divided into chicken wing type and non-chicken wing type. At the same time, TEE was performed to determine left atrial appendage flow velocity (LAAFV), and the relationship between the left atrial appendage orifice area and LAAFV was analyzed. The LAAFV in Non-chicken wing group was lower than that in Chicken wing group (36.2 ± 15.0 cm/s vs. 49.1 ± 22.0 cm/s, p-value < 0.05). In the subgroup analysis, the LAAFV in Non-chicken wing group was lower than that in Chicken wing group in the paroxysmal AF (44.0 ± 14.3 cm/s vs. 60.2 ± 22.8 cm/s, p-value < 0.05). In the persistent AF, similar results were observed (29.7 ± 12.4 cm/s vs. 40.8 ± 17.7 cm/s, p-value < 0.05). The LAAFV in persistent AF group was lower than that in paroxysmal AF group (34.6 ± 15.8 cm/s vs. 49.9 ± 20.0 cm/s, p-value < 0.001). The LAAFV was negatively correlated with left atrial dimension (R = − 0.451, p-value < 0.001), LAA orifice area (R= − 0.438, p-value < 0.001) and left ventricular mass index (LVMI) (R= − 0.624, p-value < 0.001), while it was positively correlated with LVEF (R = 0.271, p-value = 0.014). Multiple linear regression analysis showed that LAA morphology (β = − 0.335, p-value < 0.001), LAA orifice area (β = − 0.185, p-value = 0.033), AF type (β = − 0.167, p-value = 0.043) and LVMI (β = − 0.465, p-value < 0.001) were independent factors of LAAFV. Read conclusions.
Microbiota and Myopericarditis: The New Frontier in the Car-Diological Field to Prevent or Treat Inflammatory Cardiomyo-Pathies in COVID-19 Outbreak
Biomedicines, September 16, 2021
Myopericarditis is an inflammatory heart condition involving the pericardium and myocardium. It can lead to heart failure, dilated cardiomyopathy, arrhythmia and sudden death. Its pathogenesis is mainly mediated by viral infections but also can be induced by bacterial infections, toxic substances and immune mediated disorders. All these conditions can produce severe inflammation and myocardial injury, often associated with a poor prognosis. The specific roles of these different pathogens (in particular viruses), the interaction with the host, the interplay with gut microbiota, and the immune system responses to them are still not completely clear and under investigation. Interestingly, some research has demonstrated the contribution of the gut microbiota, and its related metabolites (some of which can mimic the cardiac myosin), in cardiac inflammation and in the progression of this disease. They can stimulate a continuous and inadequate immune response, with a subsequent myocardial inflammatory damage. The aim of our review is to investigate the role of gut microbiota in myopericarditis, especially for the cardiovascular implications of COVID-19 viral infection, based on the idea that the modulation of gut microbiota can be a new frontier in the cardiological field to prevent or treat inflammatory cardiomyopathies.
Heart Failure’s ‘Golden Moment’ Not Translating into Better Health
MedPage Today, September 12, 2021
Cardiology leaders complained that heart failure specialists may know how to treat their patients and to employ the latest therapies, but their actual reach is stunted by poor implementation within the wasteful U.S. healthcare system. It sounds like a tale of two cities: The COVID-19 pandemic continues to overwhelm patients and healthcare workers across the country; at the same time, heart failure patients are enjoying more therapies than ever, with new SGLT2 inhibitors hitting the market and sacubitril/valsartan (Entresto) use expanding to the historically hard-to-treat population of patients with preserved ejection fraction. Yet these advances are not being put into practice to improve the lives of many people in the U.S. “The heart failure ecosystem is full of well-intentioned people, but the way it operates, like the U.S. healthcare business in general, creates a very unusual situation where the whole is much less than the sum of its parts,” said former FDA commissioner Robert Califf, MD, now of Verily Life Sciences and Google Health, during a plenary session at the Heart Failure Society of America (HFSA) meeting held both virtually and in Denver. Califf said the heart failure field is “in one of its golden moments” amid what he called the “abject failure” of the U.S. healthcare system. “No one can argue that COVID didn’t make evidently clear the depth of health disparity in the U.S. We learned it is place that matters as much as race,” said Clyde Yancy, MD, of Northwestern University Feinberg School of Medicine in Chicago, during the HFSA session. “Achieving health equity is like treating heart failure,” Yancy said. He quoted Winston Churchill: “Success consists of going from failure to failure without loss of enthusiasm. We have done that well in heart failure. We need to do the same to achieve health equity,” he urged.
Resistant hypertension and COVID-19: tip of the iceberg?
Journal of Human Hypertension, September 10, 2021
Since the outbreak of COVID-19 pandemic many epidemiological studies revealed that common cardiovascular risk factors are frequently seen in these patients, but it was not clear which of them represented an independent predictor of adverse outcomes including mortality. Data coming from China indicated that arterial hypertension might be responsible for worse outcome irrespective of other risk factors and comorbidities, including age, diabetes, coronary artery disease, and renal dysfunction. However, this was not confirmed in studies and some authors claimed that this relationship was a consequence of other confounding factors that frequently meet in hypertensive patients, including antihypertensive treatment, which was at the early stage of pandemic considered responsible for increased admissions in intensive care unit and even higher mortality. This mainly referred to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor II blockers (ARBs). However, many studies and meta-analysis that followed the first false alarm dismissed any relation between the aforementioned drug classes and cardiac injury and adverse outcomes in COVID-19 patients. Moreover, investigations showed the beneficial effect of ACEIs and ARBs on the outcome in COVID-19 patients. Many questions still remained unanswered. In this issue of the Journal, Işik et al. investigated the influence of resistant arterial hypertension on in-hospital mortality in large cohort of COVID-19 patients. The authors used the definition of the American Heart Association for resistant arterial hypertension. Therefore, resistant hypertension was diagnosed in all patients with blood pressure (BP) ≥ 130/80 mmHg who were treated with three antihypertensive drugs including a diuretic or reached <130/80 mmHg with at least four antihypertensive medications. The influence of resistant hypertension on outcomes in COVID-19 patients has not been investigated so far. In the present study the mortality of COVID-19 was surprisingly high (18.7%) in the whole population of 1897 patients. Interestingly, there were no many significant differences in demographic and clinical characteristics between regulated and resistant hypertensive patients. The patients with resistant hypertension had higher prevalence of heart failure and, by definition, higher percentage of different antihypertensive medications than their controlled counterparts.
Heart transplantation in the era of COVID-19 pandemic: delirium, post-transplant depression and visitor restrictions The role of liaison and inpatient psychosomatic treatment. A case report
European Heart Journal – Case Reports, September 9, 2021
Heart transplant recipients show a high risk of developing major depression with an increased risk of post-transplant morbidity and mortality. Heart transplant specialists and patients face unprecedented challenges during the COVID-19 pandemic, which have enormous clinical implications such as increased risk of COVID-19 as well as visitor restrictions with social isolation during the post-transplant inpatient treatment. We present a case of a 64-year-old woman with end-stage heart failure caused by noncompaction cardiomyopathy who received an orthotopic heart transplant (OHT) without any intraoperative complications. Postoperatively, she showed acute psychotic symptoms in the ICU with improvement after switching intravenous tacrolimus treatment to an oral intake. Furthermore, the patient developed severe depressive symptoms with malnutrition and had a prolonged hospitalization. Standard medical care was complemented by intensive psychocardiological treatment to overcome the crisis. High complexity of the post-transplant management after OHT underlines the importance of multidisciplinary teamwork, involving heart transplant specialist and allied mental health professionals. This collaboration led to an excellent long-term result. Facing the COVID-19 pandemic, the hospital visitor policies may be scrutinized, carefully looking at the role of social isolation, postoperative experience in the ICU, and medical complications after OHT.
Case Report of Cardiogenic Shock Secondary to Covid-19 Myocarditis: Peculiarities on Diagnosis, Histology and Treatment
European Heart Journal – Case Reports, September 9, 2021
The year 2020 was dramatically characterized by SARS-CoV-2 pandemic outbreak. COVID-19-related heart diseases and myocarditis have been reported. A 45-year-old healthy male was admitted to the intensive care unit of our hospital because of cardiogenic shock. A diagnosis of COVID-19 infection and myocarditis was done. We present here several peculiarities about diagnostic workup, myocardial histological findings, choice of treatment and the patient clinical course at three and eight-months of follow-up. COVID-19 myocardial damage and myocarditis are mainly linked to the cytokine storm with mild myocardial inflammatory infiltrate and very unusual platelet microclots in the setting of the microvascular obstructive thrombo-inflammatory syndrome. Counteracting the inflammatory burden with an interleukine-1 inhibitor appeared safe and led to a dramatic and stable improvement of cardiac function.
Metoprolol in Critically Ill Patients With COVID-19
Journal of the American College of Cardiology, September 7, 2021
Severe COVID-19 can progress to an acute respiratory distress syndrome (ARDS), which involves alveolar infiltration by activated neutrophils. The beta-blocker metoprolol has been shown to ameliorate exacerbated inflammation in the myocardial infarction setting. The purpose of this study was to evaluate the effects of metoprolol on alveolar inflammation and on respiratory function in patients with COVID-19–associated ARDS. A total of 20 COVID-19 patients with ARDS on invasive mechanical ventilation were randomized to metoprolol (15 mg daily for 3 days) or control (no treatment). All patients underwent bronchoalveolar lavage (BAL) before and after metoprolol/control. The safety of metoprolol administration was evaluated by invasive hemodynamic and electrocardiogram monitoring and echocardiography. Metoprolol administration was without side effects. At baseline, neutrophil content in BAL did not differ between groups. Conversely, patients randomized to metoprolol had significantly fewer neutrophils in BAL on day 4 (median: 14.3 neutrophils/µl [Q1, Q3: 4.63, 265 neutrophils/µl] vs median: 397 neutrophils/µl [Q1, Q3: 222, 1,346 neutrophils/µl] in the metoprolol and control groups, respectively; P = 0.016). Metoprolol also reduced neutrophil extracellular traps content and other markers of lung inflammation. Oxygenation (PaO2:FiO2) significantly improved after 3 days of metoprolol treatment (median: 130 [Q1, Q3: 110, 162] vs median: 267 [Q1, Q3: 199, 298] at baseline and day 4, respectively; P = 0.003), whereas it remained unchanged in control subjects. Metoprolol-treated patients spent fewer days on invasive mechanical ventilation than those in the control group (15.5 ± 7.6 vs 21.9 ± 12.6 days; P = 0.17). In this pilot trial, intravenous metoprolol administration to patients with COVID-19–associated ARDS was safe, reduced exacerbated lung inflammation, and improved oxygenation. Repurposing metoprolol for COVID-19–associated ARDS appears to be a safe and inexpensive strategy that can alleviate the burden of the COVID-19 pandemic.
Prevalence of right ventricular dysfunction and impact on all-cause death in hospitalized patients with COVID-19: a systematic review and meta-analysis
Scientific Reports, September 7, 2021
The Coronavirus Disease (COVID-19) pandemic imposed a high burden of morbidity and mortality. In COVID-19, direct lung parenchymal involvement and pulmonary microcirculation dysfunction may entail pulmonary hypertension (PH). PH and direct cardiac injury beget right ventricular dysfunction (RVD) occurrence, which has been frequently reported in COVID-19 patients; however, the prevalence of RVD and its impact on outcomes during COVID-19 are still unclear. This study aims to evaluate the prevalence of RVD and associated outcomes in patients with COVID-19, through a Systematic Review and Meta-Analysis. MEDLINE and EMBASE were systematically searched from inception to 15th July 2021. All studies reporting either the prevalence of RVD in COVID-19 patients or all-cause death according to RVD status were included. The pooled prevalence of RVD and Odds Ratio (OR) for all-cause death according to RVD status were computed and reported. Subgroup analysis and meta-regression were also performed. Among 29 studies (3813 patients) included, pooled prevalence of RVD was 20.4% (95% CI 17.1–24.3%; 95% PI 7.8–43.9%), with a high grade of heterogeneity. No significant differences were found across geographical locations, or according to the risk of bias. Severity of COVID-19 was associated with increased prevalence of RVD at meta-regression. The presence of RVD was found associated with an increased likelihood of all-cause death (OR 3.32, 95% CI 1.94–5.70). RVD was found in 1 out of 5 COVID-19 patients, and was associated with all-cause mortality. RVD may represent one crucial marker for prognostic stratification in COVID-19; further prospective and larger are needed to investigate specific management and therapeutic approach for these patients.
Spatio-temporal hybrid neural networks reduce erroneous human “judgement calls” in the diagnosis of Takotsubo syndrome
EClinicalMedicine, September 4, 2021
We investigate whether deep learning (DL) neural networks can reduce erroneous human “judgment calls” on bedside echocardiograms and help distinguish Takotsubo syndrome (TTS) from anterior wall ST segment elevation myocardial infarction (STEMI). We developed a single-channel (DCNN[2D SCI]), a multi-channel (DCNN[2D MCI]), and a 3-dimensional (DCNN[2D+t]) deep convolution neural network, and a recurrent neural network (RNN) based on 17,280 still-frame images and 540 videos from 2-dimensional echocardiograms in 10 years (1 January 2008 to 1 January 2018) retrospective cohort in University of Iowa (UI) and eight other medical centers. Echocardiograms from 450 UI patients were randomly divided into training and testing sets for internal training, testing, and model construction. Echocardiograms of 90 patients from the other medical centers were used for external validation to evaluate the model generalizability. A total of 49 board-certified human readers performed human-side classification on the same echocardiography dataset to compare the diagnostic performance and help data visualization. The DCNN (2D SCI), DCNN (2D MCI), DCNN(2D+t), and RNN models established based on UI dataset for TTS versus STEMI prediction showed mean diagnostic accuracy 73%, 75%, 80%, and 75% respectively, and mean diagnostic accuracy of 74%, 74%, 77%, and 73%, respectively, on the external validation. DCNN(2D+t) (area under the curve [AUC] 0·787 vs. 0·699, P = 0·015) and RNN models (AUC 0·774 vs. 0·699, P = 0·033) outperformed human readers in differentiating TTS and STEMI by reducing human erroneous judgement calls on TTS. Spatio-temporal hybrid DL neural networks reduce erroneous human “judgement calls” in distinguishing TTS from anterior wall STEMI based on bedside echocardiographic videos.
Association of renin–angiotensin system blockers with COVID-19 diagnosis and prognosis in patients with hypertension: a population-based study
Clinical Kidney Journal, September 3, 2021
The effect of renin-angiotensin (RAS) blockade either by angiotensin-converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARBs) on coronavirus disease 2019(COVID-19) susceptibility, mortality and severity is inadequately described. We examined the association between renin-angiotensin system (RAS) blockade and COVID-19 diagnosis and prognosis in a large population-based cohort of patients with hypertension. This is a cohort study using regional health records. We identified all individuals aged 18-95 years from 87 health care reference areas of the main health provider in Catalonia (Spain), with a history of hypertension from primary care records. Data were linked to COVID-19 test results, hospital, pharmacy and mortality records from 1 March 2020 to 14 August 2020. We defined exposure to RAS blockers as the dispensation of ACEi/ARBs during the three months before COVID-19 diagnosis or 1 March 2020. Primary outcomes were: COVID-19 infection, and severe progression in hospitalized patients with COVID-19(the composite of need for invasive respiratory support or death). For both outcomes and for each exposure of interest (RAAS blockade, ACEi or ARB) we estimated associations in age-sex-area-propensity matched samples. From a cohort of 1,365,215 inhabitants we identified 305,972 patients with hypertension history. Recent use of ACEi/ARBs in patients with hypertension was associated with a lower 6 month-cumulative incidence of COVID-19 diagnosis (3.78% [95% CI: 3.69% – 3.86%] vs 4.53% [95% CI: 4.40% – 4.65%]; p < 0.001). In the 12,344 patients with COVID-19 infection, the use of ACEi/ARBs was not associated with a higher risk of hospitalization with need for invasive respiratory support or death (OR = 0.91 (0.71 – 1.15); p = 0.426).
Mobile health and cardiac arrhythmias: patient self-management in digital care pathways
European Journal of Cardiovascular Nursing, September 2, 2021
The use of technology in cardiovascular care has emerged significantly over the last decade. This includes telemedicine and cardiac monitoring devices to remotely monitor and manage cardiac conditions, as well as the use of activity trackers and educational applications to support a healthy lifestyle and to activate and support patients in self-management of their condition. The COVID-19 global pandemic accelerated the uptake of these technologies, given that numerous interventions and models of care delivery were converted from face-to-face into virtual and remote models of care using digital healthcare solutions. Patient roles have changed from passively receiving treatment, to actively being involved in their care process, treatment decisions and being an active member of the treatment team. Co-design methodologies are required to develop novel approaches incorporating the aims and requirements from the perspective of healthcare professionals but equally important, the needs, values, and preferences of the patients involved in this. In clinical practice, such co-design methodologies are referred to as shared decision-making, which plays an important role in the management of patients with chronic conditions such as atrial fibrillation (AF). A recent study published in the European Journal of Cardiovascular Nursing, stated that patients with symptomatic AF may experience severe symptoms such as palpitations, shortness of breath, and chest pain, which can be scary, and the emotional stress may even worsen or trigger episodes of AF. This study included 821 women who had symptomatic palpitations were provided a handheld electrocardiogram (ECG), which was connected to their smartphone for a 60-day period. Participants were instructed to record an ECG twice a day and in case of symptoms and received immediate responses based on an automated algorithm interpretation. Most recordings demonstrated sinus rhythm or premature atrial/ventricular contractions, and only 6% demonstrated AF. Using validated questionnaires, it was demonstrated that anxiety and depression levels decreased significantly. Interestingly and contrastingly, the frequency and severity of symptoms improved, which resulted in the improved quality of life. This demonstrates the huge potential of technology on the wellbeing of patients by providing direct feedback on heart rate and rhythm as an integrated part of a comprehensive care approach.
COVID-19 pandemic and cardiovascular disease: the double sentence
European Journal of Preventive Cardiology, September 1, 2021
Coronavirus disease 2019 (COVID-19) pandemic affected every level of our healthcare systems, especially hospitals, which faced a huge human and logistical burden. To face the exponential growth of COVID-19 patients, national or local authorities declared lockdowns and urged people to avoid seeking medical care for unnecessary situations. This translated into reductions of hospital admissions, including for acute problems such as myocardial infarctions. During the first lockdown, for instance, studies reported a ∼20–30% decrease in admissions for myocardial infarction in France or Denmark. In New Zealand, despite a low incidence rate of COVID-19 infections during the first wave, hospitalizations for acute coronary syndrome also decreased by 28%, especially due to fewer admissions for non-ST-segment elevation acute coronary syndromes. It is also noteworthy that rates of admission for acute coronary syndromes during COVID-19 pandemic were comparable to pre-pandemic levels in countries that established strict controls of the epidemics. Reasons for the reduction in admissions for acute coronary syndromes are probably multifactorial, but less engagement in stressful situations due to lockdown is a frequently proposed explanation. Beyond admission rates during a pandemic situation, there remains the question of the fate of patients still admitted, especially those hospitalized with cardiovascular diseases that account for a large proportion of admissions. Cannata et al. report in the Journal the results of a meta-analysis comprising studies investigating in-hospital mortality of people admitted with cardiovascular disease but without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the first wave of the pandemic compared to a pre-pandemic period. Comprising data from more than 27 000 individuals, their study showed a 62% higher risk (relative risk) of in-hospital mortality during the pandemic period. In absolute numbers, mortality amounted to 10.4% during the COVID-19 first wave compared to 5.7% during the pre-pandemic period.
Types of myocardial injury and mid-term outcomes in patients with COVID-19
European Heart Journal – Quality of Care and Clinical Outcomes, August 30, 2021
Our aim was to evaluate the acute and chronic patterns of myocardial injury among patients with coronavirus disease-2019 (COVID-19), and their mid-term outcomes. Patients with laboratory-confirmed COVID-19 who had a hospital encounter within the Mount Sinai Health System (New York City) between 27 February 2020 and 15 October 2020 were evaluated for inclusion. Troponin levels assessed between 72 h before and 48 h after the COVID-19 diagnosis were used to stratify the study population by the presence of acute and chronic myocardial injury, as defined by the Fourth Universal Definition of Myocardial Infarction. Among 4695 patients, those with chronic myocardial injury (n = 319, 6.8%) had more comorbidities, including chronic kidney disease and heart failure, while acute myocardial injury (n = 1168, 24.9%) was more associated with increased levels of inflammatory markers. Both types of myocardial injury were strongly associated with impaired survival at 6 months [chronic: hazard ratio (HR) 4.17, 95% confidence interval (CI) 3.44–5.06; acute: HR 4.72, 95% CI 4.14–5.36], even after excluding events occurring in the first 30 days (chronic: HR 3.97, 95% CI 2.15–7.33; acute: HR 4.13, 95% CI 2.75–6.21). The mortality risk was not significantly different in patients with acute as compared with chronic myocardial injury (HR 1.13, 95% CI 0.94–1.36), except for a worse prognostic impact of acute myocardial injury in patients <65 years of age (P-interaction = 0.043) and in those without coronary artery disease (P-interaction = 0.041). Chronic and acute myocardial injury represent two distinctive patterns of cardiac involvement among COVID-19 patients. While both types of myocardial injury are associated with impaired survival at 6 months, mortality rates peak in the early phase of the infection but remain elevated even beyond 30 days during the convalescent phase.
Risk prediction in patients with COVID-19 based on haemodynamic assessment of left and right ventricular function
European Heart Journal – Cardiovascular Imaging, August 28, 2021
Cardiovascular involvement is common in COVID-19. We sought to describe the haemodynamic profiles of hospitalized COVID-19 patients and determine their association with mortality. Consecutive hospitalized patients diagnosed with COVID-19 infection underwent clinical evaluation using the Modified Early Warning Score (MEWS) and a full non-invasive echocardiographic haemodynamic evaluation, irrespective of clinical indication, as part of a prospective predefined protocol. Patients were stratified based on filling pressure and output into four groups. Multivariable Cox-Hazard analyses determined the association between haemodynamic parameters with mortality. Among 531 consecutive patients, 44% of patients had normal left ventricular (LV) and right ventricular (RV) haemodynamic status. In contrast to LV haemodynamic parameters, RV parameters worsened with higher MEWS stage. While RV parameters did not have incremental risk prediction value above MEWS, LV stroke volume index, E/e′ ratio, and LV stroke work index were all independent predictors of outcome, particularly in severe disease. Patients with LV or RV with high filling pressure and low output had the worse outcome, and patients with normal haemodynamics had the best (P < 0.0001). In hospitalized patients with COVID-19, almost half have normal left and right haemodynamics at presentation. RV but not LV haemodynamics are related to easily obtainable clinical parameters. LV but not RV haemodynamics are independent predictors of mortality, mostly in patients with severe disease.
Comparison of Outcomes in Patients with COVID-19 and Thrombosis vs. Those Without Thrombosis
American Journal of Cardiology, August 28, 2021
Venous thromboembolism (VTE) in coronavirus disease 2019 (COVID-19) has been established. We sought to evaluate the clinical impact of thrombosis in COVID-19-positive patients over the span of the pandemic to date. We analyzed COVID-19-positive patients with the diagnosis of thrombosis who presented to the MedStar Health system (11 hospitals in Washington, DC, and Maryland) during the pandemic (March 1, 2020 – March 31, 2021). We compared clinical course and outcomes based on the presence or absence of thrombosis and then, specifically, cardiac thrombosis. The cohort included 11,537 COVID-19-positive admitted patients. Of these patients, 1,248 had non-cardiac thrombotic events and 1,009 had cardiac thrombosis (myocardial infarction) during their hospital admission. Of the non-cardiac thrombotic events, 562 (45.0%) were pulmonary embolism, 480 (38.5%) were deep venous thromboembolism, and 347 (27.8%) were stroke. In the thrombosis arm, the cohort’s mean age was 64.5 ± 15.3 years, 53.3% were men, and a majority were African American (64.9%). Patients with thrombosis tended to be older, with more co-morbidities. In-hospital mortality was significantly higher (16.0%) in COVID-19-positive patients with concomitant thrombosis versus those without thrombosis (7.9%; p <0.001) but lower than in COVID-19-positive patients with cardiac thrombosis (24.7%; p <0.001). In conclusion, COVID-19 patients with thrombosis are at higher risk for in-hospital mortality. However, this prognosis is not as grim as cardiac thrombosis. Efforts should focus on early recognition, evaluation, and intensifying antithrombotic management of these patients.
COVID-19 and ROS Storm: What is the Forecast for Hypertension
American Journal of Hypertension, August 25, 2021
As of 12 May 2021, the Center for Disease Control data tracker reports that more than 32 million Americans were infected with the SARS-CoV-2 virus. The death toll of the ongoing COVID-19 pandemic has surpassed the mark of 580,000, and despite the recent availability of vaccines, it continues to increase on American soil, though at a lower rate. Unfortunately, the full impact of the disease is not yet reflected in many countries, such as Brazil and India, where all victims may not be fully accounted for, and which are battling the virus and witnessing a disproportional toll on their citizens. While our understanding of COVID-19 has drastically improved since its first case in Wuhan (Hubei Province, China), there is still a myriad of open questions regarding the pathophysiology of this disease. Cumulative evidence, however, suggests that patients with cardiometabolic diseases are at a greater risk of developing the severe form of COVID-19, but the specific contribution of each disrupted pathway is unclear. Previous studies highlighted the significance of a cytokine storm to the severity of SARS-CoV-2 infection, and more recently, the possibility of another storm, the bradykinin one, also contributing to the widespread tissue damage observed in some COVID-19 patients, involving those with hypertension comorbidity. Under these unprecedented conditions, there is yet, another equally relevant, still overlooked, storm on the forecast for hypertension: the reactive oxygen species (ROS) storm. ROS are signaling molecules that exert critical biological roles. Conversely, dysregulated ROS production, leading to oxidative stress, contributes to the pathophysiology of several diseases, including hypertension. While different mechanisms could trigger the generation of ROS, it is widely accepted that NADPH oxidase is a main source of these molecules, and not surprisingly, the expression levels of this enzyme are altered during hypertension.
Arterial Hypertension and Diabetes Mellitus in COVID-19 Patients: What Is Known by Gender Differences?
Journal of Clinical Medicine, August 23, 2021
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected >160 million people around the world. Hypertension (HT), chronic heart disease (CHD), and diabetes mellitus (DM) increase susceptibility to SARS-CoV-2 infection. Aims. We designed this retrospective study to assess the gender differences in hypertensive diabetic SARS-CoV-2 patients. We reported data, by gender differences, on the inflammatory status, on the hospital stays, intensive care unit (ICU) admission, Rx and CT report, and therapy. Methods. We enrolled 1014 patients with confirmed COVID-19 admitted into different Hospitals of Campania from 26 March to 30 June, 2020. All patients were allocated into two groups: diabetic-hypertensive group (DM-HT group) that includes 556 patients affected by diabetes mellitus and arterial hypertension and the non-diabetic- non-hypertensive group (non-DM, non-HT group) comprising 458 patients. The clinical outcomes (i.e., discharges, mortality, length of stay, therapy, and admission to intensive care) were monitored up to June 30, 2020. Results. We described, in the DM-HT group, higher proportion of cardiopathy ischemic (CHD) (47.5% vs. 14.8%, respectively; p < 0.0001) and lung diseases in females compared to male subjects (34.8% vs. 18.5%, respectively; p < 0.0001). In male subjects, we observed higher proportion of kidney diseases (CKD) (11% vs. 0.01%, respectively; p < 0.0001), a higher hospital stay compared to female subjects (22 days vs. 17 days, respectively, p < 0.0001), a higher admission in ICU (66.9% vs. 12.8%, respectively, p < 0.0001), and higher death rate (17.3% vs. 10.7%, respectively, p < 0.0001). Conclusion. These data confirm that male subjects, compared to female subjects, have a higher hospital stay, a higher admission to ICU, and higher death rate.
The Effects of Reduced Physical Activity on the Lipid Profile in Patients with High Cardiovascular Risk during COVID-19 Lockdown
International Journal of Environmental Research and Public Health, August 23, 2021
The COVID-19 pandemic is a serious global health problem. In Italy, to limit the infections, the government ordered lockdown from March 2020. This measure, designed to contain the virus, led to serious limitations on the daily life of the individuals it affected, and in particular in the limitation of physical exercise. The aim of this study was to evaluate the effects of reduced physical activity on the lipid profile in patients with high cardiovascular risk. We enrolled 38 dyslipidemic patients, 56% male, with an age range of 44–62 years, considered to be at high cardiovascular risk. All patients were prescribed statin drug therapy (atorvastatin 40 mg) and a vigorous physical activity program four times a week, 1 h per session. In addition, a personalized Mediterranean diet was prescribed to all the patients. Total cholesterol, LDL, HDL and triglycerides were measured in patients at T0 before lockdown and at T1 during lockdown. Data showed a significant increase (p < 0.01) in total cholesterol (+6,8%) and LDL (+15,8%). Furthermore, the analysis of the data revealed a reduction in HDL (−3%) and an increase in triglycerides (+3,2%), although both were not significant (p > 0.05). Our study showed that the reduction in physical activity during lockdown led to an increase in LDL levels, and therefore, in the risk of ischemic heart disease in dyslipidemic patients with high cardiovascular risk.
Prevalence and Prognostic Value of Myocardial Injury in the Initial Presentation of SARS-CoV-2 Infection among Older Adults
Journal of Clinical Medicine, August 23, 2021
Myocardial involvement during SARS-CoV-2 infection has been reported in many prior publications. We aim to study the prevalence and the clinical implications of acute myocardial injury (MIN) during SARS-CoV-2 infection, particularly in older patients. The method includes a longitudinal observational study with all consecutive adult patients admitted to a COVID-19 unit between March–April 2020. Those aged ≥65 were considered as older adult group. MIN was defined as at least 1 high-sensitive troponin (hs-TnT) concentration above the 99th percentile upper reference limit with different sex-cutoff. Results. Among the 634 patients admitted during the period of observation, 365 (58%) had evidence of MIN, and, of them, 224 (61%) were older adults. Among older adults, MIN was associated with longer time to recovery compared to those without MIN (13 days (IQR 6-21) versus 9 days (IQR 5-17); p < 0.001, respectively. In-hospital mortality was significantly higher in older adults with MIN at admission versus those without it (71 (31%) versus 11 (12%); p < 0.001). In a logistic regression model adjusting by age, sex, severity, and Charlson Comorbidity Index, the OR for in-hospital mortality was 2.1 (95% CI: 1.02–4.42; p = 0.043) among those older adults with MIN at admission. Older adults with acute myocardial injury had greater time to clinical recovery, as well as higher odds of in-hospital mortality.
COVID-19 and Cardiovascular Disease: a Global Perspective
Current Cardiology Reports, August 19, 2021
It has already been more than one year since the novel coronavirus disease 2019 (COVID-19), officially known as SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), pandemic has started, and surely it has become a remarkable challenge for healthcare systems around the world. This review aims to assess the global impact of the COVID-19 pandemic on the cardiovascular diseases (CVDs), trying to assess the possible future trajectory of the CVDs and their management. The COVID-19 pandemic has had a deleterious impact on the CV risk factors, with an increase in both sedentary and unhealthy food habits. The fear of contagion has decreased the access to the emergency systems with an increase in out-of-hospital-cardiac-arrests and late presentation of acute myocardial infarctions. The closure of the non-urgent services has delayed cardiac rehabilitation programmes and chronic clinical care. As a result of the COVID-19 pandemic impact on the population habits and on the management of CVDs, we will probably face an increase in CVD and heart failure cases. It is crucial to use all the non-traditional approaches, such as telemonitoring systems, in order to overcome the difficulties raised by the pandemic.
The use of remote monitoring of cardiac implantable devices during the COVID-19 pandemic: an EHRA physician survey
EP Europace, August 19, 2021
It is unclear to what extent the COVID-19 pandemic has influenced the use of remote monitoring (RM) of cardiac implantable electronic devices (CIEDs). The present physician-based European Heart Rhythm Association (EHRA) survey aimed to assess the influence of the COVID-19 pandemic on RM of CIEDs among EHRA members and how it changed the current practice. The survey comprised 27 questions focusing on RM use before and during the pandemic. Questions focused on the impact of COVID-19 on the frequency of in-office visits, data filtering, reasons for initiating in-person visits, underutilization of RM during COVID-19, and RM reimbursement. A total of 160 participants from 28 countries completed the survey. Compared to the pre-pandemic period, there was a significant increase in the use of RM in patients with pacemakers (PMs) and implantable loop recorders (ILRs) during the COVID-19 pandemic (PM 24.2 vs. 39.9%, P = 0.002; ILRs 61.5 vs. 73.5%, P = 0.028), while there was a trend towards higher utilization of RM for cardiac resynchronization therapy-pacemaker (CRT-P) devices during the pandemic (44.5 vs. 55%, P = 0.063). The use of RM with implantable cardioverter-defibrillators (ICDs) and CRT-defibrillator (CRT-D) did not significantly change during the pandemic (ICD 65.2 vs. 69.6%, P = 0.408; CRT-D 65.2 vs. 68.8%, P = 0.513). The frequency of in-office visits was significantly lower during the pandemic (P < 0.001). Nearly two-thirds of participants (57 out of 87 respondents), established new RM connections for CIEDs implanted before the pandemic with 33.3% (n = 29) delivering RM transmitters to the patient’s home address, and the remaining 32.1% (n = 28) activating RM connections during an in-office visit. The results of this survey suggest that the crisis caused by COVID-19 has led to a significant increase in the use of RM of CIEDs.
Epicardial ablation of ventricular tachycardia in patients with structural heart disease: a single-centre experience over 12 years
EP Europace, August 18, 2021
Epicardial ablation has risen to an essential part of the treatment of ventricular tachycardias (VTs). In this study, we report the efficacy, risks, and current trends of epicardial ablation in structural heart disease as reported in a tertiary single centre over a 12-year period. Two hundred and thirty-six patients referred for VT ablation underwent a successful epicardial access and were included in the analysis (89% non-ischaemic cardiomyopathy, 90% males, mean age 60 years, mean left ventricular ejection fraction 38.4%). After performing epicardial ablation the clinical VTs were eliminated in 87% of the patients and 71% of the cohort achieved freedom from VT during 22-month follow-up. Twelve patients (5%) suffered major procedure-related complications. Until the end of follow-up 47 (20%) patients died, 9 (4%) underwent a left ventricular assist device implantation and 10 (4%) patients received a heart transplantation. Antiarrhythmic drugs at baseline and during follow-up were independent predictors of VT recurrence. Atrial fibrillation, renal dysfunction, worse New York Heart Association class, and antiarrhythmic drugs at follow-up were associated with worse survival in our cohort. In this large tertiary single-centre experience, percutaneous epicardial access was feasible in the large majority of the cohort with acceptably low complications rates. A combined endo-/epicardial approach resulted in 87% acute and 71% long-term success. Further studies are needed to clarify the role of routine combined endo-/epicardial ablation in these complex cardiomyopathies.
Cardiovascular Disease Complicating COVID-19 in the Elderly
Medicina, August 17, 2021
SARS-CoV-2, a single-stranded RNA coronavirus, causes an illness known as coronavirus disease 2019 (COVID-19). The highly transmissible virus gains entry into human cells primarily by the binding of its spike protein to the angiotensin-converting enzyme 2 receptor, which is expressed not only in lung tissue but also in cardiac myocytes and the vascular endothelium. Cardiovascular complications are frequent in patients with COVID-19 and may be a result of viral-associated systemic and cardiac inflammation or may arise from a virus-induced hypercoagulable state. This prothrombotic state is marked by endothelial dysfunction and platelet activation in both macrovasculature and microvasculature. In patients with subclinical atherosclerosis, COVID-19 may incite atherosclerotic plaque disruption and coronary thrombosis. Hypertension and obesity are common comorbidities in COVID-19 patients that may significantly raise the risk of mortality. Sedentary behaviors, poor diet, and increased use of tobacco and alcohol, associated with prolonged stay-at-home restrictions, may promote thrombosis, while depressed mood due to social isolation can exacerbate poor self-care. Telehealth interventions via smartphone applications and other technologies that document nutrition and offer exercise programs and social connections can be used to mitigate some of the potential damage to heart health.
Clinical Characteristics and Outcomes of Hypertensive Patients Infected with COVID-19: A Retrospective Study
International Journal of General Medicine, August 17, 2021
Hypertension has been reported as the most prevalent comorbidity in patients with coronavirus disease 2019 (COVID-19). This retrospective study aims to compare the clinical characteristics and outcomes in COVID-19 patients with or without hypertension. A total of 944 hospitalized patients with laboratory-confirmed COVID-19 were included from January to March 2020. Information from the medical record, including clinical features, radiographic and laboratory results, complications, treatments, and clinical outcomes, were extracted for the analysis. A total of 311 (32.94%) patients had comorbidity with hypertension. In COVID-19 patients with hypertension, the coexistence of type 2 diabetes (56.06% vs 43.94%), coronary heart disease (65.71% vs 34.29%), poststroke syndrome (68.75% vs 31.25%) and chronic kidney diseases (77.78% vs 22.22%) was significantly higher, while the coexistence of hepatitis B infection (13.04% vs 86.96%) was significantly lower than in COVID-19 patients without hypertension. Computed tomography (CT) chest scans show that COVID-19 patients with hypertension have higher rates of pleural effusion than those without hypertension (56.60% vs 43.40%). In addition, the levels of blood glucose [5.80 (IQR, 5.05– 7.50) vs 5.39 (IQR, 4.81– 6.60)], erythrocyte sedimentation rate (ESR) [28 (IQR, 17.1– 55.6) vs 21.8 (IQR, 11.5– 44.1), P=0.008], C-reactive protein (CRP) [17.92 (IQR, 3.11– 46.6) vs 3.15 (IQR, 3.11– 23.4), P=0.013] and serum amyloid A (SAA) [99.28 (IQR, 8.85– 300) vs 15.97 (IQR, 5.97– 236.1), P=0.005] in COVID-19 patients with hypertension were significantly higher than in patients without hypertension. It is common for patients with COVID-19 to have the coexistence of hypertension, type 2 diabetes, coronary heart disease and so on, which may exacerbate the severity of COVID-19.
COVID-19 may affect long-term ‘fight or flight’ response in young adults
Medical News Today, August 16, 2021
Around a third of otherwise healthy people who have recovered from mild COVID-19 experience the lingering symptoms of long COVID. The most common symptoms include fatigue and shortness of breath, but some individuals also report heart palpitations. This may be a sign that their “autonomic nervous system” is out of balance. The two wings of the autonomic nervous system act together automatically to regulate vital functions such as heart rate and breathing. When the body perceives a life threatening situation, the sympathetic nervous system increases heart rate and breathing rate, a reaction that people call the “fight-or-flight response.” By contrast, the parasympathetic nervous system restores the body to a more stable, restful state, known as “rest and digest.” Individuals with hypertension (high blood pressure), diabetes, and obesity often have increased activity in their sympathetic nervous system, which COVID-19 may exacerbate. For the first time, researchers have now assessed sympathetic nerve activity in otherwise healthy young people recovering from the infection. They ran a series of tests on 16 individuals aged approximately 20 years old who had tested positive for SARS-CoV-2, the virus that causes COVID-19, around 35 days previously. Before the pandemic, the scientists carried out identical tests on an age-matched group of 14 healthy volunteers, who served as controls. The tests revealed changes in the sympathetic nervous system of people recovering COVID-19, both at rest and in response to a stress test. There were also differences in heart rate and sympathetic nerve activity in a test designed to simulate standing up. The researchers believe that the same changes in older adults could have adverse effects on their cardiovascular health. “This is because, with aging, we tend to lose some of the compensatory mechanisms in place to offset the blood-pressure-raising effects of high sympathetic activity,” said senior author Dr. Abigail Stickford, from the department of health and exercise science at Appalachian State University in Boone, NC. “Ultimately, this could also place more strain on the heart,” she told Medical News Today.
FDA Authorizes COVID Booster Shots for Certain Populations
MedPage Today, August 13, 12021
After weeks of speculation, the FDA amended the emergency use authorizations (EUAs) for Pfizer and Moderna’s COVID-19 vaccines to include an additional booster dose for certain immunocompromised people, the agency said late Thursday. These populations include solid-organ transplant recipients or others diagnosed with conditions “considered to have a similar level of immunocompromise” who previously received one of the two mRNA vaccines. After weeks of speculation, the FDA amended the emergency use authorizations (EUAs) for Pfizer and Moderna’s COVID-19 vaccines to include an additional booster dose for certain immunocompromised people, the agency said late Thursday. These populations include solid-organ transplant recipients or others diagnosed with conditions “considered to have a similar level of immunocompromise” who previously received one of the two mRNA vaccines. The FDA kept the language purposely vague, as clinical considerations are set to be defined Friday during CDC’s Advisory Committee on Immunization Practices (ACIP) meeting. FDA merely added that individuals immunocompromised “in a manner similar” to those who underwent solid-organ transplantation have a reduced ability to fight disease and are vulnerable to infections, such as COVID-19.
Cardiac MRI in Patients with Prolonged Cardiorespiratory Symptoms after Mild to Moderate COVID-19 Infection
Radiology, August 10, 2021
Myocardial injury and inflammation on cardiac MRI in patients suffering from coronavirus disease 19 (COVID-19) have been described in recent publications. Concurrently, a chronic COVID-19 syndrome (CCS) after COVID-19 infection has been observed manifesting with symptoms like fatigue and exertional dyspnea. To explore the relationship between CCS and myocardial injury and inflammation as an underlying cause of the persistent complaints in previously healthy individuals. In this prospective study from January 2021 to April 2021, study participants without known cardiac or pulmonary diseases prior to COVID-19 infection with persisting CCS symptoms like fatigue or exertional dyspnea after convalescence and healthy control participants underwent cardiac MRI. Cardiac MRI protocol included T1 and T2 relaxation times, extracellular volume (ECV), T2 signal intensity ratio, and late gadolinium enhancement (LGE). Student t test, Mann-Whitney U test, and χ2 test were used for statistical analysis. 41 participants with CCS (39±13 years; 18 men) and 42 control participants (39±16 years; 26 men) were evaluated. Median time between initial mild to moderate COVID-19 disease without hospitalization and cardiac MRI was 103 days (interquartile range: 88-158). Troponin T levels were normal. Parameters indicating myocardial inflammation and edema were comparable between participants with CCS and control participants: T1 relaxation time (978±23 ms vs 971±25 ms; P=.17), T2 relaxation time (53±2 ms vs 52±2 ms; P=.47), T2 signal intensity ratio (1.6±0.2 vs 1.6±0.3; P=.10). Visible myocardial edema was present in none of the participants. Three of 41 (7%) participants with CCS demonstrated non-ischemic LGE compared to none in the control group (0 of 42 [0%]; P=.07). None of the participants fulfilled the 2018 Lake Louise criteria for the diagnosis of myocarditis. Individuals without hospitalization for COVID-19 and with CCS did not demonstrate signs of active myocardial injury or inflammation on cardiac MRI.
Prognostic Value of Electrocardiographic QRS Diminution in Patients Hospitalized With COVID-19 or Influenza
American Journal of Cardiology, August 8, 2021
During the clinical care of hospitalized patients with COVID-19, diminished QRS amplitude on the surface electrocardiogram was observed to precede clinical decompensation, culminating in death. This prompted investigation into the prognostic utility and specificity of low QRS complex amplitude (LoQRS) in COVID-19. We retrospectively analyzed consecutive adults admitted to a telemetry service with SARS-CoV-2 (n=140) or influenza (n=281) infection with a final disposition – death or discharge. LoQRS was defined as a composite of QRS amplitude <5mm or <10 mm in the limb or precordial leads, respectively, or a ≥50% decrease in QRS amplitude on follow-up ECG during hospitalization. LoQRS was more prevalent in patients with COVID-19 than influenza (24.3% vs 11.7%, p=0.001), and in patients who died than survived with either COVID-19 (48.1% vs 10.2%, p<0.001) or influenza (38.9% vs 9.9%, p<0.001). LoQRS was independently associated with mortality in patients with COVID-19 when adjusted for baseline clinical variables (OR 11.5, 95%CI 3.9-33.8, p<0.001), presenting and peak troponin, D-dimer, C-reactive protein, albumin, intubation, and vasopressor requirement (OR 13.8, 95% CI 1.3-145.5, p=0.029). The median time to death in COVID-19 from the first ECG with LoQRS was 52 hours (IQR 18-130). Dynamic QRS amplitude diminution is a strong independent predictor of death over not only the course of COVID-19 infection, but also Influenza infection. In conclusion, this finding may serve as a pragmatic prognostication tool reflecting evolving clinical changes during hospitalization, over a potentially actionable time interval for clinical reassessment.
Prognostic utility of pulmonary artery and ascending aorta diameters derived from computed tomography in COVID-19 patients
Echocardiography, August 6, 2021
Chest computed tomography (CT) imaging plays a diagnostic and prognostic role in Coronavirus disease 2019 (COVID-19) patients. This study aimed to investigate and compare predictive capacity of main pulmonary artery diameter (MPA), ascending aorta diameter (AAo), and MPA-to-AAo ratio to determine in-hospital mortality in COVID-19 patients. This retrospective study included 255 hospitalized severe or critical COVID-19 patients. MPA was measured at the level of pulmonary artery bifurcation perpendicular to the direction of the vessel through transverse axial images and AAo was measured by using the same CT slice at its maximal diameter. MPA-to-AAo ratio was calculated by division of MPA to AAo. Multivariate logistic regression model yielded MPA ≥29.15 mm (OR: 4.95, 95% CI: 2.01–12.2, p = 0.001), MPA (OR: 1.28, 95% CI: 1.13–1.46, p < 0.001), AAo (OR: .90, 95% CI: .81–.99, p = 0.040), and MPA-to-AAo ratio ≥.82 (OR: 4.67, 95% CI: 1.86–11.7, p = 0.001) as independent predictors of in-hospital mortality. Time-dependent multivariate Cox-proportion regression model demonstrated MPA ≥29.15 mm (HR: 1.96, 95% CI: 1.03–3.90, p = 0.047) and MPA (HR: 1.08, 95% CI: 1.01–1.17, p = 0.048) as independent predictors of in-hospital mortality, whereas AAo and MPA-to-AAo ratio did not reach statistical significance. Pulmonary artery enlargement strongly predicts in-hospital mortality in hospitalized COVID-19 patients. MPA, which can be calculated easily from chest CT imaging, can be beneficial in the prognostication of these patients.
Prognostic implications of biventricular strain measurement in COVID-19 patients by speckle-tracking echocardiography
Clinical Cardiology, August 6 2021
Recent reports have indicated the beneficial role of strain measurement in COVID-19 patients. To determine the association between right and left global longitudinal strain (RVGLS, LVGLS) and COVID-19 patients’ outcomes. Hospitalized COVID-19 patients between June and August 2020 were included. Two-dimensional echocardiography and biventricular global longitudinal strain measurement were performed. The outcome measure was defined as mortality, ICU admission, and need for intubation. Appropriate statistical tests were used to compare different groups. In this study 207 patients (88 females) were enrolled. During 64 ± 4 days of follow-up, 22 (10.6%) patients died. Mortality, ICU admission, and intubation were significantly associated with LVGLS and RVGLS tertiles. LVGLS tertiles could predict poor outcome with significant odds ratios in the total population (OR = 0.203, 95% CI: 0.088–0.465; OR = 0.350, 95% CI: 0.210–0.585; OR = 0.354, 95% CI: 0.170–0.736 for mortality, ICU admission, and intubation). Although odds ratios of LVGLS for the prediction of outcome were statistically significant among hypertensive patients, these odds ratios did not reach significance among non-hypertensive patients. RVGLS tertiles revealed significant odds ratios for the prediction of mortality (OR = 0.322, 95% CI: 0.162–0.640), ICU admission (OR = 0.287, 95% CI: 0.166–0.495), and need for intubation (OR = 0.360, 95% CI: 0.174–0.744). Odds ratios of RVGLS remained significant even after adjusting for hypertension when considering mortality and ICU admission. RVGLS and LVGLS can be acceptable prognostic factors to predict mortality, ICU admission, and intubation in hospitalized COVID-19 patients. However, RVGLS seems more reliable, as it is not confounded by hypertension.
What lies behind the pandemic’s inequitable impact on Black men
American Medical Association, August 4, 2021
COVID-19’s profound impact on Black men has been well documented, but the virus’s deeply inequitable impact has not necessarily been well explained. The answer might be found in the pandemic’s convergence of chronic disease epidemics intersecting with social factors such as structural racism. The pandemic “has surfaced that minoritized communities, communities of color, or low-income communities, have all been disproportionately impacted by the virus,” said Christopher S. Holliday, PhD, MPH, the director of population health and clinical-community linkages at the AMA. “But then, when you parse those numbers out, Black men tend to—again—fall toward the bottom of those disparities.” Holliday co-wrote a commentary published in Public Health Reports that explores how COVID-19 combined with the concurring (or co-occurring) epidemics of heart disease, obesity , hypertension, diabetes and drug overdoses to create a “syndemic.” Syndemics are defined as “two or more epidemics interacting synergistically in ways that exacerbate health consequences because of their interaction.” In the commentary, “Using Syndemics and Intersectionality to Explain the Disproportionate COVID-19 Mortality Among Black Men,” Holliday and his colleagues from Vanderbilt, Georgetown and George Washington universities use syndemics to “identify how the clustering of structural forces precipitates clustering of disease in specific populations, moving beyond the assumption that these phenomena are separate or coincidental.”
Myocarditis Following COVID-19 Vaccination
Radiology, August 3, 2021
A healthy 15-year-old boy received his second vaccination dose and the following day he developed fever, myalgia, and intermittent tachycardia. At presentation to the hospital, his electrocardiogram showed ST-segment elevation in the left precordial leads. High-sensitive cardiac troponin and C-reactive protein levels were elevated. Serology tests for cardiotropic viruses were negative. Transthoracic echocardiography showed normal myocardial function without wall motion abnormalities. Cardiac MRI at 1.5 T showed a normal left ventricular size, normal left ventricular ejection fraction and a small pericardial effusion. T2-weighted short TI inversion recovery sequences displayed focal myocardial edema involving the lateral wall, most emphasized in the basal inferolateral segment. Corresponding subepicardial enhancement was detected by late gadolinium enhancement imaging indicating inflammatory necrosis. Cardiac MRI characteristics of vaccine-induced hypersensitivity myocarditis are similar to other virus-induced causes of myocarditis. This case shows that clinicians should be aware of vaccine-induced myocarditis as a possible adverse effect in children with thoracic/cardiovascular complaints after mRNA SARS-CoV-2-vaccination. As children are now scheduled to be vaccinated in many countries, cases of vaccine-induced myocarditis will have been noted in association with mRNA vaccines. Vaccine associated myocarditis is rare, but more common in the young population, especially in males (e.g. incidence of 40.6 cases per million second doses of mRNA SARS-CoV-2 vaccinations in males aged 12-29 years).
Cardiac magnetic resonance in recovering COVID-19 patients. Feature tracking and mapping analysis to detect persistent myocardial involvement
IJC Heart & Vasculature, August 3, 2021
Post-COVID-19 patients may incur myocardial involvement secondary to systemic inflammation. Our aim was to detect possible oedema/diffuse fibrosis using cardiac magnetic resonance imaging (CMR) mapping and to study myocardial deformation of the left ventricle (LV) using feature tracking (FT). Prospective analysis of consecutively recruited post-COVID-19 patients undergoing CMR. T1 and T2 mapping sequences were acquired and FT analysis was performed using 2D steady-state free precession cine sequences. Statistical significance was set to p<0.05. Included were 57 post-COVID-19 patients and 20 healthy controls, mean age 59±15 years, men 80.7%. The most frequent risk factors were hypertension (33.3%) and dyslipidaemia (36.8%). The contact-to-CMR interval was 81±27 days. LV ejection fraction (LVEF) was 61±10%. Late gadolinium enhancement (LGE) was evident in 26.3% of patients (19.3%, non-ischaemic). T2 mapping values (suggestive of oedema) were higher in the study patients than in the controls (50.9±4.3 ms vs 48±1.9 ms, p<0.01). No between-group differences were observed for native T1 nor for circumferential strain (CS) or radial strain (RS) values (18.6±3.3% vs 19.2±2.1% (p=0.52) and 32.3±8.1% vs 33.6±7.1% (p=0.9), respectively). A sub-group analysis for the contact-to-CMR interval (<8 weeks vs ≥8 weeks) showed that FT-CS (15.6±2.2% vs 18.9±2.6%, p<0.01) and FT-RS (24.9±5.8 vs 33.5±7.2%, p<0.01) values were lower for the shorter interval. Post-COVID-19 patients compared to heathy controls had raised T2 values (related to oedema), but similar native T1, FT-CS and FT-RS values. FT-CS and FT-RS values were lower in post-COVID-19 patients undergoing CMR after <8 weeks compared to ≥8 weeks.
Troponin elevation in COVID-19 patients: An important stratification biomarker with still some open questions
International Journal of Cardiology, August 2, 2021
[Editorial] The SARS-CoV-2 infection determines a disease predominantly affecting lungs. Its clinical spectrum is wide, including asymptomatic infection, mild upper respiratory tract illness and severe viral pneumonia leading to respiratory failure and death. However, heart and vessels can represent other targets of the virus. On this level, SARS-CoV-2 has been associated to many Cardiovascular (CV) disorders such as myocardial injury, acute coronary syndrome, pulmonary embolism, myocarditis and arrhythmias. Focusing on myocardial injury, which is defined as a sudden raise in troponin levels over the 99th percentile, its incidence as a COVID-19 related complication ranges from 7.2% to 36%. The article published in this issue of the International Journal of Cardiology by Maino et al. entitled “Prevalence and characteristics of myocardial injury during COVID-19 pandemic: a new role for high-sensitive troponin” provides new data about the link between SARS-CoV2 infection and the damage exerted over cardiomyocites. Designed as a retrospective single-centre study, in this work the authors analysed 189 patients from the emergency room of “Fondazione Policlinico Universitario A. Gemelli IRCCS” in Rome (Italy) with a COVID-19 diagnosis, in which high-sensitive troponin I levels were measured within the first 24 h from admission. Results confirmed a high prevalence of myocardial damage (16%), which is more common among COVID-19 patients reporting more frequently features of frailty (older age, greater burden of CV comorbidities) and presenting a prominent inflammatory state (higher biochemical levels of inflammation). Furthermore, the multivariate analysis confirmed troponin as one of the most significant determinants of disease severity: higher levels of this biomarker appeared to be in connection with higher prevalence of intensive care unit admission, increased need of endotracheal intubation and higher mortality rate, resulting in a worse intercourse of disease and a poorer outcome. From the present study and the previously published one, three questions arise.
Deceleration capacity is associated with acute respiratory distress syndrome in COVID-19
Heart & Lung, August 2, 2021
Acute respiratory distress syndrome (ARDS) is considered the main cause of COVID-19 associated morbidity and mortality. Early and reliable risk stratification is of crucial clinical importance in order to identify persons at risk for developing a severe course of disease. Deceleration capacity (DC) of heart rate as a marker of cardiac autonomic function predicts outcome in persons with myocardial infarction and heart failure. We hypothesized that reduced modulation of heart rate may be helpful in identifying persons with COVID-19 at risk for developing ARDS. We prospectively enrolled 60 consecutive COVID-19 positive persons presenting at the University Hospital of Tuebingen. Arterial blood gas analysis and 24h-Holter ECG recordings were performed and analyzed at admission. The primary end point was defined as development of ARDS with regards to the Berlin classification. 61.7% (37 of 60 persons) developed an ARDS. In persons with ARDS DC was significantly reduced when compared to persons with milder course of infection (3.2 ms vs. 6.6 ms, p < 0.001). DC achieved a good discrimination performance (AUC = 0.76) for ARDS in COVID-19 persons. In a multivariate analysis, decreased DC was associated with the development of ARDS. Our data suggest a promising role of DC to risk stratification in COVID-19.
The Effect of COVID-19 on Adult Cardiac Surgery in the United States in 717,103 Patients
The Annals of Thoracic Surgery, July 31, 2021
COVID-19 has changed the world as we know it, and the United States continues to accumulate the largest number of COVID-related deaths worldwide. There exists a paucity of data regarding the effect of COVID-19 on adult cardiac surgery trends and outcomes on regional and national levels. The STS Adult Cardiac Surgery Database was queried from January 1, 2018 to June 30, 2020. The Johns Hopkins COVID-19 database was queried from February 1, 2020 to January 1, 2021. Surgical and COVID-19 volumes, trends, and outcomes were analyzed on a national and regional level. Observed-to-expected ratios were used to analyze risk-adjustable mortality. 717,103 adult cardiac surgery patients and over 20 million COVID-19 patients were analyzed. Nationally, there was 52.7% reduction in adult cardiac surgery volume, and 65.5% reduction in elective cases. The Mid-Atlantic region was most affected by the first COVID-19 surge, with 69.7% reduction in overall case volume and 80.0% reduction in elective cases. In the Mid-Atlantic and New England regions, the observed-to-expected mortality for isolated coronary bypass increased as much as 1.48 times (148% increase) pre-COVID rates. After the first COVID-19 surge, nationwide cardiac surgical case volumes did not return to baseline, indicating a COVID-19-associated deficit of cardiac surgery patients. This is the largest analysis of COVID-19 related impact on adult cardiac surgery volume, trends, and outcomes. During the pandemic, cardiac surgery volume suffered dramatically, particularly in the Mid-Atlantic and New England regions during the first COVID-19 surge, with a concurrent increase in observed-to-expected 30-day mortality.
COVID-19 may have stirred a silent killer. Find out what to do.
American Medical Association, July 30, 2021
Your patients could have no signs, no symptoms. They might not feel different at all. Or they could get headaches or nosebleeds, but they might never connect the dots. In other words, hypertension is easy to miss. And if left unchecked, high blood pressure can increase your patients’ risk of life-threatening conditions, including heart disease and stroke. Which is why it has been so important during the COVID-19 pandemic for patients with high blood pressure to continue to work together with their primary care physicians—to keep it under control. Early in the pandemic, in addition to the health risks directly related to COVID-19, serious concerns surfaced about what the indirect impact from the COVID-19 pandemic might be due to the disruption of health care-related services. “What would be the toll of deferring treatment for acute cardiovascular conditions like chest pain, heart attacks, heart failure exacerbations and strokes?” said Michael Rakotz, MD, vice president of improving health outcomes at the AMA. The effects were, in fact, dramatic. How prepared were we to remotely manage conditions like high blood pressure without in-person visits? According to research published this year based on data from 2019 pre-pandemic, nearly 70% of health professionals recommended the use of self-measured blood pressure (SMBP) monitoring to their patients with hypertension. And, more than 60% of patients with hypertension reported measuring their blood pressure outside of the office. The problem is that only about 7% reported sharing their readings with their health professionals via the internet or email, which is an important strategy to improve hypertension control. Read more to see key steps physicians can take to overcome the challenges.
The Role of Statins in COVID-19, With a Focus on Patients With Cardiovascular Risk Factors
Cardiology Advisor, July 30, 2021
A recent study suggests that patients taking statin medications have a significantly lower risk for in-hospital death from COVID-19. The findings, published in PLOS ONE, demonstrated that the use of statins prior to admission was associated with a 41% reduction of in-hospital death and a greater than 25% reduction in risk of developing a severe outcome, after adjusting for age, sex, other medical conditions, insurance status, and hospital site. “We also found, in a propensity-matched analysis, that most of this benefit was seen in patients with a history of prior heart disease or high blood pressure. For patients without those underlying conditions, there was the suggestion of benefit (16% lower odds of death). However, the results were not statistically significant,” said the lead study author Lori Daniels, MD, professor and director of the cardiovascular intensive care unit at University of California San Diego Health, San Diego, California. Study findings revealed that outpatient use of statins (alone or with antihypertensive agents) was associated with a reduced risk for death (adjusted odds ratio [aOR,] 0.59; 95% CI, 0.50-0.69), after adjusting for demographic characteristics, insurance status, hospital site, and concurrent medications. The use of statins and/or antihypertensive agents was associated with a reduced risk for death among patients with a history of CVD and/or hypertension (aOR, 0.68; 95% CI, 0.58-0.81) in propensity-matched analyses.
Long-term effects of coronavirus disease 2019 on the cardiovascular system, CV COVID registry: A structured summary of a study protocol
PLOS ONE, July 29, 2021
Patients presenting with the coronavirus-2019 disease (COVID-19) may have a high risk of cardiovascular adverse events, including death from cardiovascular causes. The long-term cardiovascular outcomes of these patients are entirely unknown. We aim to perform a registry of patients who have undergone a diagnostic nasopharyngeal swab for SARS-CoV-2 and to determine their long-term cardiovascular outcomes. This is a multicenter, observational, retrospective registry to be conducted at 17 centers in Spain and Italy (ClinicalTrials.gov number: NCT04359927). Consecutive patients older than 18 years, who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 in the participating institutions, will be included since March 2020, to August 2020. Patients will be classified into two groups, according to the results of the RT-PCR: COVID-19 positive or negative. The primary outcome will be cardiovascular mortality at 1 year. The secondary outcomes will be acute myocardial infarction, stroke, heart failure hospitalization, pulmonary embolism, and serious cardiac arrhythmias, at 1 year. Outcomes will be compared between the two groups. Events will be adjudicated by an independent clinical event committee. The results of this registry will contribute to a better understanding of the long-term cardiovascular implications of the COVID19.
Cardiovascular Adverse Events Reported from COVID-19 Vaccines: A Study Based on WHO Database
International Journal of General Medicine, July 27, 2021
Thirteen COVID-19 vaccines are granted emergency approval. It is crucial to monitor their adverse events post vaccination. The present study focuses on cardiovascular adverse events post-COVID-19 vaccination and aims to determine adverse events with the administered vaccine. The cardiovascular (CVS) adverse events were extracted for three broad headings (SOCs) – cardiac disorders, vascular disorders, and investigations. Descriptive statistics were reported in the form of percentage and frequency, and the disproportionality analysis was conducted. For the cardiovascular system, 4863 adverse events (AEs) were reported from BNT162b2 Pfizer, 1222 AstraZeneca, Moderna, and other COVID-19 vaccines. Common adverse events observed with vaccines under study were tachycardia (16.41%), flushing (12.17%), hypertension (5.82%), hypotension (3.60%) and peripheral coldness (2.41%). Based on disproportionality analysis (IC025 values), acute myocardial infarction, cardiac arrest, and circulatory collapse were linked to the vaccines in the age group > 75 years. Hypertension, severe hypertension, supraventricular tachycardia, sinus tachycardia, and palpitations were associated across all age groups and either gender. Amongst the investigations, abnormal ECG findings raised C-reactive protein, elevated D dimer, and troponin were reported in specific age groups or gender or all subjects. Although cardiovascular events have been reported with the COVID-19 vaccines, the causality is yet to be established because such CVS AEs are also usually associated with the general public even without intervention. Hence, people should be administered these vaccines, and sustained monitoring of these AEs should be done.
Algorithm developed for managing suspected ACS in patients hospitalized with COVID-19
Helio | Cardiology Today, July 25, 2021
Diagnosis of ACS in concomitant COVID-19 infection can be made difficult due to an overlap of symptoms, fewer patients presenting to the hospital and a lack of guidance diagnosing hospitalized patients, a speaker reported. At the virtual American Society for Preventive Cardiology Congress on CVD Prevention, Amit Khera, MD, MSc, FACC, FAHA, FASPC, immediate past president of the ASPC and professor of medicine, director of preventive cardiology and the Dallas Heart Ball chair in hypertension and heart disease at UT Southwestern Medical Center, discussed the etiologies of ACS and COVID-19 infection and the importance of patient education. “At every one of my patient visits over last year, I always remind people that if you have a symptom, the hospital is safe. You must present. Hopefully, we are on the tail end of all this, but there are variants and other lessons learned that may come up in the future,” Khera said. “But communication to our patients is key. How do we avoid having this increase of ACS-related COVID-19? Vaccination. People know that quite well. We have all seen clinical trial data. This is real world data.” According to a study published in the American Journal of Preventive Cardiology, patients with atherosclerotic CVD who contract COVID-19 experienced greater relative risk for COVID-19 related ACS compared with individuals without ASCVD (RR = 5.9). Researchers reported even greater relative risk among patients with COVID-19 and familial hypercholesterolemia vs. those without FH (RR = 14.3). For patients with COVID-19 and suspected ACS, Khera said that point-of-care ultrasound may be able to rule other explanations such as myocarditis, congestive HF, pulmonary embolism, right ventricular dysfunction and stress cardiomyopathy. “Point-of-care ultrasound has been a godsend at our institution and many others in that we can get quick data, it avoids exposure,” Khera said.
Predictive Value of Neutrophil/Lymphocyte Ratio (NLR) on Cardiovascular Events in Patients with COVID-19
International Journal of General Medicine, July 24, 2021
The research on the association between coronavirus disease 2019 (COVID-19) and cardiovascular disease (CVD) is still insufficient. This study aimed to investigate the association between neutrophil/lymphocyte ratio (NLR) and risk of cardiovascular events in patients with COVID-19. Our study included 159 patients with COVID-19 who were measured for NLR value within the first 24 hours of admission. They were followed up for 6 months after discharge and then the relationship between levels of NLR and risk of cardiovascular events was assessed. In all included patients with COVID-19, NLR values in patients with cardiovascular events [16.28 (4.95– 45.18)] were significantly higher than patients without cardiovascular events [4.75 (2.60– 7.47)]. A multivariate logistic regression model revealed that elevated NLR value [increased per SD, 2.41 (1.43– 4.29), P< 0.001; increased 1 of NLR, 2.05 (1.33–4.01), P=0.010] was significantly and independently associated with increased risk of CVD history on admission after adjustment of related confounding factors. Cox regression analysis revealed that elevated NLR value had a significant association with increased risk of cardiovascular events [increased per SD, 2.36 (1.42– 4.36), P< 0.001; Increased 1 of NLR, 2.00 (1.30– 3.97), P=0.014] after adjustments of these same confounding factors. Furthermore, the ROC curve suggested that NLR value (AUC=0.803, 95% CI=0.731– 0.875, P< 0.001, sensitivity 81.2%, and specificity 82.6%) has a good predictive value for cardiovascular events during follow-up.
Epidemiological and Clinical Characteristics of Deceased COVID-19 Patients
International Journal of General Medicine, July 24, 2021
Fatalities due to COVID-19 continue to increase, and information on the epidemiological and clinical characteristics of deceased patients who were hospitalized with COVID-19 is limited in the Arab region. The current study aimed to address this gap. Three hundred and four Saudi patients in Jazan Region, Saudi Arabia, who died after being hospitalized with COVID-19, were analyzed in this retrospective cohort study. A greater proportion of male patients (59%), compared to female patients (41%), died due to COVID-19. Just over half (55%) of the deaths due to COVID-19 affected patients aged ≥ 65 years. More than two-thirds of the deceased COVID-19 patients had diabetes (70%) and hypertension (69%); other comorbidities were obesity (30%), heart disease (30%), and chronic kidney disease (14%). Dyspnea (91%), cough (80%), and fever (70%) were the most frequently reported clinical symptoms. Eighty-five per cent of COVID-19 deaths occurred in patients admitted to the intensive care unit (ICU), and 90% of the patients required mechanical ventilation. Typically, lymphopenia, and neutrophilia were observed on admission and 24 hours prior to death. Creatinine and serum ferritin levels and erythrocyte sedimentation rate and D-dimer plasma levels increased significantly following infection with COVID-19. Lung infiltrates and pulmonary opacity (83%) were the most common findings on chest X-ray. Respiratory failure (70%) and acute respiratory distress syndrome (52%) were the leading complications to death. Logistic and Cox regression revealed that a higher age, smoking, high creatinine and aspartate transaminase levels, and respiratory failure were significantly associated with the risk of mortality during the early stay in hospitals. The proportion of comorbidities was high in deceased patients who were hospitalized with COVID-19 in Jazan region, Saudi Arabia. A higher age, smoking, and respiratory failure were significant predictors of mortality during the early stay in hospitals.
Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial
The Lancet, July 21, 2021
COVID-19 can lead to multiorgan failure. Dapagliflozin, a SGLT2 inhibitor, has significant protective benefits for the heart and kidney. We aimed to see whether this agent might provide organ protection in patients with COVID-19 by affecting processes dysregulated during acute illness. DARE-19 was a randomised, double-blind, placebo-controlled trial of patients hospitalised with COVID-19 and with at least one cardiometabolic risk factor. Patients critically ill at screening were excluded. Patients were randomly assigned 1:1 to dapagliflozin (10 mg daily orally) or matched placebo for 30 days. Dual primary outcomes were assessed in the intention-to-treat population: the outcome of prevention (time to new or worsened organ dysfunction or death), and the hierarchial composite outcome of recovery (change in clinical status by day 30). Safety outcomes, in patients who received at least one study medication dose, included serious adverse events, adverse events leading to discontinuation, and adverse events of interest. Between April 22, 2020 and Jan 1, 2021, 1250 patients were randomly assigned with 625 in each group. The primary composite outcome of prevention showed organ dysfunction or death occurred in 70 patients (11·2%) in the dapagliflozin group, and 86 (13·8%) in the placebo group (hazard ratio [HR] 0·80, 95% CI 0·58–1·10; p=0·17). For the primary outcome of recovery, 547 patients (87·5%) in the dapagliflozin group and 532 (85·1%) in the placebo group showed clinical status improvement, although this was not statistically significant (win ratio 1·09, 95% CI 0·97–1·22; p=0·14). There were 41 deaths (6·6%) in the dapagliflozin group, and 54 (8·6%) in the placebo group (HR 0·77, 95% CI 0·52–1·16). Serious adverse events were reported in 65 (10·6%) of 613 patients treated with dapagliflozin and in 82 (13·3%) of 616 patients given the placebo. In patients with cardiometabolic risk factors who were hospitalised with COVID-19, treatment with dapagliflozin did not result in a statistically significant risk reduction in organ dysfunction or death, or improvement in clinical recovery, but was well tolerated.
Epicardial adipose tissue and severe Coronavirus Disease 19
Cardiovascular Diabetology, July 20, 2021
Both visceral adipose tissue and epicardial adipose tissue (EAT) have pro-inflammatory properties. The former is associated with COVID-19 severity. We aimed to investigate whether an association also exists for EAT. We retrospectively measured EAT volume using computed tomography (CT) scans (semi-automatic software) of inpatients with COVID-19 and analyzed the correlation between EAT volume and anthropometric characteristics and comorbidities. We then analyzed the clinicobiological and radiological parameters associated with severe COVID-19 (O2 ≥≥ 6 l/min), intensive care unit (ICU) admission or death, and 25% or more CT lung involvement, which are three key indicators of COVID-19 severity. We included 100 consecutive patients; 63% were men, mean age was 61.8 ± 16.2 years, 47% were obese, 54% had hypertension, 42% diabetes, and 17.2% a cardiovascular event history. Severe COVID-19 (n = 35, 35%) was associated with EAT volume (132 ± 62 vs 104 ± 40 cm3, p = 0.02), age, ferritinemia, and 25% or more CT lung involvement. ICU admission or death (n = 14, 14%) was associated with EAT volume (153 ± 67 vs 108 ± 45 cm3, p = 0.015), hypertension and 25% or more CT lung involvement. The association between EAT volume and severe COVID-19 remained after adjustment for sex, BMI, ferritinemia and lung involvement, but not after adjustment for age. Instead, the association between EAT volume and ICU admission or death remained after adjustment for all five of these parameters. Our results suggest that measuring EAT volume on chest CT scans at hospital admission in patients diagnosed with COVID-19 might help to assess the risk of disease aggravation.
Cardiac Abnormalities Depicted with MRI in COVID-19: Ongoing Concern for Myocardial Injury
Radiology, July 20, 2021
[Editorial, Review and Commentary] COVID-19 is a systemic disease induced by the SARS-CoV-2 virus affecting the endothelium of different vascular beds throughout the entire human body. The magnitude of pulmonary parenchymal and vascular involvement in large part defines overall prognosis and the probability of severe outcomes in COVID-19, including death. By extension, it also determines the need for hospitalization in the majority of patients admitted for standard and critical care. Yet, the extent of involvement of other organ systems in patients without potentially significant pulmonary disease remains largely unknown. Prior studies suggest that myocardial involvement is associated with unfavorable prognosis in patients with COVID-19, but clinically significant myocardial injury is currently believed to occur in a subgroup of patients with symptoms requiring hospitalization. However, recent MRI studies suggest the presence of cardiac sequelae not only in hospitalized patients with COVID-19 but also in outpatients, including elite athletes. Thus, the clinical significance of myocardial alterations identified in convalescing patients with COVID-19 remains incompletely understood. In the May 2021 issue of Radiology, Li et al, demonstrated myocardial extracellular volume expansion and reduced myocardial strain in a group of convalescing patients with COVID-19 hospitalized with severe or moderate pulmonary disease, compared with age- and sex-matched healthy control participants. In this prospective observational cohort study, the median extracellular volume was 31.4%, 29.7%, and 25.0% (P < .001) for comparisons of both patients with severe and moderate COVID-19 versus control participants. The corresponding mean global longitudinal strain values were less negative (representing reduced cardiac function) in both participants with severe and moderate COVID-19 compared with control participants (severe and moderate COVID-19 [both −12.5%] vs healthy control participants [−15.4%]; [P = .002 and P = .001, respectively]).
Cardiomyocytes Recruit Monocytes upon SARS-CoV-2 Infection by Secreting CCL2
Stem Cell Reports, July 20, 2021
Heart injury has been reported in up to 20% of COVID-19 patients, yet the cause of myocardial histopathology remains unknown. Here, using an established in vivo hamster model, we demonstrate that SARS-CoV-2 can be detected in cardiomyocytes of infected animals. Furthermore, we found damaged cardiomyocytes in hamsters and COVID-19 autopsy samples. To explore the mechanism, we show that both human pluripotent stem cell-derived cardiomyocytes (hPSC-derived CMs) and adult cardiomyocytes (CMs) can be productively infected by SARS-CoV-2, leading to secretion of the monocyte chemoattractant cytokine CCL2 and subsequent monocyte recruitment. Increased CCL2 expression and monocyte infiltration was also observed in the hearts of infected hamsters. Although infected CMs suffer damage, we find that the presence of macrophages significantly reduces SARS-CoV-2 infected CMs. Overall, our study provides direct evidence that SARS-CoV-2 infects CMs in vivo and suggests a mechanism of immune-cell infiltration and histopathology in heart tissues of COVID-19 patients.
Myocarditis Associated with mRNA COVID-19 Vaccination
Radiology, July 20, 2021
[Research Letter] In this retrospective, IRB approved HIPPA compliant study, cardiac MRI exams performed at our institution between 1/1/2021-5/25/2021 were reviewed for MRI findings of myocarditis/pericarditis. Subsequently, electronic health records were reviewed, and all patients who received COVID-19 vaccine preceding cardiac MRI were included (consecutive sample). Informed consent was waived per IRB protocol. Patients with a history of prior COVID were excluded. Cardiac MRI was performed at 1.5T/3T (GE Healthcare) and evaluated as recently described. Clinical radiology reports were reviewed by three cardiovascular radiologists (7-27 years of experience; initials blinded for review) in consensus. Demographic and clinical data including COVID-19 vaccination, 12-lead electrocardiogram (ECG), and serum markers of cardiac injury were documented. Five patients (4:1 male:female, age range 17-38 years) were identified who had abnormal MRI findings and were vaccinated against COVID-19 prior to MRI. Cardiac troponin and ECG were abnormal in all patients. All patients were hospitalized due to acute onset of chest pain with diagnosis of acute myocarditis. Patients 1-3 received their second dose of BNT162b2 vaccine two, three and two days, respectively, before onset of chest pain; Patients 4 and 5 both received their second dose of mRNA-1273 three days before onset of chest pain. In all patients, MRI showed myocarditis-like findings including non-ischemic pattern of late gadolinium enhancement, corresponding signal abnormalities on T2-weighted images, and pericardial enhancement. Diagnostic considerations included pulmonary embolus or acute coronary event with additional imaging-based testing (Table). Ipsilateral axillary lymphadenopathy to the vaccination site was identified in four patients. COVID-19 testing at the time of diagnosis (and history of prior COVID-19) were negative. No respiratory symptoms, prodrome or skin rash were present prior to vaccination. Further, medical history did not reveal any pre-existing cardiac disease in these patients.
Clinical characteristics and outcomes of patients with heart failure admitted to the intensive care unit with coronavirus disease 2019 (COVID-19): A multicenter cohort study
American Heart Journal Plus: Cardiology Research and Practice, July 19, 2021
Patients with underlying heart failure (HF) in the setting of COVID-19 who require admission to the intensive care unit (ICU) might present with a unique set of challenges. This study aims to extensively describe the characteristics and outcomes of patients with HF who were admitted to ICU with COVID-19. We conducted a multicenter retrospective analysis for all adult patients with HF and an objectively confirmed diagnosis of COVID-19 who were admitted to ICUs between March 1 and August 31, 2020, in Saudi Arabia. A total of 723 critically ill patients with COVID-19 were admitted into ICUs during the study period: 59 patients with HF and 664 patients with no HF before admission to ICU. Patients with HF had statistically significant more comorbidities, including diabetes mellitus, hypertension, dyslipidemia, atrial fibrillation, and acute coronary syndrome. Moreover, higher baseline severity scores (APACHE II & SOFA score) and nutritional risk (NUTRIC score) were observed in HF patients. Overall, patients with HF had more in-hospital and ICU deaths in comparison to patients without HF: (64.3% vs. 44.6%, P-value < 0.01) and (54.5% vs. 39%, P-value = 0.02), respectively. Patients with HF had a similar incidence of thrombosis, ICU length of stay, duration of mechanical ventilation, and hospital length of stay compared to patients with no HF.
Atrial fibrillation in patients with SARS-CoV-2 infection
Medicina Clínica, July 19, 2021
The SARS-CoV-2 infection ranges from asymptomatic to critical forms and several prognostic factors have been described. Atrial fibrillation (AF) is common in acute situations where it is linked with more complications and mortality. We aimed to evaluate the prognostic information of AF in this population. This was a retrospective analysis of a cohort of 517 patients consecutively admitted in a tertiary hospital due to SARS-CoV-2 infection. We divided the patients in two groups according the development of AF and compared the main features of both groups. An univariable and multivariable analysis of mortality were also performed. Among 517 patients with SARS-CoV-2 infection admitted in a tertiary center, 54 (10.4%) developed AF. These patients are older (81.6 vs 66.5 years old, p < 0.001) and present more hypertension (74% vs 47%, p < 0.001), cardiomyopathy (9% vs 1%, p = 0.002), previous heart failure admission (9% vs 0.4%, p < 0.001), previous episodes of AF (83% vs 1%, p < 0.001) and bigger left atrium (47.8 vs 39.9 mm, p < 0.001). AF COVID-19 patients present more acute respiratory failure (72% vs 40%, p < 0.001) and higher in-hospital mortality (50% vs 22%, p < 0.001). Predictors of AF development are age and previous AF. AF is not an independent predictor of in-hospital mortality. Predictors are age, creatinine > 1.5 mg/dL at admission, LDH > 250 UI/L at admission and acute respiratory failure. According to the results, AF appears in 10% of hospitalized patients with SARS-CoV-2 infection. These patients present more comorbidities and two-fold increase in hospital mortality. Atrial fibrillation is not an independent prognostic factor.
Statin Use Linked to Reduced Death Risk in Hospitalized COVID-19 Patients
Cardiology Advisor, July 19, 2021
Statin use appears to reduce the risk of severe COVID-19 disease or death among hospitalized patients, particularly in those with a history of cardiovascular disease and/or hypertension, according to research published in The Public Library of Science (PLOS) ONE. To evaluate the relationship between the use of statins and COVID-19 outcomes, study authors analyzed data from 10,541 hospitalized patients with active COVID-19 disease who were enrolled in the American Heart Association’s COVID-19 Cardiovascular Disease (CVD) Registry from January 2020 to September 2020. Prior to admission, 42% (n=4449) of patients used statins, with 7% of patients using statins alone and 35% using statins plus antihypertensives. “Because the use of statins and [antihypertensives] is strongly linked to the underlying high-risk conditions for which they are prescribed, we used propensity score matching techniques to investigate the use of these medications, separately for patients with and without a history of CVD and/or hypertension,” the study authors reported. They used logistic regression to adjust for demographic characteristics, insurance status, hospital site, and concurrent medications. The primary outcome of the study was in-hospital all-cause death or discharge to hospice care.
Admission Rates During a Second COVID-19 Lockdown
American Heart Journal, July 15, 2021
Societal lockdowns during the first wave of the COVID-19 pandemic were associated with decreased admission rates for acute cardiovascular conditions worldwide. In this nationwide Danish study of the first five weeks of a second pandemic lockdown, incidence of new-onset heart failure and atrial fibrillation remained stable, but there was a significant drop in new-onset ischemic heart disease and ischemic stroke during the fourth week of lockdown, which normalized promptly. The observed drops were lower compared to the first Danish lockdown in March 2020; thus, our data suggest that declines in acute CVD admission rates during future lockdowns are avoidable.
Effects of Renin-Angiotensin-Aldosterone Inhibitors on Early Outcomes of Hypertensive COVID-19 Patients: A Randomized Triple-Blind Clinical Trial
American Journal of Hypertension, July 15, 2021
The role of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) has been addressed in some studies related to the current coronavirus disease-2019 (COVID-19) pandemic with possible higher severity and mortality in patients with hypertension. A triple-blind randomized controlled trial was designed to evaluate the effects of these medications on the COVID-19 progression. Patients were enrolled in this trial between April and September 2020. They were randomized in two groups. The former dosage of ACEis/ARBs was continued in one group while in another group, the ACEis/ARBs were replaced by amlodipine ± carvedilol according to the dose equivalents. The primary outcomes were length of stay in hospitals and intensive care units. Other outcomes include mechanical ventilation, non-invasive ventilation, readmission, and COVID-19 symptoms after discharge. We randomized 64 patients with COVID-19 into two groups. Most patients were aged 66-80 and 46-65 years-old, 33 (51.6%) and 27 (42.2%), respectively. The study groups were nearly similar in baseline vital signs and characteristics. In addition, there was no significant difference in terms of recorded systolic and diastolic blood pressure measurements between groups. Furthermore, we did not find a significant difference between the days of intensive care unit or ward admission, the discharge rate, or readmission rates between the two groups.
More than 1 in 3 cardiology professionals reported burnout during COVID-19 pandemic
Cardiology Today, July 15, 2021
The COVID-19 pandemic has increased burnout among CV professionals, with many surveyed citing their basic, emotional and safety needs were not well supported by health care organizations, which, for some, led to a desire to change careers. The prevalence of burnout among all CV professionals nearly doubled after the start of the COVID-19 pandemic, from 20% in 2019 to 38% during the pandemic, according to data from the American College of Cardiology 2020 Well Being Study, a survey sent to ACC members in fall 2020. Looking closer at the overall respondents, among U.S. cardiologists, peak COVID-19 burnout rates increased to 40% from a pre-pandemic rate of 27% and among international cardiologists, burnout doubled to 21% from a pre-pandemic rate of 10%. Burnout rates rose to 43%, from 21% in 2019, among U.S. fellows in training. The largest increase was reported by U.S. CV team members — a 139% increase, from 23% in 2019 to 55% during the pandemic. “The issue of burnout has been simmering for years and was brought to a boil by mounting changes in the health care system — most predominantly, the widespread institution of electronic health records and performance metrics,” Cardiology Today Editorial Board Member Laxmi Mehta, MD, noninvasive cardiologist, Sarah Ross Soter Endowed Chair in Women’s Cardiovascular Health and professor of medicine in the division of cardiovascular medicine at The Ohio State University, said during a presentation. “COVID-19 has had a devastating health, social and economic effect worldwide. The impact of COVID-19 on the well-being of CV professionals has not been reported. The potential long-term psychological effects are real and concerning.” These new results come on the heels of 2019 survey data from the ACC, which found that the prevalence of burnout in cardiology increased by 32% since 2015, especially among women and mid-career cardiologists, despite efforts to alleviate job-related pressures. The increase in the prevalence of burnout was 90% from 2019 to 2020.
Cardiac Pathology in COVID-19: A Single Center Autopsy Experience
Cardiovascular Pathology, July 14, 2021
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is commonly associated with myocardial injury and heart failure. The pathophysiology behind this phenomenon remains unclear, with many diverse and multifaceted hypotheses. To contribute to this understanding, we describe the underlying cardiac findings in fifty patients who died with coronavirus disease 2019 (COVID-19). Included were autopsies performed on patients with a positive SARS-CoV-2 reverse-transcriptase-polymerase-chain reaction test from the index hospitalization. In the case of out-of-hospital death, patients were included if post-mortem testing was positive. Complete autopsies were performed according to a COVID-19 safety protocol, and all patients underwent both macroscopic and microscopic examination. If available, laboratory findings and echocardiograms were reported. The median age of the decedents was 63.5 years. The most common comorbidities included hypertension (90.0%), diabetes (56.0%) and obesity (50.0%). Lymphocytic inflammatory infiltrates in the heart were present in eight (16.0%) patients, with focal myocarditis present in two (4.0%) patients. Acute myocardial ischemia was observed in eight (16.0%) patients. The most common findings were myocardial fibrosis (80.0%), hypertrophy (72.0%), and microthrombi (66.0%). The most common causes of death were COVID-19 pneumonia in 18 (36.0%), COVID-19 pneumonia with bacterial superinfection in 12 (24.0%), and COVID-19 pneumonia with pulmonary embolism in 10 (20.0%) patients.
Post congress highlights in acute cardiovascular care: a report from the ACC scientific sessions 2021
European Heart Journal. Acute Cardiovascular Care, July 13, 2021
Two studies evaluated novel therapeutic interventions in the setting of hospitalized COVID-19. These studies established the feasibility of performing randomized controlled trials even in the midst of a pandemic. The DARE-19 trial included 1250 patients with cardiometabolic risk factors hospitalized with active COVID-19 infection and oxygen saturation ≥94% while receiving ≤5 L/min of oxygen. Patients were randomized in a 1:1 ratio to receive dapagliflozin 10 mg/day or matching placebo. Although not statistically significant, time to organ failure or death was numerically lower with dapagliflozin (86 vs. 70 events) and the drug was well tolerated with similar rates of discharge and length of stay. Finally, the ACTION trial enrolled 615 hospitalized COVID-19 patients with elevated D-dimer levels. Stable patients were randomized to rivaroxaban 20 mg daily or standard of care, while unstable patients were randomized to enoxaparin 1 mg/kg twice daily versus standard of care. The test strategy did not improve the primary composite endpoint (hierarchical analysis of mortality, duration of hospitalization and duration of oxygen therapy through 30 days) and was associated with increased risk of International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant non-major bleeding [8.4 vs. 2.3%, relative risk 3.64 (1.61–8.27)].
The prognostic value of myocardial injury in COVID-19 patients and associated characteristics
Immunity, Inflammation and Disease, July 9, 2021
Since December 2019, coronavirus disease 2019 (COVID-19) has emerged as an international pandemic. COVID-19 patients with myocardial injury might need special attention. However, an understanding on this aspect remains unclear. This study aimed to illustrate clinical characteristics and the prognostic value of myocardial injury to COVID-19 patients. This retrospective, single-center study finally included 304 hospitalized COVID-19 cases confirmed by real-time reverse-transcriptase polymerase chain reaction from January 11 to March 25, 2020. Myocardial injury was determined by serum high-sensitivity troponin I (Hs-TnI). The primary endpoint was COVID-19-associated mortality. Of 304 COVID-19 patients (median age, 65 years; 52.6% males), 88 patients (27.3%) died (61 patients with myocardial injury, 27 patients without myocardial injury on admission). COVID-19 patients with myocardial injury had more comorbidities (hypertension, chronic obstructive pulmonary disease, cardiovascular disease, and cerebrovascular disease); lower lymphocyte counts, higher C-reactive protein (CRP; median, 84.9 vs. 28.5 mg/L; p < .001), procalcitonin levels (median, 0.29 vs. 0.06 ng/ml; p < .001), inflammatory and immune response markers; more frequent need for noninvasive ventilation, invasive mechanical ventilation; and was associated with higher mortality incidence (hazard ratio [HR] = 7.02; 95% confidence interval [CI], 4.45–11.08; p < .001) than those without myocardial injury. Myocardial injury (HR = 4.55; 95% CI, 2.49–8.31; p < .001), senior age, CRP levels, and novel coronavirus pneumonia types on admission were independent predictors to mortality in COVID-19 patients. COVID-19 patients with myocardial injury on admission is associated with more severe clinical presentation and biomarkers. Myocardial injury and higher Hs-TnI are both strongest independent predictors to COVID-19-related mortality after adjusting confounding factors.
9 ways to reduce inequity in hypertension treatment and control
American Medical Association, July 2, 2021
COVID-19 did not create disparities in hypertension management and control, but it did exacerbate preexisting inequities, especially among people without health insurance and difficulty accessing care. Steps have been identified that can be taken to promote a more equitable health system and better BP control. That was a conclusion drawn by a diverse expert panel of clinicians and researchers that convened virtually during the 4th Annual University of Utah Translational Hypertension Symposium to discuss environmental and socioeconomic factors contributing to disparities. Their discussion was summarized in an open-access report, “Inequities in Hypertension Control in the United States Exposed and Exacerbated by COVID‐19 and the Role of Home Blood Pressure and Virtual Health Care During and After the COVID‐19 Pandemic” published in the Journal of the American Heart Association. “COVID-19 has also reminded us that when we design interventions, it is important to consider health equity from the beginning rather than as an afterthought,” lead author Adam Bress, Pharm.D., University of Utah School of Medicine associate professor of population health science, said in a news release. “Too often, individuals are blamed for their health care conditions, without considering the multiple levels of social factors and context that contribute to persistent and pervasive health inequities,” added Bress, who is also an investigator at the VA Salt Lake City Health Care System.
Absence of Both Right and Left Main Coronary in a COVID Survivor
Diagnostics, July 1, 2021
The prevalence of isolated right coronary artery (RCA) absence ranges from 0.014% to 0.066% in the general population, but its combination with an absent left main (dual ostium left anterior descending [LAD] and super-dominant left circumflex [LCx]) has not been previously described. We report the case of a rare coronary artery anomaly: an absent RCA with LAD and LCx coronary arteries arising separately from the left coronary sinus. A 53-year-old male with recent COVID-19 infection was referred to our service for coronary computed tomography angiography (CCTA) due to the recent onset of atypical chest pain. The RCA was absent, with no vessel leaving the right or non-coronary sinus. The LAD and LCx emerged from the left coronary sinus, with a “double-barrel” appearance. The LAD was unremarkable, with small, non-stenosed calcified plaque. The LCx had a 3 mm diameter, arching downward in the left atrioventricular groove, passing through the crux cordis, continuing into the right atrioventricular groove, and ending as a left acute artery and sinonodal artery. No significant stenosis was found on any of the vessels, ruling out atherosclerotic coronary disease.
Patients With Acute Myocarditis Following mRNA COVID-19 Vaccination
JAMA Cardiology, June 29, 2021
Vaccine-associated myocarditis is an unusual entity that has been described for the smallpox vaccine, but only anecdotal case reports have been described for other vaccines. Whether COVID-19 vaccination may be linked to the occurrence of myocarditis is unknown. Our objective was to describe a group of 7 patients with acute myocarditis over 3 months, 4 of whom had recent messenger RNA (mRNA) COVID-19 vaccination. All patients referred for cardiovascular magnetic resonance imaging at Duke University Medical Center were asked to participate in a prospective outcomes registry. Two searches of the registry database were performed: first, to identify patients with acute myocarditis for the 3-month period between February 1 and April 30 for 2017 through 2021, and second, to identify all patients with possible vaccine-associated myocarditis for the past 20 years. Once patients with possible vaccine-associated myocarditis were identified, data available in the registry were supplemented by additional data collection from the electronic health record and a telephone interview. In the 3-month period between February 1 and April 30, 2021, 7 patients with acute myocarditis were identified, of which 4 occurred within 5 days of COVID-19 vaccination. Three were younger male individuals (age, 23-36 years) and 1 was a 70-year-old female individual. All 4 had received the second dose of an mRNA vaccine (2 received mRNA-1273 [Moderna], and 2 received BNT162b2 [Pfizer]). All presented with severe chest pain, had biomarker evidence of myocardial injury, and were hospitalized. Coincident testing for COVID-19 and respiratory viruses provided no alternative explanation. Cardiac magnetic resonance imaging findings were typical for myocarditis, including regional dysfunction, late gadolinium enhancement, and elevated native T1 and T2.
Portable single-lead electrocardiogram device is accurate for QTc evaluation in hospitalized patients
Heart Rhythm O2, June 28, 2021
The objective of the study was to assess the impact of diabetes, hypertension and cardiovascular diseases on inpatient mortality from COVID-19, and its relationship to ethnicity and social deprivation. This retrospective, single-centre observational study in Birmingham, UK, consisted of 907 hospitalised patients with laboratory-confirmed COVID-19 from a multi-ethnic community, admitted between 1 March 2020 and 31 May 2020. The primary analysis was an evaluation of cardiovascular conditions and diabetes in relation to ethnicity and social deprivation, with the end-point of inpatient death or death within 30 days of discharge. A multivariable logistic regression model was used to calculate HRs while adjusting for confounders. 361 of 907 (39.8%) died in hospital or within 30 days of discharge. The presence of diabetes and hypertension together appears to confer the greatest mortality risk (OR 2.75; 95% CI 1.80 to 4.21; p < 0.001) compared with either condition alone. Age > 65 years (OR 3.32; 95% CI 2.15 to 5.11), male sex (OR 2.04; 95% CI 1.47 to 2.82), hypertension (OR 1.69; 95% CI 1.10 to 2.61) and cerebrovascular disease (OR 1.87; 95% CI 1.31 to 2.68) were independently associated with increased risk of death. The mortality risk did not differ between the quintiles of deprivation. High-sensitivity troponin I was the best predictor of mortality among biomarkers (OR 4.43; 95% CI 3.10 to 7.10). Angiotensin-receptor blockers (OR 0.57; 95% CI 0.33 to 0.96) and ACE inhibitors (OR 0.65; 95% CI 0.43 to 0.97) were not associated with adverse outcome. The Charlson Index of Comorbidity scores were significantly higher in non-survivors. The combined prevalence of hypertension and diabetes appears to confer the greatest risk, where diabetes may have a modulating effect. Hypertension and cerebrovascular disease had a significant impact on inpatient mortality.
Hypertension is the major predictor of poor outcomes among inpatients with COVID-19 infection in the UK: a retrospective cohort study
BMJ Open, June 26, 2021
The objective of the study was to assess the impact of diabetes, hypertension and cardiovascular diseases on inpatient mortality from COVID-19, and its relationship to ethnicity and social deprivation. This retrospective, single-centre observational study in Birmingham, UK, consisted of 907 hospitalised patients with laboratory-confirmed COVID-19 from a multi-ethnic community, admitted between 1 March 2020 and 31 May 2020. The primary analysis was an evaluation of cardiovascular conditions and diabetes in relation to ethnicity and social deprivation, with the end-point of inpatient death or death within 30 days of discharge. A multivariable logistic regression model was used to calculate HRs while adjusting for confounders. 361 of 907 (39.8%) died in hospital or within 30 days of discharge. The presence of diabetes and hypertension together appears to confer the greatest mortality risk (OR 2.75; 95% CI 1.80 to 4.21; p < 0.001) compared with either condition alone. Age > 65 years (OR 3.32; 95% CI 2.15 to 5.11), male sex (OR 2.04; 95% CI 1.47 to 2.82), hypertension (OR 1.69; 95% CI 1.10 to 2.61) and cerebrovascular disease (OR 1.87; 95% CI 1.31 to 2.68) were independently associated with increased risk of death. The mortality risk did not differ between the quintiles of deprivation. High-sensitivity troponin I was the best predictor of mortality among biomarkers (OR 4.43; 95% CI 3.10 to 7.10). Angiotensin-receptor blockers (OR 0.57; 95% CI 0.33 to 0.96) and ACE inhibitors (OR 0.65; 95% CI 0.43 to 0.97) were not associated with adverse outcome. The Charlson Index of Comorbidity scores were significantly higher in non-survivors. The combined prevalence of hypertension and diabetes appears to confer the greatest risk, where diabetes may have a modulating effect. Hypertension and cerebrovascular disease had a significant impact on inpatient mortality.
Pulmonary adverse drug event data in hypertension with implications on COVID-19 morbidity
Scientific Reports, June 25, 2021
Hypertension is a recognized comorbidity for COVID-19. The association of antihypertensive medications with outcomes in patients with hypertension is not fully described. However, angiotensin-converting enzyme 2 (ACE2), responsible for host entry of the novel coronavirus (SARS-CoV-2) leading to COVID-19, is postulated to be upregulated in patients taking angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). Here, we evaluated the occurrence of pulmonary adverse drug events (ADEs) in patients with hypertension receiving ACEIs/ARBs to determine if disparities exist between individual drugs within the respective classes using data from the FDA Spontaneous Reporting Systems. For this purpose, we proposed the proportional reporting ratio to provide a statistical summary for the commonality of an ADE for a specific drug as compared to the entire database for drugs in the same or other classes. In addition, a statistical procedure, multiple logistic regression analysis, was employed to correct hidden confounders when causative covariates are underreported or untrusted to correct analyses of drug-ADE combinations. To date, analyses have been focused on drug classes rather than individual drugs which may have different ADE profiles depending on the underlying diseases present. A retrospective analysis of thirteen pulmonary ADEs showed significant differences associated with quinapril and trandolapril, compared to other ACEIs and ARBs. Specifically, quinapril and trandolapril were found to have a statistically significantly higher incidence of pulmonary ADEs compared with other ACEIs as well as ARBs (P < 0.0001) for group comparison (i.e., ACEIs vs. ARBs vs. quinapril vs. trandolapril) and (P ≤ 0.0007) for pairwise comparison (i.e., ACEIs vs. quinapril, ACEIs vs. trandolapril, ARBs vs. quinapril, or ARBs vs. trandolapril). This study suggests that specific members of the ACEI antihypertensive class (quinapril and trandolapril) have a significantly higher cluster of pulmonary ADEs.
Investigating the implications of COVID-19 outbreak on systems of care and outcomes of STEMI patients: A systematic review and meta-analysis
Indian Heart Journal, June 25, 2021
There has been a concern whether the decrease in ST-segment elevation myocardial infarction (STEMI) cases during the COVID-19 pandemic era is related to unsatisfactory performance of STEMI systems of care as well as worsening of the clinical outcomes in STEMI patients. Thus, our meta-analysis was conducted to evaluate this matter. We compared the predetermined variables in this meta-analysis during the early and late pandemic. Using a combination of adapted search terms to fit the requirements of several search engines (PubMed, EuropePMC, SCOPUS, ProQuest, and EBSCOhost), we reviewed all observational studies citing our outcomes of interest before and during the outbreak. Thirty-five records comprising a total of 62,244 participants were identified. Overall, our meta-analysis showed that there was a huge reduction of nearly 80% for STEMI admission during the outbreak (n=10,263) in contrast to before the outbreak period (n=51,984). STEMI patients who were admitted during the outbreak received less primary PCI and had longer symptom-to-FMC (first medical contact) time along with prolonged door-to-balloon time. A decrease in the achievement of final TIMI 3 flow after primary PCI was also observed in this study. However, the number of in-hospital mortality was similar between two groups.
FDA Authorizes IL-6 Inhibitor for Severe COVID-19 Patients
MedPage Today, June 25, 2021
Tocilizumab (Actemra), an interleukin-6 (IL-6) inhibitor, was authorized to treat certain hospitalized COVID-19 patients, the FDA announced late on Thursday. The drug received emergency use authorization (EUA) for hospitalized patients ages 2 and up who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). It is not authorized for outpatients, the agency said. “Providing additional therapies for those who do become hospitalized is an important step in combating this pandemic,” said Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research, in a statement. Tocilizumab is an IL-6 inhibitor given by intravenous infusion, which is approved to treat inflammatory diseases such as rheumatoid arthritis, and is used in certain hematologic cancers to quell cytokine release syndrome following CAR T-cell therapy. Results of early trials in COVID-19 patients were mixed, but the FDA pointed to the results of four randomized trials, two of which showed either a mortality benefit or an improvement in composite clinical outcomes. Chief among them was the UK’s pragmatic RECOVERY trial, which found a significantly lower risk of death by day 28 compared to usual care (31% vs 35%, respectively) among patients with COVID-19 pneumonia treated with tocilizumab. The tocilizumab group also had a shorter hospital stay (19 vs 28 days). The agency also noted results of the EMPACTA trial, where a significantly lower proportion of COVID-19 patients treated with tocilizumab progressed to mechanical ventilation or died by day 28 versus those receiving only usual care (12% vs 19%).
FDA to Add Warning on Rare Myocarditis Risk After COVID Vaccination
MedPage Today, June 23, 2021
Given the reported cases of myocarditis in young people who received mRNA COVID-19 vaccines, FDA will include a warning statement about the risks and characteristics of this rare condition, an agency representative said at CDC’s Advisory Committee on Immunization Practices (ACIP) meeting on Wednesday. Data presented by CDC staff estimated a rate of 12.6 cases per million within 3 weeks of a second dose of either Pfizer’s or Moderna’s mRNA vaccine for individuals ages 12 to 39. Rates were highest among boys and younger men. The side effect was rare, but when it occurred, it was typically within a week of vaccination. FDA liaison representative, Doran Fink, MD, PhD, noted the agency will add a warning about the risk of myocarditis or pericarditis following vaccination that states “these events have occurred in some recipients following dose 2, onset of symptoms was several days to a week” and based on limited follow-up, “most cases had a resolution of symptoms.” The warning would also advise anyone experiencing these symptoms to “seek medical attention” and state that information on long-term sequelae with the condition is limited. CDC staff said they would update their vaccine fact sheets with more comprehensive information in the coming days. While there was no vote scheduled during the ACIP meeting, the committee seemed to agree with CDC staff that the benefits of COVID-19 vaccination continue to outweigh the risks of vaccination in people ages 12 and older.
Researchers find losartan is not effective in reducing hospitalization from mild COVID-19
Science Daily, June 18, 2021
University of Minnesota Medical School researchers determined that the common blood pressure medication, losartan, is not effective in reducing hospitalization for mildly-ill COVID-19 outpatients. In the multicenter, randomized, double-blinded clinical trial, non-hospitalized patients recently diagnosed with COVID-19 were given either losartan or a placebo and monitored for 15 days. The study’s results, which were published in EClinicalMedicine, showed that although losartan does not reduce the likelihood of hospitalization, the medication does not appear to worsen symptoms of COVID-19 or have any significant or harmful side effects on patients with mild COVID-19. “Based on our results, there is no benefit to starting losartan for newly diagnosed outpatients with COVID-19, but those who are already taking the medication for pre-existing health conditions should feel safe continuing it,” said Michael Puskarich, MD, an associate professor in the Department of Emergency Medicine at the U of M Medical School and co-principal investigator of this study. He is also an emergency physician at Hennepin Healthcare. “Given SARS-CoV-2 binding with ACE2 there has been significant research interest into the utility of ACE and AT1R blocking agents to combat COVID-19. This study provides insight that for patients with mild COVID-19, who do not require hospital admission, that there is no benefit or harm from such agents,” said co-principal investigator Christopher Tignanelli, MD, MS, an assistant professor in the Department of Surgery at the U of M Medical School and critical care surgeon with M Health Fairview.
Decline in CV testing at start of pandemic varied by region
Healio | Cardiology Today, June 17, 2021
At the beginning of the COVID-19 pandemic, diagnostic CV volumes declined, but the drops varied by U.S. region, according to data from the INCAPS-COVID registry. “Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for CVD morbidity and mortality,” Cole B. Hirschfeld, MD, internal medicine resident at Columbia University Irving Medical Center and NewYork-Presbyterian Hospital, and colleagues wrote in JACC: Cardiovascular Imaging. “We compared laboratory characteristics, practices and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States.” The researchers analyzed 1.3 million imaging studies from the INCAPS-COVID registry of 909 centers in 108 countries, including 155 centers in 40 U.S. states. They compared data from April 2020, at the start of the COVID-19 pandemic, with data from March 2019. Diagnostic CV procedures fell in April 2020 across the globe, at rates similar in and outside of the U.S. (U.S., 68%; non-U.S., 63%; P = .237), according to the researchers. However, they found, invasive coronary angiography procedures declined more sharply in the U.S. compared with elsewhere (69% vs. 53%; P < .001). U.S. centers were more likely than non-U.S. centers to report increased use of telehealth (90% vs. 65%; P < .001), of temperature checks for on-site patients (87% vs. 77%; P = .008), of symptom screening (97% vs. 86%; P < .001) and of COVID-19 testing (46% vs. 26%; P < .001). In the U.S., reduction in diagnostic CV procedure volume varied by region, with the decline higher in the Northeast (76%) and Midwest (74%) than in the South (62%) and the West (44%), according to the researchers.
Cardiovascular biomarkers in COVID-19
European Heart Journal: Acute Cardiovascular Care, June 14, 2021
Although primarily a respiratory infectious disease that may be complicated with acute respiratory distress syndrome (ARDS), cardiovascular involvement is common in COVID-19. Cardiovascular complications are commonly observed in hospitalized patients with COVID-19, and individuals with pre-existing cardiovascular disease are disproportionately affected. Accordingly, cardiovascular biomarkers, including markers of myocardial injury (cardiac troponins), haemodynamic stress (B-type natriuretic peptides), and fibrin degradation products (D-dimer), are commonly elevated in proportion to disease severity in COVID-19. The frequency of myocardial injury is particularly high in critically ill patients with ARDS, those requiring mechanical ventilation and in non-survivors. Notably, the range of myocardial injury in COVID-19 is wide, and most patients demonstrate lower levels than commonly observed in acute myocardial infarction. A variety of mechanisms may contribute to myocardial injury in COVID-19. In addition to pre-existing chronic myocardial injury, these include direct viral injury to the myocardium, i.e. viral myocarditis, and acute myocardial infarction. However, these complications are considered to be relatively rare in COVID-19. COVID-19 may also be associated with a pronounced pro-inflammatory state reflected in increased levels of C-reactive protein and IL6, sometimes alluded to as a cytokine storm, which may also cause myocardial injury reflected in rise in cardiac troponin levels. Biomarkers that provide information from different pathophysiological axes, such as growth differentiation factor 15 (GDF-15), may provide particularly strong prognostic information. COVID-19 is also associated with a prothrombotic state. As a result, platelet and clotting factor consumption is reflected in a lower platelet count and increased D-dimer. Direct viral effects in the bone marrow and interactions with platelets, may also contribute to thrombocytopenia.
COVID-19 related cardiac complications – from clinical evidences to basic mechanisms. Opinion paper of the ESC Working Group on Cellular Biology of the Heart
Cardiovascular Research, June 12, 2021
The pandemic of Coronavirus disease (COVID)-19 is a global threat, causing high mortality, especially in the elderly. The main symptoms and the primary cause of death are related to interstitial pneumonia. Viral entry also into myocardial cells mainly via the angiotensin converting enzyme type 2 (ACE2) receptor and excessive production of pro-inflammatory cytokines, however, also make the heart susceptible to injury. In addition to the immediate damage caused by the acute inflammatory response, the heart may also suffer from long-term consequences of COVID-19, potentially causing a post-pandemic increase in cardiac complications. Although the main cause of cardiac damage in COVID-19 remains coagulopathy with micro- (and to a lesser extent macro-) vascular occlusion, open questions remain about other possible modalities of cardiac dysfunction, such as direct infection of myocardial cells, effects of cytokines storm, and mechanisms related to enhanced coagulopathy. In this opinion paper, we focus on these lesser appreciated possibilities and propose experimental approaches that could provide a more comprehensive understanding of the cellular and molecular bases of cardiac injury in COVID-19 patients. We first discuss approaches to characterize cardiac damage caused by possible direct viral infection of cardiac cells, followed by formulating hypotheses on how to reproduce and investigate the hyperinflammatory and pro-thrombotic conditions observed in the heart of COVID-19 patients using experimental in vitro systems. Finally, we elaborate on strategies to discover novel pathology biomarkers using omics platforms.
FDA Approves Third COVID-19 Antibody Treatment for Emergency Use
Pulmonology Advisor, June 11, 2021
[Press Release] A third antibody treatment designed to keep high-risk COVID-19 patients from being hospitalized was approved for emergency use by the U.S. Food and Drug Administration on Wednesday. Importantly, in lab tests, the newly authorized drug, dubbed sotrovimab, neutralized the highly infectious virus variant that is crippling India, as well as variants first spotted in Britain, South Africa, Brazil, California, and New York. “With the authorization of this monoclonal antibody treatment, we are providing another option to help keep high-risk patients with COVID-19 out of the hospital,” Patrizia Cavazzoni, M.D., director of the FDA Center for Drug Evaluation and Research, said in an agency news release. “It is important to expand the arsenal of monoclonal antibody therapies that are expected to retain activity against the circulating variants of COVID-19 in the United States.” Developed by GlaxoSmithKline, in concert with the American company Vir Biotechnology, the drug should become available to Americans “in the coming weeks,” company officials said in a statement. “Sotrovimab is a critical new treatment option in the fight against the current pandemic and potentially for future coronavirus outbreaks as well,” said George Scangos, Ph.D., Vir’s chief executive officer. GSK and Vir’s treatment is a single drug, designed to mimic the antibodies generated when the immune system fights off the coronavirus. Its emergency use authorization was based on a study of 583 volunteers who had started experiencing symptoms within the previous five days. The study showed that those who received the GSK-Vir treatment had an 85 percent reduction in their risk for hospitalization or death compared with those who received placebo.
AMA survey: 96% of physicians fully vaccinated against COVID-19
Healio | Primary Care, June 11, 2021
Most practicing physicians in the United States who were surveyed reported being fully vaccinated against COVID-19, with no significant differences in vaccination by gender, age or geographic location, according to the AMA. The organization administered the survey from June 3 to 8. About 300 physicians responded to the survey; half of them were primary care physicians. Of the 11 non-vaccinated physicians who participated in the survey, five said that they plan on receiving the COVID-19 vaccine. The AMA said that the most common reason for not being vaccinated was that the COVID-19 vaccine is “too new and has unknown long-term effects.” With more than 96% of physicians reporting to be fully vaccinated, the data yield a 20% increase in vaccinated physicians compared with a poll conducted by Medscape last month, according to an AMA press release. “Practicing physicians across the country are leading by example, with an amazing uptake of the COVID-19 vaccines,” AMA President Susan R. Bailey, MD, said in the release. “Physicians and clinicians are uniquely positioned to listen to and validate patient concerns, and one of the most powerful anecdotes a physician can offer is that they themselves have been vaccinated.”
Improving heart health may reduce the severity of COVID-19 disease
European Society of Cardiology, June 10, 2021
[Press Release] High blood pressure, smoking, obesity, heart disease and diabetes are associated with worse outcomes in patients with COVID-19, according to a study published today in European Heart Journal – Quality of Care and Clinical Outcomes, a journal of the European Society of Cardiology (ESC). “Many of the cardiovascular risk factors associated with more severe consequences from COVID-19 are potentially modifiable,” said study author Dr. Stephanie Harrison of the University of Liverpool, UK. “Clinicians and policy makers should consider that strategies which improve cardiovascular health may also improve outcomes for people following COVID-19.” Emerging evidence has suggested that COVID-19 patients with heart disease may be more likely to need hospitalisation or ventilation or die from COVID-19 compared to those without heart disease. Studies have also examined whether risk factors for cardiovascular disease such as high blood pressure and smoking may be linked with poor outcomes from COVID-19. Many reviews have been conducted to consolidate the research linking cardiovascular disease and COVID-19. The aim of this study, commissioned by Public Health England, was to summarise the evidence in these reviews – i.e. a review of reviews – to address two questions: 1) What is the association between cardiovascular risk factors or cardiovascular disease and outcomes for patients with COVID-19? 2) What is the impact of COVID-19 on cardiovascular health? The authors identified the highest quality reviews – a total of 32 reviews including studies of up to ~45,000 patients with COVID-19. The factors associated with a higher likelihood of worse outcomes from COVID-19 were high blood pressure, current or past smoking, obesity, diabetes, previous stroke or pre-existing cardiovascular disease, liver disease, and kidney disease. Heart disease was linked with a nearly four-fold odds of severe COVID-19, while the odds were more than doubled for hypertension and diabetes, and 80% higher in smokers compared to non-smokers”
Cardiovascular risk factors, cardiovascular disease, and COVID-19: an umbrella review of systematic reviews
European Heart Journal – Quality of Care and Clinical Outcomes, June 9, 2021
Our aims were to consolidate evidence to determine (i) the association between cardiovascular risk factors and health outcomes with coronavirus 2019 (COVID-19); and (ii) the impact of COVID-19 on cardiovascular health. An umbrella review of systematic reviews was conducted. Fourteen medical databases and pre-print servers were searched from 1 January 2020 to 5 November 2020. The review focused on reviews rated as moderate or high-quality using the AMSTAR 2 tool. Eighty-four reviews were identified; 31 reviews were assessed as moderate quality and one was high-quality. The following risk factors were associated with higher mortality and severe COVID-19: renal disease [odds ratio (OR) (95% confidence interval) for mortality 3.07 (2.43–3.88)], diabetes mellitus [OR 2.09 (1.80–2.42)], hypertension [OR 2.50 (2.02–3.11)], smoking history [risk ratio (RR) 1.26 (1.20–1.32)], cerebrovascular disease [RR 2.75 (1.54–4.89)], and cardiovascular disease [OR 2.65 (1.86–3.78)]. Liver disease was associated with higher odds of mortality [OR 2.81 (1.31–6.01)], but not severe COVID-19. Current smoking was associated with a higher risk of severe COVID-19 [RR 1.80 (1.14–2.85)], but not mortality. Obesity associated with higher odds of mortality [OR 2.18 (1.10–4.34)], but there was an absence of evidence for severe COVID-19. In patients hospitalized with COVID-19, the following incident cardiovascular complications were identified: acute heart failure (2%), myocardial infarction (4%), deep vein thrombosis (7%), myocardial injury (10%), angina (10%), arrhythmias (18%), pulmonary embolism (19%), and venous thromboembolism (25%). Many of the risk factors identified as associated with adverse outcomes with COVID-19 are potentially modifiable. Primary and secondary prevention strategies that target cardiovascular risk factors may improve outcomes for people following COVID-19.
COVID-19 Increases Health Inequities in Patients With Hypertension
Cardiology Advisor, June 8, 2021
Among individuals with high blood pressure, COVID-19 has disproportionately affected underserved racial, ethnic, and socioeconomic groups, according to a report recently published in the Journal of the American Heart Association. This report draws on the work of several sources, including a diverse group of experts that discussed this matter as well as rectification strategies at the recent Fourth Annual University of Utah Translational Hypertension Symposium. The results of a nationwide blood pressure study of more than 50,000 adults show that a decrease in the numbers of people with healthy blood pressure levels is linked with inadequate health care and insurance. From 2017 to 2018, 40% to 46% of insured Americans had healthy blood pressure, compared with 22% of those who were uninsured. Compared with White adults, Black adults had a 12% lower likelihood for healthy blood pressure. The threshold for high blood pressure in this study was above 140/90 mmHg. Lifestyle modifications, a lack of in-person visits, and poor medication adherence are challenges to healthy blood pressure. During the COVID-19 pandemic, hospitalizations for stroke, heart attack, and heart failure decreased, but out-of-hospital deaths increased by 20%. Other researchers showed that bias among health care professionals resulted in differing care quality and clinical inertia, both of which affect blood pressure management. A concerning trend, according to investigators, is distrust of health care professionals by people of color. Trust can be improved through community intervention programs such as the successful BARBER trial in Los Angeles. A low percentage of health care researchers and medical school students are from under-resourced communities. The study researchers concluded that “COVID-19 has disproportionately affected people from different racial and ethnic groups, those who are from under-resourced populations and communities that face historic or systemic disadvantages.”
Vaccine-induced Thrombotic Thrombocytopenia (VITT) and COVID-19 Vaccines: What Cardiovascular Clinicians Need to Know
American College of Cardiology, June 8, 2021
Organized in an FAQ format for easy navigation, this guidance is summarized from more extensive documents and approved by the ACC Science and Quality Committee. This FAQ is intended to be topical, not comprehensive. In extremely rare cases, the Johnson & Johnson/Jansen and Astra Zeneca COVID-19 vaccinations may cause vaccine-induced thrombotic thrombocytopenia (VITT), a condition characterized by simultaneous acute thrombosis and thrombocytopenia. The condition is similar to heparin-induced thrombocytopenia. Specific risk factors for VITT have yet to be determined given the extremely low case count, though presentation seems to appear between 5-28 days post vaccination. Patients should be reassured that the benefits of vaccination against COVID-19 far outweigh any potential risk. Diagnostic, therapeutic, and patient communication recommendations are included.
Improved Outcomes With Methylprednisolone in Hospitalized Hypoxic Patients With COVID-19
Cardiology Advisor, June 4, 2021
Treatment with methylprednisolone led to significantly greater improvements in clinical status and shortened hospital length of stay than treatment with dexamethasone in hospitalized COVID-19 patients with hypoxia, according to the results of a study published in BMC Infectious Diseases. This prospective trial included 86 hospitalized patients with COVID-19 in Iran. Participants were randomly assigned to either methylprednisolone 2 mg/kg/d (n=44) or dexamethasone 6 mg/kg/d (n=42). Treatment was administered in conjunction with standard of care for 10 days. The primary endpoint was 28-day mortality rate and clinical status at 5 and 10 days. The data were examined using a 9-point World Health Organization (WHO) ordinal scale ranging from uninfected (point 0) to death (point 8). Secondary endpoints included intensive care unit admission and the need for invasive mechanical ventilation. No significant differences were observed between the treatment groups in terms of demographic variables, comorbid diseases, or disease severity at time of admission. At day 5, however, patients treated with methylprednisolone reached a significantly better clinical status compared with patients who received dexamethasone (4.02 vs 5.21, respectively; P =.002). Patients in the methylprednisolone group also had better clinical status at day 10 (2.90 vs 4.71; P =.001). Patients in the methylprednisolone group had a significantly better overall mean 9-point WHO score (3.909 vs 4.873; P =.004). The use of methylprednisolone was also associated with a significantly shorter mean length of hospital stay (7.43±3.64 vs 10.52±5.47 days; P =.015). A lower proportion of patients in the methylprednisolone group required a ventilator during hospitalization (18.2% vs 38.1%; P =.040).
COVID-19 may increase risk for MI in patients with ASCVD, familial hypercholesterolemia
Healio | Cardiology Today, June 4, 2021
Adults with preexisting atherosclerotic CVD and/or familial hypercholesterolemia have increased risk for acute MI if infected with COVID-19, according to an analysis published in the American Journal of Preventive Cardiology. “CVD, hypertension and heart failure are associated with higher rates of COVID-19-related morbidity and mortality,” Kelly D. Myers, BS, chief technology officer at the FH Foundation and CEO of Atomo Inc. in Austin, Texas, and colleagues wrote. “However, studies have documented fewer individuals presenting to hospital with acute MI during the pandemic.” Researchers assessed laboratory data and diagnostic, procedural and prescription claims from Symphony Health from May 2012 to June 2020. In total, 55,441,462 adults who were evaluated or treated for CVD with valid demographic data and at least one record before COVID-19 and one after the pandemic were analyzed. Acute MI rates for all individuals were assessed through COVID-19 status and history. Individuals with and without COVID-19 were then categorized into groups and matched based on the presence or lack of comorbidities before COVID-19: ASCVD (176,946 with COVID-19; 12,051,757 without COVID-19); familial hypercholesterolemia (FH; 1,216 with COVID-19; 121,396 without COVID-19); probable FH (3,369 with COVID-19; 334,724 without COVID-19); FH and ASCVD (1,399 with COVID-19; 89,396 without COVID-19); probable FH and ASCVD (3,833 with COVID-19; 253,449 without COVID-19); and no FH nor ASCVD (447,192 with COVID-19; 41,956,785 without COVID-19). According to the researchers, there were increased rates of acute MI among individuals with COVID-19 compared with matched individuals without COVID-19 in the group with ASCVD (1.4% vs. 0.46%; P < .0002), in the group with FH (0.41% vs. 0.12%; P = .003), in the group with probable FH (0.5% vs. 0.12%; P < .0002), in the group with FH and ASCVD (1.57% vs. 0.56%; P < .0002), in the group with probable FH and ASCVD (2.09% vs. 0.5%; P < .0002) and in the group with neither disease (0.34% vs. 0.11%; P < .0002).
Inverse association between hypertension treatment and COVID-19 prevalence in Japan
International Journal of Infectious Diseases, June 3, 2021
Cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) depends on angiotensin-converting enzyme II (ACE2). ACE2 is homologous with, but acts antagonistically to, angiotensin-converting enzyme (ACE), and has the critical function of protecting the lungs. ACE inhibitors are major antihypertensive agents. Thus, we aimed to analyze the impact of the prevalence of preexisting hypertension on the local spread of coronavirus disease 2019. Data on SARS-CoV-2 infection and the estimated number of patients who received medical treatment based on disease classification using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, in each prefecture were obtained from the official Japanese notifications database. We analyzed the association between the proportion of patients with each disease and SARS-CoV-2-infection prevalence. The ratio of patients treated for diseases of the circulatory system, especially hypertensive disorders, per population demonstrated the most significant negative correlation with SARS-CoV-2-infection prevalence (Spearman’s rank correlation, p < 0.01). Age group analysis revealed a significant negative correlation in age groups 35–44, 45–54, 55–64, 75–84, and ≥85. Our findings suggest that hypertension treatment may play a protective role against the local spread of SARS-CoV-2 infection.
Hypertension, renin-angiotensin-aldosterone-system-blocking agents, and COVID-19
Clinical Hypertension, June 1, 2021
There have been concerns regarding the safety of renin-angiotensin-aldosterone-system (RAAS)-blocking agents including angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) during the coronavirus disease 2019 (COVID-19) pandemic. This study sought to evaluate the impact of hypertension and the use of ACEI/ARB on clinical severity in patients with COVID-19. A total of 3,788 patients aged 30 years or older who were confirmed with COVID-19 with real time reverse transcription polymerase chain reaction were identified from a claims-based cohort in Korea. The primary study outcome was severe clinical events, a composite of intensive care unit admission, need for ventilator care, and death. Patients with hypertension (n = 1,190, 31.4 %) were older and had higher prevalence of comorbidities than those without hypertension. The risk of the primary study outcome was significantly higher in the hypertension group, even after multivariable adjustment (adjusted odds ratio [aOR], 1.67; 95 % confidence interval [CI], 1.04 to 2.69). Among 1,044 patients with hypertensive medical treatment, 782 (74.9 %) were on ACEI or ARB. The ACEI/ARB subgroup had a lower risk of severe clinical outcomes compared to the no ACEI/ARB group, but this did not remain significant after multivariable adjustment (aOR, 0.68; 95 % CI, 0.41 to 1.15).
Dysrhythmias in Patients With COVID-19
Cardiology Advisor, May 27, 2021
A 76-year-old man who was diagnosed with COVID-19 and discharged from the emergency department (ED) 2 days prior, returns to the ED with worsening shortness of breath, fatigue, and nonproductive cough. The patient has no associated fevers, chest pain, or gastrointestinal symptoms. An electrocardiogram (ECG) reveals new-onset atrial fibrillation (AF) with a ventricular rate of 115 beats per minute and elevated troponin level. The patient’s oxygen saturation is 80% on room air. He is initially placed on a nonrebreather mask, which is quickly escalated to a high-flow oxygen therapy via nasal cannula. Oxygen saturation improves to 93% with 80% fraction of inspired oxygen on 35 L/min flow. He is admitted for COVID-19 pneumonia and initiated on dexamethasone, remdesivir, empiric IV antibiotics, and enoxaparin for venous thromboembolism prophylaxis. Cardiology and pulmonology are consulted. Laboratory results of note include elevated white blood cell count (14,300/µL), neutrophil (1000/µL), troponin (0.52 ng/mL), creatine kinase (642 U/L), C-reactive protein (289.8 mg/dL), D-dimer (3.82 µg/mL), and N-terminal pro-BNP (brain natriuretic peptide; 700 pg/mL) levels. Mild decreases in sodium (133 mEq/L), chloride (97 mEq/L), and albumin (2.7 g/dL) are also noted. The remainder of the basic metabolic panel, liver panel, complete blood count, and coagulation studies are within normal limits. The patient’s chest radiograph reveals bilateral interstitial pneumonitis. An echocardiogram reveals severe aortic stenosis and normal ejection fraction with moderate aortic regurgitation. Pulmonary computed tomography angiogram does not demonstrate pulmonary emboli but does show evidence of COVID-19 infection, noting bilateral ground-glass opacities with possible underlying pulmonary fibrosis.
Prevalence of Clinical and Subclinical Myocarditis in Competitive Athletes With Recent SARS-CoV-2 Infection: Results From the Big Ten COVID-19 Cardiac Registry
JAMA Cardiology, May 27, 2021
Myocarditis is a leading cause of sudden death in competitive athletes. Myocardial inflammation is known to occur with SARS-CoV-2. Different screening approaches for detection of myocarditis have been reported. The Big Ten Conference requires comprehensive cardiac testing including cardiac magnetic resonance (CMR) imaging for all athletes with COVID-19, allowing comparison of screening approaches. The objective was to determine the prevalence of myocarditis in athletes with COVID-19 and compare screening strategies for safe return to play. For athletes with myocarditis, presence of cardiac symptoms and details of cardiac testing were recorded. Myocarditis was categorized as clinical or subclinical based on the presence of cardiac symptoms and CMR findings. Subclinical myocarditis classified as probable or possible myocarditis based on other testing abnormalities. Myocarditis prevalence across universities was determined. The utility of different screening strategies was evaluated. Representing 13 universities, cardiovascular testing was performed in 1597 athletes (964 men [60.4%]). Thirty-seven (including 27 men) were diagnosed with COVID-19 myocarditis (overall 2.3%; range per program, 0%-7.6%); 9 had clinical myocarditis and 28 had subclinical myocarditis. If cardiac testing was based on cardiac symptoms alone, only 5 athletes would have been detected (detected prevalence, 0.31%). Cardiac magnetic resonance imaging for all athletes yielded a 7.4-fold increase in detection of myocarditis (clinical and subclinical). Follow-up CMR imaging performed in 27 (73.0%) demonstrated resolution of T2 elevation in all (100%) and late gadolinium enhancement in 11 (40.7%).
Acute myocarditis related to Covid-19 infection: 2 cases report
Annals of Medicine & Surgery, May 26, 2021
Since COVID 19 was described for the first time in December 2019, we have not stopped discovering its different clinical manifestations. Despite the respiratory complication, which is the most common symptomatology, multi-organ dysfunction, and multiple cardiovascular complications were described such as acute myocarditis, heart failure and even arrhythmias. Two patients aged 26 and 56 year-old, developed acute myocarditis related to Covid-19 infection but with different symptomatology. Case 1 presented to the emergency room with digestive symptomatology, Covid-19 infection was confirmed by a positive chest CT scan and positive COVID-19 serology testing. Clinical, biological, radiological findings allowed making the diagnosis of a Covid-19 infection with a bacterial superinfection complicated by a fulminant myocarditis. Case 2 presented to the emergency department with a chest pain, dyspnoea, paroxistic cough, myalgia and fever. A Covid-19 infection was confirmed. The electrocardiogram showed a diffuse ST elevation, echocardiography showed normal systolic function and the high-sensitivity cardiac troponin I level was high. Invasive coronary angiography was performed, revealing angiographically normal coronary arteries. Our 2 cases was treated differently, case 1 received antibiotherapy because of the bacterial superinfection and inotropic support for the septic and cardiogenic choc. Contrarily to case 2 who received inotropic support, immunoglobulin and corticosteroid. With a total recovery for both patients.
Takotsubo syndrome during the COVID-19 pandemic, state-of -the- art review
CJC Open, May 26, 2021
The current coronavirus disease 2019 (COVID-19) presents an ongoing medical challenge with multiple organs involvement, including the cardiovascular system. Takotsubo syndrome (TTS) has been described in the context of COVID-19 in two different scenarios: as a direct complication of the infection, and as an indirect outcome secondary to psychological burden of quarantine and social isolation (i.e., stress induced cardiomyopathy). Confirming the diagnosis of TTS in COVID-19 may be challenging due to the limited use of coronary angiography consistent with the recommended guidelines aimed to minimize contact with infected individuals. The use of natriuretic peptide as a diagnostic and prognostic marker in this context may not be reliable since this peptide is already elevated in severe cases of COVID-19 regardless of TTS diagnosis. A relatively high incidence of complications has been reported in these cases, probably related to the severity of the underlying infectious disease. Although quarantine-induced stress cardiomyopathy is a reasonable outcome of the powerful stress during the current pandemic, conflicting results have been reported, and further studies are encouraged to determine the true incidence.
Classification of COVID-19 electrocardiograms by using hexaxial feature mapping and deep learning
BMC Medical Informatics and Decision Making, May 25, 2021
Coronavirus disease 2019 (COVID-19) has become a pandemic since its first appearance in late 2019. Deaths caused by COVID-19 are still increasing day by day and early diagnosis has become crucial. Since current diagnostic methods have many disadvantages, new investigations are needed to improve the performance of diagnosis. A novel method is proposed to automatically diagnose COVID-19 by using Electrocardiogram (ECG) data with deep learning for the first time. Moreover, a new and effective method called hexaxial feature mapping is proposed to represent 12-lead ECG to 2D colorful images. Gray-Level Co-Occurrence Matrix (GLCM) method is used to extract features and generate hexaxial mapping images. These generated images are then fed into a new Convolutional Neural Network (CNN) architecture to diagnose COVID-19. Two different classification scenarios are conducted on a publicly available paper-based ECG image dataset to reveal the diagnostic capability and performance of the proposed approach. In the first scenario, ECG data labeled as COVID-19 and No-Findings (normal) are classified to evaluate COVID-19 classification ability. According to results, the proposed approach provides encouraging COVID-19 detection performance with an accuracy of 96.20% and F1-Score of 96.30%. In the second scenario, ECG data labeled as Negative (normal, abnormal, and myocardial infarction) and Positive (COVID-19) are classified to evaluate COVID-19 diagnostic ability. The experimental results demonstrated that the proposed approach provides satisfactory COVID-19 prediction performance with an accuracy of 93.00% and F1-Score of 93.20%. Furthermore, different experimental studies are conducted to evaluate the robustness of the proposed approach.
Despite being fully vaccinated, transplant recipients remain at greater risk for COVID-19
Helio | Nephrology News & Issues, May 24, 2021
After a second dose of either the Moderna or Pfizer-BioNTech COVID-19 vaccine, solid organ transplant recipients failed to achieve an antibody response against SARS-CoV-2 comparable to the general population. According to a related press release, this study continues research that the team from Johns Hopkins School of Medicine conducted earlier in 2021, which showed 17% of transplant recipients “produced sufficient antibodies” after one dose of the two-dose regimen. “While there was an increase in those with detectable antibodies — 54% overall — after the second shot, the number of transplant recipients in our second study whose antibody levels reached high enough levels to ward off a SARS-CoV-2 infection was still well below what’s typically seen in people with healthy immune systems,” Brian J. Boyarsky, MD, PhD, said in the release. “Based on our findings, we recommend that transplant recipients and other immunocompromised patients continue to practice strict COVID-19 safety precautions, even after vaccination.” For the study, Boyarsky and colleagues included 658 transplant recipients who completed a two-dose vaccine regimen between December 2020 and March 2021. Researchers found the first dose led to a detectable antibody response in 15% of transplant recipients; the response occurred at a median of 21 days after the first dose was administered. After the second dose, an antibody response was detectable in 54% of participants, occurring a median of 29 days later (46% had no response after either dose).
Inequities in Hypertension Care Magnified by the COVID-19 Pandemic
Cardiology Advisor, May 24, 2021
During the 4th Annual University of Utah Translational Hypertension Symposium, there was a discussion about the inequities in health care for the diagnosis and management of hypertension in the United States and how these inequities have been exacerbated by the COVID-19 pandemic. A synopsis of this discussion was published in the Journal of the American Heart Association. As of March of 2021, more than half a million Americans have died from COVID-19. Due to the increased burden on the healthcare system the management of chronic conditions has been interrupted for many patients and this disruption will likely have long-term consequences. This is particularly concerning for hypertension, as it is one of the leading causes of cardiovascular disease. During the conference, clinicians described that they had substantially reduced or completely discontinued in-person outpatient hypertension consultations. During telemedicine visits, it was apparent that most patients did not have access to validated at-home blood pressure monitors, as only 15% on the market are validated. During the few years before the pandemic, there has been a trend for blood pressure control rates to be on the decline. This pattern has been more pronounced among minority populations in the United States, likely due to disparities in healthcare access. Inadequate control of blood pressure has been associated with healthcare disparities, lack of physical activity, poor access to healthy foods, low health literacy, and distrust of the healthcare system. Addressing inequalities in hypertension health care must include national and state health policies, local community outreach, the healthcare organization and practice, the clinical team, and the individual patient and support network.
COVID-19 vaccine benefits still outweigh risks, despite possible rare heart complications
American Heart Association, May 23, 2021
Late last week, the U.S. Centers for Disease Control and Prevention (CDC) alerted health care professionals that they are monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of young adults developing the rare heart-related complication myocarditis, after receiving a COVID-19 vaccine manufactured by Pfizer-BioNTech or Moderna. The COVID-19 Vaccine Safety Technical Work Group (VaST) of the CDC’s Advisory Committee on Immunization Practices (ACIP) is reviewing several dozen cases of myocarditis that have been reported in adolescents and young adults: more often in males rather than females; more frequently after the second dose rather than the first dose of either the Pfizer-BioNTech or Moderna vaccine; and typically appearing within 4 days of vaccination. The benefits of COVID-19 vaccination enormously outweigh the rare, possible risk of heart-related complications, including inflammation of the heart muscle, or myocarditis. The American Heart Association/American Stroke Association, a global force for longer, healthier lives, urges all adults and children ages 12 and older in the U.S. to receive a COVID vaccine as soon as they can
Echocardiographic Correlates of In-Hospital Death in Patients with Acute COVID-19 Infection: The World Alliance Societies of Echocardiography (WASE-COVID) Study
Journal of the American Society of Echocardiography, May 20, 2021
The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus which has led to the global Coronavirus disease-2019 (COVID-19) pandemic is known to adversely affect the cardiovascular system through multiple mechanisms. In this international, multi-center study conducted by the World Alliance Societies of Echocardiography (WASE), we aim to determine the clinical and echocardiographic phenotype of acute cardiac disease in COVID-19 patients, to explore phenotypic differences in different geographic regions across the world, and to identify parameters associated with in-hospital mortality. We studied 870 patients with acute COVID-19 infection from 13 medical centers in four world regions (Asia, Europe, United States, Latin America) who had undergone transthoracic echocardiograms (TTEs). Clinical and laboratory data were collected, including patient outcomes. Anonymized echocardiograms were analyzed with automated, machine learning-derived algorithms to calculate left ventricular (LV) volumes, ejection fraction (EF), and LV longitudinal strain (LS). Right-sided echocardiographic parameters that were measured included right ventricular (RV) LS, RV free wall strain (FWS), and RV basal diameter (RVBD). Multivariate regression analysis was performed to identify clinical and echocardiographic parameters associated with in-hospital mortality. Significant regional differences were noted in terms of patient co-morbidities, severity of illness, clinical biomarkers, and LV and RV echocardiographic metrics. Overall in-hospital mortality was 21.6%. Parameters associated with mortality in a multivariate analysis were age (OR 1.12 [1.05, 1.22], p = 0.003), previous lung disease (OR 7.32 [1.56, 42.2], p = 0.015), LVLS (OR 1.18 [1.05, 1.36], p = 0.012), lactic dehydrogenase (LDH) (OR 6.17 [1.74, 28.7], p = 0.009), and RVFWS (OR 1.14 [1.04, 1.26], p = 0.007).
Cardiologists making strides in COVID-19 research
Helio | Cardiology Today, May 19, 2021
COVID-19 is predominantly considered an infectious and respiratory disease, but it is intertwined with the CV system as well. That means cardiologists have a lot to contribute to battle it, especially in the area of pathophysiology. Because COVID-19 is often considered an ICU issue and an infectious disease, cardiologists have at times been left on the sideline during the pandemic. But we now know that there are many CV implications of COVID-19. There have been cases of myocarditis, although not as many as initially thought. There are many patients with elevation of biomarkers of cardiomyocyte injury (high-sensitivity cardiac troponin T or I). There have been a lot of cases of right HF, often from pulmonary embolism and many with thrombophlebitis. We have learned that the pathways that lead to HF and even CAD — the inflammatory pathways and the cytokine pathways that produce HF — are some of the same pathways that we see in COVID-19. This is an aspect of the disease that is not discussed in infectious disease or pulmonary journals. The challenge for cardiologists is to get out that science and make an impact. To that end, I am part of a group of cardiologists from around the world that early in the pandemic began to meet — virtually, of course — regularly to communicate about what we were seeing regarding the impact of the pandemic in our respective regions, and about what research projects we might be able to undertake to prevent and treat COVID-19.
INSPIRATION-S: Statin therapy fails to prevent thrombosis, death in severe COVID-19
Helio | Cardiology Today, May 19, 2021
Atorvastatin therapy did not reduce risk for venous or arterial thrombosis or all-cause death among patients with COVID-19 admitted to the ICU compared with placebo, according to data from the INSPIRATION-S study. A smaller treatment effect and findings within specific subgroups warrant additional investigation, Behnood Bikdeli, MD, MS, a clinical fellow in the cardiovascular medicine division at Brigham and Women’s Hospital and Harvard Medical School, said during a presentation at the American College of Cardiology Scientific Session. INSPIRATION-S was a double-blind, randomized controlled trial assessing the use of 20 mg atorvastatin once daily vs. placebo in 605 patients with confirmed COVID-19 who were admitted to the ICU across 11 hospitals in Iran (mean age, 57 years; 44% women; 16% with diabetes). Enrollment began in July 2020. Participants were naive to statin therapy prior to randomization; those with severe liver dysfunction were excluded. More than 90% of patients were receiving corticosteroids while hospitalized. The primary outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO) or death within 30 days. Researchers also assessed liver enzyme levels and incidence of clinically diagnosed myopathy as the main safety outcomes. Researchers found statin therapy was not associated with a significant reduction in the primary outcome (HR = 0.84 95% CI, 0.58-1.21; P = .35); however, numerically fewer events occurred in the statin group compared with the placebo group (95 vs. 108). Individual endpoint components of all-cause death (HR = 0.84; 95% CI, 0.58-1.22; P = .39) and adjudicated venous thromboembolism (HR = 0.71; 95% CI, 0.24-2.06; P = .53) failed to reach significance, though fewer events for each occurred in the statin group vs. placebo, according to the researchers.
Prior RAAS Inhibitor Use Reduces hs-cTnT Levels in SARS-CoV-2 Infection
Cardiology Advisor, May 13, 2021
Renin-angiotensin-aldosterone system (RAAS) inhibitor use prior to SARS-CoV-2 infection may lead to decreased high-sensitivity cardiac troponin T (hs-cTnT) values in patients with hypertension, according to research results presented at the American College of Cardiology (ACC) 2021 Annual Meeting, held virtually May 15-17, 2021. To clarify the relationship between RAAS inhibitors and cardiac troponin levels in people with COVID-19, researchers conducted a single-institution, retrospective cohort study of adult patients diagnosed via PCR with SARS-CoV-2 infection. The primary study objective was to determine if evidence exists to support the current hypothesis that adults with hypertension receive cardioprotective benefits from daily RAAS inhibitor use prior to acquiring COVID-19. The study cohort included 112 patients with hypertension and PCR-confirmed SARS-CoV-2 infection. Within this group, 57.1% were taking a RAAS inhibitor at the time of their diagnosis. At 0- and 2-hours evaluation, patients on RAAS inhibitor therapy had median hs-cTnT values of 16.0 ng/L and 16.5 ng/L (interquartile range [IQR], 12.0-36.5 ng/L and 12.0-33.5 ng/L), respectively, compared with median hs-cTnT values of 34.5 ng/L and 32.0 ng/L (IQR, 17.8-77.5 ng/L and 16.0-67.0 ng/L), respectively, in patients not on RAAS inhibitor therapy. “RAAS inhibitor use prior to acquisition of COVID-19 is associated with decreased hs-cTnT values on [emergency department] presentation,” the researchers concluded. “RAAS inhibitors may attenuate myocardial injury in patients with COVID-19 and their role in this setting warrants further study.”
Myocardial Injury in COVID-19 Patients: Association with Inflammation, Coagulopathy and In-Hospital Prognosis
Journal of Clinical Medicine, May 13, 2021
The exact mechanisms leading to myocardial injury in the coronavirus disease 2019 (COVID-19) are still unknown. In this retrospective observational study, we include all consecutive COVID-19 patients admitted to our center. They were divided into two groups according to the presence of myocardial injury. Clinical variables, Charlson Comorbidity Index (CCI), C-reactive protein (CRP), CAC (COVID-19-associated coagulopathy), defined according to the ISTH score, treatment and in-hospital events were collected. Between March and April 2020, 331 COVID-19 patients were enrolled, 72 of them (21.8%) with myocardial injury. Patients with myocardial injury showed a higher CCI score (median (interquartile range), 5 (4–7) vs. 2 (1–4), p = 0.001), higher CRP values (18.3 (9.6–25.9) mg/dL vs. 12.0 (5.4–19.4) mg/dL, p ˂ 0.001) and CAC score (1 (0–2) vs. 0 (0–1), p = 0.001), and had lower use of any anticoagulant (57 patients (82.6%) vs. 229 patients (90.9%), p = 0.078), than those without. In the adjusted logistic regression, CRP, myocardial injury, CCI and CAC score were positive independent predictors of mortality, whereas anticoagulants resulted as a protective factor. Myocardial injury in COVID-19 patients is associated with inflammation and coagulopathy, resulting in a worse in-hospital prognosis. Treatment with anticoagulant agents may help to improve in-hospital outcomes.
COVID-19 pandemic and coronary angiography for ST-elevation myocardial infarction, use of mechanical support and mechanical complications in Canada; a Canadian Association of Interventional Cardiology national survey
CJC Open, May 12, 2021
As a result of the COVID-19 pandemic first wave, reductions in STEMI invasive care ranging from 23% to 76% have been reported from various countries. Whether it had any impact on coronary angiography (CA) volume or on mechanical support device use for ST-elevation myocardial infarction (STEMI) and post-STEMI mechanical complications in Canada is unknown. We administered a Canada-wide survey to all Cardiac Catheterization Laboratory Directors seeking the volume of CA for STEMI performed during 01/03/2020-31/05/2020 (pandemic period) and from two control periods (01/03/2019-31/05/2019 and 01/03/2018-31/05/2018). The number of left ventricular support devices used, as well as the number of ventricular septal defects or papillary muscle rupture cases diagnosed, were also recorded. We also assessed if the number of COVID-19 cases recorded in each province was associated with STEMI CA volume. Forty-one out of 42 Canadian catheterization laboratories (98%) provided data. There was a modest but statistically significant 16% reduction (Incidence Rate Ratio or IRR 0.84; 95%CI 0.80-0.87) in CA for STEMI during the first wave of the pandemic compared to control periods. IRR was not associated with provincial COVID-19 caseload. We observed a 26% reduction (IRR 0.74; 95%CI 0.61-0.89) in the use of intra-aortic balloon pump in STEMI. Use of Impella® and mechanical complications from STEMI were exceedingly rare. We observed a modest 16% decrease in CA for STEMI during the pandemic first wave in Canada, lower than reported in other countries.
ACC 2021 to highlight ‘silver lining lessons’, future challenges attributable to COVID-19
Helio | Cardiology Today, May 10, 2021
The 2021 American College of Cardiology Scientific Session will be held virtually from May 15 through 17 and will feature 25 late-breaking clinical trials, 17 featured clinical research presentations and numerous abstract presentations. “While this meeting is being delivered virtually, you will see that there have been benefits in the time to plan and also the lessons that ACC has learned in virtual education over the past year,” Pamela B. Morris, MD, FACC, FAHA, FASPC, FNLA, director of preventive cardiology, co-director of women’s heart care at the Medical University of South Carolina and chair of the 2021 ACC Scientific Session, said during a press conference. “This has come together to create a robust educational and scientific agenda. This meeting will feature everything you’ve come to expect from our annual scientific sessions and more.” This year, the meeting will be delivered through a new virtual education program with the goal of improving real-time discussion between learners and faculty. Subsequently, all streamed sessions and meeting content will be made available on demand, including more than 200 talks in addition to the “Heart to Heart Conversation” podcast. This year’s scientific session will also feature a COVID-19 intensive that will be co-chaired by David Rizik, MD, interventional cardiologist at HonorHealth in Scottsdale, Arizona, and Doreen DeFaria Yeh, MD, director of the Massachusetts General Hospital cardiovascular disease fellowship program.
Social Determinants of Adherence to COVID-19 Risk Mitigation Measures Among Adults with Cardiovascular Disease
Circulation, May 6, 2021
Social determinants of health (SDOH) may limit the practice of COVID-19 risk mitigation guidelines with health implications for individuals with underlying cardiovascular disease (CVD). Population-based evidence of the association between SDOH and practicing such mitigation strategies in adults with CVD is lacking. We used the National Opinion Research Center’s COVID-19 Household Impact Survey conducted between April and June 2020 to evaluate sociodemographic disparities in adherence to COVID-19 risk mitigation measures in a sample of respondents with underlying CVD representing 18 geographic areas of the United States (US). CVD status was ascertained by self-reported history of receiving heart disease, heart attack, or stroke diagnosis. We built de novo, a cumulative index of SDOH burden using education, insurance, economic stability, 30-day food security, urbanicity, neighborhood quality, and integration. We described the practice of measures under the broad strategies of personal protection (mask, hand hygiene, physical distancing), social distancing (avoiding crowds, restaurants, social activities, and high-risk contact), and work flexibility (work-from-home, canceling/postponing work). We reported prevalence ratios (PR) and 95% confidence intervals (CIs) for the association between SDOH burden (quartiles of cumulative indices) and practicing these measures adjusting for age, sex, race/ethnicity, comorbidity, and interview wave. 2036/25269 (7.0%) adults, representing 8.69 million in 18 geographic areas of the US, reported underlying CVD. Compared to the least SDOH burden, fewer individuals with the greatest SDOH burden practiced all personal protection (75.6% vs 89.0%) and social distancing measures (41.9% vs 58.9%) and had any flexible work schedule (26.2% vs 41.4%). These associations remained statistically significant after full adjustment: personal protection, (PR = 0.83; 95% CI [0.73-0.96]; P = 0.009); social distancing (PR = 0.69; 95% CI [0.51-0.94]; P = 0.018); and work flexibility (PR = 0.53; 95% CI [0.36-0.79]; P = 0.002).
ACC Offers Statement on Use of CBME for Training of Fellows During COVID-19
Pulmonary Advisor, May 5, 2021
In light of the recent pandemic, the American College of Cardiology (ACC) offered a statement drafted by the ACC Competency Management Committee and published in the Journal of the American College of Cardiology regarding specialized guidance for the administration of competency-based medical education (CBME) for cardiology fellows undergoing training during the continuing COVID-19 crisis. Whereas conventional CBME training relies heavily on numerical quotas for procedures performed and/or hours logged, COVID-19 has disrupted all aspects of health care, including this standard of operations, potentially putting some fellows in jeopardy of failing to meet these requirements. For this reason, the ACC recommends that the CBME principles outlined in the Core Cardiovascular and Advanced Training Statements be implemented and assessed with flexibility during this uniquely challenging time, offering several specific considerations regarding how to do so effectively. Program directors are advised that numerical or time-based requirements are approximate estimates based on “typical” trainees and that some time- and case-based requirements can be satisfied concurrently. Final responsibility for reviewing and evaluating trainees’ progress lies with the director, who can and must use their discretion to certify competency, regardless of whether all quotas have been met.
QTc Interval Prolonged in Some Patients Hospitalized With COVID-19
Pulmonology Advisor, May 5, 2021
COVID-19 infection is associated with significant mean QTc prolongation at days 2 and 5 of hospitalization, according to a study published online April 23 in JAMA Network Open. Geoffrey A. Rubin, M.D., from the Vagelos College of Physicians and Surgeons at Columbia University in New York City, and colleagues conducted a cohort study involving 3,050 patients aged 18 years and older who underwent severe acute respiratory syndrome coronavirus 2 testing and had electrocardiograms (ECGs) from March 1 through May 1, 2020. Overall, 965 patients had more than two ECGs and were included in the study; 76.0 and 24.0 percent were with and without COVID-19, respectively. The researchers found that by two-day and five-day multivariable models, COVID-19 infection was associated with significant mean QTc prolongation from baseline. Compared with COVID-19-negative status, COVID-19 infection was independently associated with a modeled mean 27.32 millisecond increase in QTc at five days. Compared with patients without COVID-19, more patients with COVID-19 not receiving hydroxychloroquine and azithromycin had QTc of 500 milliseconds or greater (25.0 versus 10.8 percent). In a multivariable analysis, QTc prolongation was seen in association with age 80 years and older versus younger than 50 years, severe chronic kidney disease versus no chronic kidney disease, elevated high-sensitivity troponin levels, and elevated lactate dehydrogenase levels.
Severe valvular disease, COVID-19 mortality ‘approaching’ 50% at 30 days
Helio | Cardiology Today, May 4, 2021
Thirty-day mortality among patients with severe valvular heart disease and COVID-19 topped more than 40%, according to data presented at the virtual Society for Cardiovascular Angiography and Interventions Scientific Sessions. Performing an invasive surgical or transcatheter procedure for valvular disease management in appropriate patients, even during the infection, was associated with lower prevalence of 30-day all-cause mortality, a speaker reported. “Patients with COVID-19 and severe valvular heart disease have poor clinical outcomes with mortality approaching 50% within 30 days of hospital admission,” Danny Dvir, MD, director of interventional cardiology at the Shaare Zedek Medical Centre at Hebrew University in Jerusalem, said during the presentation. “It seemed that valve repair or replacement in appropriate patients should still be considered in those at risk for infection, possibly during the infection. Although the present study suggests that this approach might be lifesaving, further studies are warranted to confirm the results.” For this multicenter trial, researchers included 136 patients (mean age, 80 years; 52% men) hospitalized with concomitant COVID-19 infection and severe valvular heart disease from an international valve disease registry.
At height of pandemic, patients presenting with acute MI dropped drastically
Helio | Cardiology Today, May 1, 2021
The number of patients presenting with acute MI significantly declined during the peak of the COVID-19 pandemic, according a presentation at the virtual Society for Cardiovascular Angiography and Interventions Scientific Sessions. According to the researchers, there was a 70% decline in the number of patients presenting with acute MI between April 2020 compared with April 2019, and patients who received care developed more severe symptoms due to delays in patients seeking emergency services. “We observed a dramatic decrease in patients presenting with acute myocardial infarction during the COVID-19 pandemic. Of the patients that did seek medical care for MI during the pandemic, we observed a trend toward delay between symptom onset and hospital presentation, compared to during the previous year. This may have contributed to increased overall MI in these patients. Our findings indicate a need for improved public health messaging to ensure timely and appropriate cardiovascular care,” Nina Talmor, MD, internal medicine resident at NYU Langone Health, told Healio. Researchers conducted a single-center, retrospective, observational study that compared patients with MI who underwent urgent invasive coronary angiography at NYU Langone Health in April 2020, during the peak of the pandemic, with those presenting in April 2019. According to the researchers, 13 patients with acute MI underwent invasive angiography in 2020, compared with 59 in 2019, a reduction of 78%. Due to limitations of testing in the early stages of the pandemic, few patients underwent COVID-19 testing before angiography, but two of 13 patients tested positive.
Mortality high, PCI common in patients with concomitant STEMI, COVID-19: NACMI Registry
Helio | Cardiology Today, April 29, 2021
In-hospital mortality remains high and primary PCI is common in patients with STEMI and COVID-19, according to new data from the North American COVID-19 Myocardial Infarction Registry. “One in three [patients with STEMI and COVID-19] does not make it out of the hospital,” Payam Dehghani, MD, FRCPC, FACC, FSCAI, co-director of Prairie Vascular Research Inc. and associate professor at the University of Saskatchewan, said during a press conference at the virtual Society for Cardiovascular Angiography and Interventions Scientific Sessions. Moreover, he said, “primary PCI is common, it’s feasible and it’s associated with reduced mortality. That’s in keeping with our current guidelines.” Dehghani reported results from nearly 1,000 patients with a positive diagnosis of COVID-19 or individuals with suspected COVID-19 who presented with STEMI to various sites in the U.S. and Canada and were enrolled in the North American COVID-19 Myocardial Infarction (NACMI) Registry. NACMI is an ongoing, prospective, observational registry that was created under the guidance of SCAI, the American College of Cardiology and the Canadian Association of Interventional Cardiology. The aim of the registry is to compare demographics, clinical findings, outcomes and management strategies of patients with COVID-19 and STEMI compared with a matched historical control of STEMI activation patients from the Midwest STEMI Consortium, and to develop data-driven treatment plans, guidelines and diagnostic acumen for this unique patient population.
The Clinical Challenge of ST-Segment Elevation Myocardial Infarction and COVID-19
Journal of the American College of Cardiology, April 27, 2021
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the cause of coronavirus disease 2019 (COVID-19), has major cardiovascular implications including myocardial injury, myocarditis, stress-induced cardiomyopathy, and arterial and venous thrombotic complications presenting as acute coronary syndromes (ACS) and venous thromboembolism (VTE). The combination of COVID-19 and ACS is particularly challenging for diagnosis and management strategies. Significant overlap in presenting symptoms, such as respiratory signs (dyspnea, hypoxia, cough), pulmonary infiltrates (mostly ground glass opacities), and chest pain may lead to missed or delayed diagnosis of significant cardiovascular scenarios and complications. Furthermore, elevated cardiac biomarkers, such as high-sensitivity cardiac troponin, N-terminal pro–B-type natriuretic peptide, and d-dimer may be elevated in both ACS and COVID-19 patients, making it even more difficult to distinguish between the clinical syndromes at the time of presentation to the hospital. In addition, hospital and health care system reorganization status in reaction to COVID-19 has jeopardized access to emergency treatment, including reperfusion therapy, by limiting or reducing coronary procedures and/or routine diagnostic cardiac evaluations. ST-segment elevation myocardial infarction (STEMI) and COVID-19 have exceptional considerations. In line with current guidelines, patients with suspected STEMI should be managed with primary percutaneous coronary intervention (PPCI) without delay while the safety of health care providers is ensured. In this case, PPCI should be performed routinely even if the patient is presumed to have COVID-19, because PPCI should not be postponed. Confirmation of SARS-CoV-2 infection should not delay urgent decision management concerning reperfusion strategy.
Impact of COVID-19 Pandemic on Presentation and Outcome of Consecutive Patients Admitted to Hospital Due to ST-Elevation Myocardial Infarction
American Journal of Cardiology, April 26, 2021
Impact of COVID-19 pandemic and pandemic-related social restrictions on clinical course of patients treated for acute ST-elevation myocardial infarction (STEMI) is unclear. In the present study presentation and outcome of patients with STEMI in 2020 were compared to the years before in a German registry that includes all patients hospitalized for acute STEMI in a region with approximately 1 million inhabitants. In the year 2020 726 patients with STEMI were registered compared to 10.226 patients in the years 2006-2019 (730 ± 57 patients per year). No significant differences were observed between the groups regarding age, sex and medical history of patients. However, in the year 2020 a significantly higher rate of patients admitted with cardiogenic shock (21.9% vs. 14.2%, p<0.01) and out-of-hospital cardiac arrest (OHCA) (14.3% vs. 11.1%, p<0.01) was observed. The rate of patients with subacute myocardial infarction (14.3% vs. 11.6%, p<0.05) was elevated in 2020. Hospital mortality increased by 52% from the years 2006-2019 (8.4%) to the year 2020 (12.8%, p<0.01). Only 4 patients (0.6%) with STEMI in the year 2020 had SARS-CoV-2 infection, none of those died in-hospital. In conclusion, in the year 2020 a highly significant increase of STEMI-patients admitted to hospital with advanced infarction and poor prognosis was observed. As the structure of the emergency network to treat patients with STEMI was unchanged during the study period, the most obvious reason for these changes was COVID-19 pandemic-related lockdown and the fear of many people to contact medical staff during the pandemic.
Can Heart Failure Show Up in COVID Patients Out of the Blue?
MedPage Today, April 26, 2021
It was rare but possible for COVID-19 patients without cardiovascular disease (CVD) or cardiovascular risk factors to develop new heart failure (HF) during their illness, according to a center in New York. A retrospective analysis of 6,439 hospitalized COVID-19 patients found that 0.6% had new HF and 6.6% had a history of HF, reported Anuradha Lala, MD, of Icahn School of Medicine at Mount Sinai in New York City, and colleagues. As shown in their research letter online in the Journal of the American College of Cardiology, out of the 37 people who experienced new HF, 13 had presented with shock (four cardiogenic, six septic, three mixed) and five with acute coronary syndrome. Just eight had neither CVD nor any related risk factors, whereas 14 had a history of CVD and another 15 at least one risk factor. The eight individuals developing new HF despite a lack of CVD tended to be younger and have a lower body mass index and fewer comorbidities compared with other new HF patients. These eight had similar lengths of stay in the hospital as peers with existing CVD or cardiovascular risk factors. However, these patients were more likely to require intensive care admission and intubation, and had a lower risk of in-hospital mortality, Lala’s group reported.
Certain younger patients with COVID-19, no risk factors or CVD may be at risk for new HF
Helio | Cardiology Today, April 26, 2021
While not great in number, there exists a distinct subgroup of younger patients with COVID-19 but no risk factors or prior CVD who are at elevated risk for new HF, according to a research letter. “This is one of the largest studies to date to specifically capture instances of new heart failure diagnosis among patients hospitalized with COVID-19. While rare, the finding of new heart failure was more common among patients with preexisting cardiovascular risk factors or disease. But, there were select individuals who developed new heart failure without risk factors or disease. We need to learn more about how SARS-CoV-2 [the virus that causes COVID-19] may directly affect the cardiovascular system and precipitate new heart failure — as to whether it is an indirect effect of critical illness or direct viral invasion,” Anuradha Lala, MD, director of heart failure research at the Icahn School of Medicine at Mount Sinai, said in a press release. “Importantly, though symptoms of heart failure — namely shortness of breath — can mimic symptoms associated with COVID-19, being alerted to the findings of this study may prompt clinicians to monitor for signs of congestion more consistent with heart failure than COVID-19 alone.” Of 6,439 patients with a positive COVID-19 test, 0.6% had new HF and 6.6% had a history of HF. Of those with new HF, 13 presented with shock and five presented with ACS. The researchers found 22% of patients with new HF had no CV risk factors or CVD; 38% had a history of CVD; and 40% had at least one risk factor.
Coronary angioplasty and COVID-19: are heparin requirements and thrombotic complications increasing?
American Heart Journal | Acute Cardiovascular Care, April 26, 2021
Covid-19 infection is associated with coagulopathy and possible heparin resistance, raising concerns that routine heparin during percutaneous coronary intervention (PCI) is failing to achieve adequate anticoagulation. We examined heparin requirements and efficacy in patients treated by PCI before and after the first reported UK case of Covid-19 (January 31, 2020). We retrospectively compared heparin dose, Activated Clotting Time (ACT) and coronary flow (TIMI grade) for PCI procedures at a London cardiac centre in the 3 months before the UK pandemic and the three months afterwards. Testing for COVID was not routinely performed. Pre-specified analyses in patients with STEMI, NSTEMI and Stable angina were undertaken. Of 1227 PCI procedures performed over the period of observation, 690 were pre-pandemic and 537 were afterwards. Overall median heparin dose per case was 11000 units versus 11500 units (p = 0.137) and maximum ACTs were 291s versus 305s, respectively (p = 0.135). Pre-PCI TIMI 3 flow was lower during the pandemic than before (60% v 65%, p = 0.005) but Post-PCI flow was similar (96% versus 96%, p = 0.839). There were no statistically significant differences in heparin dose or achieved ACT among patients with STEMI, NSTEMI or Stable presentations.
Prevalence and clinical significance of relative bradycardia at hospital admission in patients with Coronavirus Disease 2019 (COVID-19)
Clinical Microbiology and Infection, April 24, 2021
The clinical relevance of relative bradycardia in patients with Coronavirus Disease 2019 (COVID-19) has been poorly investigated. We evaluated the prevalence and clinical significance of relative bradycardia at hospital admission in patients with COVID-19 in a retrospective single-center study including all adult patients with confirmed COVID-19. Relative bradycardia was observed in 41.6% of patients presenting with COVID-19 and fever. Patients with relative bradycardia were older and with higher body temperature than patients without relative bradycardia. No statistical differences were observed between the two groups as for Intensive Care Unit admission and in-hospital mortality. Relative bradycardia is a common feature of COVID-19. The presence of relative bradycardia at admission was not associated with worse outcomes.
A NOVEL CORONAVIRUS MEETS THE CARDIOVASCULAR SYSTEM: SOCIETY FOR CARDIOVASCULAR PATHOLOGY SYMPOSIUM 2021
Cardiovascular Pathology, April 23, 2021
The year 2020 will go down in history as an annus horribilis due to the rampant pandemic of the novel human coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus. While COVID-19 begins as a respiratory illness, severe COVID-19 is a systemic disease with multifaceted manifestations of involvement of the cardiovascular system. Clinical evidence of cardiovascular involvement portents an adverse, and often fatal, outcome. Cardiovascular pathologists, individually and through their organizations, the Society for Cardiovascular Pathology (SCVP) and the Association for European Cardiovascular Pathology (AECVP), have been committed to proactively studying and providing credible information about the pathological basis for the diverse manifestations of cardiovascular system involvement in COVID-19. Cardiovascular pathologists have advocated for autopsy-based investigation, participated in a multi-institutional autopsy interest group, published initial reports describing the pathological features of multi-organ involvement in COVID-19, and lead investigative efforts to determine the multifaceted clinical manifestations of involvement of the cardiovascular system in COVID-19. Fittingly, the SCVP Symposium in 2021 was focused on COVID-19. The SCVP 2021 Symposium was organized by the SCVP program committee led by Dr. Dylan Miller and was held virtually on Saturday March 13 as part of the SCVP Companion Meeting accompanying the United States and Canadian Academy of Pathology (USCAP) Annual Meeting. The title was, “A Novel Coronavirus Meets the Cardiovascular System: What We Know and How We Know It.” An important feature of the Symposium was the multidisciplinary approach to addressing the issues related to the topic. Read more on the speakers and titles of their presentations.
Commentary: The silver lining of CABG in the COVID-19 era
JTCVS Open, April 22, 2021
There has been a substantial decline in patients presenting for emergent and routine cardiovascular care in the United States after the onset of the corona-virus disease 2019 (COVID-19) pandemic. We sought to assess the risk of adverse clinical outcomes among patients undergoing coronary artery bypass graft (CABG) surgery during the 2020 COVID-19 pandemic period and compare the risks with those undergoing CABG before the pandemic in the year 2019. A retrospective cross-sectional analysis of the TriNetX Research Network database was performed. Patients undergoing CABG between January 20, 2019, and September 15, 2019, contributed to the 2019 cohort, and those undergoing CABG between January 20, 2020, and September 15, 2020, contributed to the 2020 cohort. Propensity-score matching was performed, and the odds of mortality, acute kidney injury, stroke, acute respiratory distress syndrome, and mechanical ventilation occurring by 30 days were evaluated. The number of patients undergoing CABG in 2020 declined by 35.5% from 5534 patients in 2019 to 3569 patients in 2020. After propensity-score matching, 3569 patient pairs were identified in the 2019 and the 2020 cohorts. Compared with those undergoing CABG in 2019, the odds of mortality by 30 days were 0.96 (95%confidence interval [CI], 0.69-1.33; P = .80) in those undergoing CABG in 2020. The odds for stroke (odds ratio [OR], 1.201; 95%CI, 0.96-1.39), acute kidney injury (OR, 0.76; 95%CI, 0.59-1.08), acute respiratory distress syndrome (OR, 1.01; 95%CI, 0.60-2.42), and mechanical ventilation (OR, 1.11; 95%CI, 0.94-1.30) were similar between the 2 cohorts.
COVID-19 and hypertension: Is there a role for dsRNA and activation of Toll-like receptor 3?
Vascular Pharmacology, April 22, 2021
The virus responsible for the coronavirus disease of 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidences suggest that COVID-19 could trigger cardiovascular complications in apparently healthy patients. Coronaviruses are enveloped positive-strand RNA viruses acting as a pathogen-associated molecular pattern (PAMP)/ danger-associated molecular patterns (DAMP). Interestingly, Toll-like receptor (TLR) 3 recognize both PAMPs DAMPs and is activated by viral double-stranded RNA (dsRNA) leading to activation of TIR receptor domain-containing adaptor inducing IFN-β (TRIF) dependent pathway. New evidence has shown a link between virus dsRNA and increased BP. Hence, we hypothesize that COVID-19 infection may be over activating the TLR3 through dsRNA, evoking further damage to the patients, leading to vascular inflammation and increased blood pressure, favoring the development of several cardiovascular complications, including hypertension.
Wide QRS complex and left ventricular lateral repolarization abnormality: The importance of ECG markers on outcome prediction in patients with COVID-19
American Journal of the Medical Sciences, April 21, 2021
[Editorial] There is a clear reported increased morbidity and mortality with coronavirus disease 2019 (COVID-19) with the presence of cardiac injury. Non-ischemic events and ischemic myocardial involvement are the two main pathophysiological mechanisms described for acute cardiac injury in COVID-19 patients. This pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Up to November 5, 2020, this disease resulted in considerable morbidity and mortality worldwide with 47,596,852 laboratory-confirmed cases and 1,216,357 deaths. Most of the studies that reported myocardial involvement were based on elevated serum cardiac biomarkers, while others on cardiac magnetic resonance imaging. It was reported recently that there is also evidence of direct viral damage of the myocardium causing acute myocarditis detected by histological studies. This was manifested as myocardial edema and acute myocardial injury with the presence of SARS-CoV-2 on electron microscopy. Electrocardiogram (ECG) abnormalities commonly seen in cardiac injury are ST elevation and PR depression. Other ECG abnormalities that can be observed in acute cardiac injury include new-onset bundle branch block, QT prolongation, pseudoinfarct pattern, premature ventricular complexes, bradyarrhythmias and ventricular tachycardia (VT). In this issue of the American Journal of The Medical Sciences, Sonsoz MR, et al. demonstrated that two simple ECG parameters can be associated with markers of myocardial injury and clinical outcomes in hospitalized patients with COVID-19. The authors succeeded in finding that the presence of QRS duration longer than 120 ms and left ventricular (LV) lateral ST-T segment abnormalities were associated with worse clinical outcome and higher levels of myocardial injury biomarkers.
Cardiology in the COVID-19 era: Performing TAVR in unprecedented times
Helio | Cardiology Today, April 20, 2021
The early days of the COVID-19 pandemic challenged interventional cardiologists in unexpected ways, including the disruption of all aspects of care and the halting of most transcatheter aortic valve replacements. As cases rose in the spring of 2020, statewide mandates forced many hospitals to stop performing elective procedures. TAVR, which is primarily performed on an elective basis, was among them. Consequently, for several months, cath labs and operating rooms stood silent, except for urgent or emergent cases. In an interview with Healio, Jordan G. Safirstein, MD, FACC, FSCAI, director of transradial intervention at Morristown Medical Center in New Jersey, discussed his personal experiences with COVID-19; how the disease affected care of patients with aortic stenosis and the decision to perform TAVR; what has changed within the past year; and a slow return to some degree of normalcy with the resumption of elective TAVR procedures.
Adverse outcomes elevated in concomitant COVID-19, STEMI
Helio | Cardiology, April 19, 2021
Patients with STEMI and COVID-19 were less likely to undergo primary PCI and were more likely to experience adverse outcomes compared with those who presented with STEMI before the pandemic, researchers reported. Also, according to new data from the North American COVID-19 STEMI Registry, underrepresented groups more often tested positive for COVID-19 when presenting with STEMI. For the present analysis, researchers divided patients into those with STEMI and confirmed COVID-19 (n = 230), those with STEMI and suspected COVID-19 infection (n = 495) and age- and sex-matched patients with STEMI treated from 2015 to 2019, who served as controls (n = 460). The primary outcome was a composite endpoint that comprised in-hospital death, stroke, recurrent MI or repeat unplanned revascularization. Researchers observed that patients who tested positive for COVID-19 were mostly men (71%) and from an underrepresented group (23% Hispanic; 24% Black; 6% Asian). White patients represented 39% of those who tested positive. Among the cohort who tested positive for COVID-19, 18% had cardiogenic shock and 11% had cardiac arrest.
Prevalence and prognostic associations of cardiac abnormalities among hospitalized patients with COVID-19: a systematic review and meta-analysis
Scientific Reports, April 19, 2021
Although most patients recover from COVID-19, it has been linked to cardiac, pulmonary, and neurologic complications. Despite not having formal criteria for its diagnosis, COVID-19 associated cardiomyopathy has been observed in several studies through biomarkers and imaging. This study aims to estimate the proportion of COVID-19 patients with cardiac abnormalities and to determine the association between the cardiac abnormalities in COVID-19 patients and disease severity and mortality. Observational studies were obtained from electronic databases (PubMed, Embase, Cochrane Library, CNKI) and preprint servers (medRxiv, bioRxiv, ChinaXiv). Studies that have data on prevalence were included in the calculation of the pooled prevalence, while studies with comparison group were included in the calculation of the odds ratio. If multiple tests were done in the same study yielding different prevalence values, the largest one was used as the measure of prevalence of that particular study. A total of 400 records were retrieved from database search, with 24 articles included in the final analysis. Pooled prevalence of cardiac abnormalities in 20 studies was calculated to be 0.31 [95% Confidence Intervals (CI) of (0.23; 0.41)], with statistically significant heterogeneity (percentage of variation or I-squared statistic I2 = 97%, p < 0.01). Pooled analysis of 19 studies showed an overall odds ratio (OR) of 6.87 [95%-CI (3.92; 12.05)] for cardiac abnormalities associated with disease severity and mortality, with statistically significant heterogeneity (I2 = 85%, between-study variance or tau-squared statistic τ2 = 1.1485, p < 0.01). Due to the high uncertainty in the pooled prevalence of cardiac abnormalities and the unquantifiable magnitude of risk (although an increased risk is certain) for severity or mortality among COVID-19 patients, much more long-term prognostic studies are needed to check for the long-term complications of COVID-19 and formalize definitive criteria of “COVID-19 associated cardiomyopathy”.
High-Sensitivity Cardiac Troponin T for the Detection of Myocardial Injury and Risk Stratification in COVID-19
Clinical Chemistry, April 16, 2021
We conducted a multicenter, retrospective, observational, US-based study of COVID-19 patients undergoing hs-cTnT. Outcomes included short-term mortality (in-hospital and 30-days post-discharge) and a composite of major adverse events including respiratory failure requiring mechanical ventilation, cardiac arrest, and shock within the index presentation and/or mortality during the index hospitalization or within 30-days post-discharge. Among 367 COVID-19 patients undergoing hs-cTnT, myocardial injury was identified in 46%. They had a higher risk for mortality (20% vs. 12%, P<0.0001; unadjusted HR 4.44, 95% CI 2.13-9.25, P<0.001) and major adverse events (35% vs. 11%, P<0.0001; unadjusted OR 4.29, 95% CI 2.50-7.40, P<0.0001). Myocardial injury was associated with major adverse events (adjusted OR 3.84, 95% CI 2.00-7.36, P<0.0001) but not mortality. Baseline (adjusted OR 1.003, 95% CI 1.00-1.007, P=0.047) and maximum (adjusted OR 1.005, 95% CI 1.001-1.009, P=0.0012) hs-cTnT were independent predictors of major adverse events. Most (95%) increases were due to myocardial injury, with 5% (n = 8) classified as type 1 or 2 myocardial infarction. A single hs-cTnT <6 ng/L identified 26% of patients without mortality, with a 94.9% (95% CI 87.5-98.6) negative predictive value and 93.1% sensitivity (95% CI 83.3-98.1) for major adverse events in those presenting to the ED. Myocardial injury is frequent and prognostic in COVID-19. While most hs-cTnT increases are modest and due to myocardial injury, they have important prognostic implications. A single hs-cTnT <6 ng/L at presentation may facilitate the identification of patients with a favorable prognosis.
FDA rescinds EUA for bamlanivimab monotherapy as COVID-19 treatment
Infectious Disease News, April 16, 2021
The FDA has rescinded the emergency use authorization for bamlanivimab monotherapy for the treatment of mild-to-moderate COVID-19 in adults and certain children. The emergency use authorization (EAU) has been revoked because of the sustained increase in COVID-19 viral variants that are resistant to bamlanivimab (Eli Lilly) alone, resulting in treatment failure, according to an FDA-issued press release. Last year, the FDA issued an EUA to Eli Lilly for the emergency use of bamlanivimab, a monoclonal antibody, alone. Eli Lilly has now requested the FDA to revoke the EUA because they want to focus on the combination of bamlanivimab and etesevimab. Alternative monoclonal antibody therapies remain available under EUA for this same indication. These include the combination of casirivimab (REGN10933, Regeneron Pharmaceuticals) and imdevimab (REGN10987, Regeneron Pharmaceuticals), or REGEN-COV, and bamlanivimab combined with etesevimab, according to the FDA.
How The COVID-19 Pandemic Has Affected Cardiology Fellow Training
American Journal of Cardiology, April 15, 2021
With the advent of the COVID-19 pandemic in the United States, resources have been reallocated and elective cases have been deferred to minimize the spread of the disease, altering the workflow of cardiac catheterization laboratories across the country. This has in turn affected the training experience of cardiology fellows, including diminished procedure numbers and a narrow breadth of cases as they approach the end of their training before joining independent practice. It has also taken a toll on the emotional well-being of fellows as they see their colleagues, loved ones, patients or even themselves struggling with COVID-19, with some succumbing to it. The aim of this opinion piece is to focus attention on the impact of the COVID-19 pandemic on fellows and their training, challenges faced as they transition to practicing in the real world in the near future and share the lessons learned thus far. We believe that this is an important contribution and would be of interest not only to cardiology fellows-in-training and cardiologists but also trainees in other procedural specialties.
Stroke occurs infrequently in large cohort study of patients hospitalized with COVID-19
American Academy of Neurology, April 15, 2021
Acute stroke occurred rarely in a cohort of nearly 2,700 “critically ill” patients with COVID-19, according to findings from an international registry that also demonstrated greater mortality with hemorrhagic, but not ischemic, stroke. Study results showed that 59 of the 2,699 patients with COVID-19 (2.2%) had an acute stroke during their ICU admission. The researchers presented their findings at the American Academy of Neurology annual meeting, which is being held virtually. The researchers registered 2,699 patients from more than 370 sites in 52 countries. The study comprised mostly men (65%) and the median age of patients was 53 years. Of these patients, 59 (2.2%) experienced an acute stroke during their ICU stay, including 19 patients who had an ischemic stroke (32%) and 27 patients who had a hemorrhagic stroke (46%). The type of stroke was unspecified in 13 patients (22%), according to the study results. The researchers observed high mortality in patients who had a hemorrhagic stroke (72%), but stroke was the primary cause of death in only 15% of patients. Multiorgan failure represented the leading cause of death, according to the study results.
Out-of-hospital cardiac arrests rose when local COVID-19 prevalence high
Cardiology Today, April 14, 2021
Most cities experienced significant increases in out-of-hospital cardiac arrest that paralleled spikes in local COVID-19 prevalence, researchers reported. “The highly stressful clinical challenge of out-of-hospital cardiac arrest occurs frequently and somewhat predictable with about 30,000 cases routinely presenting each month in North America and a similar proportionate number in European nations,” Kevin E. McVaney, MD, specialist in the department of emergency medicine at the University of Colorado School of Medicine and the Denver Health and Hospital Authority, and colleagues wrote in EClinicalMedicine. “However, as SARS-CoV-2 infections began to surge in the first epicenters such as Milan, London, New York and Detroit, their emergency medical services (EMS) agencies were already reporting alarming increases in out-of-hospital cardiac arrest, even prior to implementation of shelter-at-home directives and the tallying of COVID-19-related deaths.” In April 2020, there was a 1.5-fold increase in out-of-hospital cardiac arrests among 13 U.S. cities, and three COVID-19 epicenters — New York City, Detroit and Washington, D.C. — more than doubled their usual numbers for out-of-hospital cardiac arrest events; there was a 2.5-fold increase in New York City. Researchers observed unchanged or diminished numbers of out-of-hospital cardiac arrest events in cities with lesser COVID-19 impact. During April 2020, on average, there was a 59% increase in out-of-hospital cardiac arrest cases per city (P = .03). London, Milan, New York City, Detroit, St. Louis and New Orleans had the highest out-of-hospital cardiac arrest increases but returned to or approached the pre-COVID numbers after mitigation of the spread of COVID-19 in June 2020. However, cities that were minimally affected by COVID-19 during April 2020 experienced marked out-of-hospital cardiac arrest increases when they had local surges of COVID-19 infections.
The Jessa Hospital experience for cardiac rehabilitation
European Heart Journal, April 14, 2021
Everyone around the world is experiencing challenging times in dealing with the COVID-19 pandemic. It has impacted personal life as much as it has influenced the way we work. Healthcare systems and healthcare professionals are being tested to the limit and the effects will affect us even long after the acute crisis is passed. It is on the other hand impressive to see how fast healthcare organizations such as hospitals are able to reorganize and develop new ways of communicating and reaching patients through tele-medicine. Just a few months ago, COVID-19 restrictions were announced in Belgium. Suddenly every non-urgent medical contact needed to be postponed and extra caution was advised for many high-risk patients. This led to the discontinuation of ambulatory cardiac rehabilitation (CR) programmes. In this article, the experience of one of the European Association of Preventive Cardiology (EAPC) accredited CR centres (Heart Centre Hasselt, Jessa Hospital) is described. We hope it can inspire other centres in Europe to adopt new methods in order to reach our CR patients by using digital tools.
Stroke Imaging Utilization According to Age and Severity during the COVID-19 Pandemic
Radiology, April 13, 2021
Stroke imaging utilization decreased early in the pandemic, particularly for less severe strokes, but later recovered; there was no meaningful change in the age of imaged patients during the pandemic. There was a profound decrease in acute ischemic stroke (AIS) evaluations across the United States during the early Covid-19 pandemic. This decrease was attributed to stay-at-home measures that were lifted for the later “reopening” period. Here, we report trends in nationwide stroke imaging utilization, patient demographics, and imaging characteristics in the early pandemic and reopening periods. CTP data prospectively acquired at over 800 U.S. hospitals between January 1, 2019 and October 31, 2020 and processed with RAPID (iSchemaView, Inc., Menlo Park, CA) were entered into a de-identified, de-duplicated database. Counts of daily unique patients were generated from this database using imaging timestamps. Counts were subdivided by age, gender, and CTP findings and normalized by the number of active, RAPID-connected hospitals. Cases with missing or mislabeled data were retained. Patients ≤50 years were classified as young. CTP was classified as positive if hypoperfusion volume or estimated ischemic core volume was non-zero, and as substantial penumbra if it met the DEFUSE 3 target mismatch profile. Counts were grouped into epochs. The pre-pandemic epoch was January 5, 2020 to February 29, 2020, as counts from this period were similar to an earlier baseline. The early-pandemic epoch was March 26, 2020 to April 8, 2020, corresponding to nadir of the two-week moving average of daily counts. The reopening epoch was June 9, 2020 to October 26, 2020, the earliest period with no active statewide stay-at-home orders. Epochs were defined in 7-day multiples to exclude weekend effects. The per-site daily volume of CTP, positive CTP, and CTP with substantial penumbra in the early-pandemic period was 37.0% (34.7%, 39.3%), 29.7% (26.1%, 33.1%), and 26.3% (20.7%, 31.5%) lower, respectively, than the pre-pandemic baseline. Following this nadir, imaging volume recovered over 10 weeks. The per-site daily volume of CTP, positive CTP, and CTP with substantial penumbra during the reopening period was 5.1% (2.9%, 7.3%), 7.8% (5.5%, 10.0%), and 5.3% (1.4%, 8.9%) lower, respectively, than the pre-pandemic baseline.
Effect SARS-COV-2 on Cases of Transcatheter Aortic Valve Implantation
American Journal of Cardiology, April 13, 2021
The effect of SARS-COV-2 diagnosis on cases of aortic stenosis that requires a transcatheter aortic valve implantation (TAVI) is poorly understood, and the long-term effects are not well reported. The researchers aimed to determine whether there exists a difference in all-cause mortality between patients with a SARS-COV-2 diagnosis that received a TAVI compared to those that did not contract SARS-COV-2. The researchers queried the TriNetX database, a COVID-19 research network of 61 health care organizations. They analyzed the data using the ICD 10 codes used for TAVI procedures from January 20th, 2020 to January 30th, 2021, and identified 3,075 patients aged 18–90 between the two groups: 224 SARS-COV-2 TAVI and 2,851 non-SARS-COV-2 TAVI patients. Descriptive statistics were used to measure association, and the Kaplan-Meier survival curve was used to assess the endpoints of mortality. A propensity score matching of 1:1 was performed with the covariates (i.e., age, male, female, hypertension, coronary artery disease, heart failure, diabetes, smoking history, chronic obstructive pulmonary disease, and body mass index < 30) to reduce possible differences, which resulted in a matched cohort (n = 224/224) over a 365-day time frame. Adjusted hazard ratios of mortality were compared by SAR-COV-2 diagnosis using the Cox proportional hazards model. The researchers identified 3,075 patients aged 18–90 with comparable ages between the two groups (77.1± 9.26 vs. 76.9 ± 8.94; P = 0.65). Compared to the non-SARS-COV-2 TAVI group, the SARS-COV-2 TAVI group had higher baseline comorbidities, including hypertension (95.9% vs. 76.1%; P < 0.01), coronary artery disease (88.8% vs. 66.8%; P < 0.01), heart failure (86.1% vs. 47.0%; P < 0.01), diabetes (65.1% vs. 35.4%; P < 0.01), smoking history (50.4% vs. 29.4%; P < 0.01), chronic obstructive pulmonary disease (38.3% vs. 16.8%; P < 0.01), and body mass index < 30 (66.5% vs. 40.7%; P < 0.01). A log rank test illustrated that the SARS-COV-2 TAVI group had a lower survival probability at end of time window compared to the non-SARS-COV-2 TAVI group (70.7% vs. 92.9%; P < 0.01). A hazards ratio further verified the results (9.8, P < 0.02).
Cytosorb treatment in severe COVID-19 cardiac and pulmonary disease
European Heart Journal-Case Reports, April 12, 2021
A 75-year-old man was admitted for COVID-19-related respiratory failure (p/F ratio 205 on Day 1). He was treated with intravenous dexamethasone (6 mg per day), enoxaparin (4000 international units once daily), and non-invasive ventilation. Levels of cardiac damage and inflammatory biomarkers, including high-sensitivity troponin T (25 pg/mL, normal values 0–14 pg/mL), N-terminal pro-brain natriuretic peptide (2546 ng/L, normal values 0–125 ng/L), D-dimer (633 ng/mL, normal values 0–500 ng/mL), and interleukin-6 (6768 ng/L, normal values 0–7 ng/L), were significantly elevated. On Days 2 and 3 from admission, the patient received two cycles of tocilizumab therapy (two intravenous bolus of 400 mg over 2 days) but during the following 72 h his clinical conditions deteriorated due to severe respiratory failure with severe hypoxaemia (p/F ratio 95), hypotension, and hypoperfusion. He was intubated and transferred to COVID-19 intensive care. Contrast-enhanced chest computed tomography (CT) showed bilateral ground-glass lesions, subpleural consolidations, pleural effusions, and subsegmental pulmonary embolism. Echocardiography showed normal left ventricular function but signs of acute cor pulmonale with reduced tricuspid annular systolic excursion plane, fractional area change, and right ventricular (RV) longitudinal strain with increased systolic pulmonary artery pressure. Despite treatment with high-dose vasoactive drugs, unfractionated heparins and antibiotics, he developed refractory shock with anuria. Due to the presence of persisting anuria with hyperkaliaemia (6.0 mmol/L), we started continuous renal replacement therapy (CRRT) and immunoadsorption with Cytosorb™ (Cytosorbents Corporation, NJ, USA) system. After 72 h, we observed a significant haemodynamic improvement together with an important decline of inflammatory and cardiac damage markers levels and, due to the presence of spontaneous diuresis with negative fluid balance, we stopped CRRT and immunoadsorption therapy. Control chest CT showed significant reduction of consolidations, pleural effusions and ground-glass lesions, while echocardiography documented significant improvement of RV function. The patient was extubated 3 days later and on Day 14 (p/F ratio 390) transferred to a respiratory rehabilitation centre with stable haemodynamics and no need for CRRT. After 6 months, the patient has completely recovered, with normal RV function.
CARDIOVASCULAR RNA MARKERS AND ARTIFICIAL INTELLIGENCE MAY IMPROVE COVID-19 OUTCOME: POSITION PAPER FROM THE EU-CardioRNA COST Action CA17129
Cardiovascular Research, April 11, 2021
The coronavirus disease 2019 (COVID-19) pandemic has been as unprecedented as unexpected, affecting more than 105 million people worldwide as of February 8th, 2020 and causing more than 2.3 million deaths according the World Health Organization. Not only affecting the lungs and provoking acute respiratory distress, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to infect multiple cell types including cardiac and vascular cells. Hence, a significant proportion of infected patients develop cardiac events such as arrhythmias and heart failure. Patients with cardiovascular comorbidities are at highest risk of cardiac death. To face the pandemic and limit its burden, health authorities have launched several fast track calls for research projects aiming to develop rapid strategies to combat the disease, as well as longer-term projects to prepare for the future. Biomarkers have the possibility to aid in clinical decision-making and tailoring healthcare in order to improve patient quality of life. The biomarker potential of circulating RNAs has been recognized in several disease conditions, including cardiovascular disease. RNA biomarkers may be useful in the current COVID-19 situation. The discovery, validation and marketing of novel biomarkers, including RNA biomarkers, require multi-centre studies by large and interdisciplinary collaborative networks, involving both the academia and the industry. Here, members of the EU-CardioRNA COST Action CA17129 summarize the current knowledge about the strain that COVID-19 places on the cardiovascular system and discuss how RNA biomarkers can aid to limit this burden. They present the benefits and challenges of the discovery of novel RNA biomarkers, the need for networking efforts and the added value of artificial intelligence to achieve reliable advances.
COVID-19 confers elevated VTE risk in veterans
Cardiology Today, April 6, 2021
Among veterans hospitalized at Veterans Affairs facilities, patients with COVID-19 are at elevated risk for venous thromboembolism, according to a study published in the American Heart Journal. “This study of patients at U.S. VA hospitals demonstrates that patients hospitalized with COVID-19, despite thromboprophylaxis, are at increased risk for VTE during admission and following discharge,” the researchers wrote. The elevated risk is “potentially resulting from propagation of a consumptive coagulopathy due to activation of inflammatory pathways or via endotheliitis,” J. Antonio Gutierrez, MD, MHS, assistant professor of medicine at Duke University School of Medicine, and colleagues wrote.
The researchers analyzed 4,461 veterans who tested positive for COVID-19 and 76,929 with negative test results (median age, 68 years; 93% men) who were hospitalized at VA centers from May 1 to Aug. 1, 2020. Researchers found that among patients with COVID-19, 9.2% had VTE compared with 6.8% of those without COVID-19 (P < .0001). After propensity score matching, patients with a positive COVID-19 test remained at elevated risk for VTE compared with those without one (HR = 1.28; 95% CI, 1.1-1.48; P = .001).
Temporal Relation Between Second Dose BNT162b2 mRNA Covid-19 Vaccine and Cardiac involvement in a Patient with Previous SARS-COV-2 Infection
IJC Heart & Vasculature, April 5, 20221
Coronavirus disease (COVID)-19 caused by severe acute respiratory syndrome coronarvirus (SARS-COV)-2 infection has been demonstrated to be associated with cardiac injury. Cases of acute myocarditis have been reported, even in patients with COVID-19 in the absence of significant lung involvement, suggesting a viral triggered immune-mediated injury. The modified RNA vaccines, the BNT162b2 and mRNA-1273, that encode the prefusion SARS-COV-2 spike glycoprotein, have shown to confer 94-95% protection against COVID-19 with a safe profile. Although these vaccines can counteract the COVID-19 pandemic, there is apprehension for patients who experienced previous SARS-COV-2 infection, as these subjects have not been tested in the trials. Systemic reactogenicity, leading to systemic adverse events often occurred after dose 2 and within 2 days after vaccination. The present report describes a case of cardiac involvement in a patient with previous SARS-COV-2 infection within days of the second dose of BNT162b2 mRNA vaccine.
Current Testing Strategies for SARS-CoV-2 in the United States
Clinical Chemistry, April 5, 2021
Since the discovery and recognition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the official declaration of the coronavirus disease-2019 (COVID-19) pandemic at the beginning of 2020, various different test methodologies have been developed at record speeds and made available for the diagnosis, screening, surveillance, and management of SARS-CoV-2 infection and COVID-19 illness. The rapid scientific developments in the quest to learn and define the mechanisms of SARS-CoV-2 transmission, illness, and recovery, in combination with the public health challenges of a rapidly spreading virus, have forced the healthcare community to adapt continuously to the unfolding pandemic. To help answer some of the questions about how testing is being used and how the in vitro diagnostic industry can help meet diagnostic testing needs, a panel of experts was convened with the objective of gaining critical insights regarding different testing strategies for SARS-CoV-2 in a variety of healthcare, community, congregate, and public health settings. We have invited back a select group of experts who participated in the Scientific Advisory Board to share their perspectives and to provide an update on the current state of testing strategies for SARS-CoV-2 from their respective points of view.
Hyperinflammation as underlying mechanism predisposing patients with cardiovascular diseases for severe COVID-19
European Heart Journal, April 2, 2021
It was already realized early in the COVID-19 pandemic that patients with cardiovascular disease, such as arterial hypertension, have a higher risk for an adverse course of COVID-19, raising the question of the underlying mechanisms. Furthermore, when it was described that the viral spike (S) glycoprotein mediates viral entry via binding to the angiotensin-converting enzyme 2 (ACE2), the question was raised whether therapies acting on the renin-angiotensin system, such as ACE inhibitors (ACEI) or angiotensin receptor blockers (ARBs), could affect the risk of infection or the clinical course of COVID-19. In a recent study, both aspects have been approached by using in-depth single-cell sequencing data of airway samples.
Adults with congenital heart disease may be at elevated risk for complicated COVID-19
Helio | Cardiology Today, April 1, 2021
Patients with adult congenital heart disease who have general risk factors such as age, obesity and multiple comorbidities had elevated risk for complicated COVID-19, according to researchers. Cyanotic lesions, such as unrepaired cyanotic defects or Eisenmenger syndrome, were among the congenital cardiac defects that put patients at particularly high risk, the researchers wrote. “So far, COVID-19 risk stratification in patients with adult congenital heart disease was based on expert opinion. Our cohort study provides observational evidence regarding COVID-19 risk factors in patients with adult congenital heart disease and improves tailoring of recommendations for preventive measures in individual patients,” Markus Schwerzmann, MD, clinician scientist at the Center for Congenital Heart Disease, Inselspital University Hospital in Bern, Switzerland, and colleagues wrote. The researchers analyzed a cohort of 105 patients (mean age, 38 years; 58% women), of whom 13 had a complicated disease course and five died. According to the researchers, 74% of patients had a confirmed diagnosis of COVID-19 determined by testing vs. 26% who had a diagnosis based on clinical grounds.
Determining which hospitalized COVID-19 patients require an urgent echocardiogram
Journal of the American Society of Echocardiography, April 1, 2021
Patients hospitalized with COVID-19 infection often have abnormal transthoracic echocardiogram (TTE) findings. However, while not all TTE abnormalities result in changes in clinical management, performing TTEs in recently infected patients increases disease transmission risks. It remains unknown whether common biomarker tests, such as troponin and B-type natriuretic peptide (BNP), can help distinguish in which COVID-19 patients a TTE may be safely delayed until infection risks subside. Using electronic health records data and chart review, we retrospectively studied all patients hospitalized with COVID-19 infection at our multi-site healthcare system from 2/27/2020-1/15/2021 who underwent a TTE within 14 days of their first positive COVID-19 test and had a BNP and troponin measured before or within 7 days of TTE. The primary outcome was presence of ≥1 urgent echocardiographic finding defined as left ventricular ejection fraction ≤35%, wall motion score index ≥1.5, ≥moderate right ventricular dysfunction, ≥moderate pericardial effusion, intracardiac thrombus, pulmonary artery systolic pressure >50mmHg, or ≥moderate-severe valvular disease. We conducted stepwise logistic regression to determine biomarkers and comorbidities associated with the outcome. We evaluated the performance of a rule for classifying TTEs using troponin and BNP. We included 434 hospitalized and 151 ICU COVID-19 patients. Urgent TTE findings were present in 105 (24.2%) patients. Troponin and BNP were abnormal in 311 (71.7%). Heart failure (OR (95%CI) 5.41 (2.61-11.68)), troponin >0.04ng/mL (4.40 (2.05-10.05)), BNP >100pg/mL (5.85 (2.35-16.09)) remained significant predictors of urgent TTE findings after stepwise selection. 95.1% of all patients and 91.3% of ICU patients with normal troponin and BNP had no urgent TTE findings.
Aortic thrombosis in a patient with COVID-19-associated hyperinflammatory syndrome
International Journal of Infectious Diseases, April 1, 2021
A 77-year-old man was admitted for severe PCR-confirmed COVID-19. The patient presented with severe hypoxemia and biological findings suggestive of hyperinflammatory syndrome: severe lymphopenia in combination with signs of hypercytokinemia (elevated C-reactive protein), coagulopathy (elevated D-dimer levels) and hepatic injury (elevated lactate dehydrogenase). A CT-angiography of the thorax showed ground glass opacities in the 5 lobes, but no signs of pulmonary embolism. The patient was treated with dexamethasone, prophylactic dose of low molecular weight heparin (LMWH), high flow oxygen therapy and a single infusion of tocilizumab within a clinical trial. After six days of hospitalization D-dimer levels were remarkably rising to a level of 9210 ng/ml. A CT-angiography was repeated because pulmonary embolism was suspected. The images showed a partial thrombosis of the descending aorta. The patient was treated with therapeutic anti-coagulation and made a full recovery. Thrombo-embolic events are frequently described in Covid-19 patients and are the consequence of hyperinflammatory response and endothelial dysfunction. A potential role of antiphospholipid syndrome secondary to Sars-cov-2 infection has been proposed. D-dimer level increase has been shown to be associated with thrombo-embolic events, including arterial thrombosis.
Intraventricular Conundrum in a SARS-CoV-2–Positive Patient With Elevated Biomarkers of Myocardial Injury
Journal of the American College of Cardiology: Case Reports, March 31, 2021
We present a case of acute myocarditis with left ventricular dysfunction and intracavitary thrombosis in a 55-year-old man with severe acute respiratory syndrome coronavirus 2 infection (coronavirus disease 2019) who was admitted with bilateral atypical pneumonia. The patient was treated with anticoagulation and optimal heart failure therapy and had an improvement of left ventricular function and thrombus resolution.
Coronary Artery Bypass Graft Surgery Outcomes in the United States: Impact of COVID-19 Pandemic
Journal of Thoracic and Cardiovascular Surgery (JTCVS) Open, March 30, 2021
There has been a substantial decline in patients presenting for emergent and routine cardiovascular care in the United States after the onset of the coronavirus disease-2019 (COVID-19) pandemic. We sought to assess the risk of adverse clinical outcomes among patients undergoing coronary artery bypass graft (CABG) surgery during the 2020 COVID-19 pandemic period and compare the risks to those undergoing CABG prior to the pandemic in the year 2019. A retrospective cross-sectional analysis of the TriNetX Research Network database was performed. Patients undergoing CABG between January 20, 2019, and September 15, 2019, contributed to the 2019 cohort, and those undergoing CABG between January 20, 2020, and September 15, 2020, contributed to the 2020 cohort. Propensity-score matching was performed, and the odds of mortality, acute kidney injury (AKI), stroke, acute respiratory distress syndrome (ARDS), and mechanical ventilation occurring by 30-days were evaluated. The number of patients undergoing CABG in 2020 declined by 35.5% from 5,534 patients in 2019 to 3,569 patients in 2020. After propensity-score matching, 3,569 patient pairs were identified in the 2019 and the 2020 cohorts. Compared with those undergoing CABG in 2019, the odds of mortality by 30-days were 0.96 (95%CI:0.69-1.33;p=0.80) in those undergoing CABG in 2020. The odds for stroke (OR:1.21 [95%CI:0.96-1.39]), AKI (OR: 0.76 [95%CI:0.59-1.08]), ARDS (OR:1.01 [95%CI:0.60-2.42]) and mechanical ventilation (OR: 1.11 [95% CI: 0.94-1.30]) were similar between the two cohorts.
How Information About Race-based Health Disparities Affects Policy Preferences: Evidence from a Survey Experiment About the COVID-19 Pandemic in the United States
Social Science & Medicine, March 29, 2021
In this article, we report on the results of an experimental study to estimate the effects of delivering information about racial disparities in COVID-19-related death rates. On the one hand, we find that such information led to increased perception of risk among those Black respondents who lacked prior knowledge; and to increased support for a more concerted public health response among those White respondents who expressed favorable views towards Blacks at baseline. On the other hand, for Whites with colder views towards Blacks, the informational treatment had the opposite effect: it led to decreased risk perception and to lower levels of support for an aggressive response. Our findings highlight that well-intentioned public health campaigns spotlighting disparities might have adverse side effects and those ought to be considered as part of a broader strategy. The study contributes to a larger scholarly literature on the challenges of making and implementing social policy in racially-divided societies.
Impact of COVID-19 pandemic and infection on in hospital survival for patients presenting with acute coronary syndromes: A multicenter registry
International Journal of Cardiology, March 29, 2021
The impact of Covid-19 on the survival of patients presenting with acute coronary syndrome (ACS) remains to be defined. Consecutive patients presenting with ACS at 18 Centers in Northern-Italy during the Covid-19 outbreak were included. In-hospital all-cause death was the primary outcome. In-hospital cardiovascular death along with mechanical and electrical complications were the secondary ones. A case period (February 20, 2020-May 3, 2020) was compared vs. same-year (January 1–February 19, 2020) and previous-year control periods (February 20–May 3, 2019). ACS patients with Covid-19 were further compared with those without. Among 779 ACS patients admitted during the case period, 67 (8.6%) tested positive for Covid-19. In-hospital all-cause mortality was significantly higher during the case period compared to the control periods (6.4% vs. 3.5% vs. 4.4% respectively; p 0.026), but similar after excluding patients with COVID-19 (4.5% vs. 3.5% vs. 4.4%; p < 0.73). Cardiovascular mortality was similar between the study groups. After multivariable adjustment, admission for ACS during the COVID-19 outbreak had no impact on in-hospital mortality. In the case period, patients with concomitant ACS and Covid-19 experienced significantly higher in-hospital mortality (25% vs. 5%, p < 0.001) compared to patients without. Moreover, higher rates of cardiovascular death, cardiogenic shock and sustained ventricular tachycardia were found in Covid-19 patients.
Is the heart rate variability monitoring using the analgesia nociception index a predictor of illness severity and mortality in critically ill patients with COVID-19? A pilot study
PLOS ONE, March 24, 2021
The analysis of heart rate variability (HRV) has proven to be an important tool for the management of autonomous nerve system in both surgical and critically ill patients. We conducted this study to show the different spectral frequency and time domain parameters of HRV as a prospective predictor for critically ill patients, and in particular, for COVID-19 patients who are on mechanical ventilation. The hypothesis is that most severely ill COVID-19 patients have a depletion of the sympathetic nervous system and a predominance of parasympathetic activity reflecting the remaining compensatory anti-inflammatory response. A single-center, prospective, observational pilot study, which included COVID-19 patients, admitted to the Surgical Intensive Care Unit was conducted. The normalized high-frequency component (HFnu), i.e. ANIm, and the standard deviation of RR intervals (SDNN), i.e. Energy, were recorded using the analgesia nociception index monitor (ANI). To estimate the severity and mortality we used the SOFA score and the date of discharge or date of death.
Cardiac surgery outcome during the COVID-19 pandemic: a retrospective review of the early experience in nine UK centres
Journal of Cardiothoracic Surgery, March 22, 2021
Early studies conclude patients with Covid-19 have a high risk of death, but no studies specifically explore cardiac surgery outcome. We investigate UK cardiac surgery outcomes during the early phase of the Covid-19 pandemic. This retrospective observational study included all adult patients undergoing cardiac surgery between 1st March and 30th April 2020 in nine UK centres. Data was obtained and linked locally from the National Institute for Cardiovascular Outcomes Research Adult Cardiac Surgery database, the Intensive Care National Audit and Research Centre database and local electronic systems. The anonymised datasets were analysed by the lead centre. Statistical analysis included descriptive statistics, propensity score matching (PSM), conditional logistic regression and hierarchical quantile regression. Of 755 included individuals, 53 (7.0%) had Covid-19. Comparing those with and without Covid-19, those with Covid-19 had increased mortality (24.5% v 3.5%, p < 0.0001) and longer post-operative stay (11 days v 6 days, p = 0.001), both of which remained significant after PSM. Patients with a pre-operative Covid-19 diagnosis recovered in a similar way to non-Covid-19 patients. However, those with a post-operative Covid-19 diagnosis remained in hospital for an additional 5 days (12 days v 7 days, p = 0.024) and had a considerably higher mortality rate compared to those with a pre-operative diagnosis (37.1% v 0.0%, p = 0.005).
COVID Strokes: Rates, Types, Disparities
MedPage Today, March 20, 2021
Large studies reported at American Stroke Association virtual International Stroke Conference (ISC) homed in on more accurate estimates of the stroke implications of COVID-19. Ischemic stroke incidence among COVID-19 patients in the American Heart Association (AHA) COVID-19 Registry was 0.75% overall, reported Saate Shakil, MD, of the University of Washington in Seattle. That rate was lower than the 0.9% to 2% reported in other studies of stroke in COVID-19 patients, she noted during an ISC late-breaking trial session. The retrospective study included consecutive patients admitted with acute ischemic stroke and COVID-19 from March 1 to May 1, 2020, at 12 stroke centers from four countries, although three of the centers were excluded from the stroke incidence calculation as they only accepted LVO transfer patients. Large vessel occlusion was also more prominent in a separate analysis of the “Get With The Guidelines-Stroke” database, accounting for 30.4% of acute ischemic strokes in COVID-19 patients versus 23.6% among non-COVID stroke patients. The analysis of 41,971 acute ischemic stroke patients (1,143 with COVID-19) hospitalized between Feb. 4 and June 29, 2020, at 458 participating hospitals was reported by Gregg Fonarow, MD, of the University of California Los Angeles, and colleagues at ISC and online in Stroke.
Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit—The INSPIRATION Randomized Clinical Trial
Journal of the American Medical Association, March 18, 2021
Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. The objective was to evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). This was a multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran, comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment.
The association of COVID-19 occurrence and severity with the use of angiotensin converting enzyme inhibitors or angiotensin-II receptor blockers in patients with hypertension
PLOS ONE, March 18, 2021
A number of studies have reported the association between the use of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin-II receptor blocker (ARB) medications and the occurrence or severity of coronavirus disease 2019 (COVID-19). Published results are inconclusive, possibly due to differences in participant comorbidities and sociodemographic backgrounds. Since ACEI and ARB are frequently used anti-hypertension medications, we aim to determine whether the use of ACEI and ARB is associated with the occurrence and severity of COVID-19 in a large study of US Veterans with hypertension. Data were collected from the Department of Veterans Affairs (VA) National Corporate Data Warehouse (VA-COVID-19 Shared Data Resource) between February 28, 2020 and August 18, 2020. Using data from 228,722 Veterans with a history of hypertension who received COVID-19 testing at the VA, we investigated whether the use of ACEI or ARB over the two years prior to the index date was associated with increased odds of (1) a positive COVID-19 test, and (2) a severe outcome (hospitalization, mortality, and use of intensive care unit (ICU) and/or mechanical ventilation) among COVID-19-positive patients. We used logistic regression with and without propensity score weighting (PSW) to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for the association between ACEI/ARB use and a positive COVID-19 test result. The association between medication use and COVID-19 outcome severity was examined using multinomial logistic regression comparing participants who were not hospitalized to participants who were hospitalized, were admitted to the ICU, used a mechanical ventilator, or died. All models were adjusted for relevant covariates, including demographics (age, sex, race, ethnicity), selected comorbidities, and the Charlson Comorbidity Index (CCI).
The Association between Cardiovascular Disease Admission Rates and the Coronavirus Disease 2019 Lockdown and Reopening of a Nation: a Danish Nationwide Cohort Study
European Heart Journal Quality of Care & Clinical Outcomes, March 17, 2021
The objective of the study was to investigate the admission rates of cardiovascular diseases, overall and according to subgroups, and subsequent mortality rates during the Covid-19 societal lockdown (March 12, 2020) and reopening phase (April 15, 2020) in Denmark. Using Danish nationwide registries, we identified patients with a first-time acute cardiovascular admission in two periods: 1) January 2-October 16, 2019 and 2) January 2-October 15, 2020. Weekly incidence rates of a first-time cardiovascular admission, overall and according to subtypes, in the two periods were calculated. The incidence rate of first-time cardiovascular admissions overall was significantly lower during the first weeks of lockdown in 2020 compared with a similar period in 2019 but increased after the gradual reopening of the Danish society. A similar trend was observed for all subgroups of cardiovascular diseases. The mortality rate among patients admitted after March 12 was not significantly different in 2020 compared with 2019 (mortality rate ratio 0.98 [95% CI, 0.91-1.06]). In Denmark, we observed a substantial decrease in the rate of acute cardiovascular admissions, overall and according to subtypes, during the first weeks of lockdown. However, after the gradual reopening of the Danish society, the admission rates for acute cardiovascular diseases increased and returned to rates similar to those observed in 2019. The mortality rate in patients admitted with cardiovascular diseases during lockdown was similar to that of patients during the same period in 2019.
Admission Rates and Care Pathways in Patients with Atrial Fibrillation during the COVID-19 Pandemic – Insights from the German-wide Helios Hospital Network
European Heart Journal Quality of Care & Clinical Outcomes, March 16, 2021
Several reports indicate lower rates of emergency admissions in the cardiovascular sector and reduced admissions of patients with chronic diseases during the COVID-19 pandemic. The aim of this study was therefore to evaluate numbers of admissions in incident and prevalent atrial fibrillation and flutter (AF) and to analyze care pathways in comparison to 2019. A retrospective analysis of claims data of 74 German Helios hospitals was performed to identify consecutive patients hospitalized with a main discharge diagnosis of AF. A study period including the start of the German national protection phase (13th March 2020 to 16th July 2020) was compared to a previous year control cohort (15th March 2019 to 18th July 2019), with further sub-division into early and late phase. Incidence rate ratios (IRR) were calculated. Numbers of admission per day (A/day) for incident and prevalent AF and care pathways including readmissions, numbers of transesophageal echocardiogram (TEE), electrical cardioversion (CV) and catheter ablation (CA) were analyzed. During the COVID-19 pandemic, there was a significant decrease of total AF admissions both in the early (44.4 vs. 77.5 A/day, IRR 0.57 [95% CI 0.54–0.61], p < 0.01) and late phase (59.1 vs. 63.5 A/day, IRR 0.93 [95% CI 0.90–0.96], p < 0.01), length of stay was significantly shorter (3.3 ± 3.1 nights vs. 3.5 ± 3.6 nights, p < 0.01), admissions were more frequently in high volume centers (77.0% vs. 75.4%, p = 0.02) and frequency of readmissions was reduced (21.7% vs. 23.6%, p < 0.01) compared to the previous year. Incident AF admission rates were significantly lower both in the early (21.9 admission per day vs. 41.1 A/day, IRR 0.53 [95% CI 0.48 − 0.58]) and late phase (35.5 vs. 39.3 A/day, IRR 0.90 [95% CI 0.86 − 0.95]), whereas prevalent admissions were only lower in the early phase (22.5 vs 36.4 A/day IRR 0.62 [95% CI 0.56 − 0.68]), but not in the late phase (23.6 vs. 24.2 A/day IRR 0.97 [95% CI 0.92 − 1.03]).
Renin-angiotensin system inhibitors and susceptibility to COVID-19 in patients with hypertension: a propensity score-matched cohort study in primary care
BMC Infectious Diseases, March 15, 2021
Renin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality. We conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome. The incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality.
Op-Ed: COVID Shot While on a Blood Thinner?
MedPage Today, March 14, 2021
As COVID-19 vaccination continues to roll out to older and medically eligible people across the country, many questions arise for those taking blood thinners. The most important point is that COVID-19 vaccine is fine for pretty much all individuals, no matter whether they have a thrombophilia, a prior deep vein thrombosis (DVT) or pulmonary embolism (PE), or are on a blood thinner. Reasons not to get the vaccine have to do with allergies but not with the fact that a patient has had a clot or is on an anticoagulant. While COVID-19 infection is associated with an increased risk of DVT and PE, particularly in the very sick and hospitalized patient, there is no reason to believe that the vaccine would increase the risk for blood clots. Recent concerns with thrombotic side effects after vaccination with the AstraZeneca shot in Europe appear to be chance events, no causally related to the vaccine. Most patients do not need to interrupt their anticoagulant before getting the vaccine. The COVID-19 vaccine is given as a shot into the deltoid muscle, just like the flu shot. The needle diameter used for injections is very fine, typically 22-25 gauge. It has been shown that intramuscular flu shots in patients on full-dose warfarin (Coumadin, Jantoven) do not increase the risk for bleeding at the site of the injection.
What we (don’t) know about myocardial injury after COVID-19
European Heart Journal, March 13, 2021
[Editorial] The frequency of cardiac injury among hospitalized patients with acute coronavirus disease 2019 (COVID-19) is estimated at 13–41% as defined by elevated troponin levels. Evidence of cardiac involvement in hospitalized COVID-19 patients is significant because cardiac injury is associated with higher mortality. Multiple mechanisms can lead to cardiac damage, including demand ischaemia, systemic hypoxia, intravascular thrombosis and endotheliitis, and myocarditis. Myocardial inflammation can result from both a systemic inflammatory response and, less commonly, direct viral injury. Because of a low rate of histological inflammation associated with the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the tissue on autopsy or endomyocardial biopsy, some have questioned whether COVID-19-related myocarditis exists. Cardiovascular injury from COVID-19 in children and adolescents is much less common than rates seen in cohorts of older patients and includes a multisystem inflammatory syndrome (termed MIS-C) with higher rates of myocarditis and arterial aneurysms. Following recovery from the acute COVID-19 illness, shortness of breath and fatigue may persist. In a recent study, 64% of patients 2–3 months after COVID-19 reported dyspnoea and fatigue, an incidence much higher than after other viral diseases. The reasons for ‘long COVID’ are not well understood, but are associated with signs of ongoing inflammation as well as tissue abnormalities of the lungs, heart, and kidneys as identified by magnetic resonance imaging (MRI).
Postural Tachycardia an Emerging Concern During COVID-19 Recovery
MedPage Today, March 10, 2021
The possibility of COVID-19 long-haulers experiencing symptoms suggestive of postural orthostatic tachycardia syndrome (POTS) was strengthened by a small case series from Sweden. Three young patients who were suspected of having COVID-19 in the spring of 2020 were diagnosed with POTS more than 3 months later on the grounds of orthostatic tachycardia and chronic symptoms of orthostatic intolerance after exclusion of competing etiologies, reported a group led by Madeleine Johansson, MD, PhD, of Lund University and Skåne University Hospital in Malmö, Sweden, in a paper published online in JACC: Case Reports. Much remains unknown about the specific mechanisms responsible for the POTS-like symptoms in post-COVID-19 patients or how long these symptoms will last, but chronic symptoms are expected in a subset of patients based on this initial clinical experience,” Johansson’s team said. “This article from Sweden documents what many autonomic clinics are starting to see, which is an increase in referrals for patients with POTS late post-COVID…The full impact of long COVID and long COVID POTS is not yet known. With over 117 million patients who have suffered from COVID-19, we may be seeing many similar patients,” said Satish Raj, MD, of University of Calgary in Alberta, who was not involved with the study. It is important for clinicians to recognize that POTS can present as a manifestation of post-acute sequelae of SARS-CoV-2 infection, given that there are many treatment options for POTS and a delay in diagnosis leads to further physical deconditioning and poor quality of life, commented Pam Taub, MD, of UC San Diego Health System in La Jolla, California.
Machine learning models to identify low adherence to influenza vaccination among Korean adults with cardiovascular disease
BMC Cardiovascular Disorders, March 9, 2021
Annual influenza vaccination is an important public health measure to prevent influenza infections and is strongly recommended for cardiovascular disease (CVD) patients, especially in the current coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to develop a machine learning model to identify Korean adult CVD patients with low adherence to influenza vaccination. Adults with CVD (n = 815) from a nationally representative dataset of the Fifth Korea National Health and Nutrition Examination Survey (KNHANES V) were analyzed. Among these adults, 500 (61.4%) had answered “yes” to whether they had received seasonal influenza vaccinations in the past 12 months. The classification process was performed using the logistic regression (LR), random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGB) machine learning techniques. Because the Ministry of Health and Welfare in Korea offers free influenza immunization for the elderly, separate models were developed for the < 65 and ≥ 65 age groups. The accuracy of machine learning models using 16 variables as predictors of low influenza vaccination adherence was compared; for the ≥ 65 age group, XGB (84.7%) and RF (84.7%) have the best accuracies, followed by LR (82.7%) and SVM (77.6%). For the < 65 age group, SVM has the best accuracy (68.4%), followed by RF (64.9%), LR (63.2%), and XGB (61.4%).
Quick Tips and Considerations for COVID-19 Vaccination in Heart Failure and Transplant Patients
American College of Cardiology, March 5, 2021
It has been nearly a year since the World Health Organization declared SARS-CoV-2/COVID-19 as a global pandemic on March 11, 2020. While a large number of SARS-CoV-2 infections result in mild symptoms, the overall death toll is staggering with nearly 2.9 million deaths worldwide and over 500,000 deaths in the United States alone as of February 27th, 2021. Underlying co-morbidities such as diabetes, hypertension, and cardiac or pulmonary disease, significantly increase the risk of death due to COVID-19. In fact, an early systematic review and meta-analysis found a case fatality rate (CFR) of 12-14% for patients with two to five co-morbidities, nearly double the baseline CFR of 7%. Patients with heart failure and those who have undergone heart transplantation may be at increased risk of mortality from COVID-19 due to co-morbidities and immunosuppression. As vaccines for COVID-19 have recently become available, many providers are receiving questions regarding vaccine recommendations for this population. The International Society for Heart and Lung Transplantation (ISHLT) and the American Society for Transplantation (AST) have both released guidance regarding COVID-19 vaccination in patients with chronic heart or lung failure and those who have undergone thoracic transplantation.
Prognostic value of cardiac biomarkers in COVID-19 infection
Scientific Reports, March 2, 2021
Multiple Biomarkers have recently been shown to be elevated in COVID-19, a respiratory infection with multi-organ dysfunction; however, information regarding the prognostic value of cardiac biomarkers as it relates to disease severity and cardiac injury are inconsistent. The goal of this meta-analysis was to summarize the evidence regarding the prognostic relevance of cardiac biomarkers from data available in published reports. PubMed, Embase and Web of Science were searched from inception through April 2020 for studies comparing median values of cardiac biomarkers in critically ill versus non-critically ill COVID-19 patients, or patients who died versus those who survived. The weighted mean differences (WMD) and 95% confidence interval (CI) between the groups were calculated for each study and combined using a random effects meta-analysis model. The odds ratio (OR) for mortality based on cardiac injury was combined from studies reporting it. Troponin levels were significantly higher in COVID-19 patients who died or were critically ill versus those who were alive or not critically ill (WMD 0.57, 95% CI 0.43–0.70, p < 0.001). Additionally, BNP levels were also significantly higher in patients who died or were critically ill (WMD 0.45, 95% CI − 0.21–0.69, p < 0.001). Cardiac injury was independently associated with significantly increased odds of mortality (OR 6.641, 95% CI 1.26–35.1, p = 0.03). A significant difference in levels of D-dimer was seen in those who died or were critically ill. CK levels were only significantly higher in those who died versus those who were alive (WMD 0.79, 95% CI 0.25–1.33, p = 0.004). Cardiac biomarkers add prognostic value to the determination of the severity of COVID-19 and can predict mortality.
Severe acute respiratory syndrome coronavirus 2-induced acute aortic occlusion: a case report
Journal of Medical Case Reports, March 2, 2021
Severe acute respiratory syndrome coronavirus 2 infection can lead to a constellation of viral and immune symptoms called coronavirus disease 2019. Emerging literature increasingly supports the premise that severe acute respiratory syndrome coronavirus 2 promotes a prothrombotic milieu. However, to date there have been no reports of acute aortic occlusion, itself a rare phenomenon. We report a case of fatal acute aortic occlusion in a patient with coronavirus disease 2019. A 59-year-old Caucasian male with past medical history of peripheral vascular disease presented to the emergency department for evaluation of shortness of breath, fevers, and dry cough. His symptoms started 5–7 days prior to the emergency department visit, and he received antibiotics in the outpatient setting without any effect. He was found to be febrile, tachypneic, and hypoxemic. He was placed on supplemental oxygen via a non-rebreather mask. Chest X-ray showed multifocal opacifications. Intravenous antibiotics for possible pneumonia were initiated. Hydroxychloroquine was initiated to cover possible coronavirus disease 2019 pneumonia. During the hospitalization, the patient became progressively hypoxemic, for which he was placed on bilevel positive airway pressure. D-dimer, ferritin, lactate dehydrogenase, and C-reactive protein were all elevated. Severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction was positive. On day 3, the patient was upgraded to the intensive care unit. Soon after he was intubated, he developed a mottled appearance of skin, which extended from his bilateral feet up to the level of the subumbilical plane. Bedside ultrasound revealed an absence of flow from the mid-aorta to both common iliac arteries. The patient was evaluated emergently by vascular surgery. After a discussion with the family, it was decided to proceed with comfort-directed care, and the patient died later that day. We believe that healthcare providers should be aware of both venous and arterial thrombotic complications associated with coronavirus disease 2019, including possible fatal outcome.
Use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers associated with lower risk of COVID-19 in household contacts
PLOS ONE, March 2, 2021
Use of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) has been hypothesized to affect COVID-19 risk. Our objective was to examine the association between use of ACEI/ARB and household transmission of COVID-19. We conducted a modified cohort study of household contacts of patients who tested positive for COVID-19 between March 4 and May 17, 2020 in a large Northeast US health system. Household members were identified by geocoding and full address matching with exclusion of addresses with >10 matched residents or known congregate living functions. Medication use, clinical conditions and sociodemographic characteristics were obtained from electronic medical record (EMR) data on cohort entry. Cohort members were followed for at least one month after exposure to determine who tested positive for SARS-CoV-2. Mixed effects logistic regression and propensity score analyses were used to assess adjusted associations between medication use and testing positive. 1,499 of the 9,101 household contacts were taking an ACEI or an ARB. Probability of COVID-19 diagnosis during the study period was slightly higher among ACEI/ARB users in unadjusted analyses. However, ACEI/ARB users were older and more likely to have clinical comorbidities so that use of ACEI/ARB was associated with a decreased risk of being diagnosed with COVID-19 in mixed effect models (OR 0.60, 95% CI 0.44–0.81) or propensity score analyses (predicted probability 18.6% in ACEI/ARB users vs. 24.5% in non-users, p = 0.03). These associations were similar within age and comorbidity subgroups, including patients with documented hypertension, diabetes or cardiovascular disease, as well as when including other medications in the models. In this observational study of household transmission, use of ACEIs or ARBs was associated with a decreased risk of being diagnosed with COVID-19.
Evaluation of myocardial injury patterns and ST changes among critical and non-critical patients with coronavirus-19 disease
Scientific Reports, March 1, 2021
Novel coronavirus disease (COVID-19) has led to a major public health crisis globally. Currently, myocardial damage is speculated to be associated with COVID-19, which can be seen as one of the main causes of death of patients with COVID-19. We therefore, aim to investigate the effects of COVID-19 disease on myocardial injury in hospitalized patients who have been tested positive for COVID-19 pneumonia in this study. A prospective study was conducted among 201 patients with COVID-19 in the Pakistan Military Hospital from April 1 to August 31, 2020, including non-critical cases and critical cases. COVID-19 patients were stratified as critical and non-critical according to the signs and symptoms severity; with those requiring intensive care and invasive mechanical ventilation as critical, and those did not requiring invasive mechanical ventilation as non-critical. A total of 201 COVID-19 patients with critical and non-critical categories presented with myocardial injury. All patients with myocardial injury had an elevation in CKMB and Troponin-I levels. Of these patients, 43.7% presented with new electrocardiography (ECG) changes, and ST depression was typically observed in 36.3% patients. In addition, 18.7% patients presented with abnormal echocardiography findings, with right ventricular dilatation and dysfunction commonly seen among critical group patients. Results analyzed by a logistic regression model showing COVID-19 direct contribution to myocardial injury in these patients. COVID-19 disease directly leads to cardiovascular damage among critical and non-critical patients. Myocardial injury is associated not only with abnormal ECG changes but also with myocardial dysfunction on echocardiography and more commonly observed among critical patients.
Myocardial injury in hospitalized patients with COVID-19 infection—Risk factors and outcomes
PLOS ONE, February 26, 2021
Myocardial injury in hospitalized patients is associated with poor prognosis. This study aimed to evaluate risk factors for myocardial injury in hospitalized patients with coronavirus disease 2019 (COVID-19) and its prognostic value. We retrieved all consecutive patients who were hospitalized in internal medicine departments in a tertiary medical center from February 9th, 2020 to August 28th with a diagnosis of COVID-19. A total of 559 adult patients were hospitalized in the Sheba Medical Center with a diagnosis of COVID-19, 320 (57.24%) of whom were tested for troponin levels within 24-hours of admission, and 91 (28.44%) had elevated levels. Predictors for elevated troponin levels were age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01–1.06), female sex (OR, 3.03; 95% CI 1.54–6.25), low systolic blood pressure (OR, 5.91; 95% CI 2.42–14.44) and increased creatinine level (OR, 2.88; 95% CI 1.44–5.73). The risk for death (hazard ratio [HR] 4.32, 95% CI 2.08–8.99) and a composite outcome of invasive ventilation support and death (HR 1.96, 95% CI 1.15–3.37) was significantly higher among patients who had elevated troponin levels. In conclusion, in hospitalized patients with COVID-19, elevated troponin levels are associated with poor prognosis. Hence, troponin levels may be used as an additional tool for risk stratification and a decision guide in patients hospitalized with COVID-19.
Cardiac involvement in COVID-19 patients: mid-term follow up by cardiovascular magnetic resonance
Journal of Cardiac Magnetic Resonance, February 25, 2021
Coronavirus disease 2019 (COVID-19) induces myocardial injury, either direct myocarditis or indirect injury due to systemic inflammatory response. Myocardial involvement has been proved to be one of the primary manifestations of COVID-19 infection, according to laboratory test, autopsy, and cardiovascular magnetic resonance (CMR). However, the middle-term outcome of cardiac involvement after the patients were discharged from the hospital is yet unknown. The present study aimed to evaluate mid-term cardiac sequelae in recovered COVID-19 patients by CMR. A total of 47 recovered COVID-19 patients were prospectively recruited and underwent CMR examination. The CMR protocol consisted of black blood fat-suppressed T2 weighted imaging, T2 star mapping, left ventricle (LV) cine imaging, pre- and post-contrast T1 mapping, and late gadolinium enhancement (LGE). LGE were assessed in mixed both recovered COVID-19 patients and healthy controls. The LV and right ventricle (RV) function and LV mass were assessed and compared with healthy controls. A total of 44 recovered COVID-19 patients and 31 healthy controls were studied. LGE was found in 13 (30%) of COVID-19 patients. All LGE lesions were located in the mid myocardium and/or sub-epicardium with a scattered distribution. Further analysis showed that LGE-positive patients had significantly decreased LV peak global circumferential strain (GCS), RV peak GCS, RV peak global longitudinal strain (GLS) as compared to non-LGE patients (p < 0.05), while no difference was found between the non-LGE patients and healthy controls. Myocardium injury existed in 30% of COVID-19 patients.
Association of coagulation dysfunction with cardiac injury among hospitalized patients with COVID-19
Scientific Reports, February 24, 2021
Cardiac injury is a common complication of the coronavirus disease 2019 (COVID-19), and is associated with adverse clinical outcomes. In this study, we aimed to reveal the association of cardiac injury with coagulation dysfunction. We enrolled 181 consecutive patients who were hospitalized with COVID-19, and studied the clinical characteristics and outcome of these patients. Cardiac biomarkers high-sensitivity troponin I (hs-cTnI), myohemoglobin and creatine kinase-myocardial band (CK-MB) were assessed in all patients. The clinical outcomes were defined as hospital discharge or death. The median age of the study cohort was 55 (IQR, 46–65) years, and 102 (56.4%) were males. Forty-two of the 181 patients (23.2%) had cardiac injury. Old age, high leukocyte count, and high levels of aspartate transaminase (AST), D-dimer and serum ferritin were significantly associated with cardiac injury. Multivariate regression analysis revealed old age and elevated D-dimer levels as being strong risk predictors of in-hospital mortality. Interleukin 6 (IL6) levels were comparable in patients with or without cardiac injury. Serial observations of coagulation parameters demonstrated highly synchronous alterations of D-dimer along with progression to cardiac injury. Cardiac injury is a common complication of COVID-19 and is an independent risk factor for in-hospital mortality. Old age, high leukocyte count, and high levels of AST, D-dimer and serum ferritin are significantly associated with cardiac injury, whereas IL6 are not. Therefore, the pathogenesis of cardiac injury in COVID-19 may be primarily due to coagulation dysfunction along with microvascular injury.
All-cause mortality and location of death in patients with established cardiovascular disease before, during, and after the COVID-19 lockdown: a Danish Nationwide Cohort Study
European Heart Journal, February 24, 2021
On 13 March 2020, the Danish authorities imposed extensive nationwide lockdown measures to prevent the spread of the coronavirus disease 2019 (COVID-19) and reallocated limited healthcare resources. We investigated mortality rates, overall and according to location, in patients with established cardiovascular disease before, during, and after these lockdown measures. Using Danish nationwide registries, we identified a dynamic cohort comprising all Danish citizens with cardiovascular disease (i.e. a history of ischaemic heart disease, ischaemic stroke, heart failure, atrial fibrillation, or peripheral artery disease) alive on 2 January 2019 and 2020. The cohort was followed from 2 January 2019/2020 until death or 16/15 October 2019/2020. The cohort comprised 340 392 and 347 136 patients with cardiovascular disease in 2019 and 2020, respectively. The overall, in-hospital, and out-of-hospital mortality rate in 2020 before lockdown was significantly lower compared with the same period in 2019 [adjusted incidence rate ratio (IRR) 0.91, 95% confidence interval (CI) CI 0.87–0.95; IRR 0.95, 95% CI 0.89–1.02; and IRR 0.87, 95% CI 0.83–0.93, respectively]. The overall mortality rate during and after lockdown was not significantly different compared with the same period in 2019 (IRR 0.99, 95% CI 0.97–1.02). However, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during and after lockdown compared with the same period in 2019 (in-hospital, IRR 0.92, 95% CI 0.88–0.96; out-of-hospital, IRR 1.04, 95% CI1.01–1.08). These trends were consistent irrespective of sex and age.
The collateral cardiovascular damage of COVID-19: only history will reveal the depth of the iceberg
European Heart Journal, February 24, 2021
[Editorial] The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented global public health emergency that has dramatically changed all aspects of our lives. To date, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected almost 100 million people and directly caused >2 million deaths. To prevent the spread of the virus and relieve pressure on healthcare services, governments enforced lockdown measures. At the same time, healthcare systems rapidly repurposed by redeploying resources and staff to tackle this unique challenge. These strategies limited the impact of the first wave of COVID-19 but disrupted usual care pathways for non-COVID-19 conditions. The prevalence of cardiovascular diseases has consistently increased over time as effective interventions have prolonged survival. Despite this, they are still the leading cause of morbidity and mortality worldwide, mandating ongoing efforts to provide prompt diagnosis, complex interventions, structured follow-up, and uninterrupted care.2 The advent of the COVID-19 pandemic has abruptly discontinued this continuum of care for all cardiovascular conditions, with potentially devastating consequences.
Association of coagulation dysfunction with cardiac injury among hospitalized patients with COVID-19
Scientific Reports, February 24, 2021
Cardiac injury is a common complication of the coronavirus disease 2019 (COVID-19), and is associated with adverse clinical outcomes. In this study, we aimed to reveal the association of cardiac injury with coagulation dysfunction. We enrolled 181 consecutive patients who were hospitalized with COVID-19, and studied the clinical characteristics and outcome of these patients. Cardiac biomarkers high-sensitivity troponin I (hs-cTnI), myohemoglobin and creatine kinase-myocardial band (CK-MB) were assessed in all patients. The clinical outcomes were defined as hospital discharge or death. The median age of the study cohort was 55 (IQR, 46–65) years, and 102 (56.4%) were males. Forty-two of the 181 patients (23.2%) had cardiac injury. Old age, high leukocyte count, and high levels of aspartate transaminase (AST), D-dimer and serum ferritin were significantly associated with cardiac injury. Multivariate regression analysis revealed old age and elevated D-dimer levels as being strong risk predictors of in-hospital mortality. Interleukin 6 (IL6) levels were comparable in patients with or without cardiac injury. Serial observations of coagulation parameters demonstrated highly synchronous alterations of D-dimer along with progression to cardiac injury. Cardiac injury is a common complication of COVID-19 and is an independent risk factor for in-hospital mortality. Old age, high leukocyte count, and high levels of AST, D-dimer and serum ferritin are significantly associated with cardiac injury, whereas IL6 are not. Therefore, the pathogenesis of cardiac injury in COVID-19 may be primarily due to coagulation dysfunction along with microvascular injury.
In- and out-of-hospital mortality for myocardial infarction during the first wave of the COVID-19 pandemic in Emilia-Romagna, Italy: A population-based observational study
The Lancet – Regional Health Europe, February 24, 2021
The COVID-19 pandemic has put several healthcare systems under severe pressure. The present analysis investigates how the first wave of the COVID-19 pandemic affected the myocardial infarction (MI) network of Emilia-Romagna (Italy). Based on Emilia-Romagna mortality registry and administrative data from all the hospitals from January 2017 to June 2020, we analysed: i) temporal trend in MI hospital admissions; ii) characteristics, management, and 30-day mortality of MI patients; iii) out-of-hospital mortality for cardiac cause. Admissions for MI declined on February 22, 2020 (IRR -19.5%, 95%CI from -8.4% to -29.3%, p = 0.001), and further on March 5, 2020 (IRR -21.6%, 95%CI from -9.0% to -32.5%, p = 0.001). The return to pre-COVID-19 MI-related admission levels was observed from May 13, 2020 (IRR 34.3%, 95%CI 20.0%-50.2%, p<0.001). As compared to those before the pandemic, MI patients admitted during and after the first wave were younger and with fewer risk factors. The 30-day mortality remained in line with that expected based on previous years (ratio observed/expected was 0.96, 95%CI 0.84–1.08). MI patients positive for SARS-CoV-2 were few (1.5%) but showed poor prognosis (around 5-fold increase in 30-day mortality). In 2020, the number of out-of-hospital cardiac deaths was significantly higher (ratio observed/expected 1.17, 95%CI 1.08–1.27). The peak was reached in April.
COVID-19 and changes in activity and treatment of ST elevation MI from a UK cardiac centre
IJC Heart & Vasculature, February 23, 2021
The international healthcare response to COVID-19 has been driven by epidemiological data related to case numbers and case fatality rate. Second order effects have been less well studied. This study aimed to characterise the changes in emergency activity of a high-volume cardiac catheterisation centre and to cautiously model any excess indirect morbidity and mortality. Retrospective cohort study of patients admitted with acute coronary syndrome fulfilling criteria for the heart attack centre (HAC) pathway at St. Bartholomew’s hospital, UK. Electronic data were collected for the study period March 16th – May 16th 2020 inclusive and stored on a dedicated research server. Standard governance procedures were observed in line with the British Cardiovascular Intervention Society audit. There was a 28% fall in the number of primary percutaneous coronary interventions (PCIs) for ST elevation myocardial infarction (STEMI) during the study period (111 vs. 154) and 36% fewer activations of the HAC pathway (312 vs. 485), compared to the same time period averaged across three preceding years. In the context of ‘missing STEMIs’, the excess harm attributable to COVID-19 could result in an absolute increase of 1.3% in mortality, 1.9% in nonfatal MI and 4.5% in recurrent ischemia.
Impact of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Hypertensive Patients with COVID-19 (COVIDECA Study)
American College of Cardiology, February 20, 2021
Effect of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) among hypertensive patients with coronavirus disease 2019 (COVID-19) is debated. The aim of the COVIDECA study was to assess the outcome of ACEI and ARB among hypertensive patients presenting with COVID-19. We reviewed from the Assistance Publique-Hôpitaux de Paris healthcare record database all patients presenting with confirmed COVID-19 by RT-PCR. We compared hypertensive patients with ACEI or ARB and hypertensive patients without ACEI and ARB. Among 13,521 patients presenting with confirmed COVID-19 by RT-PCR, 2,981 hypertensive patients (mean age: 78.4 ± 13.6 years, 1,464 men) were included. Outcome of hypertensive patients was similar whatever the use or non-use of ACEI or ARB: admission in ICU (13.4% in patients with ACEI or ARB versus 14.8% in patients without ACEI/ARB, p = 0.35), need of mechanical ventilation (5.5% in patients with ACEI or ARB vs 6.3% in patients without ACEI/ARB, p = 0.45), in-hospital mortality (27.5% in patients with ACEI or ARB vs 26.7% in patients without ACEI/ARB, p = 0.70). In conclusion, the use of ACEI and ARB remains safe and can be maintained in hypertensive patients presenting with COVID-19.
Frequency of Atrial Arrhythmia in Hospitalized Patients with COVID-19
American Journal of Cardiology, February 20, 2021
There is growing evidence that COVID-19 can cause cardiovascular complications. However, there are limited data on the characteristics and importance of atrial arrhythmia (AA) in patients hospitalized with COVID-19. Data from 1029 patients diagnosed with of COVID-19 and admitted to Columbia University Medical Center between March 1st and April 15th 2020 were analyzed. The diagnosis of AA was confirmed by 12-lead electrocardiographic recordings, 24-hour telemetry recordings and implantable device interrogations. Patients’ history, biomarkers and hospital course were reviewed. Outcomes of death, intubation and discharge were assessed. Of 1029 patients, 82 (8%) were diagnosed with AA. Out of the 82 patients with AA. Of the AA patients, new-onset AA was seen in 46 (56%) patients, recurrent paroxysmal and chronic persistent were diagnosed in 16 (20%) and 20 (24%) individuals, respectively. Sixty-five percent of the patients diagnosed with AA (n=53) died. Patients diagnosed with AA had significantly higher mortality compared to those without AA (65% vs. 21%; p < 0.001). Predictors of mortality were older age (Odds Ratio (OR) =1.12, [95% Confidence Interval (CI), 1.04 to 1.22]); male gender (OR=6.4 [95% CI, 1.3 to 32]); azithromycin use (OR=13.4 [95% CI, 2.14 to 84]); and higher D-dimer levels (OR=2.8 [95% CI, 1.1 to7.3]). In conclusion, patients diagnosed with AA had 3.1 times significant increase in mortality rate versus patients without diagnosis of AA in COVID-19 patients. Older age, male gender, azithromycin use and higher baseline D-dimer levels were predictors of mortality.
Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic
European Journal of Preventive Cardiology, February 20, 2021
Cardiovascular diseases (CVDs) increase mortality risk from coronavirus infection (COVID-19). There are also concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both ‘direct’, through infection, and ‘indirect’, through changes in healthcare. We used (i) national mortality data for England and Wales to investigate trends in non-COVID-19 and CVD excess deaths; (ii) routine data from hospitals in England (n = 2), Italy (n = 1), and China (n = 5) to assess indirect pandemic effects on referral, diagnosis, and treatment services for CVD; and (iii) population-based electronic health records from 3 862 012 individuals in England to investigate pre- and post-COVID-19 mortality for people with incident and prevalent CVD. We incorporated pre-COVID-19 risk (by age, sex, and comorbidities), estimated population COVID-19 prevalence, and estimated relative risk (RR) of mortality in those with CVD and COVID-19 compared with CVD and non-infected (RR: 1.2, 1.5, 2.0, and 3.0). Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous (peak RR 1.14). CVD service activity decreased by 60–100% compared with pre-pandemic levels in eight hospitals across China, Italy, and England. In China, activity remained below pre-COVID-19 levels for 2–3 months even after easing lockdown and is still reduced in Italy and England. For total CVD (incident and prevalent), at 10% COVID-19 prevalence, we estimated direct impact of 31 205 and 62 410 excess deaths in England (RR 1.5 and 2.0, respectively), and indirect effect of 49 932 to 99 865 deaths.
Delayed-onset myocarditis following COVID-19
The Lancet – Respiratory Medicine, February 19, 2021
A multisystem inflammatory syndrome occurring several weeks after SARS-CoV-2 infection and that can include severe acute heart failure has been reported in children (MIS-C). In adults with acute severe heart failure, we have identified a similar syndrome (MIS-A) and describe presenting characteristics, diagnostic features, and early outcomes. Our data also complement reports of MIS-A. The recognition that three patients presenting with fulminant myocarditis also had clinical features of COVID-19, but were negative for SARS-CoV-2 on RT-PCR, was made during recruitment for a study of patients with cardiac injury associated with SARS-CoV-2. To identify implications for patient care, we audited digital records to identify similar presentations to Barts Health National Health Service (NHS) Trust, London, UK, and Guy’s and St Thomas’ NHS Trust, London, between March 1, and Sept 30, 2020. All participants had stored serum for antibody testing, and included nine patients (cases 1–9) with acute cardiac decompensation, negative RT-PCR for SARS-CoV-2, markedly increased serum troponin, and substantially raised inflammatory markers. We also studied three controls (cases 10–12) with acute heart failure and SARS-CoV-2 antibodies, but without all the other features. Patients were mostly male (seven [78%] of nine), of Black African ancestry (seven [78%] of nine), and the mean age was 36 years (IQR 23–53). Both female patients (cases 6 and 8) presented during or shortly after pregnancy, one of whom had gestational diabetes. One male patient had a significant comorbidity (case 4, hypertension secondary to primary hyperaldosteronism). The primary purpose of this Correspondence is to highlight a novel clinical presentation of a multisystem disorder that can have life-threatening features, yet might respond adroitly to therapy.
Key factors leading to fatal outcomes in COVID-19 patients with cardiac injury
Scientific Reports, February 18, 2021
Cardiac injury among patients with COVID-19 has been reported and is associated with a high risk of mortality, but cardiac injury may not be the leading factor related to death. The factors related to poor prognosis among COVID-19 patients with myocardial injury are still unclear. This study aimed to explore the potential key factors leading to in-hospital death among COVID-19 patients with cardiac injury. This retrospective single-center study was conducted at Renmin Hospital of Wuhan University, from January 20, 2020 to April 10, 2020, in Wuhan, China. All inpatients with confirmed COVID-19 (≥ 18 years old) and cardiac injury who had died or were discharged by April 10, 2020 were included. Demographic data and clinical and laboratory findings were collected and compared between survivors and nonsurvivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with mortality in COVID-19 patients with cardiac injury. A total of 173 COVID-19 patients with cardiac injury were included in this study, 86 were discharged and 87 died in the hospital. Multivariable regression showed increased odds of in-hospital death were associated with advanced age (odds ratio 1.12, 95% CI 1.05–1.18, per year increase; p < 0.001), coagulopathy (2.54, 1.26–5.12; p = 0·009), acute respiratory distress syndrome (16.56, 6.66–41.2; p < 0.001), and elevated hypersensitive troponin I (4.54, 1.79–11.48; p = 0.001). A high risk of in-hospital death was observed among COVID-19 patients with cardiac injury in this study. The factors related to death include advanced age, coagulopathy, acute respiratory distress syndrome and elevated levels of hypersensitive troponin I.
Ventricular septal defect complicating delayed presentation of acute myocardial infarction during COVID-19 lockdown: a case repor
European Heart Journal – Case Reports, February 16, 2021
Post-myocardial infarction ventricular septal defects (VSDs) have become rare in the reperfusion era but remain associated with very high morbidity and mortality. As patients defer prompt evaluation and management of acute coronary syndromes during the COVID-19 global pandemic, the incidence of these and other post-infarction mechanical complications is expected to increase. A 37-year-old gentleman with multiple coronary artery disease risk factors presented with intermittent chest discomfort and 1 week of heart failure symptoms. An echocardiogram demonstrated a large muscular VSD and coronary angiography confirmed the presence of an anterior wall infarction. He was subsequently referred for transcatheter VSD repair and showed rapid clinical improvement in his symptoms. Post-infarction VSDs remain associated with a high degree of morbidity and mortality. Surgical repair of acutely ruptured myocardium can be technically challenging, and transcatheter repair has emerged as a safe and effective alternative.
Remdesivir for COVID-19 Treatment: APA Practice Points
American College of Cardiology, February 16, 2021
This second version of a guidelines document by the Scientific Medical Policy Committee of the American College of Physicians (ACP) based on an updated systematic review provides evidence-based recommendations surrounding the use of remdesivir in the treatment of coronavirus disease 2019 (COVID-19). Read 10 key points to remember summarizing the data and guidelines.
Myocarditis in COVID-19 presenting with cardiogenic shock: a case series
European Heart Journal – Case Reports, February 16, 2021
SARS-CoV2, also known as COVID-19, is a specific strain of coronavirus that is responsible for an ongoing global pandemic. COVID-19 primarily targets the respiratory system via droplet transmission, causing symptoms similar to influenza, including fever, cough, and shortness of breath. It is now known to impact other organ systems, causing significant cardiovascular and gastrointestinal illness, among others. We describe two cases of COVID-19 induced myocarditis presenting with cardiogenic shock. These cases highlight the importance of understanding the lethal cardiac complications of COVID-19 infection, as well as its presentation, diagnosis, pathophysiology, and potential treatment options. These two cases involve patients without underlying cardiovascular disease risk factors who experienced prolonged symptoms of COVID-19 infection. Both patients presented with cardiogenic shock more than one week after symptom onset and diagnosis. These cases demonstrate the late presentation of myocarditis and cardiogenic shock, treated with corticosteroids and inotropes, with subsequent recovery of cardiac function.
Spotlight on Cardiovascular Scoring Systems in Covid-19: Severity Correlations in Real-world Setting
Current Problems in Cardiology, February 15, 2021
The current understanding of the interplay between cardiovascular (CV) risk and Covid-19 is grossly inadequate. CV risk-prediction models are used to identify and treat high risk populations and to communicate risk effectively. These tools are unexplored in Covid-19. The main objective is to evaluate the association between CV scoring systems and chest X ray (CXR) examination (in terms of severity of lung involvement) in 50 Italian Covid-19 patients. Only the Framingham Risk Score (FRS) was applicable to all patients. The Atherosclerotic Cardiovascular Disease Score (ASCVD) was applicable to half. 62% of patients were classified as high risk according to FRS and 41% according to ASCVD. Patients who died had all a higher FRS compared to survivors. They were all hypertensive. FRS≥30 patients had a 9.7 higher probability of dying compared to patients with a lower FRS. We found a strong correlation between CXR severity and FRS and ASCVD (p<0.001). High CV risk patients had consolidations more frequently. CXR severity was significantly associated with hypertension and diabetes. 71% of hypertensive patients’ CXR and 88% of diabetic patients’ CXR had consolidations. Patients with diabetes or hypertension had 8 times greater risk of having consolidations. High CV risk correlates with more severe CXR pattern and death. Diabetes and hypertension are associated with more severe CXR. FRS offers more predictive utility and fits best to our cohort. These findings may have implications for clinical practice and for the identification of high-risk groups to be targeted for the vaccine precedence.
One clot after another in COVID-19 patient: diagnostic utility of handheld echocardiogram
Oxford Medical Case Reports, February 15, 2021
A 63-year-old woman was admitted with severe respiratory distress requiring mechanical ventilation and shock requiring vasopressor support. She was found to have COVID-19 pneumonia. Focused cardiac ultrasound performed for evaluation of shock was significant for right ventricular dilation and dysfunction with signs of right ventricular pressure overload. Given worsening shock and hypoxemia systemic thrombolysis was administered for presumed massive pulmonary embolism with remarkable improvement of hemodynamics and respiratory failure. In next 24 h patient’s neurologic status deteriorated to the point of unresponsiveness. Emergent computed tomography showed multiple ischemic infarcts concerning for embolic etiology. Focused cardiac ultrasound with agitated saline showed large right to left shunt due to a patent foramen ovale. This was confirmed by transesophageal echocardiogram, 5 months later. This case highlights strengths of focused cardiac ultrasound in critical care setting and in patients with COVID-19 when access to other imaging modalities can be limited.
Clinical Features and Outcomes of Critically Ill Patients with Coronavirus Disease 2019 (COVID-19): A Multicenter Cohort Study
International Journal of Infectious Diseases, February 15, 2021
Coronavirus disease-19 (COVID-19) manifested by a broad spectrum of symptoms, ranging from asymptomatic manifestations to severe illness and death. The purpose of the study was to extensively describe the clinical features and outcomes in critically ill patients with COVID19 in Saudi Arabia. A multi-center, non-interventional, cohort study for all critically ill patients aged 18 years or older who are admitted to intensive care units (ICUs) between March 1st to August 31st, 2020 with an objectively confirmed diagnosis of COVID19. The diagnosis of COVID19 was confirmed by Reverse Transcriptase–Polymerase Chain Reaction (RT-PCR) on nasopharyngeal and/or throat swabs. Multivariate logistic regression and generalized linear regression were used. We considered a P value of < 0.05 statistically significant. A total of 560 patients met the inclusion criteria. An extensive list of clinical features were associated with higher 30-days ICU mortality rate such as requiring mechanical ventilation (MV) or developing acute kidney injury within 24 hours of ICU admission, higher body temperature, white blood cells, blood glucose level, serum creatinine, fibrinogen, procalcitonin, creatine phosphokinase, aspartate aminotransferase and Total iron-binding capacity. The most common complication during ICU stay was respiratory failure that required MV (71.4%), followed by acute kidney injury (AKI) and thrombosis with a proportion of 46.8% and 11.4% respectively. Among patients with COVID19 who were admitted to the ICU, several variables were associated with increasing the risk of ICU mortality at 30 days.
COVID-19 patients with hypertension are at potential risk of worsened organ injury
Scientific Reports, February 12, 2021
In less than 6 months, COVID-19 spread rapidly around the world and became a global health concern. Hypertension is the most common chronic disease in COVID-19 patients, but its impact on these patients has not been well described. In this retrospective study, 82 patients diagnosed with COVID-19 were enrolled, and epidemiological, demographic, clinical, laboratory, radiological and therapy-related data were analyzed and compared between COVID-19 patients with (29 cases) or without (53 cases) hypertension. The median age of the included patients was 60.5 years, and the cohort included 49 women (59.8%) and 33 (40.2%) men. Hypertension (31 [28.2%]) was the most common chronic illness, followed by diabetes (16 [19.5%]) and cardiovascular disease (15 [18.3%]). The most common symptoms were fatigue (55 [67.1%]), dry cough (46 [56.1%]) and fever ≥ 37.3 °C (46 [56.1%]). The median time from illness onset to positive RT-PCR test was 13.0 days (range 3–25 days). There were 6 deaths (20.7%) in the hypertension group and 5 deaths (9.4%) in the nonhypertension group, and more hypertensive patients with COVID-19 (8 [27.6%]) than nonhypertensive patients (2 [3.8%]) (P = 0.002) had at least one comorbid disease. Compared with nonhypertensive patients, hypertensive patients exhibited higher neutrophil counts, serum amyloid A, C-reactive protein, and NT-proBNP and lower lymphocyte counts and eGFR. Dynamic observations indicated more severe disease and poorer outcomes after hospital admission in the hypertension group. COVID-19 patients with hypertension have increased risks of severe inflammatory reactions, serious internal organ injury, and disease progression and deterioration.
COVID-19 and cardiovascular diseases
Journal of Molecular Cell Biology, February 12, 2021
The coronavirus disease 2019 (COVID-19) remains a global public health emergency. Despite being caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), besides the lung, this infectious disease also has severe implications in the cardiovascular system. In this review, we summarize diverse clinical complications of the heart and vascular system, as well as the relevant high mortality, in COVID-19 patients. Systemic inflammation and angiotensin-converting enzyme 2-involved signaling networking in SARS-CoV-2 infection and the cardiovascular system may contribute to the manifestations of cardiovascular diseases. Therefore, integration of clinical observations and experimental findings can promote our understanding of the underlying mechanisms, which would aid in identifying and treating cardiovascular injury in patients with COVID-19 appropriately.
ACC Statement Urges COVID-19 Vaccine Prioritization For Highest Risk CVD Patients
American College of Cardiology, February 12, 2021
COVID-19 vaccine prioritization should prioritize those with advanced cardiovascular disease over well-managed cardiovascular disease, according to an ACC health policy statement published Feb. 12 in the Journal of the American College of Cardiology. All cardiovascular disease patients face a higher risk of COVID-19 complications and should receive the vaccine quickly, but recommendations in the paper serve to guide clinicians in prioritizing their most vulnerable patients within the larger cardiovascular disease group, while considering disparities in COVID-19 outcomes among different racial/ethnic groups and socioeconomic levels.
Anticoagulation therapy in non-valvular atrial fibrillation in the COVID-19 era: is it time to reconsider our therapeutic strategy?
European Journal of Preventive Cardiology, February 10, 2021
Non-vitamin K antagonist oral anticoagulants (NOACs) are considered the first-line therapy to prevent stroke in non-valvular atrial fibrillation (AF) and are recommended by the recent ESC guidelines in preference to vitamin K antagonists (VKAs). Non-vitamin K antagonist oral anticoagulants offer many advantages compared to VKAs, which include fixed dosing (up to two times a day), fewer dietary and drug interactions, predictable anticoagulation effect (rapid onset and offset) precluding the need for periprocedural bridging anticoagulation, and no need for regular monitoring of anticoagulant effect. Non-vitamin K antagonist oral anticoagulants have been proven to be at least non-inferior to VKAs in large clinical trials in the prevention of stroke, while they are associated with a significant reduction in intracranial haemorrhage. On the other hand, VKAs require frequent monitoring of their anticoagulant effect and have many food and drug interactions. Moreover, the use of VKAs is limited by the narrow therapeutic interval, and consequently, the necessity for frequent international normalized ratio (INR) monitoring and dose adjustments (INR 2–3 is recommended in most cases with non-valvular AF). …in the era of COVID-19, anticoagulation therapy in non-valvular AF with NOACs seems to be the safest approach. Non-vitamin K antagonist oral anticoagulants are contraindicated in AF patients with a prosthetic mechanical valve or moderate-to-severe mitral stenosis, and long-term anticoagulation therapy with VKAs is indicated. In these patients with ‘valvular AF’, the ‘at-home’ INR test method, and consulting the results by phone may be an alternative solution to minimize healthcare centre visits.
Statin Therapy and the Risk of COVID-19: A Cohort Study of the National Health Insurance Service in South Korea
Journal of Personalized Medicine, February 10, 2021
We aimed to investigate whether statin therapy is associated with the incidence of coronavirus disease 2019 (COVID-19) among the South Korean population. In addition, we examined whether statin therapy affects hospital mortality among COVID-19 patients. The National Health Insurance Service (NHIS)-COVID-19 database in South Korea was used for data extraction for this population-based cohort study. A total of 122,040 adult individuals, with 22,633 (18.5%) in the statin therapy group and 101,697 (91.5%) in the control group, were included in the analysis. Among them, 7780 (6.4%) individuals were diagnosed with COVID-19 and hospital mortality occurred in 251 (3.2%) COVID-19 cases. After propensity score matching, logistic regression analysis showed that the odds of developing COVID-19 were 35% lower in the statin therapy group than in the control group (odds ratio: 0.65, 95% confidence interval: 0.60 to 0.71; p < 0.001). Regarding hospital mortality among COVID-19 patients, the multivariable model indicated that there were no differences between the statin therapy and control groups (odds ratio: 0.74, 95% confidence interval: 0.52 to 1.05; p = 0.094). Statin therapy may have potential benefits for the prevention of COVID-19 in South Korea. However, we found that statin therapy does not affect the hospital mortality of patients who are diagnosed with COVID-19.
Prediction of thromboembolic events and mortality by the CHADS2 and the CHA2DS2-VASc in COVID-19
EP Europace, February 10, 2021
Age, sex, and cardiovascular disease have been linked to thromboembolic complications and poorer outcomes in COVID-19. We hypothesize that CHADS2 and CHA2DS2-VASc scores may predict thromboembolic events and mortality in COVID-19. COVID-19 hospitalized patients with confirmed SARS-CoV-2 infection from 1 March to 20 April 2020 who completed at least 1-month follow-up or died were studied. CHADS2 and CHA2DS2-VASc scores were calculated. Given the worse prognosis of male patients in COVID-19, a modified CHA2DS2-VASc score (CHA2DS2-VASc-M) in which 1 point was given to male instead of female was also calculated. The associations of these scores with laboratory results, thromboembolic events, and death were analysed. A total of 3042 patients (mean age 62.3 ± 20.3 years, 54.9% male) were studied and 115 (3.8%) and 626 (20.6%) presented a definite thromboembolic event or died, respectively, during the study period [median follow 59 (50–66) days]. Higher score values were associated with more marked abnormalities of inflammatory and cardiac biomarkers. Mortality was significantly higher with increasing scores for CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-M (P < 0.001 for trend). The CHA2DS2-VASc-M showed the best predictive value for mortality [area under the receiver operating characteristic curve (AUC) 0.820, P < 0.001 for comparisons]. All scores had poor predictive value for thromboembolic events (AUC 0.497, 0.490, and 0.541, respectively). The CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-M scores are significantly associated with all-cause mortality but not with thromboembolism in COVID-19 patients. They are simple scoring systems in everyday use that may facilitate initial ‘quick’ prognostic stratification in COVID-19.
Contemporary use of cardiac imaging for COVID-19 patients: a three center experience defining a potential role for cardiac MRI
International Journal of Cardiovascular Imaging, February 9, 2021
The pandemic of coronavirus disease 2019 (COVID-19) secondary to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has bestowed an unprecedented challenge upon us, resulting in an international public health emergency. COVID-19 has already resulted in > 1,600,000 deaths worldwide and the fear of a global economic collapse. SARS-CoV-2 is notorious for causing acute respiratory distress syndrome, however emerging literature suggests various dreaded cardiac manifestations associated with high mortality. The mechanism of myocardial damage in COVID-19 is unclear but thought to be multifactorial and mainly driven by the host’s immune response (cytokine storm), hypoxemia and direct myocardial injury by the virus. Cardiac manifestations from COVID-19 include but are not limited to, acute myocardial injury, cardiac arrhythmias, congestive heart failure and acute coronary syndrome. Cardiac imaging is paramount to appropriately diagnose and manage the cardiac manifestations of COVID-19. Herein, we present cardiac imaging findings of COVID-19 patients with biomarker and imaging confirmed myocarditis to provide insight regarding the variable manifestations of COVID-19 myocarditis via Cardiac MRI (CMR) coupled with CMR-edema education along with recommendations on how to incorporate advanced CMR into the clinicians’ COVID-19 armamentarium.
Cardiac care of Non-COVID-19 patients during the SARS-CoV-2 pandemic: The pivotal role of CCTA
European Heart Journal – Cardiovascular Imaging, February 8, 2021
To describe the role of coronary CT angiography (CCTA) as the sole available non-invasive diagnostic test for symptomatic patients with suspected CAD in a hub center for cardiovascular emergencies in the presence of limited access to hospital facilities during the COVID-19 pandemic. From March 9th to April 30th, during the peak of the COVID-19 pandemic, a consecutive cohort of symptomatic patients with high clinical suspicion of CAD and clinical indication to CCTA were enrolled in a hub hospital in Milan, Italy. When obstructive coronary artery disease was detected (>70% diameter stenosis in a proximal coronary segment or >90% stenosis in any coronary segment) patients were referred to invasive coronary angiography (ICA). Clinical follow-up was assessed in patients in whom ICA was considered deferrable. Overall, 58 consecutive patients were included. Ten (17.2%) symptomatic patients underwent ICA according to CCTA findings, while in 48 (82.8%) patients ICA was deferred. No clinical events were recorded after a mean follow-up of 49.7 ± 16.8 days. In nine out of ten patients referred to ICA, severe coronary artery disease was confirmed and treated accordingly. Changes in medical therapy were significantly more prevalent in patients with vs. those without CAD at CCTA. We report a potential pivotal role for CCTA in the triage of non-COVID-19 patients with suspected CAD during the SARS-CoV-2 pandemic. CCTA may be helpful for identifying patients who necessitate ICA, ensuring adequate resource utilization during the pandemic.
Effects of COVID-19 on in-hospital cardiac arrest: incidence, causes, and outcome – a retrospective cohort study
https://sjtrem.biomedcentral.com/articles/10.1186/s13049-021-00846-w
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, February 8, 2021
SARS-CoV-2, an emerging virus, has caused a global pandemic. COVID-19 caused by SARS-CoV-2, has led to high hospitalization rates worldwide. Little is known about the occurrence of in-hospital cardiac arrest (IHCA) and high mortality rates have been proposed. The aim of this study was to investigate the incidence, characteristics and outcome of IHCA during the pandemic in comparison to an earlier period. This was a retrospective analysis of data prospectively recorded during 3-month-periods 2019 and 2020 at the University Medical Centre Hamburg-Eppendorf (Germany). All consecutive adult patients with IHCA were included. Clinical parameters, neurological outcomes and organ failure/support were assessed. During the study period hospital admissions declined from 18,262 (2019) to 13,994 (2020) (− 23%). The IHCA incidence increased from 4.6 (2019: 84 IHCA cases) to 6.6 (2020: 93 IHCA cases)/1000 hospital admissions. Median stay before IHCA was 4 (1–9) days. Demographic characteristics were comparable in both periods. IHCA location shifted towards the ICU (56% vs 37%, p < 0.01); shockable rhythm (VT/VF) (18% vs 29%, p = 0.05) and defibrillation were more frequent in the pandemic period (20% vs 35%, p < 0.05). Resuscitation times, rates of ROSC and post-CA characteristics were comparable in both periods. The severity of illness (SAPS II/SOFA), frequency of mechanical ventilation and frequency of vasopressor therapy after IHCA were higher during the 2020 period. Overall, 43 patients (12 with & 31 without COVID-19), presented with respiratory failure at the time of IHCA. The Horowitz index and resuscitation time were significantly lower in patients with COVID-19 (each p < 0.01). Favourable outcomes were observed in 42 and 10% of patients with and without COVID-19-related respiratory failure, respectively, Hospital admissions declined during the pandemic, but a higher incidence of IHCA was observed. IHCA in patients with COVID-19 was a common finding.
Gastroenteritis and cardiogenic shock in a healthcare worker: a case report of COVID-19 myocarditis confirmed with serology
European Heart Journal – Case Reports, February 8, 2021
Coronavirus disease 2019 (COVID-19) myocarditis is emerging as a component of the hyperactive inflammatory response secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Isolated gastrointestinal symptoms are uncommon presenting features in adults with COVID-19 myocarditis. The availability of antibody testing is a valuable addition to the confirmation of COVID-19, when repeated reverse transcriptase–polymerase chain reaction of nasopharyngeal swabs are negative. A young healthcare worker presented with dizziness and pre-syncope, 4 weeks after his original symptoms that included fever, lethargy, and diarrhoea. Despite 2 weeks of isolation, followed by a quiescent spell, his symptoms had returned. Shortly after, he presented in cardiogenic shock (left ventricular ejection fraction 25%), that required vasopressor support, at the height of the COVID-19 pandemic. Cardiac magnetic resonance imaging suggested florid myocarditis. Three nasopharyngeal swabs (Days 1, 3, and 5) were negative for SARS-CoV-2, but subsequent serology (Day 13) confirmed the presence of SARS-CoV-2 IgG. Treatment with intravenous immunoglobulin and glucocorticoids led to full recovery. Our case study highlights the significance of the use of the available serological assays for diagnosis of patients presenting late with SARS-CoV-2. Importantly, it supports further research in the use of immunomodulatory drugs for the hyperinflammatory microenvironment induced by COVID-19.
Cardiac function during COVID-19 intensive care unit hospitalisation – deformation analysis and outcomes
European Heart Journal – Cardiovascular Imaging, February 8, 2021
Although the cardiac burden of COVID-19 has been demonstrated, follow-up imaging studies are scarce. The aim was to use speckle-tracking deformation imaging (STE) to prospectively assess cardiac function during intensive care unit (ICU) hospitalisation, comparing ventricular and atrial function of COVID-10 patients that died and those that were discharged. In a single-centre, COVID-19 patients (n = 41) (71% male, aged 65 ± 11 years) were prospectively followed with echocardiography as part of ICU treatment. The left and right ventricles (LV, RV, respectively) were studied with STE in the 4-chamber cardiac view. The endpoint was defined as death or ICU discharge. Average values of the strain parameters from the first and final scans in the ICU, respectively, were calculated for the two outcome groups. Endpoint was not reached in 15% (n = 6) at the time of analysis. The remaining patients (n = 32) were 69% male, aged 66 (interquartile range (IQR) 60-72) years, and with an ICU mortality 26% (n = 9). The median spent in ICU was 24 (IQR 15-43) days. On average, echocardiography was performed three times during ICU hospitalisation, amounting to 103 examinations. Worsening of LV strain and lack of improvement of RV strain is linked to higher mortality in the ICU. The assessment of cardiac function might contain prognostic information in COVID-19 patients that are admitted to the ICU.
Prognostic utility of quantitative offline 2D-echocardiography in hospitalized patients with COVID-19
European Heart Journal – Cardiovascular Imaging, February 5, 2021
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared as a pandemic by the World Health Organization (WHO) on 11 March 2020. Clinical presentation ranges from asymptomatic to acute respiratory distress syndrome (ARDS) that can lead to death. Patients with concomitant cardiac diseases have an extremely poor prognosis, and SARS-CoV-2 may cause direct acute and chronic damage to the cardiovascular system. Echocardiography may provide useful information, especially in critical care patients, because it can be performed quickly at the bedside. To date, there is no means to predict the impact of the virus on patient outcome probably because the pathophysiology of COVID-19 remains unexplained. Our objective was to assess the prognostic utility of quantitative 2D-echocardiography, including strain, in patients with COVID-19 disease. COVID-19 patients admitted to the San Paolo University Hospital of Milan, that underwent a clinically indicated echocardiographic exam were included in the study. Quantitative measurements were obtained by an operator blinded to the clinical data. Among the 49 patients, non-survivors (33%) had worse respiratory parameters, index of multiorgan failure and worse markers of lung involvement. Right Ventricular (RV) dysfunction was a common finding and a powerful independent predictor of mortality. At the ROC curve analyses, RV free-wall longitudinal strain (LS) showed an AUC 0.77 ± 0.08 in predicting death, p = 0.008, and global RV LS (RV-GLS) showed an AUC 0.79 ± 0.04, p = 0.004. This association remained significant after correction for age (OR= 1.16, 95%CI 1.01-1.34, p = 0.029 for RV free-wall LS and OR = 1.20, 95%CI 1.01-1.42, p = 0.033 for RV-GLS), for oxygen partial pressure at arterial gas analysis/fraction of inspired oxygen (OR= 1.28, 95%CI 1.04-1.57, p = 0.021 for RV free wall-LS and OR = 1.30, 95%CI 1.04-1.62, p = 0.020 for RV-GLS) and for the severity of pulmonary involvement measured by a computed tomography lung score (OR = 1.27, 95%CI 1.02-1.19, p = 0.034 for RV free-wall LS, and OR = 1.30, 95%CI 1.04-1.63, p = 0.022 for RV-GLS).
COVID-19 as a Possible Cause of Myocarditis and Pericarditis
American College of Cardiology, February 5, 2021
Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is an unmatched challenge for the healthcare community across the world. Respiratory involvement is the main clinical manifestation of COVID-19, ranging from mild flu-like illness to severe pneumonia, and potentially lethal acute respiratory distress syndrome. The initial mechanism for SARS-CoV-2 infection is viral binding to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) by a protein expressed in the viral coat, termed SPIKE (S protein) followed by its priming by the serine protease TMPRSS2 mediating virus uptake. ACE2 is a membrane-bound peptidase that is expressed in all tissues but is especially represented in lung, heart, vessels, kidney, brain, and gut. At present, limited data have been published on cases with COVID-19 who develop pericarditis and pericardial effusion. Most reported cases have been associated myocardial involvement with troponin elevation. …heart and vessels are potential targets for COVID-19, however at present, there are no findings which provide evidence of direct infection and replication of SARS-CoV-2 in heart cells. Additional pathologic studies and autopsy series will be very helpful to clarify the potentiality of SARS-CoV-2 to directly infect the myocardium/pericardium and cause myocarditis and pericarditis.
Estrogen receptors are linked to angiotensin-converting enzyme 2 (ACE2), ADAM metallopeptidase domain 17 (ADAM-17), and transmembrane protease serine 2 (TMPRSS2) expression in the human atrium: insights into COVID-19
Hypertension Research, February 3, 2021
Premenopausal women have a reduced incidence of cardiovascular disease (CVD) compared to postmenopausal women or age-matched men, suggesting a cardioprotective role for estrogen [1]. Although estrogen replacement maintains cardiac structure and function in ovariectomized rodent models, clinical trials of estrogen-based hormone therapy have yielded inconsistent results with regard to improving heart function in older women. Overall, it is critical to further elucidate the functional roles of estrogen, especially its individual receptors, in the heart to develop more effective and specific hormone therapy for postmenopausal women. Estrogen interacts with the renin-angiotensin system (RAS), one of the most critical pathways in CVD, by inhibiting or downregulating renin, angiotensin-converting enzyme (ACE), and angiotensin II (Ang II) type 1 receptor (AT1-R). However, the effects on cardiac ACE2 expression involve both increases and decreases depending on the species and experimental model studied. The identification of the ACE2 enzyme receptor, which acts with host transmembrane serine protease 2 TMPRSS2, as the primary means of cellular entry by the novel β-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) justifies the importance of examining the potential contributory function of sex hormones in COVID-19 pathogenesis.
Eagle’s Eye View: COVID-19 Tip of the Week
American College of Cardiology, February 2, 2021
[Video, 1:04] Dr. Kim Eagle, MD, MACC, Editor of ACC.org, provides a weekly tip for clinicians on the front lines of the COVID-19 pandemic. How do health care workers hospitalized with COVID-19 fare when compared to the general population?
Relation of Cardiovascular Risk Factors to Mortality and Cardiovascular Events in Hospitalized Patients with Coronavirus Disease 2019 (From the Yale COVID-19 Cardiovascular Registry)
American Journal of Cardiology, February 1, 2021
Individuals with established cardiovascular disease or a high burden of cardiovascular risk factors may be particularly vulnerable to develop complications from coronavirus disease 2019 (COVID-19). We conducted a prospective cohort study at a tertiary care center to identify risk factors for in-hospital mortality and major adverse cardiovascular events (MACE; a composite of myocardial infarction, stroke, new acute decompensated heart failure, venous thromboembolism, ventricular or atrial arrhythmia, pericardial effusion, or aborted cardiac arrest) among consecutively hospitalized adults with COVID-19, using multivariable binary logistic regression analysis. The study population comprised 586 COVID-19 positive patients. Median age was 67 (IQR: 55-80) years, 47.4% were female, and 36.7% had cardiovascular disease. Considering risk factors, 60.2% had hypertension, 39.8% diabetes, and 38.6% hyperlipidemia. Eighty-two individuals (14.0%) died in-hospital, and 135 (23.0%) experienced MACE. In a model adjusted for demographic characteristics, clinical presentation, and laboratory findings, age (odds ratio [OR], 1.28 per 5 years; 95% confidence interval [CI], 1.13-1.45), prior ventricular arrhythmia (OR, 18.97; 95% CI, 3.68-97.88), use of P2Y12-inhibitors (OR, 7.91; 95% CI, 1.64-38.17), higher C-reactive protein (OR, 1.81: 95% CI, 1.18-2.78), lower albumin (OR, 0.64: 95% CI, 0.47-0.86), and higher troponin T (OR, 1.84; 95% CI, 1.39-2.46) were associated with mortality (p<0.05). After adjustment for demographics, presentation, and laboratory findings, predictors of MACE were higher respiratory rates, altered mental status, and laboratory abnormalities, including higher troponin T (p<0.05). In conclusion, poor prognostic markers among hospitalized patients with COVID-19 included older age, pre-existing cardiovascular disease, respiratory failure, altered mental status, and higher troponin T concentrations.
ACC Survey Finds Robust Interest in Video-Visitations, Telehealth Amidst COVID-19 Pandemic
American College of Cardiology, February 1, 2021
A robust interest in video-visitations and adoption of telehealth has developed in response to the COVID-19 pandemic, with valuable insight on how clinicians aim to utilize telehealth for patient care, according to survey results which will be presented as part of ACC’s Cardiovascular Summit Virtual, taking place Feb. 12 – 13. To understand the uptake and barriers to telehealth in everyday clinical practice, the ACC Health Care Innovation Section surveyed cardiologists regarding their perspectives of telehealth – specifically video-visitations – and common barriers for how telehealth is implemented. In total, 342 cardiovascular professionals (92% physicians) completed the survey from 303 different practice zip codes across 42 states. Fifty-five percent of respondent’s work setting was identified as a cardiovascular group or multi-specialty group, with 52%, 24% and 18% as part of a hospital, physician or university-owned practice, respectively. In addition, over half (54%) have been in practice for more than 15 years, a demographic not often identified to adopt digital tools. Results showed that nearly 90% of survey respondents were new telehealth users and have been using video-visitations for less than two months. In the context of integration, 69% of respondents stated that their institution required telehealth to be integrated within an electronic health record (EHR). Among those that stated this requirement, 67% stated that they would use telehealth even if not integrated.
Some of Last Year’s Deferred Cardiac Surgeries Likely Still in Backlog
MedPage Today, January 31, 2021
A nationwide database confirmed the sharp reduction of adult cardiac surgery volumes and unexpectedly high procedural mortality during the COVID pandemic, one group reported. Surgical cases had been fairly stable month to month until they dropped to 12,000 across the country during the month of April 2020, a 53% reduction (65% drop in elective cases and a 40% reduction in non-elective cases) from the 2019 monthly average that roughly coincided with the first wave of the pandemic. The Mid-Atlantic and New England regions, hit hardest by COVID during the first surge, showed the biggest drops of cardiac surgery volumes (71% and 63% reductions, respectively). The Mid-Atlantic in particular had a whopping 75% reduction in elective cases and a 59% decline in non-elective ones in April, reported Tom Nguyen, MD, of University of California San Francisco, at the Society of Thoracic Surgeons (STS) virtual meeting. These two regions also had spikes in operative mortality: their observed-to-expected (O/E) ratio for mortality rose by 75% from below 1.0 before the pandemic to nearly 1.2 in April. In particular, O/E mortality for isolated coronary artery bypass grafting (CABG) surgeries there jumped by 148%.
Temporal association of contamination obsession on the prehospital delay of STEMI during COVID-19 pandemic
American Journal of Emergency Medicine, January 31, 2021
One of the modifiable risk factors for ST elevation myocardial infarction is prehospital delay. The purpose of our study was to look at the effect of contamination contamination obsession on prehospital delay compared with other measurements during the Covid-19 pandemic. A total of 139 patients with acute STEMI admitted to our heart center from 20 March 2020 to 20 June 2020 were included in this study. If the time interval between the estimated onset of symptoms and admission to the emergency room was >120 min, it was considered as a prehospital delay. The Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), and Padua Inventory-Washington State University Revision (PI-WSUR) test were used to assess Contamination-Obsessive compulsive disorder (C-OCD). The same period STEMI count compared to the previous year decreased 25%. The duration of symptoms onset to hospital admission was longer in the first month compared to second and third months (180 (120–360), 120 (60–180), and 105 (60–180), respectively; P = 0.012). Multivariable logistic regression (model-2) was used to examine the association between 7 candidate predictors (age, gender, diabetes mellitus (DM), hypertension, smoking, pain-onset time, and coronary artery disease (CAD) history), PI-WSUR C-OCD, and admission month with prehospital delay. Among variables, PI-WSUR C-OCD and admission month were independently associated with prehospital delay (OR 5.36 (2.11–13.61) (P = 0.01); 0.26 (0.09–0.87) p < 0.001] respectively].
Clinical factors associated with massive pulmonary embolism and PE-related adverse clinical events
International Journal of Cardiology, January 31, 2021
Acute pulmonary embolism (PE) presentation varies from no symptoms and little hemodynamic consequence to massive PE with evidence of hemodynamic collapse with an estimated mortality of 20%. The annual incidence of PE has been increasing globally, and it has also been identified as an important clinical complication in SARS-COV2. Clinicians evaluating acute PE patients often have to identify risks for massive PE, a measure of hemodynamic instability and its consequence, massive PE related adverse clinical events (PEACE). We investigated the association of these risk factors with massive PE and PEACE in a consecutive PE cohort (n = 364). Massive PE was defined as an acute central clot (proximal to the lobar artery) in a patient with right heart strain and systolic blood pressure ≤ 90 mg. PEACE was defined as any massive PE who died or required one or more of the following: ACLS, assisted ventilation, vasopressor use, thrombolytic therapy, or invasive thrombectomy, within seven days of PE diagnosis. Univariate and multivariate analysis assessing associations between the risk factors (age, gender, comorbidities, PE provoking risks, and whether the PE was felt to be idiopathic) and massive PE or PEACE were performed. Significance was determined at p < 0.05. Thirteen percent (n = 48) of patients presented with massive PE, and 9% (n = 32) had PEACE. In the final multivariate model, recent invasive procedure (RR = 7.4, p = 0.007), recent hospitalization (RR = 7.3, p = 0.002), and idiopathic PE (RR = 6.5, p = 0.003) were associated with massive PE. Only idiopathic PE (RR = 5.7, p = 0.005) was significantly associated with PEACE. No comorbidities or other PE provoking risks were associated with massive PE or PEACE.
Using High Sensitivity Cardiac Troponin Values in Patients with SARS-CoV-2 Infection (COVID-19): The Padova Experience
Clinical Biochemistry, January 30, 2021
The spectrum of Coronavirus Disease 2019 (COVID-19) is broad and thus early appropriate risk stratification can be helpful. Our objectives were to define the frequency of myocardial injury using high-sensitivity cardiac troponin I (hs-cTnI) and to understand how to use its prognostic abilities. This retrospective study was performed with patients with COVID-19 presenting to an Emergency Department (ED) in Italy in 2020. Hs-cTnI was sampled based on clinical judgment. Myocardial injury was defined as values above the sex-specific 99th percentile upper reference limits (URLs). Most data is from the initial hospital value. Four hundred twenty-six unique patients were included. Hs-cTnI was measured in 313 (73.5%) patients; 85 (27.2%) had myocardial injury at baseline. Patients with myocardial injury had higher mortality during hospitalization (hazard ratio = 9 [95% confidence interval (CI) 4.55-17.79], p < 0.0001). Multivariable analysis including clinical and laboratory variables demonstrated an AUC of 0.942 with modest additional value of hs-cTnI. Myocardial injury was associated with mortality in patients with low APACHE II scores (<13) [OR (95% CI): 4.15 (1.40, 14.22), p = 0.014] but not in those with scores >13 [OR (95% CI): 0.48 (0.08, 2.65), p = 0.40]. Initial hs-cTnI < 5 ng/L identified 33% of patients that were at low risk with 97.8 % sensitivity (95% CI 88.7, 99.6) and 99.2% negative predictive value. Type 1 myocardial infarction (MI) and type 2 MI was infrequent.
Audio Interview: A Covid-19 Conversation with Anthony Fauci
New England Journal of Medicine, January 28, 2021
[Editorial, 43:42] The continuing spread of SARS-CoV-2 remains a Public Health Emergency of International Concern. What physicians need to know about transmission, diagnosis, and treatment of Covid-19 is the subject of ongoing updates from infectious disease experts at the Journal. In this audio interview conducted on January 27, 2021, the editors are joined by Dr. Anthony Fauci, U.S. Chief Medical Advisor, to discuss Covid-19 testing, therapeutics, and vaccines.
Widespread myocardial dysfunction in COVID-19 patients detected by myocardial strain imaging using 2-D speckle-tracking echocardiography
Acta Pharmacologica Sinica, January 28, 2021
COVID-19 is a multiorgan systemic inflammatory disease caused by SARS-CoV-2 virus. Patients with COVID-19 often exhibit cardiac dysfunction and myocardial injury, but imaging evidence is lacking. In the study we detected and evaluated the severity of myocardial dysfunction in COVID-19 patient population using two-dimensional speckle-tracking echocardiography (2-D STE). A total of 218 consecutive patients with confirmed diagnosis of COVID-19 who had no underlying cardiovascular diseases were enrolled and underwent transthoracic echocardiography. This study cohort included 52 (23.8%) critically ill and 166 noncritically ill patients. Global longitudinal strains (GLSs) and layer-specific longitudinal strains (LSLSs) were obtained using 2-D STE. Changes in GLS were correlated with the clinical parameters. We showed that GLS was reduced (<−21.0%) in about 83% of the patients. GLS reduction was more common in critically sick patients (98% vs. 78.3%, P < 0.001), and the mean GLS was significantly lower in the critically sick patients than those noncritical (−13.7% ± 3.4% vs. −17.4% ± 3.2%, P < 0.001). The alteration of GLS was more prominent in the subepicardium than in the subendocardium (P < 0.001). GLS was correlated to mean serum pulse oxygen saturation (SpO2, RR = 0.42, P < 0.0001), high-sensitive C-reactive protein (hsCRP, R = −0.20, P = 0.006) and inflammatory cytokines, particularly IL-6 (R = −0.21, P = 0.003). In conclusions, our results demonstrate that myocardial dysfunction is common in COVID-19 patients, particularly those who are critically sick. Changes in indices of myocardial strain were associated with indices of inflammatory markers and hypoxia, suggesting partly secondary nature of myocardial dysfunction.
Outcomes of COVID-19 Among Hospitalized Health Care Workers in North America
JAMA Network Open, January 28, 2021
Although health care workers (HCWs) are at higher risk of acquiring coronavirus disease 2019 (COVID-19), it is unclear whether they are at risk of poorer outcomes. The study objective was to evaluate the association between HCW status and outcomes among patients hospitalized with COVID-19. This retrospective, observational cohort study included consecutive adult patients hospitalized with a diagnosis of laboratory-confirmed COVID-19 across 36 North American centers. Data on patient baseline characteristics, comorbidities, presenting symptoms, treatments, and outcomes were collected, including HCW status. The primary outcome was a requirement for mechanical ventilation or death. Multivariable logistic regression was performed to yield adjusted odds ratios (AORs) and 95% CIs for the association between HCW status and COVID-19–related outcomes in a 3:1 propensity score–matched cohort, adjusting for residual confounding after matching. In total, 1790 patients were included, comprising 127 HCWs and 1663 non-HCWs. After 3:1 propensity score matching, 122 HCWs were matched to 366 non-HCWs. Women comprised 71 (58.2%) of matched HCWs and 214 (58.5%) of matched non-HCWs. Matched HCWs had a mean (SD) age of 52 (13) years, whereas matched non-HCWs had a mean (SD) age of 57 (17) years. In the matched cohort, the odds of the primary outcome, mechanical ventilation or death, were not significantly different for HCWs compared with non-HCWs (AOR, 0.60; 95% CI, 0.34-1.04). The HCWs were less likely to require admission to an intensive care unit (AOR, 0.56; 95% CI, 0.34-0.92) and were also less likely to require an admission of 7 days or longer (AOR, 0.53; 95% CI, 0.34-0.83). There were no differences between matched HCWs and non-HCWs in terms of mechanical ventilation (AOR, 0.66; 95% CI, 0.37-1.17), death (AOR, 0.47; 95% CI, 0.18-1.27), or vasopressor requirements (AOR, 0.68; 95% CI, 0.37-1.24).
Cardiovascular protective properties of oxytocin against COVID-19
Life Sciences, January 26, 2021
SARS-CoV-2 infection or COVID-19 has become a worldwide pandemic; however, effective treatment for COVID-19 remains to be established. Along with acute respiratory distress syndrome (ARDS), new and old cardiovascular injuries are important causes of significant morbidity and mortality in COVID-19. Exploring new approaches managing cardiovascular complications is essential in controlling the disease progression and preventing long-term complications. Oxytocin (OXT), an immune-regulating neuropeptide, has recently emerged as a strong candidate for treatment and prevention of COVID-19 pandemic. OXT carries special functions in immunologic defense, homeostasis and surveillance. It suppresses neutrophil infiltration and inflammatory cytokine release, activates T-lymphocytes, and antagonizes negative effects of angiotensin II and other key pathological events of COVID-19. Additionally, OXT can promote γ-interferon expression, which inhibits cathepsin L and raises superoxide dismutase expression, to reduce heparin and heparan sulphate fragmentation. Through these mechanisms, OXT can block viral invasion, suppress cytokine storm, reverse lymphocytopenia, and prevent progression to ARDS and multiple organ failures. Importantly, besides prevention of metabolic disorders associated with atherosclerosis and diabetes mellitus, OXT can protect the heart and vasculature through suppressing hypertension, brain-heart syndrome, and social stress, and promoting regeneration of injured cardiomyocytes. Unlike other therapeutic agents, exogenous OXT can be used safely without the side-effects seen in remdesivir and corticosteroid. Importantly, OXT can be mobilized endogenously to prevent pathogenesis of COVID-19. This article summarizes our current understandings of cardiovascular pathogenesis caused by COVID-19, explores the protective potentials of OXT against COVID-19-associated cardiovascular diseases, and discusses challenges in applying OXT in treatment and prevention of COVID-19.
Complete aortic thrombosis in SARS-CoV-2 infection
European Heart Journal, January 26, 2021
A 74-year-old man with a history of diabetes mellitus, coronary artery disease, and previous myocardial infarction presents to the emergency department with cardiogenic shock. Cardiopulmonary resuscitation and emergency care were performed. The patient’s consent for publication was obtained. His laboratory values were remarkable for leucocytosis of 25.2 cells/L (4.5–11.0), PT 17.2 s (12–14.5), INR 1.9 U (<1.0), PTT 30.9 s (23.9–36.6), and d-dimer >20 µg/mL (<0.5). C-reactive protein was significantly elevated at 226.3 mg/L (0–5), creatine phosphokinase was 178 UI/L (30–178), and lactate dehydrogenase 1405 UI/L (<205). Three-dimensional computed tomographic (CT) angiography revealed the complete thrombotic occlusion of the aorta, arising from the descending aorta and including all the visceral arteries, celiac trunk, superior mesenteric artery, and left and right renal arteries. Multifocal ground-glass opacities were visualized in the bilateral lungs. Diagnosis of SARS-CoV-2 was confirmed by reverse transcriptase–polymerase chain reaction analysis. The patient died immediately after the CT scan. COVID-19 infection due to the SARS-CoV-2 virus has shown to be associated with a hypercoaguable state. Excessive inflammation triggered by the cytokine storm, the massive macrophages, and platelet activation and endothelial dysfunction should be associated with the development of coagulopathy.
COVID-19 myopericarditis with cardiac tamponade in the absence of respiratory symptoms: a case report
Journal of Medical Case Reports, January 25, 2021
Previous reports have shown various cardiac complications to be associated with COVID-19 including: myocardial infarction, microembolic complications, myocardial injury, arrhythmia, heart failure, coronary vasospasm, non-ischemic cardiomyopathy, stress (Takotsubo) cardiomyopathy, pericarditis and myocarditis. These COVID-19 cardiac complications were associated with respiratory symptoms. However, our case illustrates that COVID-19 myopericarditis with cardiac tamponade can present without respiratory symptoms. A 58-year-old Caucasian British woman was admitted with fever, diarrhoea and vomiting. She developed cardiogenic shock and Transthoracic echocardiogram (TTE) found a pericardial effusion with evidence of cardiac tamponade. A nasopharyngeal swab showed a COVID-19 positive result, despite no respiratory symptoms on presentation. A pericardial drain was inserted and vasopressor support required on intensive treatment unit (ITU). The drain was removed as she improved, an antibiotic course was given and she was discharged on day 12. The case demonstrates that patients without respiratory symptoms could have COVID-19 and develop cardiac complications.
Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) may be safe for COVID-19 patients
BMC Infectious Diseases, January 25, 2021
The goal of the study was to investigate the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARBs) administration to hypertension patients with the coronavirus disease 2019 (COVID-19) induced pneumonia. We recorded the recovery status of 67 inpatients with hypertension and COVID-19 induced pneumonia in the Raytheon Mountain Hospital in Wuhan during February 12, 2020 and March 30, 2020. Patients treated with ACEI or ARBs were categorized in group A (n = 22), while patients who were not administered either ACEI or ARBs were categorized into group B (n = 45). We did a comparative analysis of various parameters such as the pneumonia progression, length-of-stay in the hospital, and the level of alanine aminotransferase (ALT), serum creatinine (Cr), and creatine kinase (CK) between the day when these patients were admitted to the hospital and the day when the treatment ended. These 67 hypertension cases counted for 33.17% of the total COVID-19 patients. There was no significant difference in the usage of drug treatment of COVID-19 between groups A and B (p > 0.05). During the treatment, 1 case in group A and 3 cases in group B progressed from mild pneumonia into severe pneumonia. Eventually, all patients were cured and discharged after treatment, and no recurrence of COVID-2019 induced pneumonia occurred after the discharge. The length of stays was shorter in group A as compared with group B, but there was no significant difference (p > 0.05). There was also no significant difference in other general parameters between the patients of the groups A and B on the day of admission to the hospital (p > 0.05). The ALT, CK, and Cr levels did not significantly differ between groups A and B on the day of admission and the day of discharge (p > 0.05).
Statins in patients with COVID-19: a retrospective cohort study in Iranian COVID-19 patients
Translational Medicine Communications, January 25, 2021
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has profoundly affected the lives of millions of people. To date, there is no approved vaccine or specific drug to prevent or treat COVID-19, while the infection is globally spreading at an alarming rate. Because the development of effective vaccines or novel drugs could take several months (if not years), repurposing existing drugs is considered a more efficient strategy that could save lives now. Statins constitute a class of lipid-lowering drugs with proven safety profiles and various known beneficial pleiotropic effects. Our previous investigations showed that statins have antiviral effects and are involved in the process of wound healing in the lung. This triggered us to evaluate if statin use reduces mortality in COVID-19 patients. After initial recruitment of 459 patients with COVID-19 (Shiraz province, Iran) and careful consideration of the exclusion criteria, a total of 150 patients, of which 75 received statins, were included in our retrospective study. Cox proportional-hazards regression models were used to estimate the association between statin use and rate of death. After propensity score matching, we found that statin use appeared to be associated with a lower risk of morbidity [HR = 0.85, 95% CI = (0.02, 3.93), P = 0.762] and lower risk of death [(HR = 0.76; 95% CI = (0.16, 3.72), P = 0.735)]; however, these associations did not reach statistical significance. Furthermore, statin use reduced the chance of being subjected to mechanical ventilation [OR = 0.96, 95% CI = (0.61–2.99), P = 0.942] and patients on statins showed a more normal computed tomography (CT) scan result [OR = 0.41, 95% CI = (0.07–2.33), P = 0.312].
Meta-analysis of Atrial Fibrillation in Patients with COVID-19
American Journal of Cardiology, January 24, 2021
A number of published papers have investigated the relation between atrial fibrillation (AF) and clinical outcomes of patients with coronavirus disease 2019 (COVID-19). However, the conclusions drawn from previous studies are not consistent. For instance, some studies observed that AF was significantly associated with an increased risk of mortality among COVID-19 patients, while several other studies reported opposite results that there was no significant relation between AF and unfavorable outcomes of COVID-19 patients. Several confounding factors such as gender, age and pre-existing medical disorders (diabetes, hypertension, autoimmune diseases, chronic kidney disease and chronic obstructive pulmonary disease, etc.) have been reported to significantly influence the clinical outcomes of COVID-19 patients, suggesting that these factors might have significant impacts on the relation between AF and unfavorable outcomes of COVID-19 patients. In this meta-analysis, the pooled effect size was estimated on the basis of adjusted effect estimates reported in published papers. Nine hundred and sixteen potentially relevant studies were screened according to the inclusion and exclusion criteria. Finally, 23 studies with 108,745 COVID-19 patients were eligibly included in the present quantitative meta-analysis. Results of our meta-analysis indicated that AF was significantly associated with an increased risk of unfavorable outcomes among COVID-19 patients (pooled effect size = 1.14, 95% CI: 1.03-1.26, P = 0.01; I2 = 63.9%, random-effects analysis.
Rate control in atrial fibrillation using Landiolol is safe in critically ill Covid-19 patients
Critical Care, January 22, 2021
[Letter to Editor] Atrial fibrillation (AF) is frequent in shock patients admitted to the intensive care unit (ICU) and is associated with increased mortality. Several mechanisms are involved in the development of AF in the context of acute circulatory failure, including hypovolemia and β1-adrenergic stimulation in response to endogenous catecholamine production as well as norepinephrine infusion. Atrial fibrillation impairs left ventricular filling and consecutively stroke volume, and in fine potentially aggravates circulatory failure. Pharmacological options to control AF-related tachycardia are limited. Calcium channel blockers are not frequently used because of long-term negative inotropic effects. Amiodarone is the most used drug but its optimal dosage to fine tune heart rate remains an issue, as well as its potential lung toxicity, especially in case of acute respiratory disease. Landiolol is a beta-blocker with highly β1 selective activity, used either in AF patients either to control heart rate or to prevent supraventricular arrhythmia occurrence in the context of cardiac surgery. Landiolol has an ultrashort half-life of 4 min and weaker negative inotropic effect compared with other intravenous β-blockers [4]. A recent randomized controlled trial in patient with sepsis/septic shock developing tachyarrhythmia showed that Landiolol infusion efficiently reduced heart rate without any significant hemodynamic side effect. Here, we described in critically ill patients admitted to the ICU for SARS-CoV-2 infections presenting with AF, our experience of Landiolol use in terms of efficacy and safety.
Advanced echocardiographic phenotyping of critically ill patients with coronavirus-19 sepsis: a prospective cohort study
Journal of Intensive Care, January 20, 2021
Sepsis is characterized by various hemodynamic alterations which could happen concomitantly in the heart, pulmonary and systemic circulations. A comprehensive demonstration of their interactions in the clinical setting of COVID-19 sepsis is lacking. This study aimed at evaluating the feasibility, clinical implications, and physiological coherence of the various indices of hemodynamic function and acute myocardial injury (AMI) in COVID-19 sepsis. Hemodynamic and echocardiographic data of septic critically ill COVID-19 patients were prospectively recorded. A dozen hemodynamic indices exploring contractility and loading conditions were assessed. Several cardiac biomarkers were measured, and AMI was considered if serum concentration of high-sensitive troponin T (hs-TNT) was above the 99th percentile, upper reference. Sixty-seven patients were assessed (55 males), with a median age of 61 [50–70] years. Overall, the feasibility of echocardiographic parameters was very good, ranging from 93 to 100%. Hierarchical clustering method identified four coherent clusters involving cardiac preload, left ventricle (LV) contractility, LV afterload, and right ventricle (RV) function. LV contractility indices were not associated with preload indices, but some of them were positively correlated with RV function parameters and negatively correlated with a single LV afterload parameter. In most cases (n = 36, 54%), echocardiography results prompted therapeutic changes. Mortality was not influenced by the echocardiographic variables in multivariable analysis. Cardiac biomarkers’ concentrations were most often increased with high incidence of AMI reaching 72%. hs-TNT was associated with mortality and inversely correlated with most of LV and RV contractility indices.
Cardiovascular Deaths During the COVID-19 Pandemic in the United States
Journal of the American College of Cardiology, January 19, 2021
Although the direct toll of COVID-19 in the United States has been substantial, concerns have also arisen about the indirect effects of the pandemic. Hospitalizations for acute cardiovascular conditions have declined, raising concern that patients may be avoiding hospitals because of fear of contracting severe acute respiratory syndrome- coronavirus-2 (SARS-CoV-2). Other factors, including strain on health care systems, may also have had an indirect toll. This investigation aimed to evaluate whether population-level deaths due to cardiovascular causes increased during the COVID-19 pandemic. The authors conducted an observational cohort study using data from the National Center for Health Statistics to evaluate the rate of deaths due to cardiovascular causes after the onset of the pandemic in the United States, relative to the period immediately preceding the pandemic. Changes in deaths were compared with the same periods in the previous year. There were 397,042 cardiovascular deaths from January 1, 2020, to June 2, 2020. Deaths caused by ischemic heart disease increased nationally after the onset of the pandemic in 2020, compared with changes over the same period in 2019 (ratio of the relative change in deaths per 100,000 in 2020 vs. 2019: 1.11, 95% confidence interval: 1.04 to 1.18). An increase was also observed for deaths caused by hypertensive disease (1.17, 95% confidence interval: 1.09 to 1.26), but not for heart failure, cerebrovascular disease, or other diseases of the circulatory system. New York City experienced a large relative increase in deaths caused by ischemic heart disease (2.39, 95% confidence interval: 1.39 to 4.09) and hypertensive diseases (2.64, 95% confidence interval: 1.52 to 4.56) during the pandemic. More modest increases in deaths caused by these conditions occurred in the remainder of New York State, New Jersey, Michigan, and Illinois but not in Massachusetts or Louisiana. There was an increase in deaths caused by ischemic heart disease and hypertensive diseases in some regions of the United States during the initial phase of the COVID-19 pandemic. These findings suggest that the pandemic may have had an indirect toll on patients with cardiovascular disease.
International Impact of COVID-19 on the Diagnosis of Heart Disease
Journal of the American College of Cardiology, January 19, 2021
The coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified. The study sought to assess COVID-19’s impact on global cardiovascular diagnostic procedural volumes and safety practices. The International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained. Surveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoracic echocardiography decreased by 59%, transesophageal echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p < 0.001 for each procedure). In multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower–middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and telehealth. COVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world’s economically challenged. Further study of cardiovascular outcomes and COVID-19–related changes in care delivery is warranted.
ACEi reduces hypertension-induced hyperinflammation in COVID-19
Nature Reviews Cardiology, January 18, 2021
Hypertension is associated with a pro-inflammatory state that worsens the prognosis of patients with coronavirus disease 2019 (COVID-19). According to a new study, antihypertensive blockade of the renin–angiotensin–aldosterone system (RAAS), particularly with the use of an angiotensin-converting enzyme inhibitor (ACEi), might improve outcomes in patients with hypertension and COVID-19. Irina Lehmann, Ulf Landmesser, Roland Eils and colleagues combined clinical data from 144 patients with COVID-19, single-cell sequencing data from 48 airway tissue samples and data from in vitro experiments. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to ACE2 to gain entry into cells. Uncertainty had been raised whether RAAS blockade upregulates the expression of ACE2, causing ACEi-treated or angiotensin-receptor blocker (ARB)-treated patients to be more susceptible to SARS-CoV-2 infection. However, the researchers found no evidence that treatment with either an ACEi or an ARB increased the expression of ACE2 in patients with or without SARS-CoV-2 infection. “This result is in line with findings from observational studies that patients receiving antihypertensive treatment with an ACEi or ARB are not more susceptible to SARS-CoV-2 infection,” comments Lehmann. Moreover, the induction of ACE2 expression that occurs after SARS-CoV-2 infection was unaltered by either ACEi or ARB therapy. The investigators identified a hypertension-associated increase in immunological activity as being the prominent factor contributing to the worse prognosis of patients with high blood pressure and COVID-19.
Bioinformatics and system biology approach to identify the influences of COVID-19 on cardiovascular and hypertensive comorbidities
Briefings in Bioinformatics, January 18, 2021
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected individuals that have hypertension or cardiovascular comorbidities have an elevated risk of serious coronavirus disease 2019 (COVID-19) disease and high rates of mortality but how COVID-1919 and cardiovascular diseases interact are unclear. We therefore sought to identify novel mechanisms of interaction by identifying genes with altered expression in SARS-CoV-22 infection that are relevant to the pathogenesis of cardiovascular disease and hypertension. Some recent research shows the SARS-CoV-22 uses the angiotensin converting enzyme-22 (ACE-22) as a receptor to infect human susceptible cells. The ACE2 gene is expressed in many human tissues, including intestine, testis, kidneys, heart and lungs. ACE2 usually converts Angiotensin I in the renin–angiotensin-aldosterone system to Angiotensin II, which affects blood pressure levels. ACE inhibitors prescribed for cardiovascular disease and hypertension may increase the levels of ACE-22, although there are claims that such medications actually reduce lung injury caused by COVID-1919. We employed bioinformatics and systematic approaches to identify such genetic links, using messenger RNA data peripheral blood cells from COVID-1919 patients and compared them with blood samples from patients with either chronic heart failure disease or hypertensive diseases. We have also considered the immune response genes with elevated expression in COVID-1919 to those active in cardiovascular diseases and hypertension. Differentially expressed genes (DEGs) common to COVID-1919 and chronic heart failure, and common to COVID-1919 and hypertension, were identified; the involvement of these common genes in the signalling pathways and ontologies studied. COVID-1919 does not share a large number of differentially expressed genes with the conditions under consideration. However, those that were identified included genes playing roles in T cell functions, toll-like receptor pathways, cytokines, chemokines, cell stress, type 2 diabetes and gastric cancer. We also identified protein–protein interactions, gene regulatory networks and suggested drug and chemical compound interactions using the differentially expressed genes. The result of this study may help in identifying significant targets of treatment that can combat the ongoing pandemic due to SARS-CoV-22 infection.
Nearly 1 in 4 hospitalized patients with HF, COVID-19 die
Helio | Cardiology Today, January 15, 2021
Patients with HF and COVID-19 had high risk for complications, with nearly 1 in 4 dying during hospitalization, researchers reported. “Patients with heart failure have lower reserve, in general, than people without severe cardiovascular disease, and they are at increased risk from many respiratory infections, including influenza,” Scott D. Solomon, MD, professor of medicine at Harvard Medical School and senior physician at Brigham and Women’s Hospital, told Healio. “In addition, patients with cardiovascular disease, in general, appear to be at greater risk for COVID-19-related complications.” Researchers assessed the Premier Healthcare Database to identify patients with at least one HF hospitalization or two related outpatient visits from 2019 to March 2020 who were then hospitalized from April to September 2020. Predictors of in-hospital mortality were identified among patients with HF hospitalized with COVID-19. The researchers also compared this population and those hospitalized due to other factors. There were 132,312 patients with a history of HF hospitalized from April to September 2020, with 23,843 hospitalized with acute HF, 8,383 hospitalized with COVID-19 and 100,068 hospitalized for alternative causes.
Should all patients with hypertension be worried about developing severe coronavirus disease 2019 (COVID-19)?
Clinical Hypertension, January 15, 2021
Hypertension, the most common comorbidity among coronavirus disease 2019 (COVID-19) patients, is accompanied by worse clinical outcomes, but there is lack of evidence about prognostic factors among COVID-19 patients with hypertension. We have come up with some prognostic factors to predict the severity of COVID-19 among hypertensive patients. In addition, epidemiologic, clinical and laboratory differences among COVID-19 patients with and without underlying hypertension were evaluated. Medical profiles of 598 COVID-19 cases were analyzed. Patients were divided into two comparative groups according to their positive or negative history of hypertension. Then, epidemiologic, clinical, laboratory and radiological features and also clinical outcomes were compared. 176 (29.4%) patients had underlying hypertension. Diabetes was significantly higher in hypertensive group [72 (40.9%) vs 76 (18%)] (P-value: 0.001). Cardiovascular and renal disorders were significantly higher in hypertensive patients. (P-value: 0.001 and 0.013 respectively). In COVID-19 patients with hypertension, severe/critical types were significantly higher. [42(23.8%) vs. 41(9.7%)], (P-value: 0.012). In the logistic regression model, Body mass index > 25 (ORAdj: 1.8, 95% CI: 1.2 to 2.42; P-value: 0.027), age over 60 (ORAdj: 1.26, 95% CI: 1.08 to 1.42; P-value: 0.021), increased hospitalization period (ORAdj: 2.1, 95% CI: 1.24 to 2.97; P-value: 0.013), type 2 diabetes (ORAdj: 2.22, 95% CI: 1.15 to 3.31; P-value: 0.001) and chronic kidney disease (ORAdj: 1.83, 95% CI: 1.19 to 2.21; P-value: 0.013) were related with progression of COVID-19.
COVID-19 VTE Prevention: The Case for Intermediate and Outpatient Dosing
MedPage Today, January 15, 2021
Should patients hospitalized for COVID-19 routinely receive extra anticoagulation or go home with a course of antithrombotics? The first randomized controlled trial data are still emerging, leaving those questions to the realm of expert consensus statements with only observational and pre-COVID data from which to extrapolate. The key fulcrum on which the decision rests is how elevated venous thromboembolism (VTE) risk is versus how much bleeding occurs in COVID-19 patients, noted speakers at a Pulmonary Embolism Response Team Consortium webinar. A widely cited meta-analysis in CHEST yielded a 17% estimated incidence of VTE across 47 studies in hospitalized COVID-19 patients largely on standard thromboprophylaxis, which individually ranged from 0% to 85%. But you also can’t ignore the 7.8% rate of bleeds in that meta-analysis, noted Rachel Rosovsky, MD, MPH, of Massachusetts General Hospital and Harvard Medical School in Boston. Still, the major bleeding rate was a more modest 3.9%, so “using these escalated doses in ward patients is probably something we should be considering” to minimize thrombotic complications that might tip patients into needing ICU care, argued Lana Castellucci, MD, of the University of Ottawa, in her presentation on the webinar.
Evaluation for Myocarditis in Competitive Student Athletes Recovering From Coronavirus Disease 2019 With Cardiac Magnetic Resonance Imaging
JAMA Cardiology, January 14, 2021
The utility of cardiac magnetic resonance imaging (MRI) as a screening tool for myocarditis in competitive student athletes returning to training after recovering from coronavirus disease 2019 (COVID-19) infection is unknown. The objective was to describe the prevalence and severity of cardiac MRI findings of myocarditis in a population of competitive student athletes recovering from COVID-19. In this case series, an electronic health record search was performed at our institution (University of Wisconsin) to identify all competitive athletes (a consecutive sample) recovering from COVID-19, who underwent gadolinium-enhanced cardiac MRI between January 1, 2020, and November 29, 2020. The MRI findings were reviewed by 2 radiologists experienced in cardiac imaging, using the updated Lake Louise criteria. Serum markers of myocardial injury and inflammation (troponin-I, B-type natriuretic peptide, C-reactive protein, and erythrocyte sedimentation rate), an electrocardiogram, transthoracic echocardiography, and relevant clinical data were obtained. COVID-19 infection, confirmed using reverse transcription–polymerase chain reaction testing. Prevalence and severity of MRI findings were consistent with myocarditis among young competitive athletes recovering from COVID-19.
COVID’s Indirect Toll on the Heart
MedPage Today, January 12, 2021
COVID-19 has had an indirect toll on heart health around the world, as cardiovascular testing volumes plummeted and cardiovascular deaths rose in 2020, researchers found. CDC data revealed that in the first U.S. coronavirus epicenters like New York, the number of people who died from ischemic heart disease and hypertension increased dramatically after mid-March compared with historical controls from the year before. It remains unclear whether the excess deaths were related to people avoiding necessary medical care for fear of contracting SARS-CoV-2 or reflected other factors, such as undiagnosed COVID-19, according to study authors led by Rishi Wadhera, MD, MPP, MPhil, of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, reporting in the Journal of the American College of Cardiology (JACC). However, the theory of avoidance of care would be consistent with the finding that cardiac testing centers in 108 countries were seeing sharp decreases in cardiac diagnostic procedures by the summer, as reported in the same issue of JACC by another group. “Clearly, the overwhelming priority should be emphasizing the importance of public health measures to prevent the spread of COVID-19. … Such a strategy may allow the economy, schools, and less urgent but important health services, including selective cardiac diagnostic tests, to be provided to a limited extent,” according to an accompanying editorial.
Elevated Extracellular Volume Fraction and Reduced Global Longitudinal Strains in Patients Recovered from COVID-19 without Clinical Cardiac Findings
Radiology, January 12, 2021
The purpose of this study was to evaluate cardiac involvement in participants recovered from COVID-19 without clinical evidence of cardiac involvement using cardiac MRI. In this prospective observational cohort study, 40 participants recovered from COVID-19 with moderate (n=24) or severe (n=16) pneumonia and no cardiovascular medical history, without cardiac symptoms, with normal ECG, normal serological cardiac enzyme levels, and discharged > 90 days between May and September 2020. Demographic characteristics, serum cardiac enzymes, and cardiac MRI were obtained. Cardiac function, native T1, ECV and Two-dimensional (2D) strain were quantitatively evaluated and compared with controls (n = 25).The Comparison among the 3 groups were performed using one-way analysis of variance (ANOVA) with Bonferroni corrected post-hoc comparisons(for normal distribution) or Kruskal-Wallis tests with post-hoc pairwise comparisons(for non-normal distribution). Forty participants (54±12 years; 24 men) enrolled with a mean time between admission and CMR of 158 ±18 days and discharge and CMR examination of 124 ±17 days. There was no LV and RV size or functional differences among participants recovered from COVID-19 and healthy controls. Only one (3%) participants had positive LGE located at the mid inferior wall. Global ECV values were elevated in both participants recovered from COVID-19 with moderate or severe pneumonia, compared to the healthy controls [median ECV (IQR)], [29.7% (28.0%-32.9%), versus 31.4% (29.3%-34.0%), versus 25.0% (23.7%-26.0%); both p<.001]. The 2D-global LV longitudinal stains (GLS) were reduced in both groups of participants [COVID-19 moderate group, -12.5% (-10.7%–15.5%), COVID-19 severe group, -12.5% (-8.7%–15.4%) compared to healthy control group -15.4% (-14.6%-17.6%), p=.002 and p=.001, respectively]. CMR myocardial tissue and strain imaging parameters suggest that a proportion of participants recovered from COVID-19 had subclinical myocardial abnormalities detectable months after recovery.
International Impact of COVID-19 on the Diagnosis of Heart Disease
Journal of the American College of Cardiology, January 11, 2021
The coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified. The study sought to assess COVID-19’s impact on global cardiovascular diagnostic procedural volumes and safety practices. The International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained. Surveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoracic echocardiography decreased by 59%, transesophageal echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p < 0.001 for each procedure). In multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower–middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and telehealth.
Cardiac implantable electronic devices replacements in patients followed by remote monitoring during COVID-19 lockdown
European Heart Journal – Digital Health, January 11, 2021
Following coronavirus disease (COVID-19) outbreak, the Italian government adopted strict rules of lockdown and social distancing. The aim of our study was to assess the admission rate for cardiac implantable electronic devices (CIEDs) replacement procedures in Campania, the 3rd-most-populous region of Italy, during COVID-19 lockdown. Data were sourced from 16 referral hospitals in Campania from 10 March to 4 May 2020 (lockdown period) and during the same period in 2019. We retrospectively evaluated consecutive patients hospitalized for CIEDs replacement procedures during the two observational periods. The number and type of CIEDs replacement procedures among patients followed by remote monitoring (RM), the admission rate, and the type of hospital admission between the two observational periods were compared. In total, 270 consecutive patients were hospitalized for CIEDs replacement procedures over the two observation periods. Overall CIEDs replacement procedures showed a reduction rate of 41.2% during COVID-19 lockdown. Patients were equally distributed for sex (P = 0.581), and both age [median 76 years (IQR: 68–83) vs. 79 years (IQR: 68–83); P = 0.497]. Cardiac implantable electronic devices replacement procedures in patients followed by RM significantly increased (IR: +211%; P < 0.001), mainly driven by the remarkable increase rate trend of both PM (IR: +475%; P < 0.001) and implantable cardiac defibrillator replacement procedures (IR: +67%, P = 0.01), during COVID-19 lockdown compared with 2019 timeframe.
Highlights of American Heart Association Scientific Sessions 2020: a virtual experience
Cardiovascular Research, January 10, 2021
The year 2020 has been unique and defiant due to pandemic of COVID-19. One of the new over-used terms this year is finding the ‘new normal’. Indeed, COVID-19 has transformed the scientific congress experience significantly. Social distancing and travel restrictions have enforced congress coordinators to make a tough decision between cancelling the events or re-formatting for online presentations. The American Heart Association (AHA) presented Scientific Sessions 2020 (13–17 November) as a 100% virtual experience, reached more people than ever, in real-time and asynchronously, with live chats that inspire scientific dialogues, providing an engaging online involvement. A wide variety of subjects were presented, ranging from new heart failure (HF) treatments to cardiovascular involvement in COVID-19 and a special focus in structural racism. Some of the exciting science included fresh takes on primary cardiovascular disease (CVD) prevention. In a new first-of-its-kind international outcomes trial, TIPS-3, involving more than 5000 patients with an intermediate CVD risk but no known CVD, treatment with a polypill formulation (simvastatin, atenolol, ramipiril, and hydrochlorothiazide), plus aspirin led to a lower incidence of cardiovascular events. In VITAL-Rhythm trial, involving more than 20 000 patients, treatment with vitamin D3, Omega-3 fatty acids, or a combination had no effect on the incidence of atrial fibrillation (AF), the most common cardiac arrhythmia and a major cause of morbidity and mortality, over a median treatment duration of 5.3 years. Likewise, in the AF field, SEARCH-AF study demonstrated that enhanced cardiac rhythm monitoring detected a higher incidence of post-operative AF after cardiac surgery, as compared to the usual care, in those who had no history of AF but had a high risk of stroke. Also, the VITAL-AF trial showed that point-of-care screening did not result in more new AF diagnoses in primary care, whereas mSToPS study found that continuous monitoring with a wearable electrocardiogram patch did lead to more AF detected and even better outcomes, emphasizing the importance of the use of mobile health technology in CVD prevention/management.
Cardiovascular risk factors and mortality in hospitalized patients with COVID-19: systematic review and meta-analysis of 45 studies and 18,300 patients
BMC Cardiovascular Disorders, January 7, 2021
A high prevalence of cardiovascular risk factors including age, male sex, hypertension, diabetes, and tobacco use, has been reported in patients with Coronavirus disease 2019 (COVID-19) who experienced adverse outcome. The aim of this study was to investigate the relationship between cardiovascular risk factors and in-hospital mortality in patients with COVID-19. MEDLINE, Cochrane, Web of Sciences, and SCOPUS were searched for retrospective or prospective observational studies reporting data on cardiovascular risk factors and in-hospital mortality in patients with COVID-19. Univariable and multivariable age-adjusted analyses were conducted to evaluate the association between cardiovascular risk factors and the occurrence of in-hospital death. The analysis included 45 studies enrolling 18,300 patients. The pooled estimate of in-hospital mortality was 12% (95% CI 9–15%). The univariable meta-regression analysis showed a significant association between age (coefficient: 1.06; 95% CI 1.04–1.09; p < 0.001), diabetes (coefficient: 1.04; 95% CI 1.02–1.07; p < 0.001) and hypertension (coefficient: 1.01; 95% CI 1.01–1.03; p = 0.013) with in-hospital death. Male sex and smoking did not significantly affect mortality. At multivariable age-adjusted meta-regression analysis, diabetes was significantly associated with in-hospital mortality (coefficient: 1.02; 95% CI 1.01–1.05; p = 0.043); conversely, hypertension was no longer significant after adjustment for age (coefficient: 1.00; 95% CI 0.99–1.01; p = 0.820). A significant association between age and in-hospital mortality was confirmed in all multivariable models.
SARS-CoV-2 leads to a small vessel endotheliitis in the heart
E Bio Medicine, January 7, 2021
SARS-CoV-2 infection (COVID-19 disease) can induce systemic vascular involvement contributing to morbidity and mortality. SARS-CoV-2 targets epithelial and endothelial cells through the ACE2 receptor. The anatomical involvement of the coronary tree is not explored yet. Cardiac autopsy tissue of the entire coronary tree (main coronary arteries, epicardial arterioles/venules, epicardial capillaries) and epicardial nerves were analyzed in COVID-19 patients (n = 6). All anatomical regions were immunohistochemically tested for ACE2, TMPRSS2, CD147, CD45, CD3, CD4, CD8, CD68 and IL-6. COVID-19 negative patients with cardiovascular disease (n = 3) and influenza A (n = 6) served as controls. COVID-19 positive patients showed strong ACE2 / TMPRSS2 expression in capillaries and less in arterioles/venules. The main coronary arteries were virtually devoid of ACE2 receptor and had only mild intimal inflammation. Epicardial capillaries had a prominent lympho-monocytic endotheliitis, which was less pronounced in arterioles/venules. The lymphocytic-monocytic infiltrate strongly expressed CD4, CD45, CD68. Peri/epicardial nerves had strong ACE2 expression and lympho-monocytic inflammation. COVID-19 negative patients showed minimal vascular ACE2 expression and lacked endotheliitis or inflammatory reaction. ACE2 / TMPRSS2 expression and lymphomonocytic inflammation in COVID-19 disease increases crescentically towards the small vessels suggesting that COVID-19-induced endotheliitis is a small vessel vasculitis not involving the main coronaries.
Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults
New England Journal of Medicine, January 6, 2021
Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P=0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed.
Age, sex, comorbidities impact outcomes after COVID-19 hospitalization
Helio | Cardiology Today, January 6, 2021
In a national private health care database, age, male sex and comorbidities increased risk for death in patients hospitalized with COVID-19, according to data presented at the virtual American Heart Association Scientific Sessions. The findings were mostly consistent with data from the AHA’s COVID-19 CVD registry, also presented at the meeting. The data set of patients with COVID-19 was created by Cerner Corp. and Amazon Web Services, Cardiology Today Next Gen Innovator Ann Marie Navar, MD, PhD, associate professor of internal medicine and of population and data sciences at University of Texas Southwestern Medical Center, said during a presentation. “We need to understand who is most at risk, particularly as we are deploying immunization strategies,” she said. “We also need to understand risk factors so that people can understand their own risk of disease and make appropriately informed choices. Among people who are hospitalized with COVID-19, it’s critical that we understand risk factors for worse outcomes, as we have to have important informed conversations with patients and their families about their prognosis.” The analysis included 19,584 patients with COVID-19 (median age, 52 years; 47% women; 29.4% Hispanic) who died or were discharged to home during the study period. Among the cohort, 31.1% had diabetes, 50.4% had hypertension, 14.3% had HF, 18% had CAD and 5.6% had end-stage renal disease, Navar said.
Case report of a COVID-19-associated myocardial infarction with no obstructive coronary arteries: the mystery of the phantom embolus or local endotheliitis
European Heart Journal – Case Reports, January 6, 2021
Since the first documented outbreak of a novel severe acute respiratory syndrome inducing Coronavirus in China at the end of 2019 the virus has spread to all continents, leading the WHO to declare a pandemic in March 2020. While this virus primarily targets the alveoli in the lungs, multiple authors have described an increased rate of thrombo-embolic events in affected patients. We present this case of a myocardial infarction with no obstructive coronary atherosclerosis in an otherwise healthy 48-year-old patient. A 48-year-old female, presenting with chest pain radiating to her left shoulder with no cardiovascular risk factors other than genetic predisposition, was screened for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and tested positive. Although computed tomography angiography excluded obstructive coronary heart disease, cardiac magnetic resonance imaging showed an acute myocardial infarction with no obstructive coronary arteries of the inferior wall. The patient was treated with dual anti-platelet therapy, an angiotensin-converting-enzyme inhibitor and a statin, and assigned to a cardiac rehabilitation program. We report a serious thrombo-embolic event during an oligosymptomatic SARS-CoV-2 infection in a healthy, young patient. While these two diseases may have occurred simultaneously, by chance, it is possible that the pro-thrombotic effects of the SARS-CoV-2 infection facilitated the infarction. This case further demonstrates the significant cardiovascular morbidity potentially caused by SARS-CoV-2.
Race, Age Implicated in Pandemic Cardiac Arrest Spike
MedPage Today, January 6, 2021
Detroit-area EMS workers saw disproportionately more Black people and nursing home residents in the surge of out-of-hospital cardiac arrests (OHCAs) roughly coinciding with the first wave of COVID-19, a study found. OHCA calls in the metropolitan Detroit area recorded in the Michigan EMS Information System jumped 60% in March 23 to May 31, 2020, compared with the same period in 2019 (1,854 vs 1,162 calls), according to Adrienne Nickles, MPH, of the Michigan Department of Health and Human Services in Lansing, and colleagues. The wave of OHCAs lagged just a few weeks behind the surge of confirmed COVID-19 cases and mirrored the shape of the epidemic curve, the authors reported online in JAMA Network Open. OHCAs increased across all demographic groups in 2020 compared with 2019 but made especially large jumps in:
- Elderly individuals 85 years or older (18.4% vs 14.7% in 2019, P=0.01)
- Black individuals (39.1% vs 30.4%, P<0.001)
- Nursing home residents (22.0% vs 18.8%, P=0.03)
Patients with OHCA during the pandemic were less likely to be intubated or receive other advanced airway devices than peers the year before (21.4% vs 45.5%, P<0.001). “This study was limited to prehospital records; definitive causes of death are not known and it is not clear from these data whether the increase arose as a direct effect of COVID-19 infection or from indirect effects of the pandemic on utilization of EMS. Further investigation is needed to characterize the phenomena underlying these associations to design interventions to mitigate the impacts of the ongoing COVID-19 pandemic,” according to Nickles and colleagues.
Impact of the coronavirus disease 2019 (COVID-19) pandemic on the care of patients with acute and chronic aortic conditions
European Journal of Cardio-thoracic Surgery, January 4, 2021
The objective was to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on acute and elective thoracic and abdominal aortic procedures. Forty departments shared their data on acute and elective thoracic and abdominal aortic procedures between January and May 2020 and January and May 2019 in Europe, Asia and the USA. Admission rates as well as delay from onset of symptoms to referral were compared. No differences in the number of acute thoracic and abdominal aortic procedures were observed between 2020 and the reference period in 2019 [incidence rates ratio (IRR): 0.96, confidence interval (CI) 0.89–1.04; P = 0.39]. Also, no difference in the time interval from acute onset of symptoms to referral was recorded (<12 h 32% vs > 12 h 68% in 2020, < 12 h 34% vs > 12 h 66% in 2019 P = 0.29). Conversely, a decline of 35% in elective procedures was seen (IRR: 0.81, CI 0.76–0.87; P < 0.001) with substantial differences between countries and the most pronounced decline in Italy (−40%, P < 0.001). Interestingly, in Switzerland, an increase in the number of elective cases was observed (+35%, P = 0.02). In conclusion, there was no change in the number of acute thoracic and abdominal aortic cases and procedures during the initial wave of the COVID-19 pandemic, whereas the case load of elective operations and procedures decreased significantly.
Mediators of SARS-CoV-2 entry are preferentially enriched in cardiomyocytes
Hereditas, January 4, 2021
The coronavirus disease 2019 (COVID-19) has spread rapidly around the world. In addition to common respiratory symptoms such as cough and fever, some patients also have cardiac injury, however, the mechanism of cardiac injury is not clear. In this study, we analyzed the RNA expression atlases of angiotensin-converting enzyme 2(ACE2), cathepsin B (CTSB) and cathepsin L (CTSL) in the human embryonic heart at single-cell resolution. The results showed that ACE2 was preferentially enriched in cardiomyocytes. Interestingly, serine protease transmembrane serine protease 2 (TMPRSS2) had less expression in cardiomyocytes, but CTSB and CTSL, which belonged to cell protease, could be found to be enriched in cardiomyocytes. The results of enrichment analysis showed that differentially expressed genes (DEGs) in ACE2-positive cardiomyocytes were mainly enriched in the processes of cardiac muscle contraction, regulation of cardiac conduction, mitochondrial respiratory chain, ion channel binding, adrenergic signaling in cardiomyocytes and viral transcription. Our study suggests that both atrial and ventricular cardiomyocytes are potentially susceptible to severe acute respiratory syndrome coronavirus-2(SARS-CoV-2), and SARS-CoV-2 may enter ventricular cardiomyocytes using CTSB/CTSL for S protein priming.
Coronary calcium scoring assessed on native screening chest CT imaging as predictor for outcome in COVID-19: An analysis of a hospitalized German cohort
PLOS ONE, December 30, 2020
Since the outbreak of the COVID-19 pandemic, a number of risk factors for a poor outcome have been identified. Thereby, cardiovascular comorbidity has a major impact on mortality. We investigated whether coronary calcification as a marker for coronary artery disease (CAD) is appropriate for risk prediction in COVID-19. Hospitalized patients with COVID-19 (n = 109) were analyzed regarding clinical outcome after native computed tomography (CT) imaging for COVID-19 screening. CAC (coronary calcium score) and clinical outcome (need for intensive care treatment or death) data were calculated following a standardized protocol. We defined three endpoints: critical COVID-19 and transfer to ICU, fatal COVID-19 and death, composite endpoint critical and fatal COVID-19, a composite of ICU treatment and death. We evaluated the association of clinical outcome with the CAC. Patients were dichotomized by the median of CAC. Hazard ratios and odds ratios were calculated for the events death or ICU or a composite of death and ICU. We observed significantly more events for patients with CAC above the group’s median of 31 for critical outcome (HR: 1.97[1.09,3.57], p = 0.026), for fatal outcome (HR: 4.95[1.07,22.9], p = 0.041) and the composite endpoint (HR: 2.31[1.28,4.17], p = 0.0056. Also, odds ratio was significantly increased for critical outcome (OR: 3.01 [1.37, 6.61], p = 0.01) and for fatal outcome (OR: 5.3 [1.09, 25.8], p = 0.02).
Comparison of Characteristics and Outcomes of Patients With Acute Myocardial Infarction With Versus Without Coronarvirus-19
American Journal of Cardiology, December 29, 2020
The coronavirus disease 2019 (COVID-19) pandemic has greatly impacted the US healthcare system. Cardiac involvement in COVID-19 is common and manifested by troponin and natriuretic peptide elevation and tends to have a worse prognosis. We analyzed patients who presented to the MedStar Health system (11 hospitals in Washington, DC, and Maryland) with either an ST-elevation myocardial infarction or non-ST-elevation myocardial infarction early in the pandemic (March 1, 2020 to June 30, 2020) using the International Classification of Diseases, Tenth Revision. Patients’ clinical course and outcomes, including in-hospital mortality, were compared on the basis of the results of COVID-19 status (positive or negative). The cohort included 1533 patients admitted with an acute myocardial infarction (AMI), of whom 86 had confirmed severe acute respiratory syndrome coronavirus 2 infection, during the study period. COVID-19-positive patients were older and non-White and had more co-morbidities. Furthermore, inflammatory markers and N-terminal-proB-type-natriuretic peptide were higher in COVID-19-positive AMI patients. Only 20.0% (17) of COVID-19-positive patients underwent coronary angiography. In-hospital mortality was significantly higher in AMI patients with concomitant COVID-19-positive status (27.9%) than in patients without COVID-19 during the same period (3.7%; p < 0.001). Patients with AMI and COVID-19 tended to be older, with more co-morbidities, when compared to those with an AMI and without COVID-19. In conclusion, myocardial infarction with concomitant COVID-19 was associated with increased in-hospital mortality. Efforts should be focused on the early recognition, evaluation, and treatment of these patients.
COVID 19: in the eye of the cytokine storm
European Heart Journal, December 27, 2020
This study focused on four cytokines known to contribute to pathogenic inflammation in CRS of patients receiving CAR-T cells, with clinically available or experimental blocking drugs. The clinical picture of the cytokine storm in COVID-19 was different from that of the coordinated increase during traditional CRS, showing different patterns of cytokine expression, and potentially distinct clinical presentations based on the relative profile of each cytokine. Accordingly, serum levels of IL-6 and TNF-α were lower in COVID-19 compared to classical CRS. The plasma cytokine cluster of COVID-19 recalls the cytokine pattern associated with acute coronary syndromes (ACS). In ACS, IL-6 levels are correlated with prognosis, and IL-6 blockade by tocilizumab quenches the acute inflammatory response of ACS patients undergoing percutaneous coronary intervention. In COVID-19, the cytokine storm might evoke and/or potentiate existing or new cardiac functional abnormalities, as well as trigger ACS through a thrombo-inflammatory response. The present study convincingly demonstrated that early cytokine increases, in particular IL-6 and TNF-α, were reliable predictors of COVID-19 severity and mortality, independently of demographics, comorbidities, and clinical biomarkers of disease severity. Multiple cytokine profiling could be used to determine which individuals are likely to develop respiratory failure and end-organ damage, in order to prioritize treatment in those at highest risk. Moreover, the predictive value of these cytokines might help guide resource allocation, as well as the design of prospective interventional studies. Theoretically, patients with moderate disease severity and high IL-6 or TNF-α levels might benefit the most from cytokine blockade.
Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19
Viruses, December 26, 2020
The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a persistent threat to global public health. Although primarily a respiratory illness, extrapulmonary manifestations of COVID-19 include gastrointestinal, cardiovascular, renal and neurological diseases. Recent studies suggest that dysfunction of the endothelium during COVID-19 may exacerbate these deleterious events by inciting inflammatory and microvascular thrombotic processes. Although controversial, there is evidence that SARS-CoV-2 may infect endothelial cells by binding to the angiotensin-converting enzyme 2 (ACE2) cellular receptor using the viral Spike protein. In this review, we explore current insights into the relationship between SARS-CoV-2 infection, endothelial dysfunction due to ACE2 downregulation, and deleterious pulmonary and extra-pulmonary immunothrombotic complications in severe COVID-19. We also discuss preclinical and clinical development of therapeutic agents targeting SARS-CoV-2-mediated endothelial dysfunction. Finally, we present evidence of SARS-CoV-2 replication in primary human lung and cardiac microvascular endothelial cells. Accordingly, in striving to understand the parameters that lead to severe disease in COVID-19 patients, it is important to consider how direct infection of endothelial cells by SARS-CoV-2 may contribute to this process.
Cardiovascular Comorbidities and Pharmacological Treatments of COVID-19 Patients Not Requiring Hospitalization
International Journal of Environmental Research and Public Health, December 25, 2020
The Coronavirus disease 2019 (COVID-19) outbreak is a whole Earth health emergency related to a highly pathogenic human coronavirus responsible for severe acute respiratory syndrome (SARS-CoV-2). Despite the fact that the majority of infected patients were managed in outpatient settings, little is known about the clinical characteristics of COVID-19 patients not requiring hospitalization. The aim of our study was to describe the clinical comorbidity and the pharmacological therapies of COVID-19 patients managed in outpatient settings. We performed an observational, retrospective analysis of laboratory-confirmed COVID-19 patients managed in outpatient setting. The clinical features and pharmacological therapies of COVID-19 patients not requiring hospitalization and managed in outpatient settings have been described. A total of 351 laboratory-confirmed COVID-19 patients (mean age 54 ± 17 years; 193 males) with outpatient management were evaluated. Hypertension was the most prevalent comorbidity (35%). The distribution of cardiovascular comorbidities showed no gender-related differences. A total of 201 patients (57.3%) were treated with at least one experimental drug for COVID-19. Azithromycin, alone (42.78%) or in combination (27.44%), was the most widely used experimental anti-COVID drug in outpatient settings. Low Molecular Weight Heparin and Cortisone were prescribed in 24.87% and 19.4% of the study population, respectively. At multivariate regression model, diabetes (risk ratio (RR): 3.74; 95% CI 1.05 to 13.34; p = 0.04) and hypertension (RR: 1.69; 95% CI 1.05 to 2.7; p = 0.03) were significantly associated with the experimental anti-COVID drug administration. Moreover, only diabetes (RR: 2.43; 95% CI 1.01 to 5.8; p = 0.03) was significantly associated with heparin administration.
Clinical spectrum of ischaemic arterial diseases associated with COVID-19: a series of four illustrative cases
European Heart Journal, December 25, 2020
Severe coronavirus-induced disease 2019 (COVID-19) leads to acute respiratory distress syndrome with an increased risk of venous thrombo-embolic events. To a much lesser extent, arterial thrombo-embolic events have also been reported in this setting. This case report describes four different cases of COVID-19 infection with ischaemic arterial events, such as a myocardial infarction with high thrombus load, ischaemic stroke on spontaneous thrombosis of the aortic valve, floating thrombus with mesenteric, splenic and renal infarction, and acute limb ischaemia. Cardiovascular risk factors such as hypertension, obesity, and diabetes are comorbidities most frequently found in patients with a severe COVID-19 infection and are associated with a higher death rate. Our goal is to provide an overview of the clinical spectrum of ischaemic arterial events that may either reveal or complicate COVID-19. Several suspected pathophysiological mechanisms could explain the association between cardiovascular events and COVID-19 (role of systemic inflammatory response syndrome, endothelial dysfunction, activation of coagulation cascade leading to a hypercoagulability state, virus-induced secondary antiphospholipid syndrome). We need additional studies of larger size, to estimate the incidence of these arterial events and to assess the efficacy of anticoagulation therapy.
Multi-organ point-of-care ultrasound for COVID-19 (PoCUS4COVID): international expert consensus
Critical Care, December 24, 2020
COVID-19 has caused great devastation in the past year. Multi-organ point-of-care ultrasound (PoCUS) including lung ultrasound (LUS) and focused cardiac ultrasound (FoCUS) as a clinical adjunct has played a significant role in triaging, diagnosis and medical management of COVID-19 patients. The expert panel from 27 countries and 6 continents with considerable experience of direct application of PoCUS on COVID-19 patients presents evidence-based consensus using GRADE methodology for the quality of evidence and an expedited, modified-Delphi process for the strength of expert consensus. We searched Medline, Pubmed Central, Embase, Cochrane, Scopus and online pre-print databases from 01/01/2020 to 01/08/2020, and collected all English language publications on PoCUS in adult COVID-19 patients, using the MeSH query: [(“lung” AND “ultrasound”) OR “echocardiography” OR “Focused cardiac ultrasound” OR “point-of-care ultrasound” OR “venous ultrasound”] AND [“COVID-19” OR “SARS-CoV2”]. This systematic search strategy identified 214 records. The use of ultrasound is suggested in many clinical situations related to respiratory, cardiovascular and thromboembolic aspects of COVID-19, comparing well with other imaging modalities. The limitations due to insufficient data are highlighted as opportunities for future research.
Hypertension delays viral clearance and exacerbates airway hyperinflammation in patients with COVID-19
Nature Biotechnology, December 24, 2020
In coronavirus disease 2019 (COVID-19), hypertension and cardiovascular diseases are major risk factors for critical disease progression. However, the underlying causes and the effects of the main anti-hypertensive therapies—angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)—remain unclear. Combining clinical data (n = 144) and single-cell sequencing data of airway samples (n = 48) with in vitro experiments, we observed a distinct inflammatory predisposition of immune cells in patients with hypertension that correlated with critical COVID-19 progression. ACEI treatment was associated with dampened COVID-19-related hyperinflammation and with increased cell intrinsic antiviral responses, whereas ARB treatment related to enhanced epithelial–immune cell interactions. Macrophages and neutrophils of patients with hypertension, in particular under ARB treatment, exhibited higher expression of the pro-inflammatory cytokines CCL3 and CCL4 and the chemokine receptor CCR1. Although the limited size of our cohort does not allow us to establish clinical efficacy, our data suggest that the clinical benefits of ACEI treatment in patients with COVID-19 who have hypertension warrant further investigation.
Calcification of the thoracic aorta on low-dose chest CT predicts severe COVID-19
PLOS ONE, December 23, 2020
Cardiovascular comorbidity anticipates poor prognosis of SARS-CoV-2 disease (COVID-19) and correlates with the systemic atherosclerotic transformation of the arterial vessels. The amount of aortic wall calcification (AWC) can be estimated on low-dose chest CT. We suggest quantification of AWC on the low-dose chest CT, which is initially performed for the diagnosis of COVID-19, to screen for patients at risk of severe COVID-19. Seventy consecutive patients (46 in center 1, 24 in center 2) with parallel low-dose chest CT and positive RT-PCR for SARS-CoV-2 were included in our multi-center, multi-vendor study. The outcome was rated moderate (no hospitalization, hospitalization) and severe (ICU, tracheal intubation, death), the latter implying a requirement for intensive care treatment. The amount of AWC was quantified with the CT vendor’s software. Of 70 included patients, 38 developed a moderate, and 32 a severe COVID-19. The average volume of AWC was significantly higher throughout the subgroup with severe COVID-19, when compared to moderate cases (771.7 mm3 (Q1 = 49.8 mm3, Q3 = 3065.5 mm3) vs. 0 mm3 (Q1 = 0 mm3, Q3 = 57.3 mm3)). Within multivariate regression analysis, including AWC, patient age and sex, as well as a cardiovascular comorbidity score, the volume of AWC was the only significant regressor for severe COVID-19 (p = 0.004). For AWC > 3000 mm3, the logistic regression predicts risk for a severe progression of 0.78. If there are no visually detectable AWC risk for severe progression is 0.13, only.
COVID-19 update: the first 6 months of the pandemic
Human Genomics, December 23, 2020
The COVID-19 pandemic is sweeping the world and will feature prominently in all our lives for months and most likely for years to come. We review here the current state 6 months into the declared pandemic. Specifically, we examine the role of the pathogen, the host and the environment along with the possible role of diabetes. We also firmly believe that the pandemic has shown an extraordinary light on national and international politicians whom we should hold to account as performance has been uneven. We also call explicitly on competent leadership of international organizations, specifically the WHO, UN and EU, informed by science. Finally, we also condense successful strategies for dealing with the current COVID-19 pandemic in democratic countries into a developing pandemic playbook and chart a way forward into the future. This is useful in the current COVID-19 pandemic and, we hope, in a very distant future again when another pandemic might arise.
Myocarditis-associated necrotizing coronary vasculitis: incidence, cause, and outcome
European Heart Journal, December 23, 2020
Necrotizing coronary vasculitis (NCV) is a rare entity usually associated to myocarditis which incidence, cause, and response to therapy is unreported. Among 1916 patients with biopsy-proven myocarditis, 30 had NCV. Endomyocardial samples were retrospectively investigated with immunohistochemistry for toll-like receptor 4 (TLR4) and real-time polymerase chain reaction (PCR) for viral genomes. Serum samples were processed for anti-heart autoantibodies (Abs), IL-1β, IL-6, IL-8, tumour necrosis factor (TNF)-α. Identification of an immunologic pathway (including virus-negativity, TLR4-, and Ab-positivity) was followed by immunosuppression. Myocarditis-NCV cohort was followed for 6 months with 2D-echo and/or cardiac magnetic resonance and compared with 60 Myocarditis patients and 30 controls. Increase in left ventricular ejection fraction ≥10% was classified as response to therapy. Control endomyocardial biopsy followed the end of treatment. Twenty-six Myocarditis-NCV patients presented with heart failure; four with electrical instability. Cause of Myocarditis-NCV included infectious agents (10%) and immune-mediated causes (chest trauma 3%; drug hypersensitivity 7%; hypereosinophilic syndrome 3%; primary autoimmune diseases 33%, idiopathic 44%). Abs were positive in immune-mediated Myocarditis-NCV and virus-negative Myocarditis; Myocarditis-NCV patients with Ab+ presented autoreactivity in vessel walls. Toll-like receptor 4 was overexpressed in immune-mediated forms and poorly detectable in viral. Interleukin-1β was significantly higher in Myocarditis-NCV than Myocarditis, the former presenting 24% in-hospital mortality compared with 1.5% of Myocarditis cohort. Immunosuppression induced improvement of cardiac function in 88% of Myocarditis-NCV and 86% of virus-negative Myocarditis patients. Necrotizing coronary vasculitis is histologically detectable in 1.5% of Myocarditis. Necrotizing coronary vasculitis includes viral and immune-mediated causes. Intra-hospital mortality is 24%. The immunologic pathway is associated with beneficial response to immunosuppression.
Echocardiographic Features of Cardiac Injury Related to COVID-19 and Their Prognostic Value: A Systematic Review
Journal of Intensive Care Medicine, December 22, 2020
The available information on the echocardiographic features of cardiac injury related to the novel coronavirus disease 2019 (COVID-19) and their prognostic value are scattered in the different literature. Therefore, the aim of this study was to investigate the echocardiographic features of cardiac injury related to COVID-19 and their prognostic value. Published studies were identified through searching PubMed, Embase (Elsevier), and Google scholar databases. The search was performed using the different combinations of the keywords “echocard*,” “cardiac ultrasound,” “TTE,” “TEE,” “transtho*,” or “transeso*” with “COVID-19,” “sars-COV-2,” “novel corona, or “2019-nCOV.” Two researchers independently screened the titles and abstracts and full texts of articles to identify studies that evaluated the echocardiographic features of cardiac injury related to COVID-19 and/or their prognostic values. Of 783 articles retrieved from the initial search, 11 (8 cohort and 3 cross-sectional studies) met our eligibility criteria. Rates of echocardiographic abnormalities in COVID-19 patients varied across different studies as follow: RV dilatation from 15.0% to 48.9%; RV dysfunction from 3.6% to 40%; and LV dysfunction 5.4% to 40.0%. Overall, the RV abnormalities were more common than LV abnormalities. The majority of the studies showed that there was a significant association between RV abnormalities and the severe forms and death of COVID-19. The available evidence suggests that RV dilatation and dysfunction may be the most prominent echocardiographic abnormality in symptomatic patients with COVID-19, especially in those with more severe or deteriorating forms of the disease. Also, RV dysfunction should be considered as a poor prognostic factor in COVID-19 patients.
Potential protective effects of antihypertensive treatments during the Covid-19 pandemic: from inhibitors of the renin-angiotensin system to beta-adrenergic receptor blockers
Blood Pressure, December 21, 2020
From the beginning of the pandemic hypertension appeared as one of the most common comorbidities in patients hospitalised with a Covid-19 infection. Hypertension, diabetes, overweight, chronic pulmonary disease and heart failure, together with advanced age were the typical characteristics of patients who suffered a fatal outcome of severe Covid-19 disease. However, hypertension is highly prevalent in the adult population, particularly among the elderly, overweight people, and patients with diabetes. Therefore, it remains unclear, whether hypertension per se predisposes patients to develop Covid-19 disease, to make it more severe or to predict a poor outcome, or whether the other comorbidities or patient characteristics such as overweight or advanced age, confound the data. A major consideration in the management of hypertensive patients in the time of the Covid-19 pandemic regards the choice of antihypertensive medications and their potential impact on the disease outcome. It started with the question of whether treatment with angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are safe. ACEIs and ARBs may up-regulate ACE2, the receptor used by the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) to enter host cells. Therefore, treatment with ACEIs and ARBs could potentially increase the risk of SARS-CoV-2 infection. However, cardiopulmonary diseases are associated with decreased ACE2 activity. By limiting the effects of angiotensin II on the heart and vasculature, ACE2 could protect against the more severe complications of Covid-19 infection.
Top in cardiology: Icosapent ethyl and COVID-19, impact of BP on cognitive decline
Helio | Cardiology, December 21, 2020
Early data presented at the virtual National Lipid Association Scientific Sessions suggest that icosapent ethyl may reduce inflammation and improve symptoms in patients with COVID-19. It was the top story in cardiology last week. Another top story was about a study that found hypertension and prehypertension were associated with declines in various markers of cognitive function. In a first-in-human study, icosapent ethyl (Vascepa, Amarin) reduced levels of inflammatory biomarkers and improved symptoms in patients with COVID-19, researchers reported. BP control may be critical for the preservation of cognitive function, according to a study published in Hypertension.
Positive association of angiotensin II receptor blockers, not angiotensin-converting enzyme inhibitors, with an increased vulnerability to SARS-CoV-2 infection in patients hospitalized for suspected COVID-19 pneumonia
PLOS ONE, December 21, 2020
Angiotensin-converting enzyme 2 is the receptor that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses for entry into lung cells. Because ACE-2 may be modulated by angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), there is concern that patients treated with ACEIs and ARBs are at higher risk of coronavirus disease 2019 (COVID-19) pneumonia. This study sought to analyze the association of COVID-19 pneumonia with previous treatment with ACEIs and ARBs. We retrospectively reviewed 684 consecutive patients hospitalized for suspected COVID-19 pneumonia and tested by polymerase chain reaction assay. Patients were split into two groups, according to whether (group 1, n = 484) or not (group 2, n = 250) COVID-19 was confirmed. Multivariable adjusted comparisons included a propensity score analysis. The mean age was 63.6 ± 18.7 years, and 302 patients (44%) were female. Hypertension was present in 42.6% and 38.4% of patients in groups 1 and 2, respectively (P = 0.28). Treatment with ARBs was more frequent in group 1 than group 2 (20.7% vs. 12.0%, respectively; odds ratio [OR] 1.92, 95% confidence interval [CI] 1.23–2.98; P = 0.004). No difference was found for treatment with ACEIs (12.7% vs. 15.7%, respectively; OR 0.81, 95% CI 0.52–1.26; P = 0.35). Propensity score-matched multivariable logistic regression confirmed a significant association between COVID-19 and previous treatment with ARBs (adjusted OR 2.36, 95% CI 1.38–4.04; P = 0.002). Significant interaction between ARBs and ACEIs for the risk of COVID-19 was observed in patients aged > 60 years, women, and hypertensive patients.
Cardiovascular implications of COVID-19 versus influenza infection: a review
BMC Medicine, December 18, 2020
Due to the overlapping clinical features of coronavirus disease 2019 (COVID-19) and influenza, parallels are often drawn between the two diseases. Patients with pre-existing cardiovascular diseases (CVD) are at a higher risk for severe manifestations of both illnesses. Considering the high transmission rate of COVID-19 and with the seasonal influenza approaching in late 2020, the dual epidemics of COVID-19 and influenza pose serious cardiovascular implications. This review highlights the similarities and differences between influenza and COVID-19 and the potential risks associated with coincident pandemics. COVID-19 has a higher mortality compared to influenza with case fatality rate almost 15 times more than that of influenza. Additionally, a significantly increased risk of adverse outcomes has been noted in patients with CVD, with ~ 15 to 70% of COVID-19 related deaths having an underlying CVD. The critical care need have ranged from 5 to 79% of patients hospitalized due to COVID-19, a proportion substantially higher than with influenza. Similarly, the frequency of vascular thrombosis including deep venous thrombosis and pulmonary embolism is markedly higher in COVID-19 patients compared with influenza in which vascular complications are rarely seen. Unexpectedly, while peak influenza season is associated with increased cardiovascular hospitalizations, a decrease of ~ 50% in cardiovascular hospitalizations has been observed since the first diagnosed case of COVID-19, owing in part to deferred care.
Impact of COVID-19 pandemic and diabetes on mechanical reperfusion in patients with STEMI: insights from the ISACS STEMI COVID 19 Registry
Cardiovascular Diabetology, December 18, 2020
It has been suggested the COVID pandemic may have indirectly affected the treatment and outcome of STEMI patients, by avoidance or significant delays in contacting the emergency system. No data have been reported on the impact of diabetes on treatment and outcome of STEMI patients, that was therefore the aim of the current subanalysis conducted in patients included in the International Study on Acute Coronary Syndromes–ST Elevation Myocardial Infarction (ISACS-STEMI) COVID-19. The ISACS-STEMI COVID-19 is a retrospective registry performed in European centers with an annual volume of > 120 primary percutaneous coronary intervention (PCI) and assessed STEMI patients, treated with primary PCI during the same periods of the years 2019 versus 2020 (March and April). Main outcomes are the incidences of primary PCI, delayed treatment, and in-hospital mortality. A total of 6609 patients underwent primary PCI in 77 centers, located in 18 countries. Diabetes was observed in a total of 1356 patients (20.5%), with similar proportion between 2019 and 2020. During the pandemic, there was a significant reduction in primary PCI as compared to 2019, similar in both patients with (Incidence rate ratio (IRR) 0.79 (95% CI: 0.73–0.85, p < 0.0001) and without diabetes (IRR 0.81 (95% CI: 0.78–0.85, p < 0.0001) (p int = 0.40). We observed a significant heterogeneity among centers in the population with and without diabetes (p < 0.001, respectively). The heterogeneity among centers was not related to the incidence of death due to COVID-19 in both groups of patients. Interaction was observed for Hypertension (p = 0.024) only in absence of diabetes. Furthermore, the pandemic was independently associated with a significant increase in door-to-balloon and total ischemia times only among patients without diabetes, which may have contributed to the higher mortality, during the pandemic, observed in this group of patients.
Ventricular arrhythmia burden during the coronavirus disease 2019 (COVID-19) pandemic
European Heart Journal, December 16, 2020
Our objective was to determine the ventricular arrhythmia burden in implantable cardioverter-defibrillator (ICD) patients during COVID-19. In this multicentre, observational, cohort study over a 100-day period during the COVID-19 pandemic in the USA, we assessed ventricular arrhythmias in ICD patients from 20 centres in 13 states, via remote monitoring. Comparison was via a 100-day control period (late 2019) and seasonal control period (early 2019). The primary outcome was the impact of COVID-19 on ventricular arrhythmia burden. The secondary outcome was correlation with COVID-19 incidence. During the COVID-19 period, 5963 ICD patients underwent remote monitoring, with 16 942 episodes of treated ventricular arrhythmias (2.8 events per 100 patient-days). Ventricular arrhythmia burden progressively declined during COVID-19 (P < 0.001). The proportion of patients with ventricular arrhythmias amongst the high COVID-19 incidence states was significantly reduced compared with those in low incidence states [odds ratio 0.61, 95% confidence interval (CI) 0.54–0.69, P < 0.001]. Comparing patients remotely monitored during both COVID-19 and control periods (n = 2458), significantly fewer ventricular arrhythmias occurred during COVID-19 [incident rate ratio (IRR) 0.68, 95% CI 0.58–0.79, P < 0.001]. This difference persisted when comparing the 1719 patients monitored during both the COVID-19 and seasonal control periods (IRR 0.69, 95% CI 0.56–0.85, P < 0.001).
FDA finds Moderna vaccine 95% effective
Modern Healthcare, December 15, 2020
The Food and Drug Administration on Tuesday has found the COVID-19 vaccine from drugmaker Moderna safe and 95% effective, moving it closer to federal approval for distribution. On Thursday, a group of experts will convene in a public hearing to advise the agency on whether to grant the vaccine emergency authorization use. The agency’s report found the vaccine has “no specific safety concerns identified that would preclude issuance of an EUA.” Minor side effects, including pain at the site of injection, fatigue and headaches were common but the FDA did not report any major side effects. The vaccine, however, is less effective (86%) in people age 65 and older. Moderna’s vaccine would be the second to receive FDA approval in one week. Last Thursday, Pfizer’s vaccine received emergency authorization use. Hospitals across the country began to administer that shot yesterday.
Impact of COVID-19 on health-related quality of life in patients with cardiovascular disease: a multi-ethnic Asian study
Health and Quality of Life Outcomes, December 14, 2020
Little is known about the impact of the global coronavirus disease-2019 (COVID-19) pandemic on patients with cardiovascular disease (CVD), the biggest global killer and major risk factor for severe COVID-19 infections. We aim to explore the indirect consequences of COVID-19 on health-related quality of life (HRQoL) of patients with CVD. Eighty-one adult outpatients with CVD were assessed using the EQ-5D, a generic health status instrument with five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), before and during the pandemic. Changes in the EQ-5D dimensional responses were compared categorically as well as using the dimension-specific sum-score (range 1–3, with a higher score indicating worse health). The responses and sum-score were compared using the exact test of symmetry and the paired t-test, respectively. These patients [mean age (SD) 59.8 (10.5); 92.6% males; 56% New York Heart Association (NYHA) functional class I] had coronary artery disease (69%), heart failure (28%), or arrhythmias (15%). None experienced change in NYHA class between assessments. About 30% and 38% of patients reported problems with at least one of the EQ-5D dimensions pre-pandemic and during the pandemic, respectively. The highest increase in health problems was reported for anxiety/depression (12.5% pre-pandemic vs 23.5% during pandemic; p = 0.035) with mean domain-specific score from 1.12 (SD 0.33) to 1.25 (SD 0.46) (standardized effect size = 0.373, p = 0.012). There was no meaningful change in other dimensions as well as overall HRQoL.
Use of out-of-hospital cardiac arrest registries to assess COVID-19 home mortality
BMC Medical Research Methodology, December 14, 2020
In most countries, the official statistics for the coronavirus disease 2019 (COVID-19) take account of in-hospital deaths but not those that occur at home. The study’s objective was to introduce a methodology to assess COVID-19 home deaths by analysing the French national out-of-hospital cardiac arrest (OHCA) registry (RéAC). We performed a retrospective multicentre cohort study based on data recorded in the RéAC by 20 mobile medical teams (MMTs) between March 1st and April 15th, 2020. The participating MMTs covered 10.1% of the French population. OHCA patients were classified as probable or confirmed COVID-19 cases or as non-COVID-19 cases. To achieve our primary objective, we computed the incidence and survival at hospital admission of cases of COVID-19 OHCA occurring at home. Cardiac arrests that occurred in retirement homes or public places were excluded. Hence, we estimated the number of at-home COVID-19-related deaths that were not accounted for in the French national statistics. We included 670 patients with OHCA. The extrapolated annual incidence of OHCA per 100,000 inhabitants was 91.9 overall and 17.6 for COVID-19 OHCA occurring at home. In the latter group, the survival rate after being taken to the hospital after an OHCA was 10.9%. We estimated that 1322 deaths were not accounted in the French national statistics on April 15, 2020.
A historical perspective on ACE2 in the COVID-19 era
Journal of Human Hypertension, December 14, 2020
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Lessons learned from severe acute respiratory syndrome coronavirus (SARS-CoV) have facilitated a better understanding of the COVID-19 pandemic and efforts to develop targeted therapies. In particular, COVID-19 reminds us of the importance of the renin-angiotensin-aldosterone system (RAAS) in cardiovascular, pulmonary, and kidney physiology. After decades of RAAS research, we can apply this knowledge to better understand COVID-19 pathophysiology and to inform rigorous studies. In 2020, the rapid spread of SARS-CoV-2 has made us again reflect on the risk/benefit ratio of these important drug classes and their mechanisms of action. Based on the interaction between SARS-CoV-2 and ACE2, many postulated that possible RAAS inhibitor-induced ACE2 expression and thus viral propagation could be an important mechanism for the apparent associations between SARS-CoV-2 infection and COVID-19 severity and hypertension, cardiovascular disease, and chronic kidney disease. On the other hand, ACE inhibitors and ARBs may be novel therapeutic agents to treat patients with COVID-19 by shifting the RAAS back toward the ACE2—Ang-(1–7)Ang-(1–7) pathway. Several, albeit limited, observational studies have not shown an association between severity of COVID-19 with use of ACE inhibitors or ARBs.
Air cardiology is now on air: The Time for a Green Heart New Deal in Cardiology is now
European Heart Journal, December 14, 2020
Air pollution is a chronic risk factor for cardiovascular mortality, an acute trigger for coronary syndromes, an important co-factor for COVID-19 mortality, a modulator of results of cardiac functional stress testing, and an actionable therapeutic target at the population, community, and individual levels. Pozzer et al. add yet another piece of key evidence linking air pollution to detrimental health effects. They characterized global exposures to fine particulates based on satellite data and calculated the anthropogenic fraction with an atmospheric chemistry model. The conclusion is that particulate air pollution contributed 15% to COVID-19 mortality worldwide and 19% in Europe. Of this significant fraction, ∼50% is due to fossil fuel use, which is at least in principle avoidable with alternate energy choices. There is biological plausibility for the observed epidemiological link. Fine particulate matter and the SARS-CoV-2 virus both enter the body through the bronchial system, activate the inflammatory system, oxidative stress, and immune reaction, target endothelium, and induce a systemic pro-thrombotic state. There is increased susceptibility to viral infections from exposure to air pollution and fine particulates prolong the atmospheric lifetime of infectious viruses.
Screening of Potential Cardiac Involvement in Competitive Athletes Recovering From COVID-19: An Expert Consensus Statement
JACC: Cardiovascular Imaging, December 13, 2020
As our understanding of the complications of coronavirus disease-2019 (COVID-19) evolve, subclinical cardiac pathology such as myocarditis, pericarditis, and right ventricular dysfunction in the absence of significant clinical symptoms represents a concern. The potential implications of these findings in athletes are significant given the concern that exercise, during the acute phase of viral myocarditis, may exacerbate myocardial injury and precipitate malignant ventricular arrhythmias. Such concerns have led to the development and publication of expert consensus documents aimed at providing guidance for the evaluation of athletes after contracting COVID-19 in order to permit safe return to play. Cardiac imaging is at the center of these evaluations. This review seeks to evaluate the current evidence regarding COVID-19–associated cardiovascular disease and how multimodality imaging may be useful in the screening and clinical evaluation of athletes with suspected cardiovascular complications of infection. Guidance is provided with diagnostic “red flags” that raise the suspicion of pathology. Specific emphasis is placed on the unique challenges posed in distinguishing athletic cardiac remodeling from subclinical cardiac disease. The strengths and limitations of different imaging modalities are discussed and an approach to return to play decision making for athletes post–COVID-19, as informed by multimodality imaging, is provided.
Coronavirus disease 2019 in adults with congenital heart disease: a position paper from the ESC working group of adult congenital heart disease, and the International Society for Adult Congenital Heart Disease
European Heart Journal, December 12, 2020
We are witnessing an unparalleled pandemic caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) associated with coronavirus disease 2019 (COVID-19). Current data show that SARS-CoV-2 results in mild flu-like symptoms in the majority of healthy and young patients affected. Nevertheless, the severity of COVID-19 respiratory syndrome and the risk of adverse or catastrophic outcomes are increased in patients with pre-existing cardiovascular disease. Patients with adult congenital heart disease (ACHD)—by definition—have underlying cardiovascular disease. Many patients with ACHD are also afflicted with residual haemodynamic lesions such as valve dysfunction, diminished ventricular function, arrhythmias or cyanosis, have extracardiac comorbidities, and face additional challenges regarding pregnancy. Currently, there are emerging data of the effect of COVID-19 on ACHD patients, but many aspects, especially risk stratification and treatment considerations, remain unclear. In this article, we aim to discuss the broad impact of COVID-19 on ACHD patients, focusing specifically on pathophysiology, risk stratification for work, self-isolation, hospitalization, impact on pregnancy, psychosocial health, and longer-term implications for the provision of ACHD care.
Low LDL, high triglycerides may indicate mortality risk in COVID-19 hospitalization
Helio | Cardiology Today, December 12, 2020
Among patients hospitalized with COVID-19, LDL level below 50 mg/dL and triglycerides above 150 mg/dL were individually associated with increased odds for mortality, according to a presentation. “Prior studies have demonstrated lipid abnormalities in patients with SARS-CoV-2 that were mainly analyzing total cholesterol levels. Our study suggests that patients with COVID-19 who have unusually low LDL levels and yet elevated TG levels have more increased mortality,” Karolyn Teufel MD, assistant professor of medicine at the George Washington University Hospital in Washington D.C., and colleagues wrote in a poster presented at the virtual National Lipid Association Scientific Sessions. “These lipid biomarkers may act as an independent prognostic marker for patients on admission. Additionally, it is unusual to see low LDL and high TG in a patient with metabolic syndrome — one would expect to see elevated LDL levels in such patients.” This retrospective analysis included 254 patients hospitalized with COVID-19 (mean age, 62 years; 54% men; 70% Black) who underwent random lipid measurements performed during their stay at the George Washington University Hospital. The researchers evaluated the association between lipid biomarkers and mortality among patients hospitalized with COVID-19. “Future studies would further compare lipid biomarkers on a longer longitudinal timeline, as well as multivariate analysis to investigate the role of other conditions and biomarkers in conjunction with these lipid abnormalities in COVID-19 infection,” Teufel and colleagues wrote.
Impact of the shift to a fibrinolysis-first strategy on care and outcomes of patients with ST-segment–elevation myocardial infarction during the COVID-19 pandemic—The experience from the largest cardiovascular-specific centre in China
International Journal of Cardiology, December 11, 2020
The impact of fibrinolysis-first strategy on outcomes of patients with ST-segment-elevation myocardial infarction (STEMI) during the COVID-19 pandemic was unknown. Data from STEMI patients presenting to Fuwai Hospital from January 23 to April 30, 2020 were compared with those during the equivalent period in 2019. The primary end-point was net adverse clinical events (NACE; a composite of death, non-fatal myocardial reinfarction, stroke, emergency revascularization, and bleeding over BARC type 3). The secondary outcome was a composite of recurrent ischaemia, cardiogenic shock, and exacerbated heart failure. The final analysis included 164 acute STEMI patients from 2020 and 240 from 2019. Eighteen patients (20.2% of those with indications) received fibrinolysis therapy in 2020 with a median door-to-needle time of 60.0 (43.5, 92.0) minutes. Patients in 2020 underwent primary PCI less frequently than their counterparts (14 [14.2%] vs. 144 [86.8%] in 2019, P < 0.001), and had a longer median door-to-balloon time (175 [121,213] minutes vs. 115 [83, 160] minutes in 2019, P = 0.009). Patients were more likely to undergo elective PCI (86 [52.4%] vs. 28 [11.6%] in 2019, P < 0.001). The in-hospital NACE was similar between 2020 and 2019 (14 [8.5%] vs. 25 [10.4%], P = 0.530), while more patients developed a secondary outcome in 2020 (20 [12.2%] vs. 12 [5.0%] in 2019, P = 0.009).
Using Cardiovascular Cells from Human Pluripotent Stem Cells for COVID-19 Research: Why the Heart Fails
Stem Cell Reports, December 10, 2020
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the coronavirus disease (COVID-19) outbreak that became a pandemic in 2020, causing more than 30 million infections and 1 million deaths to date. As the scientific community has looked for vaccines and drugs to treat or eliminate the virus, unexpected features of the disease have emerged. Apart from respiratory complications, cardiovascular disease has emerged as a major indicator of poor prognosis in COVID-19. It has therefore become of utmost importance to understand how SARS-CoV-2 damages the heart. Human pluripotent stem cell (hPSC) cardiovascular derivatives were rapidly recognized as an invaluable tool to address this, not least because one of the major receptors for the virus is not recognized by SARS-CoV-2 in mice. Here, we outline how hPSC-derived cardiovascular cells have been utilized to study COVID-19, and their potential for further understanding the cardiac pathology and in therapeutic development.
Incidence rate and clinical impacts of arrhythmia following COVID-19: a systematic review and meta-analysis of 17,435 patients
Critical Care, December 10, 2020
Arrhythmia is a potential cardiovascular complication of Coronavirus Disease 2019 (COVID-19). In one case series of patients hospitalized with COVID-19, 16.7% developed unspecified arrhythmia, while another case series indicated sustained ventricular tachycardia or ventricular fibrillation among 5.9% of patients hospitalized with COVID-19. However, incidence rates of arrhythmia and mortality rates after incident arrhythmia in COVID-19 patients have not been systematically established. We searched for relevant studies cited in PubMed or Embase up to September 15, 2020, using the terms “COVID-19”, “arrhythmia”, “incidence”, “mortality,” and “prognosis” with suitable MeSH terms. All studies were selected and reviewed by two reviewers (SCL and SCS). The final list of included studies and data extractions were derived through extensive discussion with agreement from both authors. Outcomes were reported as proportions with 95% confidence interval (CI), based on the random effects model. The heterogeneity among studies was detected by the Cochran Q test with p value and the I2 statistic. Of 645 potential studies screened, we excluded 143 duplicate studies, 66 irrelevant studies, 12 conference abstracts, 241 other types of publications (e.g., pre-prints, protocols, opinions, recommendations, editorials, commentaries, retractions and reviews), 114 studies without incidence or mortality data, and 13 non-English studies. We included 56 studies from 11 countries comprising 17,435 patients with COVID-19. Compared to the incident arrhythmia in patients with community-acquired pneumonia (4.7%, 95% CI: 2.4–8.9), the present study indicates higher incidence of arrhythmia in COVID-19 patients (16.8%) with 2 out of 10 patients dying after developing arrhythmia.
A small contribution to mitigate the collision of transmissible and chronic diseases, exemplified by the management of hypertension during the COVID-19 pandemic
Journal of Human Hypertension, December 10, 2020
We want to take up the challenge posed by Nadar and cols. in their May editorial about managing hypertension during the COVID-19 pandemic. Their concern that patients with chronic illnesses would be forgotten in the fight against the paradigm of a transmissible virus and result in collateral damage reached the public domain since June. In mid October the number of new confirmed cases is still increasing in the Americas, South-East Asia and Europe according to the World Health Organization; lockdowns have been reinstalled in various zones and widely available vaccines are far from around the corner. In the present situation it is urgent to mitigate the collision of non-transmissible conditions with the rapid spread of the novel COVID infection by new patterns of interaction between all the protagonists involved in health care. An unexpected and beneficial collateral effect of the prolonged worldwide sanitary crisis is the shift in the balance between critical and stable health conditions by addressing most of the control of hypertension and other chronic conditions to the virtual attention. The American Society of Preventive Cardiology has proposed virtual team care in order to override the pandemic. This relatively new mode has been well accepted by patients and validated by randomized clinical trials, meta-analysis and systematic reviews that show similar blood pressure control than the conventional form, but if accompanied by education and counselling obtains extra benefits. In addition, telemedicine offers several advantages, including more equal and patient-centered health care in times in which vulnerable groups increase, receive the greatest economic and sanitary toll and require individual support.
Telemedicine in Heart Failure During COVID-19: A Step Into the Future
Frontiers in Cardiovascular Medicine, December 9, 2020
During the Coronavirus Disease 2019 worldwide pandemic, patients with heart failure are a high-risk group with potential higher mortality if infected. Although lockdown represents a solution to prevent viral spreading, it endangers regular follow-up visits and precludes direct medical assessment in order to detect heart failure progression and optimize treatment. Furthermore, lifestyle changes during quarantine may trigger heart failure decompensations. During the pandemic, a paradoxical reduction of heart failure hospitalization rates was observed, supposedly caused by patient reluctance to visit emergency departments and hospitals. This may result in an increased patient mortality and/or in more complicated heart failure admissions in the future. In this scenario, different telemedicine strategies can be implemented to ensure continuity of care to patients with heart failure. Patients at home can be monitored through dedicated apps, telephone calls, or devices. Virtual visits and forward triage screen the patients with signs or symptoms of decompensated heart failure. In-hospital care may benefit from remote communication platforms. After discharge, patients may undergo remote follow-up or telerehabilitation to prevent early readmissions. This review provides a comprehensive appraisal of the many possible applications of telemedicine for patients with heart failure during Coronavirus disease 2019 and elucidates practical limitations and challenges regarding specific telemedicine modalities.
Cardiovascular care delivery during the second wave of COVID-19 in Canada
Canadian Journal of Cardiology, December 8, 2020
Hospitals and ambulatory facilities significantly reduced cardiac care delivery in response to the first wave of the COVID-19 pandemic. The deferral of elective cardiovascular procedures led to a marked reduction in healthcare delivery with a significant impact on optimal cardiovascular care. International and Canadian data have reported dramatically increased wait-times for diagnostic tests and cardiovascular procedures, as well as associated increased cardiovascular morbidity and mortality.
In the wake of the demonstrated ability to rapidly create critical care and hospital ward capacity, we advocate a different approach during the second and possible subsequent COVID-19 pandemic waves. We suggest an approach, informed by local data and experience, which balances the need for an expected rise in demand for healthcare resources to ensure appropriate COVID-19 surge capacity, with continued delivery of essential cardiovascular care. Incorporating cardiovascular care leaders into pandemic planning and operations will help healthcare systems minimize cardiac care delivery disruptions, while maintaining critical care and hospital ward surge capacity and continuing measures to reduce transmission risk in healthcare settings. Specific recommendations targeting the main pillars of cardiovascular care are presented: ambulatory, inpatient, procedural, diagnostic, surgical and rehabilitation.
Thromboembolic complications in critically ill COVID-19 patients are associated with impaired fibrinolysis
Critical Care, December 7, 2020
There is emerging evidence for enhanced blood coagulation in coronavirus 2019 (COVID-19) patients, with thromboembolic complications contributing to morbidity and mortality. The mechanisms underlying this prothrombotic state remain enigmatic. Further data to guide anticoagulation strategies are urgently required. We used viscoelastic rotational thromboelastometry (ROTEM) in a single-center cohort of 40 critically ill COVID-19 patients. Clear signs of a hypercoagulable state due to severe hypofibrinolysis were found. Maximum lysis, especially following stimulation of the extrinsic coagulation system, was inversely associated with an enhanced risk of thromboembolic complications. Combining values for maximum lysis with D-dimer concentrations revealed high sensitivity and specificity of thromboembolic risk prediction. This study identifies a reduction in fibrinolysis as an important mechanism in COVID-19-associated coagulopathy. The combination of ROTEM and D-dimer concentrations may prove valuable in identifying patients requiring higher intensity anticoagulation.
Acute thrombosis of the right coronary artery in a patient with COVID-19
European Society of Cardiology, December 7, 2020
[Case Report] A 49-year-old man without cardiovascular risk factors presented to the emergency department with an acute ST-elevation myocardial infarction (STEMI). The patient has had fever and dry cough in the previous 10 days. Emergency coronary angiography (Videos 1-3) showed critical thrombotic stenosis of the proximal right coronary artery. Abundant thrombotic material was distally embolized. Aspiration thrombectomy was performed and it removed the proximal thrombus entirely and the artery appeared angiographically normal, so we decided not to perform angioplasty. Enoxaparin sodium was administered at a rate of 1 mg/kg of body weight every 12 h in addition to the double antiplatelet therapy with acetylsalicylic acid 100 mg and clopidogrel 75 mg/day for the first 10 days. Read more about this exceptional case as a result of the special resistance of the coronary arteries to the formation of spontaneous thrombosis. This case strengthens the theory of the increased risk of thrombotic events in patients with COVID-19 and gives a relevant role to anticoagulant treatments for these patients.
Reduced cardiac function is associated with cardiac injury and mortality risk in hospitalized COVID-19 Patients
Clinical Cardiology, December 7, 2020
Cardiac injury is common in COVID-19 patients and is associated with increased mortality. However, it remains unclear if reduced cardiac function is associated with cardiac injury, and additionally if mortality risk is increased among those with reduced cardiac function in COVID-19 patients. The aim of this study was to assess cardiac function among COVID-19 patients with and without biomarkers of cardiac injury and to determine the mortality risk associated with reduced cardiac function. This retrospective cohort study analyzed 143 consecutive COVID-19 patients who had an echocardiogram during hospitalization between March 1, 2020 and May 5, 2020. The mean age was 67 +/- 16 years. Cardiac troponin-I was available in 131 patients and an increased value (>0.03 ng/dL) was found in 59 patients (45%). Reduced cardiac function, which included reduced left or right ventricular systolic function, was found in 40 patients (28%). Reduced cardiac function was found in 18% of patients without troponin-I elevation, 42% with mild troponin increase (0.04-5.00 ng/dL) and 67% with significant troponin increase (>5 ng/dL). Reduced cardiac function was also present in more than half of the patients on mechanical ventilation or those deceased. The in-hospital mortality of this cohort was 28% (N = 40). Using logistic regression analysis, we found that reduced cardiac function was associated with increased mortality with adjusted odds ratio (95% confidence interval) of 2.65 (1.18 to 5.96).
Vascular medicine in the COVID-19 era: The Vanderbilt experience
Journal of Vascular Nursing, December 7, 2020
Coronavirus disease of 2019 poses significant risks for patients with vascular disease. Telemedicine can help clinicians provide care for patients with vascular disease while adhering to social-distancing guidelines. In this article, we review the components of telemedicine used in the vascular medicine practice at the Vanderbilt University Medical Center. In addition, we describe inpatient and outpatient diagnosis-based algorithms to help select patients for telemedicine versus in-person evaluation.
Collaboration During Crisis: A Novel Point-of-Care Ultrasound Alliance Between Emergency Medicine, Internal Medicine, and Cardiology in the COVID-19 Era
Journal of the American Society of Echocardiography, December 6, 2020
The COVID-19 pandemic may be the greatest public health emergency we will experience in our lifetimes. It has both exposed major shortcomings in the American medical system and revealed our capacity for innovation and collaboration. Early in disaster planning at our institution, we identified several issues regarding echocardiography: 1) personal protective equipment shortages 2) large ultrasound machines posed an infection control risk, 3) heterogenous knowledge of basic point-of-care ultrasound (POCUS) echocardiography, and 4) a need for cardiac diagnostics beyond the scope of basic POCUS (eg. regional wall motion abnormalities).(1-4) Prior to COVID-19, an enterprise-level multidisciplinary POCUS committee had been organized to address POCUS training, credentialing, and image archival. With multi-specialty agreement, including members of this committee, the default method of cardiac ultrasound imaging became POCUS in COVID-19 positive or suspected patients. Echocardiography lab sonographers were available to remotely support and direct front-line providers during bedside echocardiographic image acquisition using either in-room ICU cameras when the provider was using a cart-based machine or the teleguidance feature on the handheld ultrasound systems. Echocardiography faculty, with access to the POCUS image archive, offered remote real-time image interpretation assistance. This initiative minimized the number of providers exposed to COVID-19 patients, maximized infection control precautions, while also appropriately triaging the need for comprehensive echocardiography.
Spectrum of cardiovascular diseases in children during high peak COVID-19 period infection in Northern Italy: is there a link?
Journal of Pediatric Infectious Diseases Society, December 6, 2020
Children with COVID-19 have a milder clinical course than adults. We describe the spectrum of cardiovascular manifestations during a COVID-19 outbreak in Emilia-Romagna, Italy. Cross-sectional multicenter study including all diagnosis of KD, myocarditis and multisystem inflammatory syndrome in children (MIS-C) from February to April2020. KD patients were compared to those diagnosed before the epidemic. KD: 8 patients (6/8 boys, all negative for SARS-CoV-2); complete presentation in 5/8; 7/8 IVIG-responders; 3/8 showed transient coronary lesions (CALs). One 5-year-old girl negative for SARS-CoV-2, positive for Parvovirus B19. She responded to IVIG. Four SARS-CoV-2 positive boys (3 patients with positive swab and serology, 1 patient with negative swab and positive serology). Three presented myocardial dysfunction and pericardial effusion, one developed multicoronary aneurysms and hyperinflammation; all responded to treatment. The fourth boy had mitral and aortic regurgitation that rapidly regressed after steroids. In the end, KD, myocarditis and MIS-C were distinguishable cardiovascular manifestations. KD did not show a more aggressive form compared to previous years: coronary involvement was frequent, but always transient. MIS-C and myocarditis rapidly responded to treatment without cardiac sequelae despite high markers of myocardial injury at onset suggesting a myocardial depression due to systemic inflammation rather than focal necrosis. Evidence of actual or previous SARS-CoV-2 infection was documented only in patients with MIS-C.
ACE inhibitors, ARBs do not pose additional risk in COVID-19 in two meta-analyses
Helio | Cardiology Today, December 4, 2020
Use of ACE inhibitors and angiotensin receptor blockers was not associated with an increased rate of COVID-19 infection or mortality, according to two meta-analyses reported at the virtual American Heart Association Scientific Sessions. Yujiro Yokoyama, MD, surgeon at St. Luke’s University Health Network’s Easton Hospital, Bethlehem, Pennsylvania, and colleagues conducted two meta-analyses to compare mortality and susceptibility to COVID-19 infection between patients treated and not treated with ACE inhibitors and/or angiotensin receptor blocker. The first meta-analysis evaluated the impact on rate of positive COVID-19 testing and the second meta-analysis evaluated the impact on in-hospital mortality for patients with COVID-19. “Our study results confirm that patients already taking ACE inhibitors and angiotensin receptor blockers should not discontinue takin them due to COVID-19 infection,” Yokoyama said in a press release. “Both medications have proven benefits for heart and kidney disease, and this further confirms previous findings that ACE inhibitors do not pose additional risk with COVID-19.” Earlier this year, the AHA, Heart Failure Society of America and American College of Cardiology issued a joint statement calling for the continuation of ACE inhibitors and angiotensin receptor blockers during the COVID-19 pandemic in patients prescribed these medications for HF, hypertension and/or ischemic heart disease, and recommended that patients with COVID-19 should be fully evaluated before any treatment changes.
Echocardiography Abnormal Findings and Laboratory Operations during the COVID-19 Pandemic at a High Volume Center in New York City
Healthcare, December 3, 2020
This study sought to explore how the novel coronavirus (COVID-19) pandemic affected the echocardiography (TTE) laboratory operations at a high volume medical center in New York City. Changes in cardiac imaging study volume, turn-around time, and abnormal findings were analyzed and compared to a pre-pandemic period. Volume of all cardiac imaging studies and TTE reports between 11 March 2020 to 5 May 2020 and the same calendar period in 2019 were retrospectively identified and compared. During the pandemic, our center experienced a 46.72% reduction in TTEs, 82.47% reduction in transesophageal echocardiograms, 83.16% reduction in stress echo, 70.32% reduction in nuclear tests, 46.25% reduction in calcium score, 73.91% reduction in coronary computed tomography angiography, and 87.23% reduction in cardiac magnetic resonance imaging. TTE findings were overall similar between 2020 and 2019 (all p ≥ 0.05), except for a significantly higher right ventricular systolic pressure in 2020 (39.8 ± 14.2 vs. 34.6 ± 11.2 mmHg, p = 0.012). Despite encountering an influx of critically ill patients, our hospital center experienced a reduction in the number of cardiac imaging studies, which likely represents a change in both patient mindset and physician management approach.
Reversible Myocardial Injury Associated With SARS-CoV-2 in an Infant
JACC: Case Reports, December 2, 2020
Coronavirus disease-2019 is caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and has been associated with myocardial dysfunction and heart failure in adult patients. We report a case of reversible myocardial injury and heart failure in an infant with SARS-CoV-2 infection. A 2-month-old infant presented with an episode of choking and cyanosis after feeding. There was no history of fever, cough, upper respiratory tract infection symptoms, diarrhea, vomiting, or decreased oral intake prior to the initial presentation. On arrival of emergency medical service, the patient had a pulse but poor respiratory effort and was treated with oxygen and bag mask ventilation. A transthoracic echocardiogram on DOI 1 demonstrated severely depressed left ventricular (LV) systolic function (ejection fraction [EF] 30%), severe mitral regurgitation (MR), and normal right ventricular systolic function. The origins of the coronary arteries were normal. There were no other cardiac abnormalities or pericardial effusion. Multiplex viral panel polymerase chain reaction to rule out other viral etiologies for acute myocarditis was negative. Acute myocardial injury as an atypical presentation of SARS-CoV-2 infection is currently being recognized in the adult population. Our case highlights the potential for myocardial involvement in infants with SARSCoV-2 infection.
Challenges in activation of remote monitoring in patients with cardiac rhythm devices during the coronavirus (COVID-19) pandemic
International Journal of Cardiology, December 1, 2020
Remote monitoring (RM) technology embedded in cardiac rhythm devices permits continuous monitoring of device function, and recording of selected cardiac physiological parameters and cardiac arrhythmias and may be of utmost utility during Coronavirus (COVID-19) pandemic, when in-person office visit for regular follow-up were postponed. However, patients not alredy followed-up via RM represent a challenging group of patients to be managed during the lockdown. We reviewed patient files scheduled for an outpatient visit between January 1, 2020 and May 11th, 2020 to assess the proportion of patients in whom RM activation was possible without office visit, and compared them to those scheduled for visit before the lockdown. During COVID-19 pandemic, RM activation was feasible in a minority of patients (7.8% of patients) expected at outpatient clinic for a follow-up visit and device check-up. This was possible in a good proportion of complex implantable devices such as cardiac resynchronization therapy and implantable cardioverter defibrillator but only in 3 patients with a pacemaker the RM function could be activated during the period of restricted access to hospital. Our experience strongly suggest to consider the systematic activation of RM function at the time of implantation or – by default programming – in all cardiac rhythm management devices.
A Survey-based Estimate of COVID-19 Incidence and Outcomes among Patients with Pulmonary Arterial Hypertension or Chronic Thromboembolic Pulmonary Hypertension and Impact on the Process of Care
Annals of the American Thoracic Society, December 1, 2020
Patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) typically undergo frequent clinical evaluation. The incidence and outcomes of coronavirus disease (COVID-19) and its impact on routine management for patients with pulmonary vascular disease is currently unknown. Our objective was to assess the cumulative incidence and outcomes of recognized COVID-19 for patients with PAH/CTEPH followed at accredited pulmonary hypertension centers, and to evaluate the pandemic’s impact on clinic operations at these centers. A survey was e-mailed to program directors of centers accredited by the Pulmonary Hypertension Association. Seventy-seven center directors were successfully e-mailed a survey, and 58 responded (75%). The cumulative incidence of COVID-19 recognized in individuals with PAH/CTEPH was 2.9 cases per 1,000 patients, similar to the general U.S. population. In patients with PAH/CTEPH for whom COVID-19 was recognized, 30% were hospitalized and 12% died. These outcomes appear worse than the general population. A large impact on clinic operations was observed including fewer clinic visits and substantially increased use of telehealth. A majority of centers curtailed diagnostic testing and a minority limited new starts of medical therapy. Most centers did not use experimental therapies in patients with PAH/CTEPH diagnosed with COVID-19. The cumulative incidence of COVID-19 recognized in patients with PAH/CTEPH appears similar to the broader population, although outcomes may be worse. Although the total number of patients with PAH/CTEPH recognized to have COVID-19 was small, the impact of COVID-19 on broader clinic operations, testing, and treatment was substantial.
Breaking pandemic chain reactions: telehealth psychosocial support in cardiovascular disease during COVID-19
European Journal of Cardiovascular Nursing, December 1, 2020
[Editorial: This editorial refers to ‘Delivering healthcare remotely to cardiovascular patients during COVID-19: A rapid review of the evidence’, by L. Neubeck et al.] Can one pandemic intensify the existence of another? The outlook for patients with cardiovascular disease (CVD) during COVID-19 is grim. Evidence indicates a relationship exists between COVID-19 and the onset or exacerbation of heart disease; two conditions are categorized as pandemics by the World Health Organization. Pre-diagnosed CVD increases the risk of death from COVID-19 by almost 70% following acute myocardial injury and patient behaviours are compounding this risk. Initially, patients were not presenting to the hospital, and activity in cardiology units decreased anywhere from 50% to 80%. ‘Time is heart’ and time from symptom onset to first medical contact has in some instances quadrupled since late January 2020. In the context of healthcare systems being pushed to their limits in countries with adequate infrastructure and unimaginable outcomes in countries without it, our response to the array of existing and rebound cardiovascular conditions is crucial. As a global society, how do we begin to address or even consider preventing pandemic chain reactions?
Takotsubo Syndrome: Cardiotoxic Stress in the COVID Era
Mayo Clinic Proceedings: Innovations, Quality & Outcomes, November 30, 2020
Takotsubo syndrome (TTS), also known as stress cardiomyopathy and broken heart syndrome, is a neurocardiac condition that is among the most dramatic manifestations of psychosomatic disorders. This paper is based on a systematic review of TTS and stress cardiomyopathy using a PubMed literature search. Typically, an episode of severe emotional or physical stress precipitates regions of left ventricular hypokinesis or akinesis, which are not aligned with a coronary artery distribution and are out of proportion to the modest troponin leak. A classic patient with TTS is described; one who had chest pain and dyspnea while watching an anxiety-provoking evening news program on the coronavirus disease 2019 (COVID-19) pandemic. An increase in the incidence of TTS appears to be a consequence of the COVID-19 pandemic, with the TTS incidence rising 4.5-fold during the COVID-19 pandemic even in individuals without severe acute respiratory syndrome coronavirus 2 infection. Takotsubo syndrome is often mistaken for acute coronary syndrome because they both typically present with chest pain, electrocardiographic changes suggesting myocardial injury/ischemia, and troponin elevations. Recent studies report that the prognosis for TTS is similar to that for acute myocardial infarction. This review is an update on the mechanisms underlying TTS, its diagnosis, and its optimal management.
The coronavirus disease 2019 proves transformability of the cardiac surgery specialty
European Journal of Cardio-Thoracic Surgery, November 30, 2020
[Letter to the Editor] Forced by the implications of the coronavirus disease 2019 (COVID-19) crisis, the staff at the New York Presbyterian Hospital managed to rearrange their system of healthcare delivery to improve conditions to deal with the crisis. They showed what potential for evolvement lies underneath the surface in a time of need. Even though this transformation came with an economic burden due to the loss of elective cases, this is an impressive development that shall serve as an example of transformation capacity within our specialty. One area that could profit from a change in perception as shown in the COVID-19 crisis is global cardiac surgery. In 2018, the ‘Cape Town Declaration on Access to Cardiac Surgery in the Developing World’ encouraged commitment to increase the access to cardiac surgery. Cardiac surgery aims to facilitate a better and healthier world. Social components are a threat to this aim generated by inequality. There is an estimated financial benefit of $12 trillion for low- and middle-income countries based on an investment of $350 billion over 15 years. This includes the fight against burdens of society such as rheumatic heart diseases, which can affect over 80% of the world’s population. COVID-19 proved the importance of global health in all parts of medicine and society. Therefore, we should take it as a trigger to deal with global health issues in a world where 93% still lack cardiac surgical care. Hopefully, the ability of transformation prompted by the COVID-19 crisis as shown by George et al. will affect new aspects of our global cardiac community.
What Happened to Electrocardiogram as a Screening Test to Recognize Cardiovascular Complications in COVID-19 Patients?
Journal of the American College of Cardiology, November 30, 2020
[Letter to the Editor] We read with great interest the paper from Lala et al. The authors must be congratulated for focusing attention on the clinical relevance of troponin I as a marker of myocardial injury in patients with coronavirus disease 2019 (COVID-19) and on the strong prognostic implications of this simple and easily available biomarker. Unfortunately, troponin is a generic marker of myocardial damage and cannot provide any valuable insight into the pathophysiological mechanism of the damage. We believe that this limitation could have been partly resolved by the systematic evaluation of standard electrocardiogram (ECG). Paradoxically and unexpectedly, 5 months after the beginning of the “COVID-19 era,” data on standard ECG as a screening tool for cardiovascular complications are almost completely missing in the literature—1 recently published and 1 in-press paper—whereas ECG details are available only for selected patients diagnosed with myocarditis or acute coronary syndrome. The extreme lack of ECG data is all the stranger considering it is a broadly available, low-cost diagnostic test that can be quickly performed without exposing a large number of personnel to the virus. This ECG eclipse has contributed to generate the misconception that “myocardial injury” diagnosed by elevated serum troponin is synonymous with myocarditis or acute coronary syndrome, neglecting the fact, for instance, that acute pressure overload of the right ventricle can also cause an increase of this biomarker. Indeed, compared to troponin, ECG can provide not only a generic diagnosis of myocardial injury or damage but can also orient to the specific pathophysiological mechanism and foster suspicion of pulmonary thromboembolic or in situ thrombosis of the pulmonary circulation, which are being described with increasing frequency.
COVID-19 with Cardiovascular Disease: Can It Help Predict Prognosis?
The Heart Surgery Forum, November 30, 2020
Two recent articles both found that cardiovascular disease was the major comorbidity in patients with COVID-19. In a recent issue of The Lancet, Huang et al [2020] reported epidemiological, clinical, laboratory, and radiological characteristics of 41 patients with COVID-19, treatments, and clinical outcomes. Some of the infected patients had cardiovascular disease (CVD) (n = 12; 29.3%). The authors found that CVD was the most common comorbidity of patients with COVID-19 in their research. Similarly, in a recent study published in the British Medical Journal, Chen et al [2019] analyzed deceased (n = 113) and recovered (n = 161) patients with COVID-19 pneumonia among 799 symptomatic patients. The authors found that CVD was more frequent in deceased patients (n = 70; 61.9%) than recovered patients (n = 46; 28.6%). More deceased patients (n = 50; 44.2%) had arterial pressure ≥140 mmHg than recovered patients (n = 33; 20.5%). Inflammation of the cardiovascular system and hypoxemia in patients with COVID-19 are the important causes of cardiovascular system dysfunction. Through detailed analyses of the cardiovascular system, clinicians may identify specific patterns of cardiovascular abnormalities. If such a model can been established, the prognosis of COVID-19 patients with cardiovascular disease may be predicted. Judging the prognosis of patients can help clinicians formulate detailed clinical observations and effective treatment methods to improve the cure rate and reduce the mortality rate of patients with COVID-19.
Right ventricular-arterial uncoupling independently predicts survival in COVID-19 ARDS
Critical Care, November 30, 2020
Our aim was to investigate the prevalence and prognostic impact of right heart failure and right ventricular-arterial uncoupling in Corona Virus Infectious Disease 2019 (COVID-19) complicated by an Acute Respiratory Distress Syndrome (ARDS). Ninety-four consecutive patients (mean age 64 years) admitted for acute respiratory failure on COVID-19 were enrolled. Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio. The majority of patients needed ventilatory support, which was noninvasive in 22 and invasive in 37. There were 25 deaths, all in the invasively ventilated patients. Survivors were younger (62 ± 13 vs. 68 ± 12 years, p = 0.033), less often overweight or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO2)/fraction of inspired O2 (FIO2) ratio (270 ± 104 vs. 117 ± 57 mmHg, p < 0.001). In the non-survivors, PASP was increased (42 ± 12 vs. 30 ± 7 mmHg, p < 0.001), while TAPSE was decreased (19 ± 4 vs. 25 ± 4 mm, p < 0.001). Accordingly, the TAPSE/PASP ratio was lower than in the survivors (0.51 ± 0.22 vs. 0.89 ± 0.29 mm/mmHg, p < 0.001). At univariate/multivariable analysis, the TAPSE/PASP (HR: 0.026; 95%CI 0.01–0.579; p: 0.019) and PaO2/FIO2 (HR: 0.988; 95%CI 0.988–0.998; p: 0.018) ratios were the only independent predictors of mortality, with ROC-determined cutoff values of 159 mmHg and 0.635 mm/mmHg, respectively. COVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO2/FIO2 in ARDS on COVID-19.
COVID-19 vaccine developed by Moderna, NIH gets FDA review date
Helio | Infectious Disease News, November 30, 2020
The FDA’s vaccine advisory committee will meet on Dec. 17 to review an emergency use authorization (EUA) request for the COVID-19 vaccine candidate codeveloped by Moderna and the NIH, Moderna announced. It will be the second such meeting in 8 days of the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), which will review an EUA request filed by Pfizer and BioNTech for their COVID-19 vaccine candidate on Dec. 10. Moderna announced the VRBPAC date at the same time it reported that preliminary data from a primary efficacy analysis showed its messenger RNA (mRNA)-based vaccine, mRNA-1273, was 94.1% efficacious overall and 100% efficacious against severe COVID-19, with no serious safety concerns identified to date. According to a press release, the phase 3 COVE study exceeded the 2-month median follow-up following vaccination required for an EUA submission, which Moderna said it was filing Monday. “We believe that our vaccine will provide a new and powerful tool that may change the course of this pandemic and help prevent severe disease, hospitalizations and death,” Moderna CEO Stéphane Bancel said in the press release. “I want to thank the thousands of participants in our phase 1, phase 2 and phase 3 studies, as well as the staff at clinical trial sites who have been on the front lines of the fight against the virus.”
The endothelium as Achilles’ heel in COVID-19 patients
Cardiovascular Research, November 27, 2020
The COVID-19 pandemic undoubtedly influenced the focus of many scientific fields, including cardiovascular research, and is still a global challenge for healthcare systems. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) predominantly affects the respiratory tract, and in severe cases, also other organs, including the liver, kidney, heart, and intestine. The leading cause of mortality in patients with COVID-19 is a hypoxic respiratory failure caused by acute respiratory distress syndrome (ARDS). It is well established that SARS-CoV-2 hijacks angiotensin-converting enzyme 2 (ACE2) receptors to infect host cells. ACE2 receptors are widely expressed in various tissues, suggesting the broad clinical consequences of SARS-CoV-2 infection that make COVID-19 a multiorgan disease. Endothelial cells have recently been implicated as the primary cell type involved in the initiation and propagation of ARDS caused by SARS-CoV-2, resulting in severe endothelial injury and widespread thrombosis. In fact, the first reports from Wuhan, China reported an increase in D-dimers (reporting thrombosis and/or disseminated intravascular coagulation) as a very early biomarker predicting an adverse outcome in COVID-19 patients, even preceding elevations of troponin or interleukin-6. Accordingly, patients with pre-existing conditions such as hypertension, obesity, and diabetes, which are all associated with endothelial dysfunction, are more susceptible to an adverse course of COVID-19. While the exact mechanisms are incompletely resolved, SARS-CoV-2 impinging on endothelial cell function has evolved as a key unifying candidate.
Cardiac Troponin Testing in Patients with COVID-19: A Strategy for Testing and Reporting Results
Clinical Chemistry, November 25, 2020
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged late in 2019 causing COVID-19 (coronavirus disease-2019) may adversely affect the cardiovascular system. Publications from Asia, Europe, and North America have identified cardiac troponin as an important prognostic indicator for patients hospitalized with COVID-19. We recognized from publications within the first 6 months of the pandemic that there has been much uncertainty on the reporting, interpretation, and pathophysiology of an increased cardiac troponin concentration in this setting. The purpose of this mini-review is: a) to review the pathophysiology of SARS-CoV-2 and the cardiovascular system, b) to overview the strengths and weaknesses of selected studies evaluating cardiac troponin in patients with COVID-19, and c) to recommend testing strategies in the acute period, in the convalescence period and in long-term care for patients who have become ill with COVID-19. This review provides important educational information and identifies gaps in understanding the role of cardiac troponin and COVID-19. Future, properly designed studies will hopefully provide the much-needed evidence on the path forward in testing cardiac troponin in patients with COVID-19.
Testing IgG antibodies against the RBD of SARS-CoV-2 is sufficient and necessary for COVID-19 diagnosis
PLOS ONE, November 23, 2020
The COVID-19 pandemic and the fast global spread of the disease resulted in unprecedented decline in world trade and travel. A critical priority is, therefore, to quickly develop serological diagnostic capacity and identify individuals with past exposure to SARS-CoV-2. In this study serum samples obtained from 309 persons infected by SARS-CoV-2 and 324 of healthy, uninfected individuals as well as serum from 7 COVID-19 patients with 4–7 samples each ranging between 1–92 days post first positive PCR were tested by an “in house” ELISA which detects IgM, IgA and IgG antibodies against the receptor binding domain (RBD) of SARS-CoV-2. Sensitivity of 47%, 80% and 88% and specificity of 100%, 98% and 98% in detection of IgM, IgA and IgG antibodies, respectively, were observed. IgG antibody levels against the RBD were demonstrated to be up regulated between 1–7 days after COVID-19 detection, earlier than both IgM and IgA antibodies. Study of the antibody kinetics of seven COVID 19 patients revealed that while IgG levels are high and maintained for at least 3 months, IgM and IgA levels decline after a 35–50 days following infection. Altogether, these results highlight the usefulness of the RBD based ELISA, which is both easy and cheap to prepare, to identify COVID-19 patients even at the acute phase. Most importantly, our results demonstrate that measuring IgG levels alone is both sufficient and necessary to diagnose past exposure to SARS-CoV-2.
CPR success, survival to discharge in out-of-hospital cardiac arrest dropped amid COVID-19
Helio | Cardiology Today, November 23, 2020
Rates of return of spontaneous circulation and survival to discharge for out-of-hospital cardiac arrest declined in the U.S. early during the COVID-19 pandemic compared with the previous year, researchers reported. These findings were consistent throughout the U.S, even in counties with low rates of COVID-19 deaths, according to the study presented at the virtual American Heart Association Scientific Sessions. “It [was] unclear what the effects of the COVID-19 pandemic on out-of-hospital cardiac arrest outcomes have been in communities that were not as severely affected, with low and moderate COVID-19 disease burden,” Paul Chan, MD, MSc, clinical scholar at Saint Luke’s Mid America Heart Institute and professor of medicine at the University of Missouri-Kansas City, said during his presentation. “Moreover, initial reports only reported on rates of sustained return of spontaneous circulation, and rates of overall rates of survival to discharge remained unknown.” The primary outcome was sustained return of spontaneous circulation for 20 minutes or more. Secondary outcomes included in-field termination of CPR, survival to discharge and incidence of out-of-hospital cardiac arrest.
The Potential Benefit of Beta-Blockers for the Management of COVID-19 Protocol Therapy-Induced QT Prolongation: A Literature Review
Scientia Pharmaceutica, November 23, 2020
The World Health Organization (WHO) officially announced coronavirus disease 2019 (COVID-19) as a pandemic in March 2020. Unfortunately, there are still no approved drugs for either the treatment or the prevention of COVID-19. Many studies have focused on repurposing established antimalarial therapies, especially those that showed prior efficacy against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), such as chloroquine and hydroxychloroquine, against COVID-19 combined with azithromycin. These classes of drugs potentially induce prolongation of the QT interval, which might lead to lethal arrhythmia. Beta-blockers, as a β-adrenergic receptor (β-AR) antagonist, can prevent an increase in the sympathetic tone, which is the most important arrhythmia trigger. In this literature review, we aimed to find the effect of administering azithromycin, chloroquine, and hydroxychloroquine on cardiac rhythm disorders and our findings show that bisoprolol, as a cardio-selective beta-blocker, is effective for the management of the QT (i.e., the start of the Q wave to the end of the T wave) interval prolongation in COVID-19 patients.
Gov’t Prepares to Distribute Regeneron COVID-19 Drug
MedPage Today, November 23, 2020
Following the FDA’s weekend authorization of Regeneron’s monoclonal antibody cocktail for mild-moderate COVID-19, the federal government’s Operation Warp Speed (OWS) is swinging into action, officials said Monday. Department of Health and Human Services (HHS) Secretary Alex Azar said OWS would ship 30,000 doses on Tuesday — each eligible COVID-19 patient receives one dose — with thousands more to go out in the days ahead. On a phone call with reporters, he also reiterated the government’s promise that the drug would be provided to patients at no cost (Facilities may still charge for administration of the intravenous product, however). Regeneron’s CEO told CNBC on Monday that the company currently has 80,000 doses on hand and expects to ship 300,000 by early January, with 100,000 additional doses per month to come thereafter. Getting the product to patients is a major logistical challenge, officials explained, as has been the case with Eli Lilly’s bamlanivimab, another infusion therapy that received emergency authorization 2 weeks ago. Both drugs are to be used in non-hospitalized patients at risk for illness progression — meaning they are for outpatient administration. Because patients by definition have COVID-19, they need to be isolated, and sites must be prepared to provide infusions to large numbers of them given the current surge in cases.
Prevalence of Pulmonary Hypertension in Patients With Myeloproliferative Neoplasms
Pulmonology Advisor, November 23, 2020
Estimates of the prevalence of pulmonary hypertension (PH) as a complication of myeloproliferative neoplasms (MPNs) vary broadly, according to a systematic review and meta-analysis that was recently published in the European Journal of Haematology. PH is linked to a higher MPN disease burden and poorer survival, but little has been known about the prevalence and factors associated with PH in MPNs, according to the study investigators. The investigators performed searches of EMBASE, MEDLINE, and ClinicalTrials.gov databases for studies involving pulmonary hypertension, myeloproliferative disorders, polycythemia vera, essential thrombocytopenia, and/or myelofibrosis (MF) dated between 1999 and 2019. The goal was to assess the prevalence of, and risk factors associated with, PH in patients with MPNs, in addition to patient characteristics and outcomes. The searches identified 221 records, of which 17 reports met criteria for inclusion. Results for 935 patients were found, of whom 309 had PH. The prevalence of PH varied greatly across studies; PH prevalence was less than 5% in 3 studies, 11% to 14% in 3 studies, and greater than 36% in 7 studies. The prevalence of pulmonary hypertension could not be evaluated in analyses that only included patients with pulmonary hypertension, of those that were case control studies in which pulmonary hypertension was an exposure variable; therefore, 13 of the 17 reports were used as “prevalence sets” that investigated the factors that affected the prevalence of pulmonary hypertension at a study level.
Impact of the COVID-19-pandemic on thrombectomy services in Germany
Neurological Research and Practice, November 23, 2020
The outcome of patients with ischemic stroke and myocardial infarction depends on optimized pre- and intrahospital emergency workflows to minimize the time to reperfusion. The rapidly expanding Coronavirus Disease 2019 (COVID-19) pandemic has caused a reorganization of established workflows to limit spread of the disease. In addition, recent reports have also indicated that patients with acute stroke or myocardial infarction might resist or delay seeking help because of fear of COVID-19, raising concerns about worse outcomes of these conditions during the pandemic. Hence, monitoring of time-to-treatment intervals and disease outcomes during the pandemic is highly relevant for policymakers as it allows to assess and act upon the potential collateral effect of implemented COVID-19-related algorithms in the emergency sector. Here, we aimed to analyze workflow time intervals and functional outcomes of LVO patients treated with endovascular thrombectomy (ET) during the COVID-19 pandemic in a large German cohort.
FDA authorizes emergency use of casirivimab, imdevimab for COVID-19
Helio | Primary Care, November 23, 2020
The FDA granted emergency use authorization for the monoclonal antibodies casirivimab and imdevimab to be administered together intravenously for the treatment of mild to moderate COVID-19. According to a press release, this EUA pertains to adults and children aged 12 years and older with positive SARS-CoV-2 viral test results who weigh 88 pounds or more and are at high risk for progressing to severe COVID-19. Adults aged older than 65 years who have certain chronic medical conditions may also receive the treatment. The authorization does not extend to patients who are hospitalized or require oxygen therapy due to COVID-19. According to the release, the EUA for casirivimab and imdevimab is based on a randomized, double-blind, placebo-controlled clinical trial of 799 nonhospitalized adults with mild to moderate COVID-19 symptoms. The FDA said the “most important evidence” to emerge from the trial was that only 3% of the monoclonal antibody recipients were hospitalized or visited an ED compared with 9% of those who received placebo. The agency also noted that viral load reduction in patients who were treated with casirivimab and imdevimab was larger compared with patients treated with placebo at day 7. The effects on viral load, reduction in hospitalizations and ED visits were similar in patients receiving either of the two casirivimab and imdevimab doses in the study.
Dosing of thromboprophylaxis and mortality in critically ill COVID-19 patients
Critical Care, November 23, 2020
A substantial proportion of critically ill COVID-19 patients develop thromboembolic complications, but it is unclear whether higher doses of thromboprophylaxis are associated with lower mortality rates. The purpose of the study was to evaluate the association between initial dosing strategy of thromboprophylaxis in critically ill COVID-19 patients and the risk of death, thromboembolism, and bleeding. In this retrospective study, all critically ill COVID-19 patients admitted to two intensive care units in March and April 2020 were eligible. Patients were categorized into three groups according to initial daily dose of thromboprophylaxis. Thromboprophylaxis dosage was based on local standardized recommendations, not on degree of critical illness or risk of thrombosis. Multivariable models were adjusted for sex, age, body mass index, Simplified Acute Physiology Score III, invasive respiratory support, and initial dosing strategy of thromboprophylaxis. A total of 152 patients were included: 67 received low-, 48 medium-, and 37 high-dose thromboprophylaxis. Baseline characteristics did not differ between groups. For patients who received high-dose prophylaxis, mortality was lower (13.5%) compared to those who received medium dose (25.0%) or low dose (38.8%), p = 0.02. The hazard ratio of death was 0.33 (95% confidence intervals 0.13–0.87) among those who received high dose, and 0.88 (95% confidence intervals 0.43–1.83) among those who received medium dose, as compared to those who received low-dose thromboprophylaxis. There were fewer thromboembolic events in the high (2.7%) vs medium (18.8%) and low-dose thromboprophylaxis (17.9%) groups, p = 0.04.
Prevalence and prognostic value of elevated troponins in patients hospitalised for coronavirus disease 2019: a systematic review and meta-analysis
Journal of Intensive Care, November 23, 2020
The clinical significance of cardiac troponin measurement in patients hospitalised for coronavirus disease 2019 (covid-19) is uncertain. We investigated the prevalence of elevated troponins in these patients and its prognostic value for predicting mortality. Studies were identified by searching electronic databases and preprint servers. We included studies of hospitalised covid-19 patients that reported the frequency of troponin elevations above the upper reference limit and/or the association between troponins and mortality. Meta-analyses were performed using random-effects models. Fifty-one studies were included. Elevated troponins were found in 20.8% (95% confidence interval [CI] 16.8–25.0 %) of patients who received troponin test on hospital admission. Elevated troponins on admission were associated with a higher risk of subsequent death (risk ratio 2.68, 95% CI 2.08–3.46) after adjusting for confounders in multivariable analysis. The pooled sensitivity of elevated admission troponins for predicting death was 0.60 (95% CI 0.54–0.65), and the specificity was 0.83 (0.77–0.88). The post-test probability of death was about 42% for patients with elevated admission troponins and was about 9% for those with non-elevated troponins on admission. There was significant heterogeneity in the analyses, and many included studies were at risk of bias due to the lack of systematic troponin measurement and inadequate follow-up. Elevated troponins were relatively common in patients hospitalised for covid-19. Troponin measurement on admission might help in risk stratification, especially in identifying patients at high risk of death when troponin levels are elevated.
Risk and Severity of COVID-19 and ABO Blood Group in Transcatheter Aortic Valve Patients
Journal of Clinical Medicine, November 22, 2020
While cardiovascular disease has been associated with an increased risk of coronavirus disease 2019 (COVID-19), no studies have described its clinical course in patients with aortic stenosis who had undergone transcatheter aortic valve replacement (TAVR). Numerous observational studies have reported an association between the A blood group and an increased susceptibility to SARS-CoV-2 infection. Our objective was to investigate the frequency and clinical course of COVID-19 in a large sample of patients who had undergone TAVR and to determine the associations of the ABO blood group with disease occurrence and outcomes. Patients who had undergone TAVR between 2010 and 2019 were included in this study and followed-up through the recent COVID-19 outbreak. The occurrence and severity (hospitalization and/or death) of COVID-19 and their associations with the ABO blood group served as the main outcome measures. Of the 1125 patients who had undergone TAVR, 403 (36%) died before 1 January 2020, and 20 (1.8%) were lost to follow-up. The study sample therefore consisted of 702 patients. Of them, we identified 22 cases (3.1%) with COVID-19. Fourteen patients (63.6%) were hospitalized or died of disease. Multivariable analysis identified the A blood group (vs. others) as the only independent predictor of COVID-19 in patients who had undergone TAVR (odds ratio (OR) = 6.32; 95% confidence interval (CI) = 2.11−18.92; p = 0.001). The A blood group (vs. others; OR = 8.27; 95% CI = 1.83−37.43, p = 0.006) and a history of cancer (OR = 4.99; 95% CI = 1.64−15.27, p = 0.005) were significantly and independently associated with disease severity (hospitalization and/or death). We conclude that patients who have undergone TAVR frequently have a number of cardiovascular comorbidities that may work to increase the risk of COVID-19. The subgroup with the A blood group was especially prone to developing the disease and showed unfavorable outcomes.
ACE2 Interaction Networks in COVID-19: A Physiological Framework for Prediction of Outcome in Patients with Cardiovascular Risk Factors
Journal of Clinical Medicine, November 21, 2020
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019; COVID-19) is associated with adverse outcomes in patients with cardiovascular disease (CVD). The aim of the study was to characterize the interaction between SARS-CoV-2 and Angiotensin-Converting Enzyme 2 (ACE2) functional networks with a focus on CVD. Using the network medicine approach and publicly available datasets, we investigated ACE2 tissue expression and described ACE2 interaction networks that could be affected by SARS-CoV-2 infection in the heart, lungs and nervous system. We compared them with changes in ACE-2 networks following SARS-CoV-2 infection by analyzing public data of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). This analysis was performed using the Network by Relative Importance (NERI) algorithm, which integrates protein-protein interaction with co-expression networks. We also performed miRNA-target predictions to identify which miRNAs regulate ACE2-related networks and could play a role in the COVID19 outcome. Finally, we performed enrichment analysis for identifying the main COVID-19 risk groups. Results: We found similar ACE2 expression confidence levels in respiratory and cardiovascular systems, supporting that heart tissue is a potential target of SARS-CoV-2.
Possible Correlations between Atherosclerosis, Acute Coronary Syndromes and COVID-19
Journal of Clinical Medicine, November 21, 2020
An outbreak of SARS-CoV-2 infection in December 2019 became a major global concern in 2020. Since then, several articles analyzing the course, complications and mechanisms of the infection have appeared. However, there are very few papers explaining the possible correlations between COVID-19, atherosclerosis and acute coronary syndromes. We performed an analysis of PubMed, Cochrane, Google Scholar, and MEDLINE databases. As of September 15, 2020, the results were as follows: for “COVID-19” and “cardiovascular system” we obtained 687 results; for “COVID-19” and “myocardial infarction” together with “COVID-19” and “acute coronary syndrome” we obtained 328 results; for “COVID-19” and “atherosclerosis” we obtained 57 results. Some of them did not fulfill the search criteria or concerned the field of neurology. Only articles written in English, German and Polish were analyzed for a total number of 432 papers. While the link between inflammatory response, COVID- 19 and atherosclerosis still remains unclear, there is evidence that suggests a more likely correlation between them. Practitioners’ efforts should be focused on the prevention of excessive inflammatory response and possible complications, while there are limited specific therapeutic options against SARS-CoV-2. Furthermore, special attention should be paid to cardioprotection during the pandemic.
COVID-19 patient with coronary thrombosis supported with ECMO and Impella 5.0 ventricular assist device: a case report
European Heart Journal, November 20, 2020
COVID-19 can present with cardiovascular complications. We present a case report of a 43-year-old previously fit patient who suffered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with thrombosis of the coronary arteries causing acute myocardial infarction. These were treated with coronary stenting during which the patient suffered cardiac arrest. He was supported with automated chest compressions followed by peripheral veno-arterial extracorporeal membrane oxygenation (VA ECMO). No immediate recovery of the myocardial function was observed and, after insufficient venting of the left ventricle was diagnosed, an Impella 5 pump was implanted. The cardiovascular function recovered sufficiently and ECMO was explanted and inotropic infusions discontinued. Due to SARS-CoV-2 pulmonary infection, hypoxia became resistant to conventional mechanical ventilation and the patient was nursed prone overnight. After initial recovery of respiratory function, the patient received a tracheostomy and was allowed to wake up. Following a short period of agitation his neurological function recovered completely. During the third week of recovery, progressive multisystem dysfunction, possibly related to COVID-19, developed into multiorgan failure, and the patient died. We believe that this is the first case report of coronary thrombosis related to COVID-19. Despite the negative outcome in this patient, we suggest that complex patients may in the future benefit from advanced cardiovascular support, and may even be nursed safely in the prone position with Impella devices.
Cardiovascular Manifestations of COVID-19 Infection
Cells, November 19, 2020
SARS-CoV-2 induced the novel coronavirus disease (COVID-19) outbreak, the most significant medical challenge in the last century. COVID-19 is associated with notable increases in morbidity and death worldwide. Preexisting conditions, like cardiovascular disease (CVD), diabetes, hypertension, and obesity, are correlated with higher severity and a significant increase in the fatality rate of COVID-19. COVID-19 induces multiple cardiovascular complexities, such as cardiac arrest, myocarditis, acute myocardial injury, stress-induced cardiomyopathy, cardiogenic shock, arrhythmias and, subsequently, heart failure (HF). The precise mechanisms of how SARS-CoV-2 may cause myocardial complications are not clearly understood. The proposed mechanisms of myocardial injury based on current knowledge are the direct viral entry of the virus and damage to the myocardium, systemic inflammation, hypoxia, cytokine storm, interferon-mediated immune response, and plaque destabilization. The virus enters the cell through the angiotensin-converting enzyme-2 (ACE2) receptor and plays a central function in the virus’s pathogenesis. A systematic understanding of cardiovascular effects of SARS-CoV2 is needed to develop novel therapeutic tools to target the virus-induced cardiac damage as a potential strategy to minimize permanent damage to the cardiovascular system and reduce the morbidity. In this review, we discuss our current understanding of COVID-19 mediated damage to the cardiovascular system.
Business of cardiology ‘severely disrupted’ by COVID-19 pandemic
Helio | Cardiology Today, November 19, 2020
The COVID-19 pandemic has disrupted our current way of life, comparable in magnitude perhaps to transformations that followed the Great Plague of the Middle Ages and the Spanish influenza pandemic of 1918-1920. The pandemic may well be one of the seminal events of the 21st century, prompting wide-ranging and long-lasting changes in the economy, public health policy and health care delivery. The business of medicine and cardiology has been severely disrupted by the COVID-19 pandemic. Just as the rest of society adjusts to the economic and human ramifications of this crisis, we cardiologists will also change our practice operations to accommodate the new environment. The pandemic has forced society and the medical community to acknowledge the many inefficiencies and inequities in our current systems of health care delivery, not only as directly related to caring for patients infected with SARS-CoV-2, but also to make the fundamental, systemic changes needed to deliver effective, high-value care to all of our patients, finally honoring our society’s promise of health care as a basic human right. Changes is practice, use of telehealth and compensation/financial issues are all discussed.
COVID’s Heart Complications Modest in Large Registry
MedPage Today, November 18, 2020
The first results emerging from the American Heart Association (AHA) COVID-19 registry showed fewer cardiovascular complications than expected from some series, but reemphasized the higher risk with obesity and among minorities. Multiple analyses of the more than 22,500-patient database were presented at a press conference at the virtual AHA meeting by James de Lemos, MD, of UT Southwestern Medical Center in Dallas, on behalf of the researchers. The 109 participating hospitals and medical centers retrospectively abstracted all consecutive adults hospitalized with COVID-19 into the registry, which piggybacks on the Get With the Guidelines quality improvement program. In-hospital cardiac complications overall were “somewhat less common than we thought they would be when we launched the registry” in April, with just over an 8% composite rate of CV death, MI, stroke, heart failure, and shock across the January 1 to July 22 period studied, de Lemos said. The most common such event was atrial fibrillation, reported in about 8% of patients. In their analysis of 7,606 patients with BMI data, in-hospital death or mechanical ventilation was a relative 28% more likely with class I obesity, 57% more likely with class II obesity, and 80% more likely with class III obesity, which also correlated with a 26% higher likelihood of in-hospital death. Of the 7,868 patients with completed race or ethnicity data, Black and Hispanic people were overrepresented among COVID-19 cases and deaths compared with local census data for their zip code. Black people represented 25.5% of cases and 24% of deaths vs 10.6% in the census, while Hispanic people comprised 33.0% of cases and 29% of deaths vs 9.0% of the census.
Factors associated with disease severity and mortality among patients with COVID-19: A systematic review and meta-analysis
PLOS ONE, November 18, 2020
Understanding the factors associated with disease severity and mortality in Coronavirus disease (COVID-19) is imperative to effectively triage patients. We performed a systematic review to determine the demographic, clinical, laboratory and radiological factors associated with severity and mortality in COVID-19. We searched PubMed, Embase and WHO database for English language articles from inception until May 8, 2020. We included Observational studies with direct comparison of clinical characteristics between a) patients who died and those who survived or b) patients with severe disease and those without severe disease. Data extraction and quality assessment were performed by two authors independently. Among 15680 articles from the literature search, 109 articles were included in the analysis. The risk of mortality was higher in patients with increasing age, male gender (RR 1.45, 95%CI 1.23–1.71), dyspnea (RR 2.55, 95%CI 1.88–2.46), diabetes (RR 1.59, 95%CI 1.41–1.78), hypertension (RR 1.90, 95%CI 1.69–2.15). Congestive heart failure (OR 4.76, 95%CI 1.34–16.97), hilar lymphadenopathy (OR 8.34, 95%CI 2.57–27.08), bilateral lung involvement (OR 4.86, 95%CI 3.19–7.39) and reticular pattern (OR 5.54, 95%CI 1.24–24.67) were associated with severe disease. Clinically relevant cut-offs for leukocytosis (>10.0 x109/L), lymphopenia (< 1.1 x109/L), elevated C-reactive protein (>100mg/L), LDH (>250U/L) and D-dimer (>1mg/L) had higher odds of severe disease and greater risk of mortality.
Hypertension, diabetes ‘common’ in patients with neurological complications of COVID-19
Helio | Primary Care, November 18, 2020
Among patients with COVID-19, those who had hypertension or type 2 diabetes were more likely to develop neurological conditions associated with the infectious disease, data from a small study show. “We recommend that physicians include a neurological exam as part of their patients’ physical exams and consider the complications described in patients with COVID-19,” Colbey W. Freeman, MD, chief resident in the department of radiology at Penn Medicine in Philadelphia, told Healio Primary Care. Freeman and colleagues analyzed head images from 81 patients (mean age, 66.3 years; 36 women) within a tertiary health system who tested positive for SARS-CoV-2. The patients’ demographic, comorbidity information, laboratory values and neuroimaging findings from CTs and/or MRIs were also recorded. According to the researchers, 18 of the patients’ (mean age, 60.5 years; nine women, 12 Black) laboratory values and neuroimaging results showed what researchers deemed “critical” findings: 12 had acute/subacute infarct; four had large vessel intracranial occlusion; three had subarachnoid and intraparenchymal hemorrhage; and one had hypoxic-ischemic encephalopathy.
The right ventricle in COVID-19 patients: A forgotten essential chamber that may be involved in the cardiac complications of COVID-19
European Heart Journal, November 18, 2020
The right ventricle seems to have been forgotten among heart chambers, although some studies have shown its crucial role in coronavirus disease 2019 (COVID-19). Interestingly, both its size and function are believed to be associated with cardiac complications and mortality in COVID-19. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which spread globally after the first case was observed in Wuhan at the end of 2019. Recent studies suggested that COVID-19 may be accompanied by cardiac complications, including acute coronary syndrome, cardiac arrhythmia, myocarditis, pericarditis, and heart failure in nearly 20% of patients, which are associated with an increased risk of mortality. Laboratory data such as cardiac troponin as well as echocardiography parameters can be effective means of cardiac assessment in these patients. Transthoracic echocardiography (TTE) is the optimum method of cardiac imaging used in COVID-19 patients, which is able to diagnose different cardiac abnormalities including haemodynamic dysfunction. Also, it is useful for the prediction of future cardiac morbidity in these patients. Reduced right ventricular (RV) activity is a good predictor for heart failure and cardiac mortality. The effect of COVID-19 on the right ventricle activity is in the main unknown. It seems that the pathophysiological pathways of COVID-19 including increased afterload after acute respiratory distress syndrome, pulmonary embolism, cytokine-negative inotropic effects, and renin–angiotensin system dysfunction are possible mechanisms for RV dysfunction in COVID-19 patients.
Highlights from the American Heart Virtual Scientific Sessions
JAMA Medical News, November 18, 2020
[Podcast, 38:09] From the American Heart Association’s first-ever virtual Scientific Sessions conference, host Jennifer Abbasi chats with conference chair and AHA president-elect Donald Lloyd-Jones, MD, ScM. Hear about this year’s hottest clinical trials and themes: fish oil vs corn oil placebo for primary or secondary prevention; Polycap polypill with or without aspirin for primary prevention; statins, side effects, and the nocebo effect; ferric carboxymaltose iron infusion in acute heart failure; omecamtiv mecarbil, a novel cardiac myosin activator, in HFrEF; sotagliflozin, an SGLT2/1 inhibitor, in diabetes with recent worsening heart failure or in diabetes and chronic kidney disease; MINOCA’s underlying cause in women; rilonacept, an IL-1α and IL-1β Trap, in recurrent pericarditis; COVID-19’s cardiovascular effects, risk factors, and racial/ethnic disparities.
T Cells May Tell Us More About COVID Immunity
MedPage Today, November 18, 2020
While antibodies have been the focus of testing for past infection with COVID-19, T cells will also provide some insights — potentially better ones, experts say. These lymphocytes are the first responders that then coordinate the immune response while building an imprint, a memory, so that subsequent infections fade quickly, often unnoticed. T cell tests are more complex and typically reserved for research, but some may be coming to the clinic soon, with at least one company seeking FDA emergency use authorization (EUA). Recent studies indicate that assaying T cells can even improve diagnostic accuracy and possibly predict how COVID-19 will unfold. “Testing T cell responses can accelerate detection of an infection by as much as a week. The cells come in on day 2 and they divide very quickly, to detectable levels as early as 3 or 4 days from infection,” said Dawn Jelley-Gibbs, PhD, who investigated T cells in influenza at the Trudeau Institute in Saranac Lake, New York. The good news is that in COVID-19, T cells appear a day or two after symptoms start, bind the virus at several sites, and persist – so far. “Since we did not observe a substantial decline during the follow-up, we assume that the memory CD8 T cell response remains sustained for a longer period, more than a year. But only longitudinal studies over a long time will prove this assumption right or wrong,” said corresponding author Christoph Neumann-Haefelin, MD.
Meta-analysis Comparing Outcomes in Patients With and Without Cardiac Injury and Coronavirus Disease 2019 (COVID 19)
American Journal of Cardiology, November 17, 2020
Current evidence is limited to small studies describing the association between cardiac injury and outcomes in patients with COVID-19. To address this, we performed a comprehensive meta-analysis of studies in COVID-19 patients to evaluate the association between cardiac injury and all-cause mortality, intensive care unit (ICU) admission, mechanical ventilation, acute respiratory distress syndrome (ARDS), acute kidney injury (AKI) and coagulopathy. Further, studies comparing cardiac biomarker levels in survivors versus non-survivors were included. A total of 14 studies (3175 patients) were utilized for the final analysis. Cardiac 2 injury in patients with COVID-19 was associated with higher risk of mortality [RR:7.79 ; 95%CI: 4.69-13.01; I2 =58%], ICU admission [RR: 4.06; 95% CI: 1.50-10.97; I2 =61%], mechanical ventilation [RR: 5.53; 95% CI: 3.09-9.91; I2 =0%], and developing coagulopathy [RR: 3.86 ; 95% CI:2.81-5.32; I2 =0%]. However, cardiac injury was not associated with increased risk of ARDS [RR:3.22; 95% CI:0.72-14.47; I2 =73%] or AKI [RR:11.52, 95% CI:0.03-4159.80; I2 =0%]. The levels of hs-cTnI [MD:34.54 pg/ml; 95% CI: 24.67- 44.40 pg/ml; I2 =88%], myoglobin [MD:186.81 ng/ml; 95% CI: 121.52-252.10 ng/ml; I2 =88%], NT-pro BNP [MD:1183.55 pg/ml; 95% CI: 520.19-1846.91 pg/ml: I2 =96%] and CK-MB [MD:2.49 ng/ml; 95% CI: 1.86-3.12 ng/ml; I2 =90%], were significantly elevated in nonsurvivors compared with survivors with COVID-19 infection. The results of this meta-analysis suggest that cardiac injury is associated with higher mortality, ICU admission, mechanical ventilation and coagulopathy in patients with COVID-19.
Prognostic Impact of Prior Heart Failure in Patients Hospitalized With COVID-19
Journal of the American College of Cardiology, November 17, 2020
Patients with pre-existing heart failure (HF) are likely at higher risk for adverse outcomes in coronavirus disease-2019 (COVID-19), but data on this population are sparse. OBJECTIVES This study described the clinical profile and associated outcomes among patients with HF hospitalized with COVID-19. This study conducted a retrospective analysis of 6,439 patients admitted for COVID-19 at 1 of 5 Mount Sinai Health System hospitals in New York City between February 27 and June 26, 2020. Clinical characteristics and outcomes (length of stay, need for intensive care unit, mechanical ventilation, and in-hospital mortality) were captured from electronic health records. For patients identified as having a history of HF by International Classification of Diseases-9th and/or 10th Revisions codes, manual chart abstraction informed etiology, functional class, and left ventricular ejection fraction (LVEF). Mean age was 63.5 years, and 45% were women. Compared with patients without HF, those with previous HF experienced longer length of stay (8 days vs. 6 days; p < 0.001), increased risk of mechanical ventilation (22.8% vs. 11.9%; adjusted odds ratio: 3.64; 95% confidence interval: 2.56 to 5.16; p < 0.001), and mortality (40.0% vs. 24.9%; adjusted odds ratio: 1.88; 95% confidence interval: 1.27 to 2.78; p ¼ 0.002). Outcomes among patients with HF were similar, regardless of LVEF or renin-angiotensin-aldosterone inhibitor use.
Response to: How important is the assessment of soluble ACE-2 in COVID-19?
American Journal of Hypertension, November 17, 2020
The role of angiotensin converting enzyme 2 (ACE2) in coronavirus disease 2019 (COVID19) is matter of debate, because severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) utilizes ACE2 on host cells as its entry receptor. We recently reported that activity of the renin-angiotensin-aldosterone system and expression of ACE2 were not changed in patients with non-severe COVID-19 as compared to SARS-CoV-2 negative control subjects with similar symptoms. Rojas and collaborators expand this view and demonstrate that ACE2 expression is likewise unaltered in patients with more severe COVID-19 (sequential organ failure assessment score 2.043; 4C mortality score 6.174) as compared to recovered COVID-19 patients or a historic control group.3 Noteworthy, the authors found no correlation of ACE2 levels and viral load. ACE2 is a peptidase that mediates the breakdown of angiotensin II. The full-length form of ACE2 contains an extracellular catalytic domain, a structural transmembrane domain, and a small intracellular C-terminal domain. After binding of SARS-CoV-2 to the extracellular domain of membrane-bound ACE2, the virus/protein complex is internalized by the host cell. Accordingly, the affection of multiple organs in COVID-19 might be explained by the wide expression of ACE2 in different tissues, including lung, heart, kidney, or intestine. In contrast, the soluble form of ACE2 may bind SARS-CoV-2, but is not internalized due to the lack of the transmembrane domain.
Impact of COVID-19 Pandemic on Mechanical Reperfusion for Patients With STEMI
Journal of the American College of Cardiology, November 17, 2020
The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality. The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of “at-risk” patient cohorts for failure to present or delays to treatment. This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020. Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality. A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p < 0.0001). The heterogeneity among centers was not related to the incidence of death due to COVID-19. A significant interaction was observed for patients with arterial hypertension, who were less frequently admitted in 2020 than in 2019. Furthermore, the pandemic was associated with a significant increase in door-to-balloon and total ischemia times, which may have contributed to the higher mortality during the pandemic.
Cardiac catheterizations declined during COVID-19 surge at New York center
Helio | Cardiology Today, November 16, 2020
In a single-center analysis, cardiac catheterization procedures decreased during a 6-week period of the COVID-19 lockdown compared with the same span in 2019, researchers reported. However, outcomes not attributed to COVID-19 were no different during the lockdown compared with the year before at Montefiore Medical Center in Bronx, New York, according to the researchers. “We hypothesized that the COVID-19 pandemic postponed patients’ decision to seek hospital medical attention, leading to increased cardiovascular-related mortality and infrequent cardiovascular complications,” Cristina Sanina, MD, clinical fellow in cardiology at Montefiore Medical Center and Albert Einstein College of Medicine, said during a presentation at the virtual American Heart Association Scientific Sessions. Results showed a significant decrease in incidence of the outcomes of interest overall (P < .05) for the period in 2020. Cardiac catheterization procedures for non-STEMI decreased from 37 in 2019 to nine in 2020 (P = .002). “We treated a very small number of patients with non-STEMI in 2020,” Sanina said. Importantly, the mortality rates for non-STEMI were 0% in both 2019 and 2020. Similarly, 58 patients were treated with cardiac catheterization for congestive HF in 2019, whereas just 18 underwent this procedure in 2020 (P < .0001). “More patients were admitted in 2020 for systolic heart failure and not diastolic,” Sanina said. The mortality rate from HF in 2020 was 22%, according to Sanina. “It was an extremely high rate,” she said.
COVID-19 vaccine developed by Moderna, NIH is 94.5% effective, early data show
Helio | Infectious Disease News, November 16, 2020
An interim review of phase 3 data showed that a COVID-19 vaccine codeveloped by Moderna Inc. and the NIH had an efficacy rate of 94.5% with no significant safety concerns, Moderna said. The efficacy and safety data were reported by an NIH-appointed data safety monitoring board and were based on 95 cases of COVID-19, of which 90 occurred in the placebo group vs. five in the vaccine group. These included 11 cases of severe COVID-19 — all in the placebo group. The announcement was more good news for COVID-19 vaccine programs following Pfizer and BioNTech’s announcement last week that its mRNA vaccine candidate was shown to be more than 90% effective based on interim phase 3 data. “Since the vaccines are very, very similar, we can conclude that repeating the experiment led to the same outcome, which increases confidence,” Florian Krammer, PhD, a professor of vaccinology at the Icahn School of Medicine at Mount Sinai in New York, told Healio.
The second life of the ambiguous angiotensin-converting enzyme 2 as a predictive biomarker for cardiometabolic diseases and death
European Heart Journal, November 16, 2020
This nested case-cohort analysis from the multinational Prospective Urban Rural Epidemiology (PURE) study analyzed plasma levels of a component of the renin-angiotensin system (RAS), angiotensin-converting enzyme 2 (ACE2), as a predictor of cardiovascular (CV) events [CV mortality, myocardial infarction (MI), stroke, heart failure (HF)] and all-cause mortality. From a total population of 55 246 PURE participants from 14 countries across five continents, the authors took a random sample (the subcohort). The final sample consisted of participants who were members of the subcohort (n = 5084) and those who had incident events outside the subcohort (n = 5669). The median follow-up was 9.4 years (IQR, 8.7–10.5). The strongest determinants of ACE2 concentrations were sex, geographic ancestry, and body-mass index (BMI). When compared with CV risk factors (diabetes, BMI, smoking status, non-HDL cholesterol, and systolic blood pressure), plasma ACE2 was the highest-ranked predictor of all-cause mortality [hazard ratio (HR) 1.35 per 1 SD increase (95% confidence interval (CI) 1.29–1.43)], with similar HR values fort CV death (1.40 per 1 SD increase) and non-CV death (1.34 per 1 SD increase); the third-highest ranked predictor of MI, and the third-highest ranked predictor of both stroke and HF. Plasma ACE2 concentration was also associated with higher risk of diabetes [HR 1.44 per 1SD increase (95% CI 1.36–1.52)]. These results were confirmed after adjustment for clinical risk factors, age, sex, and ancestry.
Decreased admissions and change in arrival mode in patients with cerebrovascular events during the first surge of the COVID-19 pandemic
Neurological Research and Practice, November 16, 2020
[Letter to the Editor] Declining rates of admissions for cerebrovascular events (CVEs) and an impact on reperfusion therapy rates were observed during the first surge of the coronavirus disease 2019 (COVID-19) pandemic earlier this year. Given the current increase in the number of COVID-19 cases and an incipient second wave, it is paramount to take appropriate measures to prevent this particular aspect of recent history from repeating. Obtaining detailed demographic and clinical information of patients presenting with CVEs during the pandemic may provide valuable information to this end.We analyzed data of patients admitted for CVEs (transient ischemic attack (TIA), ischemic stroke, intracerebral hemorrhage) to the Department of Neurology, University Medical Centre Mannheim, Germany, in weeks 1–17/2020. Week 12/2020, when extended measures for social distancing were implemented, was designated as the beginning of the COVID-19 epoch. Poisson regression was used to test if the rate of admissions and reperfusion therapies for ischemic stroke changed as a function of year, epoch and year-by-epoch interaction (reflecting the impact of the pandemic). We found a significant reduction of the number of admissions due to a CVE during the COVID-19 epoch by 35.9% (rate ratio 0.64, 95% confidence interval (CI) 0.43–0.96, p = 0.005). During the observational period of 2019 and 2020, 115 and 69 CVE patients, respectively, presented. The number of reperfusion therapies decreased non-significantly by 27.8% (rate ratio 0.72, 95% CI 0.44–1.19, p = 0.20): 23 intravenous thrombolyses (IVT) were performed in 2019, 11 in the respective period in 2020. Mechanical thrombectomy (with/without IVT), was performed in 9 and 8 patients, respectively.
Large-Scale Plasma Analysis Revealed New Mechanisms and Molecules Associated with the Host Response to SARS-CoV-2
International Journal of Molecular Sciences, November 16, 2020
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every continent, registering over 1,250,000 deaths worldwide. The effects of SARS-CoV-2 on host targets remains largely limited, hampering our understanding of Coronavirus Disease 2019 (COVID-19) pathogenesis and the development of therapeutic strategies. The present study used a comprehensive untargeted metabolomic and lipidomic approach to capture the host response to SARS-CoV-2 infection. We found that several circulating lipids acted as potential biomarkers, such as phosphatidylcholine 14:0_22:6 (area under the curve (AUC) = 0.96), phosphatidylcholine 16:1_22:6 (AUC = 0.97), and phosphatidylethanolamine 18:1_20:4 (AUC = 0.94). Furthermore, triglycerides and free fatty acids, especially arachidonic acid (AUC = 0.99) and oleic acid (AUC = 0.98), were well correlated to the severity of the disease. An untargeted analysis of non-critical COVID-19 patients identified a strong alteration of lipids and a perturbation of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, aminoacyl-tRNA degradation, arachidonic acid metabolism, and the tricarboxylic acid (TCA) cycle. The severity of the disease was characterized by the activation of gluconeogenesis and the metabolism of porphyrins, which play a crucial role in the progress of the infection. In addition, our study provided further evidence for considering phospholipase A2 (PLA2) activity as a potential key factor in the pathogenesis of COVID-19 and a possible therapeutic target.
Canakinumab fails to improve outcomes at 14 days in COVID-19, myocardial injury
Helio | Cardiology Today, November 15, 2020
In a new study, interleukin-1-beta inhibition with IV canakinumab in patients hospitalized with COVID-19, myocardial injury and elevated inflammation markers did not appear to improve clinical recovery at 14 days. However, there was a trend toward clinical improvement at 28 days among patients who received higher-dose canakinumab (Ilaris, Novartis) compared with placebo, according to results of the Three C trial presented at the virtual American Heart Association Scientific Sessions. “Although COVID-19 is predominantly a respiratory illness, cardiovascular complications result in substantial morbidity and mortality,” Paul Cremer, MD, cardiologist at Cleveland Clinic, said. “Myocardial injury [may] occur in as many as one-third of patients hospitalized with severe COVID-19 infection. Myocardial injury is also associated with higher mortality and an increased systemic inflammatory response … [which may] result in a so-called cytokine storm. In the cardiovascular system, the consequences are predominantly endothelial cell dysfunction with capillary leak, thrombosis and local tissue injury. Canakinumab is an anti-inflammatory drug. In the CANTOS trial, canakinumab was shown to reduce recurrent CV events in patients with prior MI and elevated C-reactive protein levels.
BP control, frequency of measurements minimally impacted during COVID-19 pandemic
Helio | Cardiology Today, November 14, 2020
The number of BP readings performed by adults in a home BP management program and overall BP control were not impacted during the COVID-19 pandemic compared with data from 2019, according to new reserch. “In a nationwide sample of patients enrolled in a home BP management program, contrary to my initial beliefs, we did not see huge changes in either the number of [BP] readings being done — not a huge increase or decrease — [and] that BP control was similar, or even slightly better, in the COVID-19 period, rather than pre-COVID-19,” Eric D. Peterson, MD, MPH, distinguished professor at the Duke Clinical Research Institute, said during a presentation at the virtual American Heart Association Scientific Sessions. Peterson and colleagues assessed how quarantines and lockdowns during the COVID-19 pandemic impacted home BP readings at both the individual patient and population levels and also compared BP levels during before and during the pandemic. “Beyond its direct effects on morbidity and mortality, COVID-19 has also reduced our patients’ ability to see us in clinic,” Peterson said. He noted that these indirect effects of the pandemic could have long-lasting consequences. “For example, if prevention of cardiovascular disease risk factors were to fall off, then there may be large downstream effects that will be seen for years to come.”
‘Corona’ versus ‘coronary’: The similarities and differences of CORONA virus and Coronary Artery Diseases are presented and discussed.
European Heart Journal, November 14, 2020
Both COVID-19 and CVD predominantly affect the elderly but can also occur in the young. Both are present worldwide. Both are the consequences of drastic cultural and social changes and ways of living. Both affect the whole society rather than a single individual but with a difference. COVID-19 is a communicable disease, and its outbreak requires immediate and drastic measures, such as a population lockdown along with all the related consequences including the economic crisis that will follow. This, of course, is immediately perceived by the whole society. The same is not true for CVD, which is perceived as a disease of a single person rather than a global problem although it is even a bigger global problem than COVID-19. Governments do not impose drastic measures to reduce the known causes of CVD. They simply suggest to patients how to prevent CVD. Paradoxically, measures to reduce risk factors for diabetes, obesity, and hypertension are less drastic than a lockdown and yet, would save significantly more lives! The question is: why? Why are people more worried about COVID-19 than a CVD epidemic or other more deadly diseases? Mainly for three reasons: habits, knowledge, and care.
Myocardial Injury in Severe COVID-19 Compared to Non-COVID Acute Respiratory Distress Syndrome
Circulation, November 13, 2020
Knowledge gaps remain in the epidemiology and clinical implications of myocardial injury in COVID-19. Our goal was to determine the prevalence and outcomes of myocardial injury in severe COVID-19 compared to acute respiratory distress syndrome (ARDS) unrelated to COVID-19. We included intubated COVID-19 patients from 5 hospitals between March 15 and June 11, 2020 with troponin levels assessed. We compared them to patients from a cohort study of myocardial injury in ARDS. We performed survival analysis with primary outcome of in-hospital death associated with myocardial injury. We performed linear regression to identify clinical factors associated with myocardial injury in COVID-19. Of 243 patients intubated with COVID-19, 51% had troponin levels > upper limit of normal (ULN). Chronic kidney disease, lactate, ferritin and fibrinogen were associated with myocardial injury. Mortality was 22.7% among COVID-19 patients with troponin < ULN and 61.5% for those with troponin levels > 10xULN (P< 0.001). The association of myocardial injury with mortality was not statistically significant after adjusting for age, sex and multi-system organ dysfunction. Compared to non-COVID ARDS patients, patients with COVID-19 were older with higher creatinine and less favorable vital signs. After adjustment, COVID-19 was associated with lower odds of myocardial injury compared to non-COVID ARDS (OR 0.55 95% CI 0.36-0.84, P=0.005).
Fatal SARS-CoV-2 Inflammatory Syndrome and Myocarditis in an Adolescent: A Case Report
The Pediatric Infectious Disease Journal, November 13, 2020
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), an entity in children initially characterized by milder case presentations and better prognoses as compared with adults. Recent reports, however, raise concern for a new hyperinflammatory entity in a subset of pediatric COVID-19 patients. METHODS: We report a fatal case of confirmed COVID-19 with hyperinflammatory features concerning for both multi-inflammatory syndrome in children (MIS-C) and primary COVID-19. RESULTS: This case highlights the ambiguity in distinguishing between these two entities in a subset of pediatric patients with COVID-19-related disease and the rapid decompensation these patients may experience. CONCLUSIONS: Appropriate clinical suspicion is necessary for both acute disease and MIS-C. SARS-CoV-2 serologic tests obtained early in the diagnostic process may help to narrow down the differential but does not distinguish between acute COVID-19 and MIS-C. Better understanding of the hyperinflammatory changes associated with MIS-C and acute COVID-19 in children will help delineate the roles for therapies, particularly if there is a hybrid phenotype occurring in adolescents.
Cardiology Update 20 India: An Indo-European Online Experience for more than 7000 participants in 2020
European Heart Journal, November 13, 2020
During Covid times, education is more difficult because face-to-face meetings are almost impossible; particularly, in countries where a first or second wave has occurred recently or is about to occur. Unfortunately, India, where a Cardiology Update Course was held in Mumbai in 2019 with over 700 participants, was severely hit by Covid-19 recently. Indeed, in mid-September India had almost 6 million infected individuals and over 91 000 deaths to deplore. Therefore, a face-to-face post-graduate course was clearly impossible. Furthermore, many eminent faculty members are currently unable to travel, particularly those from the USA and the UK. As such, it was decided to run the Cardiology Update 20 India—similar to the ESC 2020 Congress as a fully online course with shorter talks over two afternoons on 19 and 20 September 2020. Importantly, panel discussion was assigned half an hour and hence was longer than usual. The course was run by distinguished chairpersons, shortened to allow for the online format and consisted of four sessions over two afternoons on Saturday and Sunday 19 and 20 September. Read more about the session topics: Prevention, Coronary Artery Disease, Cardiovascular Disease and Cardiometabolic Disorders.
Electrocardiographic Findings and Clinical Outcome in Patients with COVID-19 or Other Acute Infectious Respiratory Diseases
Journal of Clinical Medicine, November 12, 2020
Cardiac involvement in coronavirus SARS-CoV-2 infection (COVID-19) has been reported in a sizeable proportion of patients and associated with a negative outcome; furthermore, a pre-existing heart disease is associated with increased mortality in these patients. In this prospective single-center case-control study we investigated whether COVID-19 patients present different rates and clinical implications of an abnormal electrocardiogram (ECG) compared to patients with an acute infectious respiratory disease (AIRD) caused by other pathogens. We studied 556 consecutive patients admitted to the emergency department of our hospital with symptoms of AIRD; 324 were diagnosed to have COVID-19 and 232 other causes of AIRD (no-COVID-19 group). Standard 12-lead ECG performed on admission was assessed for various kinds of abnormalities, including ST segment/T wave changes, atrial fibrillation, ventricular arrhythmias, and intraventricular conduction disorders. ECG abnormalities were found in 120 (37.0%) and 101 (43.5%) COVID-19 and no-COVID-19 groups, respectively (p = 0.13). No differences in ECG abnormalities were found between the 2 groups after adjustment for clinical and laboratory variables. During a follow-up of 45 ± 16 days, 51 deaths (15.7%) occurred in the COVID-19 and 30 (12.9%) in the no-COVID-19 groups (p = 0.39). ST segment depression ≥ 0.5 mm (p = 0.016), QRS duration (p = 0.016) and presence of any ECG abnormality (p = 0.027) were independently associated with mortality at multivariable Cox regression analysis.
Amiodarone in COVID-19: let’s not forget its potential for pulmonary toxicity
European Journal of Preventive Cardiology, November 12, 2020
[Letter to the Editor] Aimo et al. presented an elegant review of the antiviral mechanism of amiodarone, which is a commonly used antiarrhythmic drug. Although in vitro experiments demonstrated the ability of amiodarone to inhibit coronavirus, we are still wary of the authors’ recommendation to evaluate amiodarone for the treatment of coronavirus disease 2019 (COVID-19) in clinical trials. In fact, when authors commented that amiodarone has been used for decades in a large number of patients for its safety profile to be well-known, authors should have acknowledged the notorious potential for amiodarone to induce pulmonary toxicity. It has been hypothesized that amiodarone may sensitize patients to high concentrations of inspired oxygen since the accumulation of amiodarone in the lysosomes of macrophages results in destabilization of their membranes and release of free oxygen radicals. The mortality rate of patients in whom ARDS developed due to amiodarone could approach 50%, which is higher than that of patients with COVID-19 related ARDS (39% as reported in a meta-analysis). Therefore, it may be worth to wait for observational studies to report outcomes in COVID-19 patients who have received chronic treatment with amiodarone for its established indications before a recommendation to repurpose amiodarone for the treatment of COVID-19. In addition, dronedarone, which is a non-iodinated congener of amiodarone with a better safety profile, may worth for more evaluation on its antiviral activity against SARS-CoV-2.
Effects of COVID-19 lockdown on heart rate variability
PLOS ONE, November 12, 2020
Strict lockdown rules were imposed to the French population from 17 March to 11 May 2020, which may result in limited possibilities of physical activity, modified psychological and health states. This report is focused on HRV parameters kinetics before, during and after this lockdown period. 95 participants were included in this study (27 women, 68 men, 37 ± 11 years, 176 ± 8 cm, 71 ± 12 kg), who underwent regular orthostatic tests (a 5-minute supine followed by a 5-minute standing recording of heart rate (HR)) on a regular basis before (BSL), during (CFN) and after (RCV) the lockdown. HR, power in low- and high-frequency bands LF, HF, respectively) and root mean square of the successive differences (RMSSD) were computed for each orthostatic test, and for each position. Subjective well-being was assessed on a 0–10 visual analogic scale (VAS). The participants were split in two groups, those who reported an improved well-being (WB+, increase >2 in VAS score) and those who did not (WB-) during CFN. Out of the 95 participants, 19 were classified WB+ and 76 WB-. There was an increase in HR and a decrease in RMSSD when measured supine in CFN and RCV, compared to BSL in WB-, whilst opposite results were found in WB+ (i.e. decrease in HR and increase in RMSSD in CFN and RCV; increase in LF and HF in RCV). When pooling data of the three phases, there were significant correlations between VAS and HR, RMSSD, HF, respectively, in the supine position; the higher the VAS score (i.e., subjective well-being), the higher the RMSSD and HF and the lower the HR. In standing position, HRV parameters were not modified during CFN but RMSSD was correlated to VAS.
AHA 2020 topics: Systemic racism, novel research, COVID-19 discussion with Fauci
Helio | Cardiology Today, November 11, 2020
Trials of novel medications and conversations on systemic racism and the ongoing COVID-19 pandemic are set to be featured at the virtual American Heart Association Scientific Sessions, which start Friday. The conference, which will run until Tuesday, will feature a talk by Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, on the CV implications of the ongoing global pandemic. One late-breaker to be presented is the phase 3 GALACTIC-HF trial. This study evaluated the effect of omecamtiv mecarbil (Amgen/Cytokinetics) in patients with HF with reduced ejection fraction. Also being presentedare the results from the AFFIRM-AHF trial, which evaluated the use of iron supplementation in patients who present with HFrEF and are also iron-deficient at the time of hospitalization. The VITAL Rhythm trial, a follow-up to the VITAL trial presented at the 2019 AHA Scientific Sessions, analyzed the impact of vitamin D, low-dose fish oil or both on initial atrial fibrillation events. As Healio previously reported, interventions with vitamin D or omega-3 did not reduce rates of first HF hospitalization among healthy adults, but researchers noted a benefit in recurrent HF hospitalization in those on fish oil supplementation.
An increase in acute heart failure offsets the reduction in acute coronary syndrome during coronavirus disease 2019 (COVID‐19) outbreak
ESC Heart Failure, November 11, 2020
[Letter to the Editor] There are worldwide reports about an unexplained decline in the frequency of acute coronary syndrome (ACS) during the present coronavirus disease 2019 (COVID‐19) pandemic. Public health interventions to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and a particular concern of infections within the elderly population and those with pre‐existing co‐morbidities might have raised the threshold to seek medical attention in case of a cardiovascular emergency. Avoidance or delayed medical contact in case of ACS could result in significant consequential damage including cardiogenic shock. The aim of the present investigation was to determine changes in both the frequency of ACS and sequels of not‐adequately treated ACS during the COVID‐19 pandemic. In a population‐based prospective registry, patients receiving medical care via the Emergency Medical Service of the city of Vienna for ACS (ST‐elevation myocardial infarction, n = 282; and non‐ST‐elevation myocardial infarction, n = 123) were analysed during the COVID‐19 pandemic (March 13–10 April 2020) and compared with two time periods: immediately before the outbreak (1–28 February 2020) and the corresponding period in 2019 (13 March–10 April). ACS cases decreased significantly compared with those in the time period before the outbreak and in 2019 (P = 0.001). Time trends show an inverse association with increasing numbers of new COVID‐19 cases. Of note, parallel to the decline in ACS—with a delay of about 2 weeks—an increase of ACS patients presenting with acute heart failure was observed as compared with both of the control periods in 2020 (from 6.9% to 23.7%, P 60; 0.001) and in 2019 (from 13.1% to 23.7%, P 60; 0.001).
The Experience of a Plasma Donor: A cardiologist discusses the emotions of donating plasma to a fellow human being during this COVID-19 pandemic
European Heart Journal, November 11, 2020
A 50-year-old obese male with COVID, diabetes, and hypertension was transferred from an outside hospital with shortness of breath. He had been in this hospital for the past 2 days, but his clinical status had deteriorated. He was now on a ventilator in the ICU but still not saturating well. Several hours earlier, his nephew had contacted me and I could snse the hope and desperation in his voice.
It was a Sunday, and I walked into the hospital wearing my street clothes covered by protective clothing that we medical professionals are so used to nowadays. I had never met the nephew before and until a few hours ago neither of us knew we even existed. He had received my information from a registry. As I walked into the hospital, I felt different—this was not my hospital! We were supposed to meet at the side entrance close to the blood bank and he leapt with joy as he saw me walking in. As we talked, he became teary and said—‘Thank you so much for coming doctor, your plasma may be what will cure him’.I did not go to the hospital in the capacity of a doctor to provide treatment but as a donor—A Plasma Donor. This is not about diagnostic skills. This is not about intelligence, problem-solving, or clinical experience. This is about being supportive of another human being during these tough times. In a pandemic, we are all in this together. Read more about the experience.
Cardiac damage in patients with the severe type of coronavirus disease 2019 (COVID-19)
BMC Cardiovascular Disorders, November 10, 2020
Coronavirus disease 2019 (COVID-19) has become a global pandemic. Studies showed COVID-19 affected not only the lung but also other organs. In this study, we aimed to explore the cardiac damage in patients with COVID-19. We collected data of 100 patients diagnosed as severe type of COVID-19 from February 8 to April 10, 2020, including demographics, illness history, physical examination, laboratory test, and treatment. In-hospital mortality were observed. Cardiac damage was defined as plasma hypersensitive troponin I (hsTnI) over 34.2 pg/ml and/or N-terminal-pro brain natriuretic peptide (NTproBNP) above 450 pg/ml at the age < 50, above 900 pg/ml at the age < 75, or above 1800 pg/ml at the age ≥ 75. The median age of the patients was 62.0 years old. 69 (69.0%) had comorbidities, mainly presenting hypertension, diabetes, and cardiovascular disease. Fever (69 [69.0%]), cough (63 [63.0%]), chest distress (13 [13.0%]), and fatigue (12 [12.0%]) were the common initial symptoms. Cardiac damage occurred in 25 patients. In the subgroups, hsTnI was significantly higher in elder patients (≥ 60 years) than in the young (median [IQR], 5.2 [2.2–12.8] vs. 1.9 [1.9–6.2], p = 0.018) and was higher in men than in women (4.2 [1.9–12.8] vs. 2.9 [1.9–7.4], p = 0.018). The prevalence of increased NTproBNP was significantly higher in men than in women (32.1% vs. 9.1%, p = 0.006), but was similar between the elder and young patients (20.0% vs. 25.0%, p = 0.554). After multivariable analysis, male and hypertension were the risk factors of cardiac damage. The mortality was 4.0%.
Impact of Prior Heart Failure on Hospitalized COVID-19 Patients
American College of Cardiology, November 9, 2020
This study questions, among patients with a prior diagnosis of heart failure (HF), what are the clinical outcomes during and immediately following hospitalization for coronavirus disease (COVID-19)? The retrospective cohort study included consecutive adult patients hospitalized with COVID-19 at five sites within the Mount Sinai Healthcare System in New York City. International Classification of Diseases, 9th and/or 10th Revision (ICD-9/10) codes were used to identify patients with a prior diagnosis of HF. Manual chart review was performed for all HF patients to collect data such as HF etiology and left ventricular ejection fraction (LVEF). Clinical outcomes of interest included in-hospital mortality, mechanical ventilation, intensive care unit (ICU) admission, length of stay (LOS), and 30-day readmission rate. A total of 6,439 patients were included (mean age 63.5 years, 45% women, 17.1% requiring ICU care, 12.6% mechanically ventilated), and 422 (6.6%) had a history of HF. Patients with HF were older (mean age 72.5 vs. 62.9 years, p < 0.001). Prevalence of major comorbidities such as obesity, hypertension, diabetes mellitus, atrial fibrillation, and chronic kidney disease was higher in the HF group (all p < 0.001). Median LOS for the HF group was 8 days, as compared with 6 days for the overall cohort. Based on a multivariable logistic regression model, HF was shown to be independently associated with ICU admission (adjusted odds ratio [OR], 1.71; 95% confidence interval [CI], 1.25-2.34; p = 0.001), mechanical ventilation (OR, 3.64; 95% CI, 2.56-5.16; p < 0.001), and in-hospital mortality (OR, 1.88; 95% CI, 1.27-2.78; p = 0.002). In analyses of HF patients stratified by LVEF, there were no significant differences in LOS, ICU admission, mechanical ventilation, or 30-day readmission rates.
The outcomes of the postulated interaction between SARS-CoV-2 and the renin-angiotensin system on the clinician’s attitudes toward hypertension treatment
Journal of Human Hypertension, November 9, 2020
Concern has arisen about the role played in coronavirus disease 2019 (COVID-19) infection by angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). This study was designed to assess the practice behaviors of physicians toward hypertension treatment with ACE-i or ARBs during the COVID-19 pandemic. A self-administered survey questionnaire consisting of 26 questions about current hypertension treatment with ACE-i/ ARBs was applied to cardiologists, internists, and family physicians in central and western Turkey, between 01 and 19 May 2020. A total of 460 physicians were approached, and 220 (47.8%) participated in the study. Of the total respondents, 78.7% reported that they had not changed their antihypertensive medication prescribing pattern, 8.6% of clinicians had changed ACE-i/ ARBs medicine of patients during the COVID-19 pandemic and 12.7% of them were undecided. The median (±interquartile range) score indicating general reliance level of physicians in ACE-i/ARBs therapy was 8 ± 4 (range, 1–10). In multiple comparison analyses, the general reliance level in ACE-i/ARBs, reliance level when starting a new ACEi/ARBs and changing behavior in heart failure patients were significantly different with regard to the specialties (p:0.02, p:0.009, p:0.005 respectively). Although most of the physicians found the publications about ACE-i/ ARBs during the COVID-19 pandemic untrustworthy, there were variable levels of knowledge and reliance among different physicians and specialty groups. In general, the ACE-i/ ARBs prescribing habits were not affected by safety concerns during the COVID-19 pandemic in Turkey.
A cohort study of 676 patients indicates D-dimer is a critical risk factor for the mortality of COVID-19
PLOS ONE, November 9, 2020
Coronavirus Disease 2019 (COVID-19) has recently become a public emergency and a worldwide pandemic. However, the information on the risk factors associated with the mortality of COVID-19 and of their prognostic potential is limited. In this retrospective study, the clinical characteristics, treatment and outcome data were collected and analyzed from 676 COVID-19 patients stratified into 140 non-survivors and 536 survivors. We found that the levels of Dimerized plasmin fragment D (D-dimer), C-reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin (PCT) were significantly higher in non-survivals on admission (non-survivors vs. survivors: D-Dimer ≥ 0.5 mg/L, 83.2% vs. 44.9%, P<0.01; CRP ≥10 mg/L, 50.4% vs. 6.0%, P <0.01; LDH ≥ 250 U/L, 73.8% vs. 20.1%, P <0.01; PCT ≥ 0.5 ng/ml, 27.7% vs. 1.8%, P <0.01). Moreover, dynamic tracking showed D-dimer kept increasing in non-survivors, while CRP, LDH and PCT remained relatively stable after admission. D-dimer has the highest C-index to predict in-hospital mortality, and patients with D-dimer levels ≥0.5 mg/L had a higher incidence of mortality (Hazard Ratio: 4.39, P<0.01). Our study suggested D-dimer could be a potent marker to predict the mortality of COVID-19, which may be helpful for the management of patients.
COVID-19 vaccine more than 90% effective, Pfizer says
Helio | Infectious Disease News, November 9, 2020
A vaccine candidate developed by Pfizer and BioNTech was more than 90% effective in preventing COVID-19 and showed no serious safety concerns, according to an interim analysis of phase 3 clinical trial results released by the companies. Pfizer and BioNTech said they plan to submit the mRNA-based vaccine candidate, now called BNT162b2, to the FDA for an emergency use authorization after a required safety milestone is met, likely in the third week of November. The analysis, which was conducted by an external and independent data monitoring committee, evaluated 94 confirmed cases of COVID-19 among more than 43,000 participants enrolled in the global trial, including more than 38,000 who have received two doses of the vaccine candidate. Around 42% of participants globally and 30% in the United States are from racially and ethnically diverse backgrounds, the companies said. At 7 days after the second dose, the vaccine was more than 90% effective compared with placebo among participants with no prior exposure to SARS-CoV-2. “This means that protection is achieved 28 days after the initiation of the vaccination, which consists of a 2-dose schedule. As the study continues, the final vaccine efficacy percentage may vary,” the companies said.
Elevated Troponin and Mortality Risk in Patients Hospitalized With COVID-19
Pulmonary Advisor, November 9, 2020
Patients who are hospitalized with coronavirus disease 2019 (COVID-19) and have an elevated vs normal troponin levels were found to be at higher risk for death, according to a study published in the American Journal of Cardiology. Researchers reviewed data for all patients with COVID-19 who were admitted to hospitals within the Northwell Health system in New York between March 1, 2020 and April 27, 2020, and had a troponin assessment within 48 hours of admission. They used logistic regression to calculate odds ratios (ORs) for mortality during hospitalization and controlled for demographic factors, comorbidities, and inflammation markers. The researchers suggested that multiple mechanisms of myocardial injury may be associated with COVID-19, including injury related to inflammation and cytokine storm, direct viral-mediated injury, hypoxic respiratory failure, downregulation of angiotensin-converting enzyme 2 receptors, hypercoagulability, diffuse myocardial endothelial injury, and acute plaque rupture. “While we did not measure changes in troponin over time, elevations in troponin likely reflected imbalance between myocardial oxygen supply and demand,” noted the investigators. “However, direct myocardial involvement cannot be excluded and myocarditis associated with COVID-19 remains poorly defined.”
Studies find mixed results for tocilizumab to treat COVID-19
Helio | Infectious Diseases, November 9, 2020
Three studies recently published in JAMA Internal Medicine evaluated the effects of tocilizumab against COVID-19. The studies were conducted in the United States, France and Italy, and all involved patients who were hospitalized with COVID-19. In an editorial accompanying the studies, Jonathan B. Parr, MD, MPH, assistant professor of medicine in the division of infectious diseases at the University of North Carolina School of Medicine, wrote that the “newly released randomized trials suggest a potential role for tocilizumab in COVID-19 but do not show clear evidence of efficacy, in contrast to observational studies.”
Infectious endocarditis of the prosthetic mitral valve after COVID-19 infection
European Heart Journal, November 7, 2020
A 24-year-old male, known case of rheumatic heart disease, who had undergone mechanical mitral valve replacement 4 years ago, was referred to our echocardiography laboratory, due to fever, chills, and severe anorexia, 3 weeks after being discharged due to COVID-19 infection. He had been diagnosed due to a chest X-ray suggestive of viral pneumonia and a positive RT–PCR for SARS-COV-2. On admission, he was febrile (38°C), had tachycardia (heart rate: 100/min), and a normal oxygen saturation in room air and his electrocardiogram displayed sinus tachycardia. Due to a high suspicion of infectious endocarditis (IE) on echocardiographic examination, a transoesophageal echocardiogram was performed, which revealed several typical vegetations on the posterior prosthetic mitral valve leaflet. His previous echocardiogram had demonstrated normal functioning mitral valve prosthesis and a left ventricular ejection fraction of 45%. Blood culture results came back positive for Staphylococcus aureus. Other noticeable laboratory tests included leucocytosis and an elevated C-reactive protein (72 mg/L, normal level <3). Patient was treated with Azithromycin, Hydroxychloroquine, and corticosteroids and was discharged 2 weeks later. After 6 weeks of antibiotic treatment, repeated trans-thoracic oesophageal echocardiogram (TEE) displayed healing of the vegetative lesions. Up till now, there has been limited evidence on COVID-19 and IE, but since the process of vegetation development begins through transient bacteraemia, followed by binding of bacteria to damaged endothelium, Coronavirus infection and the systemic inflammation caused by it can be a potential risk factor for IE, particularly in susceptible patients with underlying diseases.
Cardiovascular Active Peptides of Marine Origin with ACE Inhibitory Activities: Potential Role as Anti-Hypertensive Drugs and in Prevention of SARS-CoV-2 Infection
International Journal of Molecular Sciences, November 7, 2020
Growing interest in hypertension—one of the main factors characterizing the cardiometabolic syndrome (CMS)—and anti-hypertensive drugs raised from the emergence of a new coronavirus, SARS-CoV-2, responsible for the COVID19 pandemic. The virus SARS-CoV-2 employs the Angiotensin-converting enzyme 2 (ACE2), a component of the RAAS (Renin-Angiotensin-Aldosterone System) system, as a receptor for entry into the cells. Several classes of synthetic drugs are available for hypertension, rarely associated with severe or mild adverse effects. New natural compounds, such as peptides, might be useful to treat some hypertensive patients. The main feature of ACE inhibitory peptides is the location of the hydrophobic residue, usually Proline, at the C-terminus. Some already known bioactive peptides derived from marine resources have potential ACE inhibitory activity and can be considered therapeutic agents to treat hypertension. Peptides isolated from marine vertebrates, invertebrates, seaweeds, or sea microorganisms displayed important biological activities to treat hypertensive patients. Here, we reviewed the anti-hypertensive activities of bioactive molecules isolated/extracted from marine organisms and discussed the associated molecular mechanisms involved. We also examined ACE2 modulation in sight of SARS2-Cov infection prevention.
ILCOR’s revised Covid-19 defibrillation recommendation requires a new approach to training
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, November 7, 2020
In-hospital resuscitation practices have changed by necessity in the Covid-19 era, principally due to precautions intended to protect caregivers from infection. This has resulted in serious delays in resuscitation response. ILCOR has recently modified its guidelines to separate defibrillation from other interventions, recognizing that shock success is extremely time-dependent and that defibrillation poses relatively little risk of Covid-19 transmission. The new recommendation calls for sending one caregiver into the isolation room in order to initiate bedside monitoring and defibrillate if indicated, while the code team is donning their personal protective equipment. Implementing this change requires focused training in that specific role. This can be accomplished by intensively training a subset of clinical staff to assume the responsibility and act without hesitation when a code occurs. Focused defibrillation training promises to avoid compromising the care of patients experiencing tachyarrhythmic arrests in the setting of Covid-19. Such a training program might even result in better survival than before the pandemic for this subset of patients.
A mutation may have made COVID-19 more contagious
Medical News Today, November 6, 2020
Between March and July 2020, a particular mutation became almost ubiquitous in SARS-CoV-2 infections in Houston, TX. This strongly suggests that it makes the virus more infectious. However, there is no evidence to suggest that it makes the virus any more deadly. Metropolitan Houston reported its first case of COVID-19, which is the illness that develops due to SARS-CoV-2, on March 5, 2020. A week later, the virus was spreading within the community. A previous study found that strains of the virus containing a particular mutation, called G614, caused 71% of cases in Houston in the early phase of this first wave of infections. A follow-up study by the same team now reveals that by summer, during the second wave, this variant accounted for 99.9% of all COVID-19 infections in the area. The researchers at Houston Methodist Hospital — in collaboration with scientists at the University of Texas at Austin and the University of Chicago, IL — discovered that one of these mutations may allow the spike to evade a neutralizing antibody produced by the human immune system. It is unclear whether or not this mutation also increases infectivity. However, the researchers report that it is currently rare and does not appear to make the disease more severe. They also found no evidence to suggest that the virus has acquired mutations that might render either the vaccines in development or existing antibody treatments ineffective. Concluding their report, the authors write, “The findings will help us to understand the origin, composition, and trajectory of future infection waves and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution.”
Long-term sequelae following previous coronavirus epidemics
Clinical Medicine Journal, November 5, 2020
Before the current pandemic, there had been two global epidemics from major coronavirus outbreaks since the turn of the century: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Both epidemics left survivors with fatigue, persistent shortness of breath, reduced quality of life and a significant burden of mental health problems.
It is likely that some of the chronic problems encountered by survivors of SARS and MERS may be relevant for medical planning of the services required for survivors of coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2. Given the similarities between the diseases, the recovery and rehabilitation of the survivors of COVID-19 is likely to be focused around cardiopulmonary sequelae, fatigue and the psychological burden of COVID-19, but in a much larger population.
The Japanese version of the Fear of COVID-19 scale: Reliability, validity, and relation to coping behavior
PLOS ONE, November 5, 2020
COVID-19 is spreading worldwide, causing various social problems. The aim of the present study was to verify the reliability and validity of the Japanese version of the Fear of COVID-19 Scale (FCV-19S) and to ascertain FCV-19S effects on assessment of Japanese people’s coping behavior. After back-translation of the scale, 450 Japanese participants were recruited from a crowdsourcing platform. These participants responded to the Japanese FCV-19S, the Japanese versions of the Hospital Anxiety and Depression scale (HADS) and the Japanese versions of the Perceived Vulnerability to Disease (PVD), which assesses coping behaviors such as stockpiling and health monitoring, reasons for coping behaviors, and socio-demographic variables. Results indicated the factor structure of the Japanese FCV-19S as including seven items and one factor that were equivalent to those of the original FCV-19S. The scale showed adequate internal reliability (α = .87; ω = .92) and concurrent validity, as indicated by significantly positive correlations with the Hospital Anxiety and Depression Scale (HADS; anxiety, r = .56; depression, r = .29) and Perceived Vulnerability to Disease (PVD; perceived infectability, r = .32; germ aversion, r = .29). Additionally, the FCV-19S not only directly increased all coping behaviors (β = .21 – .36); it also indirectly increased stockpiling through conformity reason (indirect effect, β = .04; total effect, β = .31). These results suggest that the Japanese FCV-19S psychometric scale has equal reliability and validity to those of the original FCV-19S. These findings will contribute further to the investigation of various difficulties arising from fear about COVID-19 in Japan.
Cardiac Echoes Reveal COVID’s Toll on the Heart
MedPage Today, November 5, 2020
The goal of this study was to characterize echocardiographic abnormalities associated with myocardial injury and their prognostic impact in patients with COVID-19. This retrospective study suggests utility of TTE in patients with SARS-CoV-2 infection and myocardial injury. Myocardial injury is associated with critical conditions such as myocarditis, pulmonary embolism, heart attack, and heart failure. According to a recent retrospective study, hospitalized patients with COVID-19 and myocardial injury had a broad range of echocardiographic abnormalities that put them at higher risk of in-hospital mortality. Among 305 patients with lab-confirmed SARS-CoV-2 infection who underwent transthoracic echocardiography (TTE) and ECG evaluation, 62.6% had troponin elevations suggestive of myocardial injury (either at hospital admission or later during the hospitalization), reported Gennaro Giustino, MD, of Icahn School of Medicine at Mount Sinai in New York City, and colleagues in the Journal of the American College of Cardiology. These findings expand on previous Mount Sinai research, which showed a correlation between increasing levels of troponin and more heart damage among hospitalized patients with COVID-19. [CME Available]
Characteristics and outcomes of COVID-19-associated stroke: a UK multicentre case-control study
Journal of Neurology, Neurosurgery & Psychiatry, November 5, 2020
Ischemic strokes in COVID-19 patients tended to be more severe than those in other individuals, according to a case-control study from the U.K. Among 86 stroke patients with COVID-19, stroke characteristics and outcomes differed from uninfected stroke patients treated during the same period. The COVID-19-associated strokes:
- Were more likely to involve multiple large vessel occlusions (17.9% vs 8.1%, P<0.03)
- Were more severe (median NIH Stroke Scale score 8 vs 5, P<0.002
- Were associated with higher D-dimer levels (3.4 vs 3.0 ng/ml on the log10 scale, P<0.01
- Resulted in more severe disability on discharge (median modified Rankin Scale score 4 vs 3, P<0.0001
- Resulted in more deaths during index admission (19.8% vs 9.6%, P<0.0001)
Our study provides the most compelling evidence yet that COVID-19-associated ischaemic strokes are more severe and more likely to result in severe disability or death, although the outlook is not quite as bleak as previous studies have suggested. Our results suggest the following recommendations for management of stroke patients during the ongoing COVID-19 pandemic.
Cardiovascular Disease and SARS-CoV-2: the Role of Host Immune Response Versus Direct Viral Injury
LitCovid, November 5, 2020
The 2019 novel coronavirus [2019-nCoV], which started to spread from December 2019 onwards, caused a global pandemic. Besides being responsible for the severe acute respiratory syndrome 2 [SARS-CoV-2], the virus can affect other organs causing various symptoms. A close relationship between SARS-CoV-2 and the cardiovascular system has been shown, demonstrating an epidemiological linkage between SARS-CoV-2 and cardiac injury. There are emerging data regarding possible direct myocardial damage by 2019-nCoV. In this review, the most important available evidences will be discussed to clarify the precise mechanisms of cardiovascular injury in SARS-CoV-2 patients, even if further researches are needed.
Diagnosis of acute myocardial infaction in the time of the COVID-19 pandemic
European Heart Journal, November 4, 2020
Dyspnoea may occasionally represent an equivalent of angina in the case of acute myocardial infarction. In the time of COVID-19, the work up of patients presenting in the emergency department (ED) for dyspnoea may often include computed tomography (CT) scan; the diagnosis of acute myocardial infarction may therefore be occasionally incidental and unconventional. We report the case of a 46-year old hypertensive female patient admitted to the ED for suspected transitory ischaemic attack (referred dysarthria), dyspnoea, and fever 37.5°C. As this was during the time of the COVID-19 pandemic, an admission nasopharyngeal swab was performed. Admission electrocardiogram showed signs of left ventricular hypertrophy without acute ischaemia and significant ST-segment elevation. Despite normal neurological examination without focal signs, a head and chest CT scan was performed in order to exclude neurological acute lesions and COVID-19 interstitial pneumonia. Unexpectedly, CT scan showed normal lung findings but evident hypo-enhancement of the posterior left ventricular wall. A second electrocardiogram showed evident left ventricle hypertrophy with ST-segment elevation in inferior leads. After immediate cath lab admission, coronary angiography showed an occluded right coronary artery, treated with a drug-eluting stent. Although the standard 12-lead electrocardiogram is considered the first-line exam for the diagnosis of acute myocardial infarction, chest CT scan may provide detailed information on the presence and the extension of acute myocardial infarction. In the time of COVID-19, diagnosis of acute myocardial infarction may occasionally occur in radiology rather than in the ED.
Reimagining Cardiac Rehabilitation in the Era of Coronavirus Disease 2019
JAMA Network, November 4, 2020
The coronavirus pandemic has spurred significant growth in home-based cardiology care, facilitated by delivery and financing innovations. Since February2020, the Centers for Medicare & Medicaid Services have issued 190 ambulatory care waivers, including allowing virtual cardiology visits. As a result, 25% to 34% of Medicare beneficiaries have received telehealth care during the pandemic, compared with less than 1% in 2016. On October 14, in an unprecedented move, the Centers for Medicare and Medicaid Services initiated reimbursements for virtual cardiac rehabilitation. Lessons learned from virtual delivery during the pandemic should inform delivery and payment reform for cardiac rehabilitation going forward. Cardiac rehabilitation integrates patient education, behavior modification, and exercise. The traditional in-person, center-based cardiac rehabilitation model has been shown to reduce all-cause hospital readmissions by 31% and all-cause mortality by 24% over 1 to 3 years. For patients with a recent acute myocardial infarction, coronary revascularization, or acute heart failure exacerbation, cardiac rehabilitation reduces spending on future hospitalizations by approximately $900 per patient over 21 months. Yet uptake has been disappointing. Even before COVID-19, less than a third of eligible patients attended a single session. Supply-and-demand challenges have impeded uptake, and both must be addressed to expand this life-saving therapy. Although cardiovascular disease accounts for one-sixth of healthcare spending and affects half of American adults, cardiac rehabilitation—an effective prevention strategy with strong evidence of safety, efficacy, and cost savings—remains underused. As the ongoing pandemic changes how cardiac care is delivered, it provides an unprecedented opportunity to reimagine how cardiac rehabilitation is prescribed, delivered, and financed.
Questions and Answers on Practical Thrombotic Issues in SARS-CoV-2 Infection: A Guidance Document from the Italian Working Group on Atherosclerosis, Thrombosis and Vascular Biology
American Journal of Cardiovascular Drugs, November 3, 2020
In patients with coronavirus disease 2019 (COVID-19), the prevalence of pre-existing cardiovascular diseases is elevated. Moreover, various features, also including pro-thrombotic status, further predispose these patients to increased risk of ischemic cardiovascular events. Thus, the identification of optimal antithrombotic strategies in terms of the risk–benefit ratio and outcome improvement in this setting is crucial. However, debated issues on antithrombotic therapies in patients with COVID-19 are multiple and relevant. In this article, we provide ten questions and answers on risk stratification and antiplatelet/anticoagulant treatments in patients at risk of/with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on the scientific evidence gathered during the pandemic.
COVID-19 associated aortitis
Rheumatology Advances in Practice, November 3, 2020
Since the emergence of Coronavirus disease 2019 (COVID-19) there has been increasing recognition of the potential associated cardio-vascular manifestations. There have been reports of Kawasaki like disease in children. However, in adults there are very few reports of non-cutaneous vasculitis. Here we report the case of an adult male presenting with an inflammatory aortitis associated with COVID-19 infection. A 71-year-old Caucasian male with a background of cholecystectomy and rotator cuff repair presented to hospital in May 2020 with a 3-month history of feeling generally unwell, weight loss and worsening thoraco-lumbar back pain. Prior to the onset of these symptoms, he had had a 2-week illness in March 2020 clinically consistent with COVID-19 infection comprising fevers, hot sweats, dry cough, and chest tightness for which he had not sought medical attention. He had no recent travel history. Physical examination was unremarkable. On admission, COVID-19 tests revealed evidence of prior infection with negative SARS-CoV-2 polymerase chain reaction test but positive SARS-CoV-2 antibodies. Blood tests revealed a marked inflammatory state with a C- reactive protein of 122mg/L, plasmas viscosity of 2.76, Ferritin 777ug/L, Interleukin-6 of 25 ng/L and normocytic anaemia with a Haemoglobin of 77g/L.
Human recombinant soluble ACE2 (hrsACE2) shows promise for treating severe COVID¬19
Signal Transduction and Targeted Therapy, November 3, 2020
A recent study by Zoufaly et al. published in The Lancet Respiratory Medicine describes encouraging data from the first severe COVID-19 patient successfully treated with human recombinant soluble angiotensin-converting enzyme-2 (hrsACE2). The published data document upon treatment of an adaptive immune response, the disappearance of the virus swiftly from the serum, the nasal cavity and lungs, and a reduction of inflammatory cytokine levels that are critical for COVID-19 pathology. Notably, the use of hrsACE2 did not impede the generation of neutralizing antibodies, leading to a significant clinical improvement of the treated patient. ACE2 is a crucial receptor target of SARS-CoV-2, which plays a vital role in the pathogenesis of COVID-19, as it enables viral entry into target cells. The binding affinity between ACE2 and the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein is 10- to 20-fold higher compared to that with the RBD of SARS-CoV, which likely underpins the higher pathogenesis of SARS-CoV-2 infections. ACE2 is a transmembrane protein typically known for its carboxypeptidase activity and its physiological role in the renin-angiotensin system. ACE2 hydrolyzes angiotensin II to its metabolite, angiotensin 1–7 and angiotensin I to angiotensin 1–9 to protect diverse tissues from injury. ACE2 is expressed in several human organs at varying levels. It is highly expressed in the lungs (on the surface of type II alveolar epithelial cells), heart (on myocardial cells, coronary vascular endothelial cells, and vascular smooth muscle), kidney (on proximal tubule cells), and small intestine (on the enterocytes).
The pivotal role of the angiotensin-II–NF-κB axis in the development of COVID-19 pathophysiology
Hypertension Research, November 2, 2020
Coronavirus disease 2019 (COVID-19) is caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 can infect host cells by interacting with membrane-bound angiotensin-converting enzyme 2 (ACE2) on the respiratory epithelium. ACE2 is part of the renin–angiotensin system (RAS), and treatment with RAS inhibitors can increase the tissue expression of ACE2 and its presentation at the cell surface. Thus, it has been suggested that treatment with ACE inhibitors or angiotensin receptor blockers might increase the risk of COVID-19 after exposure to SARS-CoV-2. However, there are several reports showing that the treatment of hypertension with RAS inhibitors is not associated with a substantial increase in the likelihood of a positive test for COVID-19 or in the risk of severe COVID-19. Recently, Matsuzawa et al. suggested that RAS inhibitors do not increase the risk of COVID-19. Furthermore, they propose that RAS inhibitors reduce the risk of disease severity among older age individuals and patients with diabetes. RAS inhibitors have been reported to play a role in the reduction of inflammation by blocking the downregulation of ACE2 and the hyperactivation of RAS. It is also suggested that elevated angiotensin II plays a crucial pathological role in the development of severe COVID-19.
Lack of Association of Antihypertensive Drugs with the Risk and Severity of COVID-19: A Meta-Analysis
Journal of Cardiology, November 2, 2020
The association of antihypertensive drugs with the risk and severity of COVID-19 remains unknown. We systematically searched PubMed, MEDLINE, The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and medRxiv for publications before July 13, 2020. Cohort studies and case-control studies that contain information on the association of antihypertensive agents including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium-channel blockers (CCBs), β-blockers, and diuretics with the risk and severity of COVID-19 were selected. The random-effects or fixed-effects models were used to pool the odds ratio (OR) with 95% confidence interval (CI) for the outcomes. Our literature search yielded 53 studies that satisfied our inclusion criteria, which comprised 39 cohort studies and 14 case-control studies. These studies included a total of 2,100,587 participants. We observed no association between prior usage of antihypertensive medications including ACEIs/ARBs, CCBs, β-blockers, or diuretics and the risk and severity of COVID-19. Additionally, when only hypertensive patients were included, the severity and mortality were lower with prior usage of ACEIs/ARBs (overall OR of 0.81, 95% CI 0.66-0.99, p < 0.05 and overall OR of 0.77, 95% CI 0.66-0.91, p < 0.01).
Hypertension management in 2030: a kaleidoscopic view
Journal of Human Hypertension, November 2, 2020
The last decade has witnessed the healthcare system going paperless with increased use of electronic healthcare records. Artificial intelligence tools including smartphones and smart watches have changed the landscape of day-to-day lives. Digitisation, decentralisation of healthcare and empowerment of allied healthcare providers and patients themselves have made shared clinical decision-making a reality. The year 2020 quickly turned into an unprecedented time in our lives with the entry of COVID-19. Amidst a pandemic, healthcare systems rapidly adapted and transformed, and changes that otherwise would have taken a decade, took a mere few weeks (Webster, Lancet 395:1180–1, 2020). This essay reviews evidence of transformation in the realm of hypertension management, namely diagnosis, lifestyle changes, therapeutics and prevention of hypertension at both individual and population levels, and presents an extrapolation of how this transformation might shape the next decade.
Q&A: Is convalescent plasma effective for COVID-19?
Helio | Infectious Disease, November 2, 2020
Researchers reported recently in The BMJ that convalescent plasma was not associated with a reduction in progression to severe COVID-19 or all-cause mortality in adults with moderate disease. The results were from a phase 2 randomized controlled trial conducted at 39 hospitals in India. Healio spoke with Shmuel Shoham, MD, an associate professor of medicine at Johns Hopkins University School of Medicine, about the clinical implications of the new study, and how convalescent plasma has been used since receiving emergency use authorization (EUA) from the FDA in August.
Statins lower COVID-19 mortality rate for hospitalized adults with diabetes
Helio | Endocrinology, November 2, 2020
Adults with diabetes admitted to a New York City hospital with COVID-19 had a lower mortality risk if they received a statin, according to a study published in the Journal of the American Heart Association.
“In this analysis involving a large cohort of hospitalized patients with COVID-19, statin use was associated with reduced in-hospital mortality in patients with diabetes,” Omar Saeed, MD, attending cardiologist at Montefiore Medical Center and assistant professor of medicine at Albert Einstein College of Medicine in New York, and colleagues wrote. “This observation was made despite older age, higher prevalence of hypertension and atherosclerotic heart disease in diabetic statin users.” In the diabetes group, a greater number of statin recipients had a history of hypertension (91% vs. 84%; P < .01) and atherosclerotic heart disease (46% vs. 28%; P < .01) than nonrecipients. The statin recipient group also had lower C-reactive protein (10.2 mg/dL vs. 12.9 mg/dL; P < .01) and ferratin (683 ng/mL vs. 786 ng/mL; P = .048) at presentation when compared with nonrecipients. Blood glucose level was similar between the two groups.
Stay-At-Home Orders; Heart Injury and COVID-19
MedPage Today, October 31, 2020
[Podcast/Transcript] This podcast, TTHealthWatch, is a weekly feature from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week. A transcript of the podcast is below the summary. This week’s topics include the impact of stay-at-home orders, taking care of sequelae of mild and moderate COVID, giving acute health problems a miss, and cardiac complications of COVID.
Noncoding RNAs implication in cardiovascular diseases in the COVID-19 era
Journal of Translational Medicine, October 31, 2020
COronaVIrus Disease 19 (COVID-19) is caused by the infection of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). Although the main clinical manifestations of COVID-19 are respiratory, many patients also display acute myocardial injury and chronic damage to the cardiovascular system. Understanding both direct and indirect damage caused to the heart and the vascular system by SARS-CoV-2 infection is necessary to identify optimal clinical care strategies. The homeostasis of the cardiovascular system requires a tight regulation of the gene expression, which is controlled by multiple types of RNA molecules, including RNA encoding proteins (messenger RNAs) (mRNAs) and those lacking protein-coding potential, the noncoding-RNAs. In the last few years, dysregulation of noncoding-RNAs has emerged as a crucial component in the pathophysiology of virtually all cardiovascular diseases. Here we will discuss the potential role of noncoding RNAs in COVID-19 disease mechanisms and their possible use as biomarkers of clinical use.
Hyperthrombotic Milieu in COVID-19 Patients
Cells, October 31, 2020
COVID-19 infection has protean systemic manifestations. Experience from previous coronavirus outbreaks, including the current SARS-CoV-2, has shown an augmented risk of thrombosis of both macrovasculature and microvasculature. The former involves both arterial and venous beds manifesting as stroke, acute coronary syndrome and venous thromboembolic events. The microvascular thrombosis is an underappreciated complication of SARS-CoV-2 infection with profound implications on the development of multisystem organ failure. The telltale signs of perpetual on-going coagulation and fibrinolytic cascades underscore the presence of diffuse endothelial damage in the patients with COVID-19. These parameters serve as strong predictors of mortality. While summarizing the alterations of various components of thrombosis in patients with COVID-19, this review points to the emerging evidence that implicates the prominent role of the extrinsic coagulation cascade in COVID-19-related coagulopathy. These mechanisms are triggered by widespread endothelial cell damage (endotheliopathy), the dominant driver of macro- and micro-vascular thrombosis in these patients. We also summarize other mediators of thrombosis, clinically relevant nuances such as the occurrence of thromboembolic events despite thromboprophylaxis (breakthrough thrombosis), current understanding of systemic anticoagulation therapy and its risk–benefit ratio. We conclude by emphasizing a need to probe COVID-19-specific mechanisms of thrombosis to develop better risk markers and safer therapeutic targets.
Myopericarditis and myositis in a patient with COVID-19: a case report
European Heart Journal, October 30, 2020
[Case Report] Concurrent myopericarditis and myositis can present in patients with pre-existing systemic inflammatory diseases. Here we present a case of myopericarditis and myositis associated with COVID-19, in the absence of respiratory symptoms. This case presents a middle-aged female with a history of hypertension and previous myopericarditis. The patient was admitted with symptoms of central chest pain, and ECG and echocardiographic features of myopericarditis. Her symptoms did not improve, and CT thorax suggested possible SARS-CoV-2 infection for which she tested positive, despite no respiratory symptoms. Whilst on the ward, she developed bilateral leg weakness and a raised creatine kinase (CK), and magnetic resonance imaging (MRI) of her thighs confirmed myositis. A cardiac MRI confirmed myopericarditis. She was treated with colchicine 500 μg twice daily, ibuprofen 400 mg three times day, and prednisolone 30 mg per day, and her symptoms and weakness improved. We describe the first reported case of concurrent myopericarditis, and myositis associated with COVID-19. Conventional therapy with colchicine, non-steroidal anti-inflammatory drugs, and glucocorticoids improved her symptoms, and reduced biochemical markers of myocardial and skeletal muscle inflammation.
Osmotic Adaptation by Na+-Dependent Transporters and ACE2: Correlation with Hemostatic Crisis in COVID-19
Biomedicines, October 30, 2020
COVID-19 symptoms, including hypokalemia, hypoalbuminemia, ageusia, neurological dysfunctions, D-dimer production, and multi-organ microthrombosis reach beyond effects attributed to impaired angiotensin-converting enzyme 2 (ACE2) signaling and elevated concentrations of angiotensin II (Ang II). Although both SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus) and SARS-CoV-2 utilize ACE2 for host entry, distinct COVID-19 pathogenesis coincides with the acquisition of a new sequence, which is homologous to the furin cleavage site of the human epithelial Na+ channel (ENaC). This review provides a comprehensive summary of the role of ACE2 in the assembly of Na+-dependent transporters of glucose, imino and neutral amino acids, as well as the functions of ENaC. Data support an osmotic adaptation mechanism in which osmotic and hemostatic instability induced by Ang II-activated ENaC is counterbalanced by an influx of organic osmolytes and Na+ through the ACE2 complex. We propose a paradigm for the two-site attack of SARS-CoV-2 leading to ENaC hyperactivation and inactivation of the ACE2 complex, which collapses cell osmolality and leads to rupture and/or necrotic death of swollen pulmonary, endothelial, and cardiac cells, thrombosis in infected and non-infected tissues, and aberrant sensory and neurological perception in COVID-19 patients. This dual mechanism employed by SARS-CoV-2 calls for combinatorial treatment strategies to address and prevent severe complications of COVID-19.
CT angiography for ischemic stroke accurate in COVID-19 screening
Helio | Cardiology Today, October 29, 2020
Lung evaluation by CT angiography is accurate for fast and early detection for COVID-19 infection in patients with acute ischemic stroke, researchers reported. “CTA of the head and neck done during emergency evaluation for large vessel occlusion typically includes visualization of lung apices, providing the first objective screen for peripheral ground-glass and consolidative opacities suggestive of COVID-19-related pneumonia,” Charles Esenwa, MD, MS, assistant professor and stroke neurologist at the Albert Einstein College of Medicine, and colleagues wrote. The retrospective analysis, published in Stroke, included 57 patients with CTA of the head and neck presenting with acute ischemic stroke at three Montefiore Health System hospitals in Bronx, New York, who were screened for COVID-19 using real-time reverse transcription polymerase chain reaction from March to April. In total, 30 patients tested positive for COVID-19 and 27 tested negative. In those positive for COVID-19, 67% had lung findings highly or very suspicious for COVID-19 pneumonia compared with 7% of patients negative for COVID-19 infection (P < .001). Self-reported clinical symptoms of cough or dyspnea were reported by 13 patients positive for COVID-19, five of whom did not have evidence of COVID-19 on CT angiography apical lung assessment.
New data on soluble ACE2 in patients with atrial fibrillation reveal potential value for treatment of patients with COVID-19 and cardiovascular disease
European Heart Journal, October 29, 2020
[Editorial] In this issue of the European Heart Journal, Wallentin et al. have explored the associations between sACE2, clinical factors, and genetic variability in two international cohorts of elderly patients with atrial fibrillation. They used pre-COVID-19 plasma samples from a subset of ARISTOTLE (n = 3999) and RE-LY (n = 1088). Plasma sACE2 was measured using the Olink Proteomics® Multiplex CVD II96 × 96 panel. Additional cardiovascular biomarkers such as high-sensitive cardiac troponin T (hs-cTnT), N-terminal pro brain natriuretic peptide (NT-proBNP), and growth differentiation factor 15 (GDF-15) were measured using immunoassays. Results from both cohorts were largely similar, with hypertension, diabetes, and chronic heart failure being predominant comorbidities. Importantly, male sex was the strongest independent predictor of sACE2 levels, thus corroborating previous reports. Furthermore, GDF-15, NT-proBNP, hs-cTnT, and D-dimer, which are indicators of cardiovascular disease, diabetes, biological ageing, coagulopathy, and mortality, were associated with higher sACE2 levels. Using DNA from whole blood samples, they further investigated genetic variability to explain plasma ACE2 levels by performing genome-wide association studies (GWAS) in a smaller portion of patients (ARISTOTLE subset n = 1583/3999 and RE-LY subset n = 289/1088). No significant genetic association was found.
Q&A: Navigating ‘the COVID literature tsunami’
Helio | Infectious Disease News, October 29, 2020
As COVID-19 continues to surge across the United States, researchers have been analyzing developments to determine what areas of research should be explored next. In a recent journal article, Ferric C. Fang, MD, professor of laboratory medicine, pathology and microbiology at the University of Washington, and other editors of Clinical Infectious Diseases explored previous research related to COVID-19 virology, epidemiology, presentation, diagnosis, complications, treatment and prevention and summarized the results from several related studies to help researchers and clinicians “surf the COVID literature tsunami.” Healio spoke with Fang about the state of COVID-19 diagnostic and vaccine research, and the role of peer-reviewed studies during the pandemic.
Similar Clinical Course and Significance of Circulating Innate and Adaptive Immune Cell Counts in STEMI and COVID-19
Journal of Clinical Medicine, October 28, 2020
This study aimed to assess the time course of circulating neutrophil and lymphocyte counts and their ratio (NLR) in ST-segment elevation myocardial infarction (STEMI) and coronavirus disease (COVID)-19 and explore their associations with clinical events and structural damage. Circulating neutrophil, lymphocyte and NLR were sequentially measured in 659 patients admitted for STEMI and in 103 COVID-19 patients. The dynamics detected in STEMI (within a few hours) were replicated in COVID-19 (within a few days). In both entities patients with events and with severe structural damage displayed higher neutrophil and lower lymphocyte counts. In both scenarios, higher maximum neutrophil and lower minimum lymphocyte counts were associated with more events and more severe organ damage. NLR was higher in STEMI and COVID-19 patients with the worst clinical and structural outcomes. A canonical deregulation of the immune response occurs in STEMI and COVID-19 patients. Boosted circulating innate (neutrophilia) and depressed circulating adaptive immunity (lymphopenia) is associated with more events and severe organ damage. A greater understanding of these critical illnesses is pivotal to explore novel alternative therapies.
Universal face shield use significantly reduces SARS-CoV-2 infections among HCP
Helio | Primary Care, October 28, 2020
Universal use of face shields by health care personnel at a Texas hospital led to a significant reduction in SARS-CoV-2 infections, data presented at IDWeek show. Mayar Al Mohajer, MD, MBA, FIDSA, FSHEA, an infectious disease specialist at Baylor Saint Luke’s Medical Center, told Healio Primary Care that in April, his institution began requiring health care professionals (HCPs) and patients to wear masks. It simultaneously implemented surveillance testing every 2 weeks for high-risk HCP and for all patients upon admission and prior to undergoing invasive procedures. “Around the end of June, we noticed an increase in the rate of health care personnel testing positive for COVID-19, even though we were implementing all of the basic methods to prevent it,” Al Mohajer said. Consequently, Baylor Saint Luke’s — a quaternary health care system with more than 500 beds and 8,000 HCP — added a requirement that all HCP wear face shields upon entry to the facility, he said. The researchers found that from April 17 to July 5, before face shields were required, Baylor Saint Luke’s weekly positive SARS-CoV-2 infection rates among HCP rose from 0% to 12.9%, and health care-associated infections increased from 0 to 5. From July 6 to July 26, the first few weeks after face shields were required, the positive SARS-CoV-2 infection rate dropped to 2.3%, and health care-associated infections decreased to 0.
Coronavirus Update With Anthony Fauci
JN Learning, October 28, 2020
[Video, 29:50] View/listen in as Howard Bauchner, MD, Editor in Chief, JAMA, interviews Anthony S. Fauci, MD, to discuss the latest developments in the COVID-19 pandemic, including the continued importance of nonpharmaceutical interventions (masking, handwashing, physical distancing) for managing rising case numbers in the US and globally.
Renin–Angiotensin System: An Important Player in the Pathogenesis of Acute Respiratory Distress Syndrome
International Journal of Molecular Science, October 28, 2020
Acute respiratory distress syndrome (ARDS) is characterized by massive inflammation, increased vascular permeability and pulmonary edema. Mortality due to ARDS remains very high and even in the case of survival, acute lung injury can lead to pulmonary fibrosis. The renin–angiotensin system (RAS) plays a significant role in these processes. The activities of RAS molecules are subject to dynamic changes in response to an injury. Initially, increased levels of angiotensin (Ang) II and des-Arg9-bradykinin (DABK), are necessary for an effective defense. Later, augmented angiotensin converting enzyme (ACE) 2 activity supposedly helps to attenuate inflammation. Appropriate ACE2 activity might be decisive in preventing immune-induced damage and ensuring tissue repair. ACE2 has been identified as a common target for different pathogens. Some Coronaviruses, including SARS-CoV-2, also use ACE2 to infiltrate the cells. A number of questions remain unresolved. The importance of ACE2 shedding, associated with the release of soluble ACE2 and ADAM17-mediated activation of tumor necrosis factor-α (TNF-α)-signaling is unclear. The roles of other non-classical RAS-associated molecules, e.g., alamandine, Ang A or Ang 1–9, also deserve attention. In addition, the impact of established RAS-inhibiting drugs on the pulmonary RAS is to be elucidated. The unfavorable prognosis of ARDS and the lack of effective treatment urge the search for novel therapeutic strategies. In the context of the ongoing SARS-CoV-2 pandemic and considering the involvement of humoral disbalance in the pathogenesis of ARDS, targeting the renin–angiotensin system and reducing the pathogen’s cell entry could be a promising therapeutic strategy in the struggle against COVID-19.
Characteristics of cardiac injury in critically ill patients with COVID-19
CHEST, October 27, 2020
Cardiac injury has been reported in up to 30% of COVID-19 patients. However, cardiac injury was mainly defined by troponin elevation without description of associated structural abnormalities and its time course has never been studied. The objective of the study was to answer the question: What are the electrocardiographic and echocardiographic abnormalities as well as their time course in critically ill COVID-19 patients? The cardiac function of 43 consecutive COVID-19 patients admitted in two intensive care units (ICU) was prospectively and repeatedly assessed combining electrocardiographic, cardiac biomarkers and transthoracic echocardiographic analyses from ICU admission (D0) to ICU discharge or death or to a maximum follow-up of 14 days. Cardiac injury was defined by troponin elevation and newly diagnosed electrocardiographic and/or echocardiographic abnormalities. At D0, 49% of patients had a cardiac injury and 70% of patients experienced cardiac injury within the first 14 days of ICU stay, with a median time of occurrence of 3[0-7] days. The most frequent abnormalities were electrocardiographic and/or echocardiographic signs of left ventricular (LV) abnormalities (87% of patients with cardiac injury), right ventricular (RV) systolic dysfunction (47%), pericardial effusion (43%), new-onset atrial arrhythmias (33%), LV relaxation impairment (33%) and LV systolic dysfunction (13%). Between D0 and D14, the incidence of pericardial effusion and of new-onset atrial arrhythmias increased, the incidence of electrocardiographic and/or echocardiographic signs of LV abnormalities as well as the incidence of LV relaxation impairment remained stable, whereas the incidence of RV and LV systolic dysfunction decreased.
Top in ID: COVID-19 case counts, spike in US death rate
Helio | Infectious Diseases, October 27, 2020
During a special session at IDWeek, Anthony S. Fauci, MD, said many countries, including the United States, are experiencing a surge in COVID-19 cases. It was the top story in infectious disease last week. Another top story was about new data showing a 20% spike in mortality during a 4-month period in the U.S. Many countries are seeing a spike in COVID-19, including the U.S., where a third wave has pushed the number of cases above 8.2 million, including 220,000 deaths. The U.S. had a mortality rate that was 20% higher than expected between March and July, and it experienced high COVID-19-related mortality and excess all-cause deaths into September, according to results from two JAMA studies. As scientists test treatments and vaccines against COVID-19, Healio spoke with Infectious Disease News Editorial Board Member Peter Chin-Hong, MD, about which populations are being left out of COVID-19 research and what needs to happen to make the process more inclusive.
Higher COVID Death Risk Spelled Out by Troponins, ECG
MedPage Today, October 26, 2020
Hospitalized patients with COVID-19 and myocardial injury had a broad range of echocardiographic abnormalities that put them at higher risk of in-hospital mortality, according to registry data from spring 2020. Among 305 patients with lab-confirmed SARS-CoV-2 infection who underwent transthoracic echocardiography (TTE) and ECG evaluation, 62.6% had troponin elevations suggestive of myocardial injury (either at hospital admission or later during the hospitalization), according to Gennaro Giustino, MD, of Icahn School of Medicine at Mount Sinai in New York City, and colleagues. Those with myocardial injury had more ECG abnormalities and higher levels of inflammatory and coagulation biomarkers. Additionally, they were more likely to have any major echocardiographic abnormalities (63.2% vs 21.7% in people without myocardial injury, OR 6.17, 95% CI 3.62-10.51).”The echocardiographic abnormalities were diverse and included global LV [left ventricular] dysfunction, regional wall motion abnormalities, diastolic dysfunction, RV [right ventricular] dysfunction, and pericardial effusions, among others,” Giustino’s group wrote in the Journal of the American College of Cardiology.
FDA clears cardiopulmonary bypass support system for use in COVID-19, other conditions
Helio | Cardiology Today, October 26, 2020
Abiomed announced its compact cardiopulmonary bypass system received 510(k) clearance from the FDA. During cardiopulmonary bypass, the compact new system (Breethe OXY-1, Abiomed) can help provide oxygenation in patients with cardiogenic shock or respiratory failure from causes such as acute respiratory distress syndrome, H1N1, SARS or COVID-19 for up to 6 hours, according to a press release from the company. “The Breethe system is a breakthrough technology because it supports transition from bed to ambulation via system portability,” Zachary Kon, MD, associate professor of cardiothoracic surgery at the NYU Grossman School of Medicine, said in the release. “This system has the potential to revolutionize the way we think about extracorporeal life support therapy and can improve patient care.” According to the release, in a study of 686 consecutive patients published in Circulation, use of the new system, in combination with Abiomed’s heart pump (Impella), was associated with increased 30-day survival (43% vs. 37%; P = .03).
Performance of 5 Immunoassays for SARS-CoV-2 Compared
Pulmonology Advisor, October 26, 2020
A comparative assessment of the performance of 4 widely available antibody immunoassays and 1 novel immunoassay showed that these assays can be used for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologic testing to achieve sensitivity and specificity of at least 98%, according to study results published in The Lancet Infectious Diseases. Study authors conducted a head-to-head assessment of the following 4 commercial antibody assays, with the aim of evaluating the performance of each assay:
- SARS-CoV-2 IgG assay (Abbott, Chicago, IL, USA)
- LIAISON SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Saluggia, Italy)
- Elecsys Anti-SARS-CoV-2 assay (Roche, Basel, Switzerland)
- SARS-CoV-2 Total assay (Siemens, Munich, Germany)
The Abbott and Roche assays are known to detect antibodies to the nucleoprotein, whereas the DiaSorin and Siemens assays detect antibodies to the spike glycoprotein. The Abbott and Diasorin assays detect immunoglobulin (Ig)G only, whereas the Roche and Siemens assays detect total antibody. Study authors compared these 4 assays and a novel 384-well ELISA (the Oxford immunoassay) that detects total IgG to a trimeric spike protein.
Hypertension and renin-angiotensin system blockers are not associated with expression of angiotensin-converting enzyme 2 (ACE2) in the kidney
European Heart Journal, October 26, 2020
Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)—the cause of coronavirus disease 2019 (COVID-19). However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. In this study, we examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis.
Thromboembolism, CV Complications Common in Hospitalized COVID-19 Patients
American College of Cardiology, October 26, 2020
Patients with COVID-19 have a high frequency of major arterial or venous thromboembolism, major adverse cardiovascular events and symptomatic venous thromboembolism, despite routine thromboprophylaxis. Gregory Piazza, MD, MS, FACC, et al., abstracted data from the electronic health records (EHRs) of the Mass General Brigham integrated health network. Researchers identified 1,114 patients age 18 years or older who tested positive for COVID-19 from March 13 to April 3, 2020. Of the total cohort, 170 were treated in the intensive care unit (ICU); 229 in non-ICU settings; and 715 in an outpatient clinic. The results show 22.3% of patients were Hispanic/Latinx and 44.2% were nonwhite. Common cardiovascular risk factors included hypertension (35.8%), hyperlipidemia (28.6%) and diabetes (18%). According to the researchers, arterial or venous thromboembolism and major adverse cardiovascular events are common among ICU patients with COVID-19. They note that COVID-19 patients hospitalized in non-ICU settings are also susceptible to cardiovascular complications. The high rates of thromboembolism despite prophylaxis “suggests the need for improved risk stratification and enhanced preventive efforts,” they conclude.
6% of US adults hospitalized with COVID-19 work in health care
Helio | Infectious Disease News, October 26, 2020
In the United States, 6% of adults hospitalized with COVID-19 are health care personnel, an analysis indicated. Almost 30% of health care personnel (HCP) with COVID-19 were admitted to the ICU, according to results published in MMWR. “Findings from this analysis of data from a multisite surveillance network highlight the prevalence of severe COVID-19-associated illness among HCP and potential for transmission of SARS-CoV-2 among HCP, which could decrease the workforce capacity of the health care system,” Anita K. Kambhampati, MPH, and colleagues from the CDC’s COVID-NET Surveillance Team, wrote. “HCP, regardless of any patient contact, should adhere strictly to recommended infection prevention and control guidance at all times in health care facilities to reduce transmission of SARS-CoV-2, including proper use of recommended personal protective equipment, hand hygiene, and physical distancing.” According to Kambhampati and colleagues, among 6,760 adults hospitalized with COVID-19 in 13 states between March 1 and May 31, 5.9% were HCP. Among the infected HCP, 36.3% worked in nursing-related occupations and 67.4% were expected to have direct contact with patients. A total of 89.8% of HCP had an underlying medical condition, with obesity being the most common one (72.5%).
Majority of COVID-19 Patients With Myocardial Injury Have Cardiac Structural Abnormalities
American College of Cardiology, October 26, 2020
Cardiac structural abnormalities were present in nearly two-thirds of patients with COVID-19 and myocardial injury, according to a study published October 26, 2020. Gennaro Giustino, MD, et al., sought to identify the echocardiographic abnormalities associated with myocardial injury and their prognostic impact in patients with COVID-19 by examining data from COVID-19 patients who underwent a transthoracic echocardiographic (TTE) evaluation during their hospitalization. The data was collected at seven clinical sites in New York City and Milan, Italy between March 5 and May 2, 2020. Of the 305 patients included in the study, 190 patients (62.6%) had biomarker evidence of myocardial injury. Patients with myocardial injury had higher inflammatory biomarkers and an increased prevalence of major echocardiographic abnormalities, including left ventricular wall motion abnormalities, global left ventricular dysfunction and more. Results showed the rate of in-hospital mortality was 5.2% in patients without myocardial injury; 18.6% in patients with myocardial injury without TTE; and 31.7% in patients with myocardial injury and TTE abnormalities. “Myocardial injury is associated with increased risk of in-hospital mortality particularly in the presence of cardiac structural abnormalities detected by TTE,” write the authors.
Cardiac Adverse Events With Remdesivir in COVID-19 Infection
Cureus, October 24, 2020
[Case Report] Since December 2019, coronavirus has gradually progressed to a pandemic with no efficacious treatment. Remdesivir is an antiviral medication and inhibitor of viral RNA dependent RNA polymerase with inhibitory action against SARS-CoV virus. Remdesivir was recently approved for compassionate use intravenously for COVID-19 patients. It functions as an adenosine analog that introduces itself into viral RNA, leading to premature chain termination and viral replication inhibition. The most common adverse effects of remdesivir are increased hepatic enzymes, diarrhea, anemia, rash, renal impairment, and hypotension. Elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been shown to be reversible after discontinuation of remdesivir per studies. The purpose of our case reports is to highlight two cases of patients diagnosed with coronavirus infection with worsening respiratory status. They were initiated with multimodality therapy with antibiotics, steroids and remdesivir. After initiation of remdesivir, the patients’ developed bradycardia, with one of the two also showing signs of worsening QT interval. This reverted upon stopping remdesvir therapy. The prevalence of bradycardia with prolonged QT interval is not well-known yet with this medication.
Covid-19 and Major Organ Thromboembolism: Manifestations in Neurovascular and Cardiovascular Systems
Journal of Stroke & Cerebrovascular Diseases, October 24, 2020
COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been shown to cause multisystemic damage. We undertook a systematic literature review and comprehensive analysis of a total of 55 articles on arterial and venous thromboembolism in COVID19 and articles on previous pandemics with respect to thromboembolism and compared the similarities and differences between them. The presence of thrombosis in multiple organ systems points to thromboembolism being an integral component in the pathogenesis of this disease. Thromboembolism is likely to be the main player in the morbidity and mortality of COVID -19 in which the pulmonary system is most severely affected. We also hypothesize that D-dimer values could be used as an early marker for prognostication of disease as it has been seen to be raised even in the pre-symptomatic stage. This further strengthens the notion that thromboembolism prevention is necessary. We also examined literature on the cerebrovascular and cardiovascular systems, as the manifestation of thromboembolic phenomenon in these two systems varied, suggesting different pathophysiology of damage. Further research into the role of thromboembolism in COVID-19 is important to advance the understanding of the virus, its effects and to tailor treatment accordingly to prevent further casualties from this pandemic.
Novel Behavior of the 2019 Novel Coronavirus With Invasion of the Cardiac Conduction System in the Young
Cureus, October 23, 2020
[Case Report] On January 7, 2020, a novel coronavirus, originally abbreviated as 2019-nCoV by the World Health Organization (WHO), was identified from a throat swab sample. This pathogen was later renamed the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) by the Coronavirus Study Group, and the disease was named coronavirus disease 2019 (COVID-19) by the WHO. Based on the report of the first 425 confirmed cases in Wuhan, common symptoms include fever, dry cough, myalgia, and fatigue; less common symptoms are sputum production, headache, hemoptysis, abdominal pain, and diarrhea. A descriptive, exploratory analysis of the first 72,314 cases of COVID-19 revealed that cardiovascular involvement was reported in just 10.5% of cases, but it was never the sole manifestation. We report the case of a 35-year-old man (an oil engineer) referred as a coronavirus disease-2019 (COVID-19) case with heart block and a four-day history of headache and fever. The patient was hemodynamically stable with normal respiratory effort and oxygen saturation. Three consecutive COVID-19 tests were positive since admission. Comprehensive clinical assessment investigations were performed. Apart from mild acute phase reactants elevation, all results were within reference limits. He had no leukocytosis and normal cardiac enzymes, chest x-ray findings, echocardiography findings, and healthy coronary arteries.
Statins and SARS-CoV-2 disease: Current concepts and possible benefits
Diabetes & Metabolic Syndrome: Clinical Research & Reviews, October 23, 2020
Inflammation-mediated tissue injury is the major mechanism involved in the pathogenesis of coronavirus disease 2019 (COVID-2019), caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Statins have well-established anti-inflammatory, anti-thrombotic and immuno-modulatory effects. They may also influence viral entry into human cells. A literature search was done using PubMed and Google search engines to prepare a narrative review on this topic. Statins interact with several different signaling pathways to exert their anti-inflammatory and vasculoprotective effects. They also variably affect cholesterol content of cell membranes and interfere with certain coronavirus enzymes involved in receptor-binding. Both these actions may influence SARS-CoV-2 entry into human cells. Statins also upregulate expression of ACE2 receptors on cell surfaces which may promote viral entry into the cells but at the same time, may minimize tissue injury through production of angiotensin. The net impact of these different effects on COVID-19 pathogenesis is not clear. However, the retrospective clinical studies have shown that statin use is potentially associated with lower risk of developing severe illness and mortality and a faster time to recovery in patients with COVID-19.
COVID-19 can affect the heart COVID-19 has a spectrum of potential heart manifestations with diverse mechanisms
Science, October 23, 2020
The family of seven known human coronaviruses are known for their impact on the respiratory tract, not the heart. However, the most recent coronavirus, SARSCoV-2, has marked tropism for the heart and can lead to myocarditis (inflammation of the heart), necrosis of its cells, mimicking of a heart attack, arrhythmias, and acute or protracted heart failure (muscle dysfunction). Recent findings of heart involvement in young athletes, including sudden death, have raised concerns about the current limits of our knowledge and potentially high risk and occult prevalence of COVID-19 heart manifestations. What appears to structurally differentiate SARS-CoV-2 from SARS is a furin polybasic site that, when cleaved, broadens the types of cells (tropism) that the virus can infect. The virus targets the angiotensin-converting enzyme 2 (ACE2) receptor throughout the body, facilitating cell entry by way of its spike protein, along with the cooperation of the cellular serine protease transmembrane protease serine 2 (TMPRSS2), heparan sulfate, and other proteases. The heart is one of the many organs with high expression of ACE2. Moreover, the affinity of SARS-CoV-2 to ACE2 is significantly greater than that of SARS. The tropism to other organs beyond the lungs has been studied from autopsy specimens: SARS-CoV-2 genomic RNA was highest in the lungs, but the heart, kidney, and liver also showed substantial amounts, and copies of the virus were detected in the heart from 16 of 22 patients who died. In an autopsy series of 39 patients dying from COVID-19, the virus was not detectable in the myocardium in 38% of patients, whereas 31% had a high viral load above 1000 copies in the heart.
Relative Bradycardia in Patients with Mild-to-Moderate Coronavirus Disease, Japan
Center for Disease Control and Prevention | Emerging Infectious Diseases, October 23, 2020
Pulse rate usually increases 18 beats/min for each 1°C increase in body temperature. However, in some specific infectious diseases, pulse rate does not increase as expected, a condition called relative bradycardia. High fever (temperature >39°C) for patients with COVID-19 has been reported, but the association between fever and pulse rate has not been investigated. We investigated relative bradycardia as a characteristic clinical feature in patients with mild-to-moderate COVID-19. Retrospective analyses of routinely collected clinical records of COVID-19 patients were approved by the ethics committee of the Institute of Medical Science. During March 1–May 14, we identified all adult hospitalized patients with COVID-19 at a university hospital in Tokyo, Japan. We confirmed diagnoses of COVID-19 by using reverse transcription PCR. Patients who had known factors that could affect pulse rate (e.g., concurrent conditions or medications) were excluded. We obtained the highest body temperature in each day during hospitalization and the pulse rate at the time. To account for within-person correlation, we used 2-level mixed-effects linear regression (with random intercept) for analysis of factors associated with pulse rate: age, sex, time from first symptoms, systolic blood pressure, diastolic blood pressure, respiratory rate, and percutaneous oxygen saturation. We performed variable selection by backward elimination using a p value of 0.05 by likelihood ratio test as the cutoff value. We performed statistical analysis by using Stata MP 15.1. Relative bradycardia was defined as an increase in pulse rate <18 beats/min for each 1°C increase in body temperature. [Read the results.]
Acute kidney injury associated with COVID-19: a prognostic factor for pulmonary embolism or co-incidence?
European Heart Journal, October 23, 2020
[Case Study] An 81-year-old gentleman presented with fever (39.1°C), cough, dysuria, and urinary tract infection, which warranted antibiotic therapy. Medical history included insulin-dependent type 2 diabetes mellitus, arterial hypertension, and third-degree atrioventricular block with an implanted pacemaker. The patient was intubated and required mechanical ventilation for severe respiratory failure (Horowitz index of 64.2 mmHg) 6 days after hospitalization. SARS-CoV-2 polymerase chain reaction (PCR) test on nasopharyngeal swabs was positive and chest computed tomography (CT) illustrated bilateral ground-glass opacities (Panel A). Laboratory tests showed a remarkable increase in the inflammatory cytokine interleukin-6 (270.6 pg/mL) and C-reactive protein (CRP; 222.7 mg/L). In the second week, he developed acute kidney injury (AKI) [creatinine, 296 μmol/L; blood urea nitrogen (BUN), 14.6 μmol/L, and estimated glomerular filtration rate (eGFR) 16 mL/min/1.73 m2], and consequently continuous haemodialysis was initiated. Fifteen days later, D-dimer levels were strikingly elevated (15 293 μg/L), and CT pulmonary angiography revealed segmental pulmonary embolism (PE) in the right upper lobe (Panel B) without signs of right ventricular failure (Supplementary material online, Video 1). ECG showed new onset of atrial fibrillation. Anticoagulation with unfractionated heparin was implemented. The patient remained in the intensive care unit until recovery of pulmonary function, but dialysis continued for 24 days to be prepared for discharge.
FDA OKs Remdesivir, First Drug for COVID-19
MedPage Today, October 22, 2020
The FDA approved remdesivir (Veklury) on Thursday for treating hospitalized COVID-19 patients, a first for the disease that started a global pandemic. Remdesivir, an antiviral that works by limiting SARS-CoV-2 replication, is indicated for hospitalized patients age 12 and up (and at least 40 kg [88.2 lbs]). Previously, the intravenous drug was solely available under an emergency use authorization (EUA) from the agency. FDA also announced a new EUA for remdesivir in hospitalized kids age 12 and older weighing at least 3.5 kg (7.7 lbs) but less than 40 kg, and in kids under age 12 weighing at least 3.5 kg. The news comes exactly a week after a major international trial led by the World Health Organization (WHO) found no survival improvement for hospitalized COVID-19 patients treated with the drug, and no improvement in time to recovery. Approval was based on three randomized trials, including the National Institutes of Health-led ACTT-1 trial, a phase III trial that showed that patients with mild, moderate, and severe disease who were treated with up to 10 days of remdesivir recovered a median 5 days quicker than those on placebo (10 vs 15 days; rate ratio [RR] 1.29, 95% CI 1.12-1.49, P<0.001), and a median 7 days quicker in those requiring oxygen at baseline (11 vs 18 days; RR 1.31, 95% CI 1.12-1.52).
The Cross-Talk between Age, Hypertension and Inflammation in COVID-19 Patients: Therapeutic Targets
Drugs & Aging, October 21, 2020
This paper presents a brief overview of the complex interaction between age, hypertension, the renin–angiotensin–aldosterone system (RAAS), inflammation, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Coronavirus disease 2019 (COVID-19) is more frequent and more severe in comorbid elderly patients, especially those with hypertension, diabetes, obesity, or cardiovascular diseases. There are concerns regarding the use of RAAS inhibitors in patients with COVID-19. Some physicians have considered the need for interrupting RAAS inhibition in order to reduce the possibility of SARS-CoV2 entering lung cells after binding to angiotensin-converting enzyme 2 (ACE2) receptors. We offer a different point of view in relation to the need for continuing to use RAAS inhibitors in patients with COVID-19. We focused our article on elderly patients because of the distinctive imbalance between the immune response, which is depressed, and the exacerbated inflammatory response, ‘inflammaging’, which makes the geriatric patient an appropriate candidate for therapeutic strategies aimed at modulating the inflammatory response. Indeed, COVID-19 is an inflammatory storm that starts and worsens during the course of the disease. During the COVID-19 pandemic, various therapeutic approaches have been tested, including antiviral drugs, interferon, anti-interleukins, hydroxychloroquine, anti-inflammatories, immunoglobulins from recovered patients, and heparins. Some of these therapeutic approaches did not prove to be beneficial, or even induced serious complications. Based on current evidence, in the early stages of the disease modulation of the inflammatory response through the inhibition of neprilysin and modulation of the RAAS could affect the course and outcome of COVID-19.
The Impact of COVID-19 on Physician Burnout Globally: A Review
Healthcare, October 22, 2020
The current pandemic, COVID-19, has added to the already high levels of stress that medical professionals face globally. While most health professionals have had to shoulder the burden, physicians are not often recognized as being vulnerable and hence little attention is paid to morbidity and mortality within this group. Our objective was to analyse and summarise the current knowledge on factors/potential factors contributing to burnout amongst healthcare professionals amidst the pandemic. This review also makes a few recommendations on how best to prepare intervention programmes for physicians. In August 2020, a systematic review was performed using the database Medline and Embase (OVID) to search for relevant papers on the impact of COVID-19 on physician burnout–the database was searched for terms such as “COVID-19 OR pandemic” AND “burnout” AND “healthcare professional OR physician”. A manual search was done for other relevant studies included in this review. Results: Five primary studies met the inclusion criteria. A further nine studies were included which evaluated the impact of occupational factors (n = 2), gender differences (n = 4) and increased workload/sleep deprivation (n = 3) on burnout prior to the pandemic. Additionally, five reviews were analysed to support our recommendations. Results from the studies generally showed that the introduction of COVID-19 has heightened existing challenges that physicians face such as increasing workload, which is directly correlated with increased burnout. However, exposure to COVID-19 does not necessarily correlate with increased burnout and is an area for more research.
Bedside Evaluation of Pulmonary Embolism by Saline Contrast Enhanced Electrical Impedance Tomography: Considerations for Future Research
American Journal of Respiratory and Critical Care Medicine, October 22, 2020
[Letter to the Editor] We read with great interest the article by Huaiwu He et al. entitled “bedside evaluation of pulmonary embolism (PE) by saline contrast electrical impedance tomography method: A prospective observational study”. The authors found PE-envoked regional perfusion defection could be detected with saline-contrasted EIT and claimed that the method showed high sensitivity and specificity for diagnosis of PE. However, several factors potentially affecting the reported findings should be discussed. For measurement of pulmonary perfusion, a short apnea is needed during bolus injection of 10ml 10% NaCl to eliminate the interruption from cyclic breath. The conscious patients were required to hold their breath at the end of expiration for 8 seconds or longer. Although the shorter the apnea, the more feasible for conscious patients to hold their breath, it needs imperative time to allow blood mixed with saline to travel through the whole pulmonary circulation. Slutsky, et al. found mean pulmonary transit time (PTT) ranged from 4.3 to 12.6 seconds (mean 7.7 ±1.5 seconds) in human. In this context, it’s questionable that a period with a lower level of 8 seconds is enough for saline to pass through the lung in patients with PE. On the other hand, for those intubated, holding breath for even 8 seconds might be challenging as dyspnea is common among patients with PE, manual expiratory hold is likely to trigger spontaneous breath, which would dramatically impact the intrathoracic electric impedance. To avoid spontaneous breath, sometimes neuromuscular relaxant is needed, which was not detailed in this article. Recently, Mauri et al published a study exploring the ventilation-perfusion ratio in patients with COVID-19, in which a lower concentration (5%) of saline and end-inspiration occlusion for 20 seconds were implemented for determination of pulmonary perfusion.
Fauci: Case counts ‘stunning’ as many places see COVID-19 surge
Helio | Infectious Diseases, October 21, 2020
Many countries are seeing a spike in COVID-19, including the United States, where a third wave has pushed the number of cases above 8.2 million, including 220,000 deaths. “The numbers throughout the globe have been stunning, making this already the most disastrous pandemic that we have experienced in our civilization in over 102 years, since the 1918 influenza pandemic,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said during a special session at IDWeek focused on COVID-19. Fauci noted the global case count: “40 million cases and over 1.1 million deaths.” “Unfortunately, for the United States, we have been hit harder than virtually any other country on the planet,” he said. The Johns Hopkins coronavirus resource center, which tracks state-level trends, has reported recent sharp increases in daily cases in states like North Dakota (803 cases per 100,000 people), Wisconsin (3,317 per 100,000 people), Rhode Island (293 per 100,000 people) and Wyoming (230 per 100,000 people), and declines in states including Arkansas, Kentucky and South Dakota.
https://onlinelibrary.wiley.com/doi/10.1111/ijcp.13773
International Journal of Clinical Practice, October 20, 2020
[Letter to the Editor] We have observed hypernatraemia and hypokalaemia with normal serum urea and creatinine associated with new-onset hypertension among COVID-19 patients. We assessed the reninangiotensin-aldosterone system (RAAS) of 2 patients during the pandemic and found elevated urinary potassium (without causal medications) and hyporeninaemic hypoaldosteronism in both. We fully investigated a fit 74-year-old woman with COVID-19 who developed hypertension (peak blood pressure (BP) 195/120 mmHg), hypokalaemia (range 2.7–3.2 mmol/L) and hypernatraemia (range 150-166 mmol/L) during the first week of admission. There was metabolic alkalosis with pH 7.50, bicarbonate 31mmol/L, partial pressure of carbon dioxide 5.3 kPa. Adjusted calcium and serum magnesium were normal. Urinary potassium (K+) was 19.72 mmol/L and 24.46 mmol/L (0-10) on 2 occasions. Plasma renin and aldosterone levels remained normal thereafter. Congenital forms of hypertension, glucocorticoid resistance and syndrome of apparent mineralocorticoid excess were excluded. There were no features of hypothalamic-pituitary dysfunction. She was treated with amiloride 5mg daily increased to 7.5mg after 3 days with normalisation of serum/urinary K+ and BP within 1 week (Table). After 3 weeks, amiloride was withdrawn and she remained normotensive. Plasma renin and aldosterone levels remained normal thereafter. Transient hyporeninaemic hypoaldosteronism may be related to dysregulated sodium (Na+) channel (ENaC) pathophysiology similar to that in Liddle’s syndrome. Enhanced ENaC activity (highly selective for Na+ over K+) leads to Na+ retention in the distal nephron and K+ and hydrogen ion secretion to maintain tubular neutrality. This results in intravascular volume expansion and hypokalaemic metabolic alkalosis. This hypothesis is supported by reversibility of electrolyte abnormalities and hypertension with the diuretic amiloride, which inhibits Na+ reabsorption by selectively blocking this channel.
The Costs of Coronavirus
Journal of the American Medical Association, October 20, 2020
View/listen in as Howard Bauchner, MD, Editor in Chief, JAMA, interviews authors of three recent features in JAMA:
- David M. Cutler, PhD, of Harvard University discusses financial costs: the $16 trillion virus.
- Lisa Cooper, MD, MPH, of Johns Hopkins University discusses the costs to communities of color in excess deaths and bereavement.
- Charles R. Marmar, MD, of NYU Grossman School of Medicine discusses the mental health costs.
The overlooked tsunami of systemic inflammation in post-myocardial infarction cardiogenic shock
European Journal of Predictive Cardiology, October 20, 2020
The incidence of acute myocardial infarction (MI)-derived cardiogenic shock (CS) has increased remarkably over the past decade, from 6.5% in 2003 to 10.1% in 2010. During the same period, in-hospital mortality has remained stable in the range of 40–50% despite significant advances in revascularization and supportive care, such as the use of mechanical circulatory support (MCS). Post-MI CS is themost studied mode of CS because pump dysfunction onset in this setting is easily traceable. Nevertheless, nothing we have tried in the last 40 years has worked. In CS, we fool ourselves into thinking that we understand the problem, but what if the fundamental construct is wrong and CS is not just pump failure and low cardiac output? It may well be that our lack of understanding is actually preventing progress, for which alternative hypotheses are urgently needed before we end up insane (see quote above). Veno-arterial extracorporeal membrane oxygenation is the new kid on the block, and although it has shown some promise in survival in some series, large post-MI CS randomized controlled trials are still underway and it may be too early to claim victory. In sum, MCS devices aim to increase flow and restore macrohaemodynamics in a critical state situation characterized by low cardiac output and end-organ hypoperfusion. However, ∼50% of deaths after CS happen despite a cardiac index >2.2 L/min.
Deaths spike 20% in U.S. during 4-month period
Helio | Infectious Disease News, October 19, 2020
The United States had a mortality rate that was 20% higher than expected between March and July, and it experienced high COVID-19-related mortality and excess all-cause deaths into September, according to results from two JAMA studies. The first study explored excess deaths and their relationship to states’ reopening and easing of restrictions. “The number of deaths that are occurring as a result of the pandemic is larger than the COVID-19 death count that is being reported,” Steven Woolf, MD, MPH, director emeritus of the Center on Society and Health at Virginia Commonwealth University, told Healio. “Some of that excess is being produced by people who are dying from causes other than COVID-19 but from disruptions produced by the pandemic itself and our response to it.” In a separate study, Alyssa Bilinski, MSc, a health policy PhD candidate at Harvard University, and Ezekiel J. Emanuel, MD, PhD, vice provost for global initiatives at the University of Pennsylvania, compared COVID-19 deaths and excess all-cause mortality in the U.S. with that of 18 other countries. “The U.S. has experienced more deaths from COVID-19 than any other country and has one of the highest cumulative per capita death rates,” the researchers wrote. “An unanswered question is to what extent high U.S. mortality was driven by the early surge of cases prior to improvements in prevention and patient management vs. a poor longer-term response.”
Cardiology on the cutting edge: updates from the European Society of Cardiology (ESC) Congress 2020
BMC Cardiovascular Disorders, October 19, 2020
[Editorial] The 2020 annual Congress of the European Society of Cardiology (ESC) was the first ever to be held virtually. Under the spotlight of ‘the cutting edge of cardiology’, exciting and ground-breaking cardiovascular (CV) science was presented both in basic and clinical research. This commentary summarizes essential updates from ESC 2020—The Digital Experience. Despite the challenges that coronavirus disease 2019 (COVID-19) has posed on the conduct of clinical trials, the ESC Congress launched the results of major studies bringing innovation to the field of general cardiology, cardiac surgery, heart failure, interventional cardiology, and atrial fibrillation. In addition to three new ESC guidelines updates, the first ESC Guidelines on Sports Cardiology and Exercise in Patients with Cardiovascular Disease were presented. During the ESC 2020 Congress, BMC Cardiovascular Disorders updated to seven journal sections including Arrhythmias and Electrophysiology, CV Surgery, Coronary Artery Disease, Epidemiology and Digital health, Hypertension and Vascular biology, Primary prevention and CV Risk, and Structural Diseases, Heart Failure, and Congenital Disorders. To conclude, an important take-home message for all CV health care professionals engaged in the COVID-19 pandemic is that we must foresee and be prepared to tackle the dramatic, long-term CV complications of COVID-19 patients. In this commentary, we summarized the most important trials presented during the 2020 Virtual ESC Congress which we predict will improve our everyday clinical practice.
Plasma ACE2 and Risk of Death or Cardiometabolic Diseases
American College of Cardiology, October 19, 2020
The study aimed to answer the question, are plasma angiotensin-converting enzyme 2 (ACE2) concentrations associated with risk of death or cardiovascular (CV) events? In this case-cohort study of 10,753 subjects, determinants of plasma ACE2 levels included sex (men >women), ancestry (east Asians highest, south Asians lowest), higher BMI, older age, presence of diabetes, higher cholesterol, higher blood pressure, and smoking. The study included subjects from the PURE (Prospective Urban Rural Epidemiology) project, involving 14 countries across five continents (Africa, Asia, Europe, North America, and South America). Plasma concentrations of ACE2, a counter-regulator of the renin–angiotensin cascade that cleaves angiotensin II, were measured from biobank samples. Clinical outcomes of interest were all-cause and CV death, myocardial infarction (MI), stroke, heart failure (HF), and diabetes mellitus (DM).In models including clinical risk factors, ACE2 was the highest-ranked predictor of total deaths and cardiovascular deaths.
Fauci: No Quick End to Pandemic
MedPage Today, October 19, 2020
In a sobering message to physicians and their patients, the United States’ top infectious disease official suggests the rampaging SARS-CoV-2 pandemic is going to be with us for a while. “We are now in the middle of an explosive pandemic of historic proportions, the likes of which we have not experienced in the last 102 years with over a million deaths worldwide and 38 million cases – and the end is not in sight,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said as keynote speaker at the virtual annual meeting of the American College of Chest Physicians. “Unfortunately for the United States, we are the worst hit country in the world,” Fauci said in his pre-recorded speech. The U.S. case count surpassed 8 million and the death count was nearing 220,000 over the weekend. Fauci noted that the U.S. government is deeply involved in vaccine development, supporting six different candidate vaccines, including five now in phase III trials. “Our strategic approach means we are harmonizing these vaccine trials so they have a common data monitoring and safety board, common primary and secondary endpoints, and common immunological parameters,” he said.
Acute Aortoiliac and Infrainguinal Arterial Thrombotic Events in Four Patients Diagnosed with the Novel Coronavirus 2019 (COVID-19)
Journal of Vascular Surgery Cases and Innovative Techniques, October 19, 2020
The novel coronavirus 2019 (COVID-19) pandemic is seriously challenging the healthcare system globally. Endothelial damage and increased coagulation activity have been reported in some patients with COVID-19 resulting in a variety of thrombotic events. We report on four patients with various severities of COVID-19 presenting with acute arterial thrombosis. While these are rare events, they carry high morbidity and mortality and require prompt diagnosis and treatment. These cases highlight major life and limb threatening clinical sequalae of COVID-19 that frontline medical providers must be aware occur even in the absence of prior cardiovascular disease. Infection with SARS-CoV-2 (COVID-19) has been shown to have a wide range of clinical presentations from asymptomatic in a large percentage of patients, to devastating pulmonary failure, sepsis, and death. Hypercoagulability has been recognized as a significant cause of the morbidity in this disease, resulting in pulmonary parenchymal thrombosis, venous thrombosis and emboli, and stroke. Multiple causative factors have been implicated including cytokine storm associated with SARS, endotheliitis, and hypoxia. The cases presented demonstrate the occurrence of limb and organ threatening large vessel arterial thrombotic events with a lack of association with the severity of pulmonary infection. Only one patient required prolonged intubation after surgery, and all recovered from their respiratory illness.
Can We Count on Herd Immunity to Control COVID-19?
Journal of the American Medical Association, October 19, 2020
[Audio Clinical Review] Many people are hoping that enough people develop resistance to COVID-19, either from being exposed to the disease or from vaccination, to develop herd immunity that will enable society to return to normal. But will that happen? Saad Omer, MD, from the Yale Institute for Global Health, discusses his JAMA article on herd immunity and how much we can count on having it to return society to normal from this COVID-19 pandemic.
One in five young adults hospitalized for COVID-19 require intensive care
Helio | Infectious Diseases, October 19, 2020
Approximately one-fifth of young adults hospitalized with COVID-19 required intensive care, according to research published in JAMA Internal Medicine. “We think the vast majority of people in this age range have self-limited disease and don’t require hospitalization,” Scott Solomon, MD, director of noninvasive cardiology in the Division of Cardiovascular Medicine at the Brigham and Women’s Hospital, said in a press release. “But if you do, the risks are really substantial.” Solomon and colleagues evaluated data from the Premier Healthcare Database, which includes 1,030 U.S. hospitals and health care systems, on adults aged 18 to 34 years with COVID-19 who were discharged from the hospital between April 1 and June 30. They identified 3,222 young adults with COVID-19 who were hospitalized at 419 U.S. hospitals. Among them, 36.8% were obese, 24.5% were morbidly obese, 18.2% had diabetes and 16.1% had hypertension. Solomon and colleagues identified a greater risk for death or mechanical ventilation among patients with morbid obesity (adjusted OR = 2.30; 95% CI, 1.77-2.98) and hypertension (adjusted OR = 2.36; 95% CI, 1.79-3.12) compared with those without such conditions. They also found that male patients had a greater risk for death or mechanical ventilation compared with female patients (adjusted OR = 1.53; 95% CI, 1.20-1.95).
How does risk vary for Black and Asian patients with COVID-19?
Medical News Today, October 18, 2020
New research suggests that people of Black, mixed, and Asian ethnicity are more at risk of COVID-19, but these risks vary as the disease progresses. A new study finds that COVID-19 risks for people of Black, mixed, or Asian ethnicity vary over the course of the disease. The research also suggests that even after accounting for socioeconomic status and other comorbidities, these populations are more at risk of contracting COVID-19. For the authors of the research, which appears in the journal EClinicalMedicine, this suggests that other yet-to-be-identified factors associated with ethnicity are likely to be at play. As Dr. Winston Morgan, a Reader in Toxicology and Clinical Biochemistry at the University of East London, United Kingdom, argues, “there is as much genetic variation within racialized groups as there is between the whole human population.” For the researchers, while genetic differences can, at times, be associated with specific ethnicities and linked to particular health issues, how this could work in the context of COVID-19 is far from clear. Indeed, for Dr. Morgan: “The evidence suggests that the new coronavirus does not discriminate but highlights existing discriminations. The continued prevalence of ideas about race today – despite the lack of any scientific basis – shows how these ideas can mutate to justify the power structures that have ordered our society since the 18th century.”
Prognosis Poor for Patients With Heart Failure, COVID-19
American Journal of Managed Care, October 16, 2020
Patients with heart failure should be classified as high risk in light of the coronavirus disease 2019 (COVID-19) pandemic, because they are thought to be more susceptible to the virus, according to study results published in ESC Heart Failure. “There are limited data on outcomes in those with preexisting HF developing COVID-19, and in the UK, patients with HF are not currently included on lists to be shielded,” said the authors. “This study sought to quantify the additional risk posed by COVID-19 infection in hospitalized patients with chronic HF by assessing in-hospital mortality.” The primary outcome was in-hospital mortality, and the secondary outcomes were acute kidney injury (AKI), myocardial injury, respiratory compromise requiring noninvasive ventilation or continuous positive airway pressure, and lengths of stay in hospital. The retrospective analysis encompassed all patients (N = 134) with preexisting chronic heart failure admitted to a large London tertiary center from March 1 through May 6, 2020, including those with heart failure with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). COVID-19 diagnosis was determined with nasopharyngeal swab polymerase chain reaction assay.
Neprilysin inhibitors and angiotensin in COVID-19
British Journal of Cardiology, October 16, 2020
The renin–angiotensin system (RAS) has been at the forefront of research aimed at mitigating the infectivity and mortality associated with the coronavirus disease 2019 (COVID-19) pandemic. This stems from the observation that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes COVID-19, utilises angiotensin-converting enzyme 2 (ACE2) as its receptor to invade host cells. Since emergence of COVID-19, conflicting guidance has been published on the use of medications that may increase ACE2 levels. Specifically, initial reports suggested that ACE inhibitors and angiotensin II type 1 receptor blockers (ARBs) may result in increased virulence of COVID-19 due to elevated ACE2. Thus, discontinuation of these RAS blockers was advised. However, the data on ACE2 expression with use of RAS blockers in humans without COVID-19 are not clear, and for humans with COVID-19 are not yet available. The issue regarding use of RAS blockers in the context of COVID-19 has previously been reviewed. Most recently, emerging data suggest no harm is associated with use of ACE inhibitors or ARBs in COVID-19. In this perspective, we discuss a related aspect that was first raised by Acanfora and colleagues, namely, the potential benefit of neprilysin inhibitors and their role in modulating levels of RAS components. Similar to the situation for ACE inhibitors and ARBs, it seems there are mixed opinions on the utility of neprilysin inhibitors in COVID-19.
The effects of COVID-19 on general cardiology in Italy: A vivid description of the pandemic effects in Italy is presented by authors from the University Magna Graecia in Catanzaro, Southern Italy
European Heart Journal, October 16, 2020
Italian cardiologists have been overwhelmed in the battle against COVID-19 both because the disease has well-known cardiac involvement and because many cardiology divisions have become COVID centres, thus jeopardizing cardiological activities. In Italy, healthcare workers paid a very high price during the COVID-19 pandemic, with >160 doctors dying and many infected. Surprisingly, the World Health Organization (WHO) did not initially recommend the use of masks for medical personnel and, when these were recommended, they were simply unavailable because they were produced abroad. Initially, in Italy, the swabs were carried out only for symptomatic patients and cardiologists, and no nasopharyngeal swabs were performed on healthcare personnel in the initial phase of the pandemic, so they could have been a source of contagion themselves. At the time of writing, Italy is in phase 2 of the pandemic, but many hospitals and healthcare organizations are still focused on COVID-19. The exceptional results that cardiology has shown in the diagnosis and treatment of cardiovascular diseases could be jeopardized if cardiological care services are not quickly reorganized.
Scientific consensus on the COVID-19 pandemic: we need to act now
The Lancet, October 15, 2020
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 35 million people globally, with more than 1 million deaths recorded by WHO as of Oct 12, 2020. As a second wave of COVID-19 affects Europe, and with winter approaching, we need clear communication about the risks posed by COVID-19 and effective strategies to combat them. Here, we share our view of the current evidence-based consensus on COVID-19.
Congenital Heart Disease Does Not Increase COVID-19 Risk, Severity
docwirenews, October 15, 2020
A study analyzing COVID-19 risk and outcomes in patients with congenital heart disease (CHD) found that CHD in itself was not a risk factor, but patients with a genetic syndrome and adults at advanced physiological stage were at risk for moderate/severe disease. “At the beginning of the pandemic, many feared that congenital heart disease would be as big a risk factor for COVID-19 as adult-onset cardiovascular disease,” according to the researchers. They retrospectively reviewed CHD patients at Columbia University Irving Medical Center who received a COVID-19 diagnosis between March 1 and July 1. The main outcome measure was moderate/severe COVID-19 response, defined as death or need for hospitalization and/or respiratory support secondary to COVID-19 infection. Final analysis included 53 COVID-19 and CHD patients, 10 of whom (19%) were aged <18 years; the median age overall was 34 years. Thirty-one patients (58%) had complex congenital anatomy (10 [19%] had a Fontan repair); eight patients (15%) had a genetic syndrome, six (11%) had pulmonary hypertension, and nine (17%) were obese. About two in five of the adults (n=18; 41%) were physiologic class C or D.
Eagle’s Eye View: COVID-19 Tip of the Week
American College of Cardiology, October 15, 2020
[Video] Cardiologist Dr. Kim Eagle provides a weekly tip for clinicians on the front lines of the COVID-19 pandemic. This week’s tip focuses on three large randomized trial outcomes for lopinavir–ritonavir, dexamethasone, and remdesivir and their possible effectiveness to reduce mortality in patients hospitalized with COVID-19.
Reduced cardiac function is associated with cardiac injury and mortality risk in hospitalized COVID‐19 Patients
Clinical Cardiology, October 14, 2020
Cardiac injury is common in COVID‐19 patients and is associated with increased mortality. However, it remains unclear if reduced cardiac function is associated with cardiac injury, and additionally if mortality risk is increased among those with reduced cardiac function in COVID‐19 patients. The aim of this study was to assess cardiac function among COVID‐19 patients with and without biomarkers of cardiac injury and to determine the mortality risk associated with reduced cardiac function. This retrospective cohort study analyzed 143 consecutive COVID‐19 patients who had an echocardiogram during hospitalization between March 1, 2020 and May 5, 2020. The mean age was 67 ± 16 years. Cardiac troponin‐I was available in 131 patients and an increased value (>0.03 ng/dL) was found in 59 patients (45%). Reduced cardiac function, which included reduced left or right ventricular systolic function, was found in 40 patients (28%). Reduced cardiac function was found in 18% of patients without troponin‐I elevation, 42% with mild troponin increase (0.04‐5.00 ng/dL) and 67% with significant troponin increase (>5 ng/dL). Reduced cardiac function was also present in more than half of the patients on mechanical ventilation or those deceased. The in‐hospital mortality of this cohort was 28% (N = 40). Using logistic regression analysis, we found that reduced cardiac function was associated with increased mortality with adjusted odds ratio (95% confidence interval) of 2.65 (1.18 to 5.96).
Reduced prevalence of SARS-CoV-2 infection in ABO blood group O
Blood Advances, October 14, 2020
Identification of risk factors for contracting and developing serious illness following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of paramount interest. Here, we performed a retrospective cohort analysis of all Danish individuals tested for SARS-CoV-2 between 27 February 2020 and 30 July 2020, with a known ABO and RhD blood group, to determine the influence of common blood groups on virus susceptibility. Distribution of blood groups was compared with data from nontested individuals. Participants (29% of whom were male) included 473 654 individuals tested for SARS-CoV-2 using real-time polymerase chain reaction (7422 positive and 466 232 negative) and 2 204 742 nontested individuals, accounting for ∼38% of the total Danish population. Hospitalization and death from COVID-19, age, cardiovascular comorbidities, and job status were also collected for confirmed infected cases. ABO blood groups varied significantly between patients and the reference group, with only 38.41% (95% confidence interval [CI], 37.30-39.50) of the patients belonging to blood group O compared with 41.70% (95% CI, 41.60-41.80) in the controls, corresponding to a relative risk of 0.87 (95% CI, 0.83-0.91) for acquiring COVID-19. This study identifies ABO blood group as a risk factor for SARS-CoV-2 infection but not for hospitalization or death from COVID-19.
Effect of COVID-19 on Cardiology Highlighted in Research at ACC Quality Summit
Diagnostic and Interventional Cardiology, October 14, 2020
American College of Cardiology (ACC) Quality Summit Virtual Oct. 8-9, 2020, featured several poster presentations on COVID-19 impacts within cardiology practice over the last several months. Research was focused on the sustainability of telehealth, healthcare disparities in heart failure patients, as well as the impact on patient-centered care and interventional cardiology. Read key research on the impact of COVID-19 on cardiology.
Patients with STEMI, COVID-19 represent ‘unique and high-risk’ population
Helio | Cardiology Today, October 14, 2020
Initial outcomes from the North American COVID-19 STEMI Registry provide a snapshot of the characteristics, presentation, treatment strategies and clinical outcomes of patients with STEMI and confirmed COVID-19. Much concern in the cardiology community this year has focused on the implications of COVID-19 on the heart, as patients with CVD are at higher risk for COVID-19. An unintended consequence of the pandemic has been a 30% to 50% reduction in patients presenting to the hospital with STEMI and other CV issues and, of those who are admitted, 15% to 30% will have a positive troponin, Timothy D. Henry, MD, medical director of the Carl and Edyth Lindner Center for Research and Education at The Christ Hospital in Cincinnati, said during a press conference at the virtual TCT Connect. Henry noted that there has been “considerable controversy” on the appropriate management of patients with STEMI and COVID-19 coming to the cath lab. To date, there have been five publications on STEMI in COVID-19, with a total of 174 patients. Key findings from the five studies show that patients with COVID-19 and STEMI have more frequent in-hospital presentations; more thrombotic lesions and pathologic reports of microthrombi; more frequent nonculprit lesions; and higher mortality, Henry said.
The Impact of Coronavirus disease 2019 (COVID‐19) on Patients with Congenital Heart Disease across the Lifespan: The Experience of an Academic Congenital Heart Disease Center in New York City
Journal of the American Heart Association, October 14, 2020
We sought to assess the impact and predictors of Coronavirus Disease 2019 (COVID-19) infection and severity in a cohort of congenital heart disease (CHD) patients at a large CHD center in New York City. We performed a retrospective review of all individuals with CHD followed at Columbia University Irving Medical Center who were diagnosed with COVID-19 between 3/1/2020 and 7/1/2020. The primary endpoint was moderate/severe response to COVID19 infection defined as a) death during COVID-19 infection; or 2) need for hospitalization and/or respiratory support secondary to COVID-19 infection. Among 53 COVID-19 positive patients with CHD, 10 (19%) were <18 years old (median age 34 years). 31 (58%) had complex congenital anatomy including 10 (19%) with a Fontan repair. Eight (15%) had a genetic syndrome, six (11%) had pulmonary hypertension (PH), and nine (17%) were obese. Among adults, 18 (41%) were physiologic class C or D. For the entire cohort, nine (17%) had a moderate/severe infection, including three deaths (6%). After correcting for multiple comparisons, the presence of a genetic syndrome (OR=35.82: p=0.0002), and in adults, physiological Stage C or D (OR=19.38: p=0.002) were significantly associated with moderate/severe infection.
Two Major COVID Trials Paused for Safety Issues
WebMD, October 14, 2020
Johnson & Johnson paused dosing and enrollment in all of its COVID-19 vaccine clinical trials due to an unexplained illness in a study participant, the company announced Monday. Later in the day, Eli Lilly had to acknowledge a pause of a clinical trial of antibody treatment because of a “potential safety concern,” The New York Times reported, citing emails U.S. government officials sent to researchers. In a statement to the Times, Eli Lily spokesperson Molly McCully confirmed the pause in the trial and said, “Safety is of the upmost importance to Lilly. Lilly is supportive of the decision by the independent (safety monitoring board) to cautiously ensure the safety of the patients participating in this study.” But that wasn’t the only challenge facing Eli Lilly. Reuters reported late Monday that FDA inspectors found serious quality control problems at the Lilly plant where the antibody drugs are manufactured. Meanwhile, in the Johnson & Johnson trial, the patient’s illness is being reviewed and evaluated by an independent monitoring board and the company’s doctors that investigate safety data. “Adverse events — illnesses, accidents, etc. — even those that are serious, are an expected part of any clinical study, especially large studies,” according to the announcement.
NIH trial will test existing drugs against COVID-19
Helio | Infectious Disease News, October 14, 2020
The National Institute of Allergy and Infectious Diseases will repurpose approved or late-stage investigational therapies and test them against COVID-19 to determine if they warrant larger trials, the NIH said. The ACTIV-5 Big Effect Trial (ACTIV-5/BET) will be conducted in partnership with NIH’s public-private partnership Accelerating COVID-19 Therapeutic Innovations and Vaccines (ACTIV) program. The phase 2 adaptive, randomized, double-blind, placebo-controlled trial will recruit adult patients hospitalized with COVID-19 in up to 40 sites across the United States. Each study group will have approximately 100 volunteers, and each testing site will investigate up to three treatments. The NIH said the trial will test two monoclonal antibodies — risankizumab (Boehringer Ingelheim, AbbVie) and lenzilumab (Humanigen) — in combination with remdesivir (Gilead Sciences), compared with control groups that will receive placebo and remdesivir. The goal of the new trial “is to identify as quickly as possible the experimental therapeutics that demonstrate the most clinical promise as COVID-19 treatments and move them into larger scale testing,” NIAID Director Anthony S. Fauci, MD, said in the release. “This study design is both an efficient way of finding those promising treatments and eliminating those that are not.”
A systematic review of SARS-CoV-2 vaccine candidates
Nature, October 13, 2020
The coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to public health. SARS-CoV-2 belongs to the Betacoronavirus of the family Coronaviridae, and commonly induces respiratory symptoms, such as fever, unproductive cough, myalgia, and fatigue. To better understand the virus, numerous studies have been performed, and strategies have been established with the aim to prevent further spread of COVID-19, and to develop efficient and safe drugs and vaccines. For example, the structures of viral proteins, such as the spike protein (S protein), main protease (Mpro), and RNA-dependent RNA polymerase (RdRp), have been uncovered, providing information for the design of drugs against SARS-CoV-2. In addition, elucidating the immune responses induced by SARS-CoV-2 is accelerating the development of therapeutic approaches. In essence, diverse small molecule drugs and vaccines are being developed to treat COVID-19. According to the World Health Organization (WHO), as of September 17, 2020, 36 vaccine candidates were under clinical evaluation to treat COVID-19, and 146 candidate vaccines were in preclinical evaluation. Given that vaccines can be applied for prophylaxis and the treatment for SARS-CoV-2 infection, in this review, we introduce the recent progress of therapeutic vaccines candidates against SARS-CoV-2. Furthermore, we summarize the safety issues that researchers may be confronted with during the development of vaccines. We also describe some effective strategies to improve the vaccine safety and efficacy that were employed in the development of vaccines against other pathogenic agents, with the hope that this review will aid in the development of therapeutic methods against COVID-19.
The stethoscope: a potential vector for COVID-19?
European Heart Journal, October 12, 2020
The COVID-19 pandemic has called into question the triple-faceted role of the stethoscope: a diagnostic tool, symbol of patient–provider connection, and possible vector for infectious disease. A recent article in the American Journal of Medicine discusses developments in each arm of this triple role with reference to COVID-19, arguing that developments in stethoscope diagnostic technology, a need to bolster clinical skills, and developments in stethoscope hygiene methods will perpetuate both its relevance and safety. This argument was made in light of those who believe the stethoscope will become obsolete with the development of more advanced technologies, as well as its potential to transmit disease.1 It is clear that a contaminated stethoscope might pose a danger to patients and providers, and can be a potential vector for the transmission of COVID-19, as illustrated in the case above. Thus, providers should seek to educate themselves on stethoscope contamination, assess the current methods of hygiene, and innovate accordingly rather than cast the stethoscope aside.
Redefining the Prognostic Value of High-Sensitivity Troponin in COVID-19 Patients: The Importance of Concomitant Coronary Artery Disease
Journal of Clinical Medicine, October 12, 2020
In recent times, the available body of evidence assessing the novel Coronavirus disease (COVID19) has led to a progressive steering from a lung-centered disease paradigm in favor of a systemic disease concept. Several studies have reported the presence of an important interplay between the cardiovascular system, coagulation derangements, and COVID-19. The presence of myocardial injury, defined as high-sensitivity cardiac troponin (hs-cTn) elevation, was described especially among most critically ill patients with COVID-19. In these reports, older patients with acute myocardial injury suffered from more cardiovascular (CV) comorbidities and faced less favorable prognosis, and biomarker elevation was present also in patients without underlying obstructive coronary artery disease (CAD). Moreover, frequency of arrhythmias was noted to be higher in patients with myocardial injury, potentially leading to worse outcomes. Patients with chronic coronary syndromes (CCS) defined according to the European guidelines may be more susceptible to triggers that can lead to type 1 or 2 MI. Although CV diseases and myocardial injury are postulated to have a role in worsening clinical outcomes in COVID-19, clear links between history of CCS, myocardial injury, and in-hospital outcomes have not been described. The aim of this study was to evaluate clinical outcomes of CCS patients with COVID-19 and the potential mechanisms of myocardial injury in CCS and no-CCS patients with COVID-19.
Myocarditis and inflammatory cardiomyopathy: current evidence and future directions
Nature Reviews Cardiology, October 12, 2020
Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.
Excess Deaths From COVID-19 and Other Causes, March-July 2020
Journal of the American Medical Association, October 12, 2020
Previous studies of excess deaths (the gap between observed and expected deaths) during the coronavirus disease 2019 (COVID-19) pandemic found that publicly reported COVID-19 deaths underestimated the full death toll, which includes documented and undocumented deaths from the virus and non–COVID-19 deaths caused by disruptions from the pandemic. A previous analysis found that COVID-19 was cited in only 65% of excess deaths in the first weeks of the pandemic (March-April 2020); deaths from non–COVID-19 causes increased sharply in 5 states with the most COVID-19 deaths. This study updates through August 1, 2020, the estimate of excess deaths and explores temporal relationships with state reopenings (lifting of coronavirus restrictions). Although total US death counts are remarkably consistent from year to year, US deaths increased by 20% during March-July 2020. COVID-19 was a documented cause of only 67% of these excess deaths. Some states had greater difficulty than others in containing community spread, causing protracted elevations in excess deaths that extended into the summer. US deaths attributed to some noninfectious causes increased during COVID-19 surges. Excess deaths attributed to causes other than COVID-19 could reflect deaths from unrecognized or undocumented infection with severe acute respiratory syndrome coronavirus 2 or deaths among uninfected patients resulting from disruptions produced by the pandemic.
Genomic evidence for reinfection with SARS-CoV-2: a case study
The Lancet, October 12, 2020
The degree of protective immunity conferred by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently unknown. As such, the possibility of reinfection with SARS-CoV-2 is not well understood. We describe an investigation of two instances of SARS-CoV-2 infection in the same individual. A 25-year-old man who was a resident of Washoe County in the US state of Nevada presented to health authorities on two occasions with symptoms of viral infection, once at a community testing event in April, 2020, and a second time to primary care then hospital at the end of May and beginning of June, 2020. Nasopharyngeal swabs were obtained from the patient at each presentation and twice during follow-up. Nucleic acid amplification testing was done to confirm SARS-CoV-2 infection. We did next-generation sequencing of SARS-CoV-2 extracted from nasopharyngeal swabs. Sequence data were assessed by two different bioinformatic methodologies. A short tandem repeat marker was used for fragment analysis to confirm that samples from both infections came from the same individual. The patient had two positive tests for SARS-CoV-2, the first on April 18, 2020, and the second on June 5, 2020, separated by two negative tests done during follow-up in May, 2020. Genomic analysis of SARS-CoV-2 showed genetically significant differences between each variant associated with each instance of infection. The second infection was symptomatically more severe than the first.
Analysis of existing comorbidities and COVID-19 mortality
News Medical, October 11, 2020
As the COVID-19 pandemic continues to spread, and research related to potential risk factors for COVID-19 mortality continues, it is becoming clear that individuals with underlying comorbidities have a greater risk of death from COVID-19. The exact contribution of different comorbidities is unclear, however. Now, a new study published in the journal PLOS ONE dissects this topic and may help to quantify the risk posed by specific conditions and offer help with the prognosis. These include hypertension, cardiovascular disease, chronic kidney disease, chronic liver disease, cancer, asthma, chronic obstructive pulmonary disease, asthma, and HIV/AIDS. The researchers estimated the risk of dying from COVID-19-related conditions in individuals with these illnesses. The researchers found 25 studies suitable for quantitative analysis, including ~65,500 patients. Almost four-fifths of the studies were from China. The median patient age was 61 years, and 57% of the patients were male. The study also had a median score of 7, indicating a reasonable quality standard. In half the studies that reported this risk, there was a significant negative or positive association, with the estimated risk of mortality being anywhere from ~30% less to ~9 times higher than expected in an uninfected population. The pooling of the studies showed an overall doubling of the risk of death.
Digital cardiovascular care in COVID-19 pandemic: A potential alternative?
Journal of Cardiac Surgery, October 10, 2020
Cardiovascular patients are at increased risk of acquiring coronavirus disease 2019 (COVID‐19) infection while their visit to healthcare facilities. There is a need for alternative tools for optimal monitoring and management of cardiovascular patients in the present pandemic situation. To evaluate the role of digital health care in the present era of the COVID‐19 pandemic, we have reviewed the published literature on digital health services providing cardiovascular care. Digital health care may prove to be a new revolutionary tool to protect cardiovascular patients from coronavirus disease by avoiding routine visits to health care facilities that are already overwhelmed with COVID‐19 patients. The current situation of the COVID‐19 pandemic has unprecedentedly affected usual cardiovascular care; on the other hand, it has allowed digital health to streamline health care delivery. Although cardiovascular delivery through digital health has its limitations, it has surfaced as an effective alternative strategy in this time of pandemic by limiting exposure of both patients and HCWs and ensuring adequate cardiovascular care at the same time.
Role of angiotensin converting enzyme 2 and pericytes in cardiac complications of COVID-19 infection
Heart and Circulatory Physiology, October 10, 2020
The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly reached pandemic proportions, and knowledge about this virus and coronavirus disease 2019 (COVID-19) has expanded rapidly. This review focuses primarily on mechanisms that contribute to acute cardiac injury and dysfunction, which are common in patients with severe disease. The etiology of cardiac injury is multifactorial, and the extent is likely enhanced by pre-existing cardiovascular disease. Disruption of homeostatic mechanisms secondary to pulmonary pathology ranks high on the list, and there is growing evidence that direct infection of cardiac cells can occur. Angiotensin converting enzyme 2 (ACE2) plays a central role in COVID-19 and is a necessary receptor for viral entry into human cells. ACE2 normally not only eliminates angiotensin II (Ang II) by converting it to Ang (1-7), but also elicits a beneficial response profile counteracting that of Ang II. Molecular analyses of single nuclei from human hearts have shown that ACE2 is most highly expressed by pericytes. Given the important roles that pericytes have in the microvasculature, infection of these cells could compromise myocardial supply to meet metabolic demand. Furthermore, ACE2 activity is crucial for opposing adverse effects of locally generated Ang II, so virus-mediated internalization of ACE2 could exacerbate pathology by this mechanism. While the role of cardiac pericytes in acute heart injury by SARS-CoV-2 requires investigation, expression of ACE2 by these cells has broader implications for cardiac pathophysiology.
Acute Myocardial Infarction in the Time of COVID-19”: A Review of Biological, Environmental, and Psychosocial Contributors
International Journal of Environmental Research and Public Health, October 9, 2020
Coronavirus disease 2019 (COVID-19) has quickly become a worldwide health crisis. Although respiratory disease remains the main cause of morbidity and mortality in COVID patients, myocardial damage is a common finding. Many possible biological pathways may explain the relationship between COVID-19 and acute myocardial infarction (AMI). Increased immune and inflammatory responses, and procoagulant profile have characterized COVID patients. All these responses may induce endothelial dysfunction, myocardial injury, plaque instability, and AMI. Disease severity and mortality are increased by cardiovascular comorbidities. Moreover, COVID-19 has been associated with air pollution, which may also represent an AMI risk factor. Nonetheless, a significant reduction in patient admissions following containment initiatives has been observed, including for AMI. The reasons for this phenomenon are largely unknown, although a real decrease in the incidence of cardiac events seems highly improbable. Instead, patients likely may present delayed time from symptoms onset and subsequent referral to emergency departments because of fear of possible in-hospital infection, and as such, may present more complications. Here, we aim to discuss available evidence about all these factors in the complex relationship between COVID-19 and AMI, with particular focus on psychological distress and the need to increase awareness of ischemic symptoms.
Takotsubo Syndrome in Coronavirus Disease 2019
American Journal of Cardiology, October 9, 2020
Around one-fifth of patients with coronavirus disease 2019 (COVID-19) show evidence of acute myocardial injury. The precise etiology remains unclear and the observation that some patients do not show obstructive coronary artery disease (CAD) on coronary angiography has further complicated our understanding of the pathophysiology. Takotsubo syndrome (TTS) constitutes an acute heart failure syndrome that may represent a form of acute catecholaminergic myocardial stunning. TTS presents with the typical symptoms of an acute coronary syndrome, like that observed in some patients with COVID-19. 11 patients with COVID-19 who were diagnosed with TTS based on current criteria were included and compared to 57 patients with COVID-19 alone and 3,215 patients with TTS to elucidate features of COVID-19 patients who develop TTS and to infer the underlying pathology. Furthermore, we have stratified COVID-19 patients with myocardial injury into 2 groups: those with wall motion abnormalities and those without. While COVID-19 disproportionately affected men (68.0%), most patients with COVID-19+TTS were female (88.1%). Most COVID-19+TTS patients had either physical (72.7%) or emotional (18.2%) triggers, most likely from infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with COVID-19+TTS also tended to be older (mean age 72.4 years) compared to patients with COVID-19 alone (mean age 58.5 years) and TTS (mean age 67.8 years). Chest pain was more common among patients with TTS, irrespective of COVID-19, while dyspnea was most prevalent among COVID-19 patients who develop TTS. Importantly, patients with COVID-19 who developed TTS had significantly worse outcomes in terms of rates of respiratory therapy or in-hospital death (70.0%) than traditional cases of TTS (18.6%).
In COVID-19 hospitalizations, survival after cardiac arrest very low
Helio | Cardiology Today, October 9, 2020
In a single-center experience, no patients hospitalized with COVID-19 who developed cardiac arrest survived to discharge after receiving CPR, researchers found. “These outcomes warrant further investigation into the risks and benefits of performing prolonged CPR in this subset of patients, especially because the resuscitation process generates aerosols that may place health care personnel at a higher risk of contracting the virus,” Shrinjaya B. Thapa, MD, internist at William Beaumont Hospital in Royal Oak, Michigan, and colleagues wrote. In this single-center study, researchers analyzed data from 1,309 patients with COVID-19 admitted to the hospital between March 15 and April 3. These data were used to identify patients who underwent CPR for cardiac arrest. Primary outcomes included the initial cardiac arrest rhythm, overall survival to discharge and time to return of spontaneous circulation. Among the cohort, 4.6% (n = 60) had in-hospital cardiac arrest and underwent CPR. The sample size was reduced to 54 patients (mean age, 62 years; 61% men; 67% Black) after some lacked CPR documentation. The time to cardiac arrest from admission was a median of 8 days. The median duration of CPR was 10 minutes. None of the patients who received CPR survived to discharge (95% CI, 0-6.6).
Anticoagulation for Sickest COVID-19 Patients: Tread Carefully
MedPage Today, October 8, 2020
COVID-19 patients without overt venous thromboembolism (VTE) should receive anticoagulation in the hospital but only at relatively low doses, according to American Society of Hematology (ASH) draft guidance. ASH endorsed prophylactic-intensity anticoagulation — not intermediate- or therapeutic-intensity — to prevent clotting in COVID-19 patients who are acutely or critically ill. This conditional recommendation was based on very low certainty in the evidence about the effects of anticoagulation in affected patients, the guideline panel acknowledged. But that may change in the near future, as there are currently 20 or so global randomized trials studying the question of anticoagulation dosing for primary thromboprophylaxis in sick, hospitalized COVID-19 patients, according to Alex Spyropoulos, MD, of Northwell Health at Lenox Hill Hospital in New York City, who was not involved with the group. A pilot randomized trial, HESACOVID, recently suggested that therapeutic-level dosing of enoxaparin (Lovenox) improved respiratory outcomes in severe COVID-19. Spyropoulos said he agreed with the proposed ASH guideline recommendations, and he noted that VTE rates from large U.S. health systems have been much lower than those reported from earlier, smaller studies from China and Europe.
Remdesivir Distribution Transitioned to Gilead Under Revised EUA
Pulmonology Advisor, October 7, 2020
The Food and Drug Administration (FDA) has revised the Emergency Use Authorization (EUA) for remdesivir (Veklury; Gilead Sciences) removing the US government’s role in directing the allocation of the investigational coronavirus disease 2019 (COVID-19) treatment. Remdesivir is a nucleotide analogue with broad-spectrum antiviral activity. It is currently available in the US under an EUA for hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19, regardless of disease severity. Since the COVID-19 pandemic began, the US Department of Health and Human Services (HHS) was responsible for the allocation and distribution of remdesivir to COVID-19 patients. By increasing manufacturing capacity, Gilead has been able to expand the supply of remdesivir, which now exceeds market demand based on recent allocation numbers from HHS’ Office of the Assistant Secretary for Preparedness and Response. Under the revised EUA, Gilead Sciences will resume control of the distribution of remdesivir in the US. To ensure stable management of drug supply, AmerisourceBergen will remain the sole US distributor of the product through the end of this year and will sell directly to hospitals. The Company is now able to meet real-time demand for remdesivir and potential future surges of COVID-19.
Cardiac Tamponade in a Patient With Myocardial Infarction and COVID-19 – Electron Microscopy
Journal of the American College of Cardiology, October 7, 2020
[Case Report] We present the case of a patient with myocardial infarction and COVID-19 disease who developed hemorrhagic pericardial effusion and cardiac tamponade. The differential diagnosis included post-infarction pericarditis and mechanical complications, thrombolysis, Dressler syndrome, and viral pericarditis. The histopathologic examination of the pericardial tissue sample and electron microscopic examination established the diagnosis. A 64 year-old-man was admitted to the Ignacio Chávez National Institute of Cardiology in Mexico City, Mexico with chest pain, dry cough, and fever (38.3ºC). He was dyspneic, with 85% arterial oxygen saturation, a heart rate of 84 beats/min and blood pressure of 106/87 mm Hg. Diffuse pulmonary rales were found, predominately at the left lung base. The electrocardiogram showed ST-segment elevation on the inferior and posterior leads. The chest radiograph showed bilateral diffuse interstitial infiltrates, predominantly in the left lung. The result of real-time reverse transcription-polymerase chain reaction for detection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) RNA was positive, so antiviral therapy was added. A transthoracic echocardiogram (TTE) showed inferolateral and inferior wall akinesia and an ejection fraction of 30% without pericardial effusion.
Surgeon general: Hypertension control must be national public health priority
Helio | Cardiology Today, October 7, 2020
The Office of the Surgeon General released a report highlighting the importance of hypertension control as a national public health priority. Nearly half of U.S. adults — 108 million — have hypertension, yet only 1 in 4 people have it under control, U.S. Surgeon General Jerome M. Adams, MD, MPH, said during the release of a call to action by HHS. “I don’t want us to ever forget the tragedy of over 200,000 people who have died due to COVID-19,” Adams said. “We must keep our eyes on that ball … but I also don’t want us to turn a blind eye to the more than 500,000 people who will die this year due to uncontrolled high blood pressure. While we’re still looking for vaccines and therapeutics to treat COVID, I want you to know we have the tools already to end our national epidemic of uncontrolled hypertension.” Adams said the COVID-19 pandemic served as a catalyst for this document, especially since it has affected several subsets of the population.
Cardiovascular disease and cardiovascular outcomes in COVID‐19
Practical Diabetes, October 7, 2020
Patients with cardiovascular disease have an increased risk of severe COVID‐19 disease and an increased mortality. Clinical observations have described cardiovascular complications of COVID‐19 in patients without prior cardiovascular disease, including acute cardiac injury, myocarditis, heart failure, arrhythmias, and acute coronary syndromes. These are also associated with a worse outcome from COVID‐19. Several of the potential treatments for COVID‐19 may also have cardiovascular consequences. Some of the acute cardiovascular complications resolve on recovery from the infection and it is uncertain how many people will suffer permanent cardiovascular damage. During the emergency lockdown that was introduced to deal with the pandemic it has been observed that hospital admissions with other cardiovascular conditions, such as acute coronary syndromes and heart failure, have been greatly reduced. Prior cardiovascular disease increases the morbidity and mortality from COVID‐19, and several cardiovascular consequences of COVID‐19 have been described in hospital inpatients. Careful follow up of these patients will be required to see if these cardiovascular effects resolve completely, as was the case for most patients with SARS infection, or whether some people sustain permanent cardiovascular damage from COVID‐19.
The Impact of COVID-19 on the Continuity of Cardiovascular Care: The authors discuss the challenges and offer potential solutions to facilitate safe and effective clinical care during and after this unique pandemic
European Heart Journal, October 6, 2020
Healthcare services globally are combating the impact of SARS-CoV-2 and associated COVID-19 infection, which has caused significant morbidity and mortality across all affected countries. Whilst the medical community and resources have focused on this pandemic, it is important to consider that cardiovascular disease remains the most common cause of death globally and accounts for in excess of 17.8 million deaths annually. Of concern, there was an alarming reduction in healthcare seeking behaviours during the enforced lockdown period to contain viral spread. Admissions to hospital with an acute coronary syndrome significantly dropped and individuals who eventually sought medical help experienced a higher fatality rate. These observations are difficult to accept when prognostically important therapies such as primary percutaneous coronary intervention were widely used prior to the pandemic. Moreover, as lockdown measures are tentatively eased we enter a precarious period when delivery of cardiovascular care will face several challenges and will need to constantly adapt to the pandemic’s evolution. In this article, we aim to provide an overview of these challenges and suggest potential solutions based on current models of care.
Cardiac Involvement of COVID-19: A Comprehensive Review
American Journal of the Medical Sciences, October 6, 2020
Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. SARS-CoV-2 caused COVID-19 has reached a pandemic level. COVID-19 can significantly affect patients’ cardiovascular systems. First, those with COVID-19 and preexisting cardiovascular disease have an increased risk of severe disease and death. Mortality from COVID-19 is strongly associated with cardiovascular disease, diabetes, and hypertension. Second, therapies under investigation for COVID-19 may have cardiovascular side effects of arrhythmia. Third, COVID-19 is associated with multiple direct and indirect cardiovascular complications. Associated with a high inflammatory burden related to cytokine release, COVID-19 can induce vascular inflammation, acute myocardial injury, myocarditis, arrhythmias, venous thromboembolism, metabolic syndrome and Kawasaki disease. Understanding the effects of COVID-19 on the cardiovascular system is essential for providing comprehensive medical care for cardiac and/or COVID-19 patients. We hereby review the literature on COVID-19 regarding cardiovascular virus involvement.
Deep phenotyping of 34,128 adult patients hospitalised with COVID-19 in an international network study
Nature Communications, October 6, 2020
Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 shares similarities with influenza to the extent that both cause respiratory disease which can vary markedly in its severity and present with a similar constellation of symptoms, including fever, cough, myalgia, malaise, fatigue and dyspnoea. Early reports do, however, indicate that the proportion of severe infections and mortality rate is higher for COVID-19. Older age and a range of underlying health conditions, such as immune deficiency, cardiovascular disease, chronic lung disease, neuromuscular disease, neurological disease, chronic renal disease and metabolic diseases, have been associated with an increased risk of severe influenza and associated mortality. Here we first aimed to describe the characteristics of patients hospitalised with COVID-19. In particular, we set out to summarise individuals’ demographics, medical conditions, and medication use.
Long-term Health Consequences of COVID-19
Journal of the American Medical Association, October 5, 2020
With more than 30 million documented infections and 1 million deaths worldwide, the coronavirus disease 2019 (COVID-19) pandemic continues unabated. The clinical spectrum of severe acute respiratory syndrome coronavirus (SARS-CoV) 2 infection ranges from asymptomatic infection to life-threatening and fatal disease. Current estimates are that approximately 20 million people globally have “recovered”; however, clinicians are observing and reading reports of patients with persistent severe symptoms and even substantial end-organ dysfunction after SARS-CoV-2 infection. Because COVID-19 is a new disease, much about the clinical course remains uncertain—in particular, the possible long-term health consequences, if any. Currently, there is no consensus definition of postacute COVID-19. Based on the COVID Symptom Study, in which more than 4 million people in the US, UK and Sweden have entered their symptoms after a COVID-19 diagnosis, postacute COVID-19 is defined as the presence of symptoms extending beyond 3 weeks from the initial onset of symptoms and chronic COVID-19 as extending beyond 12 weeks. It is possible that individuals with symptoms were more likely to participate in this study than those without them. Myocardial injury, as defined by an increased troponin level, has been described in patients with severe acute COVID-19, along with thromboembolic disease. Myocardial inflammation and myocarditis, as well as cardiac arrhythmias, have been described after SARS-CoV-2 infection. In a German study of 100 patients who recently recovered from COVID-19, cardiac magnetic resonance imaging (performed a median of 71 days after COVID-19 diagnosis) revealed cardiac involvement in 78% and ongoing myocardial inflammation in 60%.
COVID-19 cardiac involvement on the rise
MayoClinic, October 4, 2020
In the early stages of the COVID-19 pandemic, the disease was recognized as a respiratory virus. Research is showing that the SARS-CoV-2 virus is causing more significant cardiac issues than initially thought. “We are finding that COVID-19 can cause direct damage to the heart,” says Dr. Leslie Cooper, chair of the Department of Cardiology at Mayo Clinic. Although individuals with cardiovascular disease are at increased risk for more severe complications from COVID-19, Dr. Cooper says any person infected with the virus may be at risk for cardiac involvement. “COVID can affect the heart indirectly through inflammatory cells that circulate in your blood that can go into the heart and by damaging heart muscle cells as well,” he says. Of late, COVID-related myocarditis, or inflammation of the heart muscle, is the condition that is causing growing concern. Myocarditis can cause significant heart damage and rarely sudden cardiac death if it’s left untreated. “Myocarditis and other forms of heart injury can affect younger individuals, such as athletes.” Though not everyone needs to be tested, Dr. Cooper says patients suspected to have COVID-19 related cardiac injury would undergo tests, including a troponin blood test, which can reveal damaged heart muscles cells, and an electrocardiogram or EKG, which can show involvement of the conduction system of the heart or damage of the heart muscle.
Circulating ACE2: a novel biomarker of cardiovascular risk
The Lancet, October 3, 2020
Dysregulation of the renin–angiotensin system plays a major role in the progression of cardiovascular disease in humans. The enzymatic reactions within the renin–angiotensin system generate angiotensin II, which promotes vasoconstriction and inflammation and deleterious cardiovascular effects. Angiotensin-converting enzyme 2 (ACE2) acts to counterbalance the renin–angiotensin system by degrading angiotensin II. In 2005, ACE2 was identified as the cellular receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and we now know that ACE2 also facilitates viral entry of SARS-CoV-2, leading to widespread systemic illness in COVID-19. Perhaps one of the most important pieces of information from the study by Narula and colleagues in the setting of the ongoing COVID-19 pandemic is the absence of any association between ACE2 levels and the use of ACE inhibitors, angiotensin-receptor blockers (ARBs), β blockers, calcium channel blockers, and diuretics. These results, validated by simultaneously performed mendelian randomisation studies, add support to the evidence that renin–angiotensin system inhibitors should not be withheld in patients with COVID-19 for the sole purpose of modifying ACE2.
Study: Heart risk factors neglected amid COVID-19, telehealth
Center for Infectious Disease Research and Policy, October 2, 2020
Substantial numbers of patients chose telemedicine over in-person visits during the early part of the COVID-19 pandemic, unintentionally missing important opportunities to have their blood pressure and cholesterol checked and putting them at risk for heart attacks and strokes, according to a study published today in JAMA Network Open. But the authors of an invited commentary in the same journal find both hope and opportunity in the study, which found no significant difference in telemedicine uptake between black and white patients or those with different kinds of health insurance, suggesting that virtual visits may be accessible to many patients traditionally subjected to systematic health inequities. Blood pressure checks dropped by 44.4 million visits (50.1%), and cholesterol checks declined by 10.2 million visits (36.9%) in second-quarter 2020, compared with the same period in 2018 and 2019. Blood pressure assessments were less likely during telemedicine than in in-person visits (9.6% vs 69.7%), as were cholesterol assessments (13.5% vs 21.6%).
Global Death Toll From COVID-19 Passes 1 Million
Pulmonology Advisor, October 2, 2020
The global COVID-19 pandemic reached a grim new milestone on Tuesday: 1 million dead. Americans made up more than 200,000 of those deaths, or one in every five, according to a running tally compiled by Johns Hopkins University. “It’s not just a number. It’s human beings. It’s people we love,” Howard Markel, M.D., a professor of medical history at the University of Michigan, told the Associated Press. He is an adviser to government officials on how best to handle the pandemic – and he lost his 84-year-old mother to COVID-19 in February. “It’s people we know,” Markel said. “And if you don’t have that human factor right in your face, it’s very easy to make it abstract.” It has taken the newly emerged severe acute respiratory syndrome coronavirus 2 virus just eight months to reach a worldwide death toll that has meant personal and economic tragedy for billions. Right now, more than 33 million people worldwide are known to have been infected with the new coronavirus, the Hopkins tally showed.
COVID-19 may increase risk for HFpEF
Helio | Cardiology Today, October 2, 2020
There may be a link between COVID-19 and HF with preserved ejection fraction, as infection from SARS-CoV-2 may cause, unmask or exacerbate HFpEF, according to a viewpoint published in JAMA. “Patients who had COVID-19 will need to be monitored long term for symptoms of heart failure,” Priya Mehta Freaney, MD, cardiology fellow at Northwestern University Feinberg School of Medicine, told Healio. “This is especially critical for those who experienced lung injury and may have cardiovascular complications related to chronic pulmonary disease following recovery from COVID-19.” The association between COVID-19 and HFpEF may reveal the bigger burden of poor heart health in the United States even before the pandemic started, Sadiya S. Khan, MD, MSc, assistant professor of medicine (cardiology) and preventive medicine (epidemiology) at Northwestern University Feinberg School of Medicine, told Healio. “People with obesity or hypertension are more likely to get COVID-19, are more likely to have a severe case and are more likely to have cardiovascular complications even without direct heart injury or myocarditis,” she said. Both COVID-19 and HFpEF share a central pathogenesis: inflammation. The SARS-CoV-2 infection results in a release of proinflammatory cytokines that affect the respiratory system and myocardium, according to the viewpoint. COVID-19 and HFpEF also have shared cardiometabolic risk profiles.
NNU report: 1,700+ HCWs died from COVID-19 in US
Helio | Primary Care, October 2, 2020
As of Sept. 16, there have been 1,718 deaths from COVID-19 and related complications among health care workers in the U.S., significantly more than the 690 deaths reported by the CDC, according to a report released by National Nurses United. “Nurses and health care workers were forced to work without personal protective equipment they needed to do their job safely,” Zenei Cortez, RN, a president of National Nurses United, said in a press release. “It is immoral and unconscionable that they lost their lives.” The report follows survey results released by the American Nurses Association last month, which found that many nurses across the United States were still facing PPE shortages, with many reusing essential N-95 masks for 5 days or longer. Researchers collected information on registered nurses and other health care workers using media reports, obituaries, union memorial pages, GoFundMe and social media platforms, including Facebook, Twitter and Reddit. They assessed deaths from COVID-19 and related complications among health care workers, which they defined as all workers in care settings, including nursing homes, hospitals, medical practices, congregate-living and home health care settings. They found that among the 1,718 health care worker deaths attributed to COVID-19-related illness, 213 deaths occurred among registered nurses.
Analysis of the clinical characteristics of 77 COVID-19 deaths
Scientific Reports October 2, 2020
The COVID-19 outbreak is becoming a public health emergency. Data are limited on the clinical characteristics and causes of death. A retrospective analysis of COVID-19 deaths were performed for patients’ clical characteristics, laboratory results, and causes of death. In total, 56 patients (72.7%) of the decedents (male–female ratio 51:26, mean age 71 ± 13, mean survival time 17.4 ± 8.4 days) had comorbidities. Acute respiratory failure (ARF) and sepsis were the main causes of death. Increases in C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer and lactic acid and decreases in lymphocytes were common laboratory results. Intergroup analysis showed that (1) most female decedents had cough and diabetes. (2) The proportion of young- and middle-aged deaths was higher than elderly deaths for males, while elderly decedents were more prone to myocardial injury and elevated CRP. (3) CRP and LDH increased and cluster of differentiation (CD) 4+ and CD8+ cells decreased significantly in patients with hypertension. The majority of COVID-19 decedents are male, especially elderly people with comorbidities. The main causes of death are ARF and sepsis. Most female decedents have cough and diabetes. Myocardial injury is common in elderly decedents. Patients with hypertension are prone to an increased inflammatory index, tissue hypoxia and cellular immune injury.
The impact of COVID-19 pandemic on cardiac surgery in Israel
Journal of Cardiothoracic Surgery, October 2, 2020
Ever since the coronavirus disease 2019 (COVID-19) has become a pandemic, worldwide efforts are being made to “flatten the curve”. Israel was amongst the first countries to impose significant restrictions. As a result, cardiac surgeons have been required to scale down their routine practice, resulting in a significant reduction in the number of cardiac surgeries. The aim of this study is to characterize the impact of COVID-19 on cardiac surgery in Israel. This is a retrospective observational study performed in two cardiac surgery departments in Israel and includes all patients who underwent cardiac surgery in March and April during the years 2019 and 2020. The patient cohort was divided into two groups based on the year of operation. Analysis of the patients’ baseline characteristics, operative data, and postoperative outcome, was performed. The 2019 group (n = 173), and the 2020 group (n = 108) were similar regarding their baseline characteristics, previous medical history, and rates of previous revascularization interventions. However, compared to the 2019 group, patients in the 2020 group were found to be more symptomatic (NYHA class IV; 2.4% vs. 6.2%, p = 0.007). While all patients underwent similar procedures, patients in the 2020 group had significantly longer procedural time (p < 0.001). In-hospital mortality rate was found to be significantly higher in group 2020 (13% vs. 5.2%, p = 0.037).
President and First Lady Test Positive for COVID-19
MedPage Today, October 2, 2020
In the dark of night, in a tweet retweeted over 600,000 times in the first three hours in which it posted, Trump announced both he and first lady Melania Trump have tested positive for COVID-19, the disease he has publicly downplayed since the start of the pandemic and which has now killed over 207,000 people in the U.S. “@FLOTUS and I tested positive for COVID-19. We will begin our quarantine and recovery process immediately. We will get through this TOGETHER!” he tweeted. The potential ramifications to this are many: At the very least, Trump will be required to temporarily halt his campaign while he quarantines, and will miss the next presidential debate, planned for October 15. Longer term, should the President exhibit symptoms, under the 25th Amendment he would have the option to transfer power to Vice President Mike Pence while he recovers.
Cardiometabolic multimorbidity is associated with a worse Covid-19 prognosis than individual cardiometabolic risk factors: a multicentre retrospective study (CoViDiab II)
Cardiovascular Diabetology, October 1, 2020
Cardiometabolic disorders may worsen Covid-19 outcomes. We investigated features and Covid-19 outcomes for patients with or without diabetes, and with or without cardiometabolic multimorbidity. We collected and compared data retrospectively from patients hospitalized for Covid-19 with and without diabetes, and with and without cardiometabolic multimorbidity (defined as ≥ two of three risk factors of diabetes, hypertension or dyslipidaemia). Multivariate logistic regression was used to assess the risk of the primary composite outcome (any of mechanical ventilation, admission to an intensive care unit [ICU] or death) in patients with diabetes and in those with cardiometabolic multimorbidity, adjusting for confounders. Of 354 patients enrolled, those with diabetes (n = 81), compared with those without diabetes (n = 273), had characteristics associated with the primary composite outcome that included older age, higher prevalence of hypertension and chronic obstructive pulmonary disease (COPD), higher levels of inflammatory markers and a lower PaO2/FIO2 ratio. The risk of the primary composite outcome in the 277 patients who completed the study as of May 15th, 2020, was higher in those with diabetes. Patients with cardiometabolic multimorbidity were at higher risk compared to patients with no cardiometabolic conditions. The risk for patients with a single cardiometabolic risk factor did not differ with that for patients with no cardiometabolic risk factors.
Antiviral activity of digoxin and ouabain against SARS-CoV-2 infection and its implication for COVID-19
Scientific Reports, October 1, 2020
The current coronavirus (COVID-19) pandemic is exacerbated by the absence of effective therapeutic agents. Notably, patients with COVID-19 and comorbidities such as hypertension and cardiac diseases have a higher mortality rate. An efficient strategy in response to this issue is repurposing drugs with antiviral activity for therapeutic effect. Digoxin (DIG) and ouabain (OUA) are FDA drugs for heart diseases that have antiviral activity against several coronaviruses. Thus, we aimed to assess antiviral activity of DIG and OUA against SARS-CoV-2 infection. The half-maximal inhibitory concentrations (IC50) of DIG and OUA were determined at a nanomolar concentration. Progeny virus titers of single-dose treatment of DIG, OUA and remdesivir were approximately 103-, 104- and 103-fold lower (> 99% inhibition), respectively, than that of non-treated control or chloroquine at 48 h post-infection (hpi). Furthermore, therapeutic treatment with DIG and OUA inhibited over 99% of SARS-CoV-2 replication, leading to viral inhibition at the post entry stage of the viral life cycle. Collectively, these results suggest that DIG and OUA may be an alternative treatment for COVID-19, with potential additional therapeutic effects for patients with cardiovascular disease.
COVID-19 and Heart Failure With Preserved Ejection Fraction
Journal of the American Medical Association, September 30, 2020
Patients with preexisting cardiovascular disease (CVD) who develop coronavirus disease 2019 (COVID-19) have worse outcomes than patients without CVD. Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly or indirectly lead to myocardial injury. Although fulminant viral myocarditis due to COVID-19 appears to be uncommon, recent data, although limited, suggest that direct myocardial injury may occur in some individuals. This Viewpoint contextualizes the emerging data on the risk of heart failure, particularly heart failure with preserved ejection fraction (HFpEF), in patients during both the acute phase of COVID-19 illness and the chronic phase of recovery in COVID-19 survivors. This is important to elucidate, because infection with COVID-19 may be associated with HFpEF through several pathways: COVID-19 may cause HFpEF via direct viral infiltration, inflammation, or cardiac fibrosis; it may unmask subclinical HFpEF in individuals with underlying risk factors; or it may exacerbate preexisting HFpEF. Key issues are discussed involving the link between COVID-19 and risk of HFpEF due to their shared inflammatory pathophysiology and cardiometabolic risk profiles and the potential for an increase in the individual- and population-level effects of HFpEF in the aftermath of the pandemic.
Managing Aortic Stenosis in the Age of COVID-19
JAMA Network Open, September 30, 2020
To state the obvious, the world is in the grip of a pandemic with profound health implications beyond mortality associated with severe acute respiratory syndrome coronavirus 2 itself. Its impact on the delivery of health care that would otherwise be classified as routine is profound, if subtle. Cardiovascular conditions requiring inpatient procedures, such as interventions to treat symptomatic aortic stenosis, are among those that are clearly lifesaving and among those contributing to a hidden mortality of coronavirus disease 2019 (COVID-19). Whether one chooses to interpret the current state of the pandemic as an ongoing first wave—perhaps with a nadir in some regions—or as the quiet before a second wave, there is a clear need for tools permitting precise triage of patients by the urgency with which procedures should be performed. The studies by Ryffel et al from Switzerland and Ro et al from New York aim to help clinicians in that regard. Taken together, these studies1 provide useful guidance. First, as we have known for many years, symptomatic aortic stenosis is a life-threatening condition, and its treatment cannot be considered elective in any way. Patients with the most echocardiographically severe stenosis, clinically advanced symptoms, or comorbid coronary artery disease or lung disease belong at the head of the line. And although not addressed by the studies by Ryffel et al or Ro et al, it certainly makes sense that, all things being equal, from the patient’s standpoint, transcatheter AVR is preferable to surgical AVR, given shorter hospitalization and consequent exposure of patients to COVID-19 in hospital and rehabilitation centers. This is true from the standpoint of the health care system as well, undoubtedly conserving intensive care unit and hospital beds relative to surgical AVR.
Electrophysiology in the time of coronavirus: coping with the great wave
EP Europace, September 30, 2020
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the agent responsible for COVID-19 has an affinity for angiotensin-converting enzyme 2 (ACE2) receptors. This is central to the pathophysiology of the condition, leading to pneumonia and in critical stages, to multiorgan failure. The organ primarily affected is the lung, but cardiovascular injury is also common and those with a rise in Troponin I are more likely to require admission into intensive care. While the pandemic disrupts the delivery of routine electrophysiology services, COVID-19 is associated with cardiac complications, which could bring an additional burden of acute problems to electrophysiology. The relative importance of the reduction in elective cases and any increase in emergency work is undefined. We reviewed the catheter lab records of electrophysiology laboratories in each contributing centre. The workflow was quantified before and during the period of restriction of normal activity imposed by COVID-19, and in the case of Wenzhou in the period after restrictions were lifted. The impact on workflow was correlated with the national burden of COVID-19. We charted the burden of emergency procedures performed to look for evidence of any augmentation of these arising from COVID-19; we also examined the record for information about procedures performed for arrhythmias in patients with COVID-19 and enquired from the front-line, arrhythmic complications encountered in the COVID-19 population. We looked for instances of COVID-19 infection acquired in hospital by electrophysiology patients and staff. We documented the protocols used to limit the risk to patients and staff during the period of high burden of COVID-19 and the protocols used to permit the resumption of activity after the first wave of the epidemic.
Characteristics and Outcomes of Patients Deferred for Transcatheter Aortic Valve Replacement Because of COVID-19
JAMA Network Open, September 30, 2020
Coronavirus disease 2019 (COVID-19) is a global pandemic that has led to diversion of resources to the front lines and postponement of elective procedures. Patients with structural heart disease are a high-risk cohort because of their age and comorbidities. Management of their underlying condition has sometimes been delayed as a result of efforts to avoid community and health care setting exposure to COVID-19. An executive order was enacted by the New York State government on March 22, 2020, leading to cancellation of elective procedures. We describe here the outcomes of patients with symptomatic, severe aortic stenosis (AS) from our structural heart disease program during the COVID-19 pandemic. This was a single-center cohort study of 77 patients with severe AS undergoing evaluation for transcatheter aortic valve replacement (TAVR) at a tertiary care hospital before the COVID-19 pandemic. This study was conducted under an institutional review board for the Structural Heart Program of Mount Sinai Hospital. The study posed minimal risk to patients, and the collected data were deidentified; thus, the need for informed consent was waived. This study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Compromised STEMI reperfusion strategy in the era of COVID-19 pandemic: pros and cons
European Heart Journal, September 30, 2020
Indeed, daily practice may be altered in response to the sudden outbreak of COVID-19 as we did in cardiology. We proposed previously a modified workflow for managing STEMI patients which had undergone repeated discussions as to achieve optimal benefits over risks. However, we have to admit that the workflow renewed is not a universal guideline but rather a local guidance which is the result of experiences from Chinese cardiologists at the forefront of the COVID-19 pandemic; there is currently no evidence to support or oppose the rationality of this altered reperfusion strategy, and we believe it will surely change over time with changes in the pandemic. In the renewed workflow, the role of fibrinolysis was somewhat strengthened mainly out of the following considerations. First, at the initial stage of the outbreak, the preparedness was insufficient in terms of medical personnel training for infection prevention and control, shortage of PPE, and lack of negative pressure catheterization rooms, etc. Medical treatment (i.e. fibrinolysis) in this sense may reduce possible nosocomial transmissions compared with mechanic reperfusion with primary percutaneous coronary intervention (PCI). Second, although primary PCI is preferred within indicated timeframes (e.g. <12 h of symptom onset), fibrinolytic therapy remains a valid choice of treatment for STEMI especially with the advent of tissue-specific thrombolytic agents.
Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers – A Randomized Clinical Trial
JAMA Internal Medicine, September 30, 2020
Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our knowledge, there is no effective pharmacologic prophylaxis for individuals at risk. The objective of the study was to evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy. This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants.
Perfect storm for heart disease created by COVID-19
World Heart Federation, September 29, 2020
The COVID-19 pandemic is creating a perfect storm for the heart, the World Heart Federation (WHF) warns on World Heart Day. Three main factors are contributing to this phenomenon. First, people with COVID-19 and heart disease are among those with the highest risk of death and of developing severe conditions. Second, after the virus attacks, the heart might be adversely affected even in people without previous heart conditions, potentially resulting in long-term damage. Finally, fear of the virus has already led to a sharp decline in hospital visits by heart patients for routine and emergency care. This World Heart Day is unlike any other that has come before. Public health is front and centre as societies face the challenges of the COVID-19 pandemic and the physical, emotional and economic toll it has taken. Almost a million lives have been lost to COVID-19 this year. As a comparison, an estimated 17.8 million people died from cardiovascular disease in 2017. While patients steer clear of hospitals out of fear of catching the virus, their health is compromised even further. WHF has the singular purpose of uniting the global health community to beat cardiovascular disease. This year, we are asking individuals, communities and governments to “use heart” to make better choices for society, our loved ones and ourselves. The “Use Heart” call to action is about using our head, influence and compassion to beat cardiovascular disease, the world’s number one killer. Given the current situation, WHF is also calling for recognition and urgent protection of frontline healthcare providers.
Study identifies thousands of deaths caused by heart disease and stroke during COVID-19 pandemic
News Medical, September 29, 2020
A major new study has identified 2085 excess deaths in England and Wales due to heart disease and stroke during the peak of the COVID-19 pandemic. On average, that is 17 deaths each day over four months that probably could have been prevented. Excess deaths are the number of deaths above what is normally expected – and the figure relates to the period from 2 March to 30 June, 2020. The scientists believe the excess deaths were caused by people not seeking emergency hospital treatment for a heart attack or other acute cardiovascular illness requiring urgent medical attention, either because they were afraid of contracting COVID-19 or were not referred for treatment. Over the same period, there was a sharp rise in the proportion of people who died at home or in a care home from acute cardiovascular diseases. Dr Jianhua Wu, Associate Professor in the School of Medicine at Leeds, led the latest study. He said: “This study is the first to give a detailed and comprehensive picture of what was happening to people who were acutely ill with cardiovascular disease cross England and Wales. “It reveals a large number of excess deaths. The findings will help Government and the NHS to develop messages that ensure people who are very ill do seek help.”
Outcomes of In-Hospital Cardiac Arrest in COVID-19
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771090
JAMA Internal Medicine, September 28, 2020
This study questions: What is the in-hospital cardiac arrest (IHCA) survival to discharge in patients with coronavirus disease 2019 (COVID-19)? Among hospitalized patients with a diagnosis of COVID-19, chart review was performed to identify those who underwent cardiopulmonary resuscitation (CPR) for cardiac arrest. Among 1,309 patients hospitalized with COVID-19, 60 (4.6%) developed IHCA and underwent CPR. Complete chart information was available in 54 patients. The initial rhythm was nonshockable for 52 patients (96.3%), with 44 (81.5%) with pulseless electrical activity and eight (14.8%) with asystole. Two patients (3.7%) developed pulseless ventricular tachycardia, and none developed ventricular fibrillation. Return of spontaneous circulation was achieved in 29 patients (53.7%). Fifteen of twenty-nine patients (51.7%) who achieved return of spontaneous circulation had their code status changed to do not resuscitate, while 14 patients (48.3%) were recoded, received additional CPR, and died. The survival to discharge was 0 of 54 (95% confidence interval, 0-6.6). At the time of cardiac arrest, 43 patients (79%) were receiving mechanical ventilation, 18 (33%) kidney replacement therapy, and 25 (46.3%) vasopressor support. There was a 100% mortality rate among COVID-19 patients who experienced an IHCA.
Decrease in cardiac catheterization and MI during COVID pandemic
American Heart Journal Plus, September 28, 2020
The consequences of severe acute viral respiratory syndrome (COVID 19) pandemic include collateral effects, one of which has been the significant reduction in routine hospital work. With widespread reports indicating reduction of cardiac procedures including MI presentation to hospitals, we aimed to analyze the local data over a 10-week period during lockdown in a tertiary cardiac centre Catheter Laboratory in England. We conducted a retrospective review of the coronary catheterisation procedures and admissions with MI over the peak COVID-19 pandemic 10-week period (23rd March-30th May) in 2020, compared with the same 10-week period (25th March-2nd June) in 2019. In 2019, 539 patients were admitted to the Cath lab for coronary catheterisation (M = 385:F = 154; mean age 65 years; STEMI = 186, NSTEMI = 192, elective = 161). In 2020, during peak period of COVID19 pandemic in England, a total of 278 patients were admitted for coronary catheterisation over the 10-week period (M = 201:F = 77; mean age 60.5 years; STEMI = 132, NSTEMI = 118, elective = 28). During peak COVID19 pandemic, this represents a 48.4% drop in all coronary catheterisations. The reduction in STEMI was 29% (54 less), in NSTEMI was 38.9% (74 less) and elective procedures dropped by 83% (133 less).
COVID-19 Cases Going Up in Half of States
WebMD, September 28, 2020
Two dozen states are reporting an increase in new daily coronavirus infections, including several states that are breaking record numbers. Cases mostly trended downward throughout August and most of September after major peaks in July, and now the numbers are moving back up again. Overall, the U.S. reported more than 55,000 new cases on Friday, and the total tally pushed above 7 million this week. The national 7-day average is also increasing, according to NPR. In Wisconsin, more than 2,800 new cases were reported on Saturday, marking a new record and breaking the previous high of 2,500 cases on Sept. 18, according to Fox 11 in Madison. More than 2,000 cases were reported three days in a row. In New York, daily cases passed 1,000 on Saturday for the first time since June 5, according to Bloomberg News. South Dakota also reported its highest daily total on Saturday with more than 500 new cases. North Dakota, Utah, and Montana set records as well. New Hampshire reported its first coronavirus-related death in 11 days on Saturday, which was associated with a long-term care facility, according to WMUR. The state reported 38 new cases, and health officials say community-based transmission is happening in every county. Public health officials expect cases to increase even more throughout the fall, and state leaders are urging people to continue measures to slow the spread of the virus. “Continue to practice the basic behaviors that drive our ability to fight COVID-19 as we move into the fall and flu season,” New York Gov. Andrew Cuomo said in a Saturday update. “Wearing masks, socially distancing and washing hands make a critical difference.”
Association of Hypertension with All-Cause Mortality among Hospitalized Patients with COVID-19
Journal of Clinical Medicine, September 28, 2020
It is unclear to which extent the higher mortality associated with hypertension in the coronavirus disease (COVID-19) is due to its increased prevalence among older patients or to specific mechanisms. Cross-sectional, observational, retrospective multicenter study, analyzing 12226 patients who required hospital admission in 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics of survivors versus non-survivors. The mean age of the study population was 67.5 ± 16.1 years, 42.6% were women. Overall, 2630 (21.5%) subjects died. The most common comorbidity was hypertension (50.9%) followed by diabetes (19.1%), and atrial fibrillation (11.2%). Multivariate analysis showed that after adjusting for gender (males, OR: 1.5, p=0.0001), age tertiles (second and third tertiles, OR: 2.0 and 4.7, p=0.0001), and Charlson Comorbidity Index scores (second and third tertiles, OR: 4.7 and 8.1, p = 0.0001), hypertension was significantly predictive of all-cause mortality when this comorbidity was treated with angiotensin-converting enzyme inhibitors (ACEIs) (OR: 1.6, p = 0.002) or other than renin-angiotensin-aldosterone blockers (OR: 1.3, p = 0.001) or angiotensin II receptor blockers (ARBs) (OR: 1.2, p = 0.035). The preexisting condition of hypertension had an independent prognostic value for all-cause mortality in patients with COVID-19 who required hospitalization. ARBs showed a lower risk of lethality in hypertensive patients than other antihypertensive drugs.
Clinical Outcomes of In-Hospital Cardiac Arrest in COVID-19
JAMA Internal Medicine, September 28, 2020
Before the outbreak of coronavirus disease 2019 (COVID-19), 25% of patients who underwent in-hospital cardiac arrest (IHCA) survived to discharge, with the initial rhythm being nonshockable in 81% of cases. Despite the outbreak causing many deaths, to our knowledge, information on IHCA among this subset of patients in the US is lacking. Between March 15 and April 3, 2020, 1309 patients with a diagnosis of COVID-19 were admitted to Beaumont Health (Royal Oak, Michigan). From this group, we identified patients who underwent cardiopulmonary resuscitation (CPR) for cardiac arrest. The exclusion criteria were an age younger than 18 years, do-not-resuscitate status, and comfort or hospice care enrollment. Primary outcomes aimed to identify the initial cardiac arrest rhythm, time to return of spontaneous circulation (ROSC), and overall survival to discharge. William Beaumont Hospital granted institutional review board approval and waived informed consent because of pandemic conditions. Among 1309 patients hospitalized with COVID-19, 60 (4.6%) developed IHCA and underwent CPR. Six patients were excluded for lack of CPR documentation, providing a sample size of 54. The initial rhythm was nonshockable for 52 patients (96.3%), with 44 (81.5%) with pulseless electrical activity and 8 (14.8%) with asystole. Two patients (3.7%) developed pulseless ventricular tachycardia, and none developed ventricular fibrillation. Return of spontaneous circulation was achieved in 29 patients (53.7%).
World Heart Day 2020 – Use Heart to Beat Cardiovascular Disease
Healthmanagement.org, September 28, 2020
On World Heart Day this year (29 September), the World Heart Federation (WHF) cautions heart patients to be aware of COVID-19 and its impact on the heart. According to the WHF, COVID-19 is creating a perfect storm for heart health. Three factors are contributing to this:
- People with COVID-19 and heart disease are at the highest risk of death and complications.
- The heart might be adversely affected by the coronavirus, even in people who do not have any pre-existing heart condition.
- Fear of the virus has resulted in a sharp decline in hospital visits by heart patients for both routine and emergency care.
Cardiovascular disease (CVD) kills approximately 17.9 million people every year. There are several causes of CVD, including smoking, diabetes, high blood pressure, obesity and air pollution. On World Heart Day, the WHF aims to unite the global health community to beat cardiovascular disease and is encouraging people to “use heart” and make better choices for themselves, for their families and for the society as a whole.
Immune dysfunction following COVID-19, especially in severe patients
Scientific Reports, September 28, 2020
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has been spread worldwide. Because it brought so much damage and negative effects, the World Health Organization (WHO) declared the outbreak a public health emergency of international concern on January 31, 2020. This disease has progressed rapidly, and patients who are in the severe stage could develop acute respiratory distress syndrome, sepsis, and even multiple organ dysfunction syndrome in just a short time. Severe cases had unfavorable outcomes according to the latest epidemiological statistics, which means that early identification and intervention for severe patients were very important, especially because no effective treatment has been made yet directly targeting at SARS-CoV-2. So, we collected and compared data of healthy people and laboratory-confirmed SARS-CoV-2 infected patients. The aim of this study was to know the clinical characteristics of COVID-19 and then identify the independent risk factors related to disease severity and so help clinicians distinguish severe cases by using clinical data in the early stage.
Angiotensin-converting enzyme 2 (ACE2) levels in relation to risk factors for COVID-19 in two large cohorts of patients with atrial fibrillation
European Heart Journal, September 27, 2020
The global COVID-19 pandemic is caused by the SARS-CoV-2 virus entering human cells using angiotensin-converting enzyme 2 (ACE2) as a cell surface receptor. ACE2 is shed to the circulation, and a higher plasma level of soluble ACE2 (sACE2) might reflect a higher cellular expression of ACE2. This study explored the associations between sACE2 and clinical factors, cardiovascular biomarkers, and genetic variability. Plasma and DNA samples were obtained from two international cohorts of elderly patients with atrial fibrillation (n = 3999 and n = 1088). The sACE2 protein level was measured by the Olink Proteomics® Multiplex CVD II96 × 96 panel. Levels of the biomarkers high-sensitive cardiac troponin T (hs-cTnT), N-terminal probrain natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), C-reactive protein, interleukin-6, D-dimer, and cystatin-C were determined by immunoassays. Genome-wide association studies were performed by Illumina chips. Higher levels of sACE2 were statistically significantly associated with male sex, cardiovascular disease, diabetes, and older age. The sACE2 level was most strongly associated with the levels of GDF-15, NT-proBNP, and hs-cTnT. When adjusting for these biomarkers, only male sex remained associated with sACE2.
Mortality Risk Assessment Using CHA(2)DS(2)-VASc Scores In Patients Hospitalized With COVID -19 Infection
American Journal of Cardiology, September 26, 2020
Early risk stratification for complications and death related to COVID-19 infection is needed. Because many patients with COVID-19 who developed acute respiratory distress syndrome have diffuse alveolar inflammatory damage associated with microvessel thrombosis, we aimed to investigate a common clinical tool, the CHA(2)DS(2)-VASc, to aid in the prognostication of outcomes for COVID-19 patients. We analyzed consecutive patients from the multicenter observational CORACLE registry, which contains data of patients hospitalized for COVID-19 infection in 4 regions of Italy, according to data-driven tertiles of CHA(2)DS(2)-VASc score. The primary outcomes were inpatient death and a composite of inpatient death or invasive ventilation. Of 1045 patients in the registry, 864(82.7%) had data available to calculate CHA(2)DS(2)-VASc score and were included in the analysis. Of these, 167(19.3%) died, 123(14.2%) received invasive ventilation, and 249(28.8%) had the composite outcome. Stratification by CHA(2)DS(2)-VASc tertiles (T1: ≤1; T2: 2-3; T3: ≥4) revealed increases in both death (8.1%, 24.3%, 33.3%, respectively; p<0.001) and the composite endpoint (18.6%, 31.9%, 43.5%, respectively; p<0.001). The odds ratios(ORs) for mortality and the composite endpoint for T2 patients versus T1 CHA(2)DS(2)-VASc score were 3.62(95% CI:2.29-5.73,p<0.001) and 2.04(95% CI:1.42-2.93, p<0.001), respectively. Similarly, the ORs for mortality and the composite endpoint for T3 patients versus T1 were 5.65(95% CI: 3.54-9.01, p<0.001) and 3.36(95% CI:2.30-4.90,p<0.001), respectively.
Statin treatment of COVID-19
American Journal of Cardiology, September 26, 2020
Statins are known to down regulate inflammatory cytokines and other biomarkers of inflammation. Studies in human volunteers showed that these effects occur in a matter of a few hours or a day or two. Moreover, in patients who have been taking statins, withdrawing treatment is followed by a rebound that increases both cytokine levels and mortality. Yan et al and Grasselli et al did not report on whether outpatient statin treatment was continued after hospital admission. A recent report of statins treatment by Gupta et al was also based on outpatient records. In this study, only 77% of outpatient statin users continued treatment as inpatients, which means that 23% of the group of statin outpatient users were at risk of a rebound effect and increased mortality after hospital admission. This could have led to an underestimate of survival in patients who received statins as inpatients. Two of the four studies reported by Kow and Hasan were correctly based on inpatient statin treatment and both showed statistically significant improvement in survival. The smaller study by de Spiegleer et al also reported benefits in statin users among nursing home residents, but the result did not reach statistical significance. The largest and most detailed study of inpatient statin treatment by Zhang et al also reported that inpatient treatment with angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) did not provide a survival benefit greater than that provided by statin treatment alone. Nonetheless, several reports have shown that in hypertensive COVID-19 patients, outpatient or inpatient treatment with ACEIs or ARBs is not harmful and, in some instances, these drugs actually improve survival.
Short-term COVID-19 treatment with hydroxychloroquine may not confer arrhythmia risk
Cardiology Today, September 25, 2020
Hydroxychloroquine may be safe for the short-term treatment of patients with COVID-19 who were chosen for therapy after undergoing risk assessment, researchers found. Researchers observed modest QTc prolongation with hydroxychloroquine, but no deaths associated with arrhythmias, according to the study published in Europace. In this multicenter cohort study, researchers analyzed data from 649 patients (mean age, 62 years; 46% men) with COVID-19 who were treated at seven institutions from March 10 to April 10. Patients were enrolled from three different settings: home management (n = 126), medical ward management (n = 495) or ICU management (n = 28). All patients underwent ECG monitoring within 5 days before the first dose of hydroxychloroquine and then at 36 to 72 hours after the first dose or at least 96 hours after the first dose. ECGs were used to assess QT-associated and QT-independent arrhythmic events, in addition to QT/QTc prolongation. Overall and arrhythmic morality were also analyzed throughout the study.
Coronavirus Q&A With Anthony Fauci, MD
JAMA Network Learning, September 25, 2020
[Video] Anthony S. Fauci, MD, returns to JAMA’s Q&A series to discuss the latest developments in the COVID-19 pandemic, hosted by Howard Bauchner, MD, Editor in Chief, JAMA.
Reducing or Eliminating Hypertension Medication Can Help Prevent Kidney Injury in COVID-19 Patients
Pharmacy Times, September 25, 2020
Reducing or eliminating high blood pressure medication if blood pressure becomes hypotensive could help prevent acute kidney injury and death in patients with coronavirus disease 2019 (COVID-19), according to a new study presented at the American Heart Association’s (AHA) Hypertension 2020 Scientific Sessions. During the early days of the COVID-19 pandemic, the AHA, the Heart Failure Society of America, and the American College of Cardiology issued a joint statement advising patients at risk of COVID-19 to continue their use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. In cardiovascular patients who have been diagnosed with COVID-19, there should be a full evaluation before adding or removing any treatments, according to the researchers. In order to determine which patients with COVID-19 were at the highest risk for kidney damage, investigators examined 392 patients treated at a hospital in Italy between March 2 and April 25, 2020. They found that nearly 60% of the patients had a history of hypertension, making it the most common comorbidity among the participants. Investigators also found that more than 86% of patients with high blood pressure were taking anti-hypertensive medication daily. According to the study, a history of hypertension was found to increase the risk of acute kidney injury by 5-fold.
The role of anti-hypertensive treatment, comorbidities and early introduction of LMWH in the setting of COVID-19: A retrospective, observational study in Northern Italy
International Journal of Cardiology, September 25, 2020
There is a great deal of debate about the role of cardiovascular comorbidities and the chronic use of antihypertensive agents (such as ACE-I and ARBs) on mortality on COVID-19 patients. Of note, ACE2 is responsible for the host cell entry of the virus. We extracted data on 575 consecutive patients with laboratory-confirmed SARS-CoV-2 infection admitted to the Emergency Department (ED) of Humanitas Center, between February 21 and April 14, 2020. The aim of the study was to evaluate the role of chronic treatment with ACE-I or ARBs and other clinical predictors on in-hospital mortality in a cohort of COVID-19 patients. MultivariatQe analysis showed that a chronic intake of ACE-I was associated with a trend in reduction of mortality (OR: 0.53; 95% CI: 0.27–1.03; p = 0.06). Increased age (ORs ranging from 3.4 to 25.2 and to 39.5 for 60–70, 70–80 and > 80 years vs < 60) and cardiovascular comorbidities (OR: 1.90; 95% CI: 1.1–3.3; p = 0.02) were confirmed as important risk factors for COVID-19 mortality. Timely treatment with low-molecular-weight heparin (LMWH) in ED was found to be protective (OR: 0.36; 95% CI: 0.21–0.62; p < 0.0001).
Heart rhythm in COVID-19 patients receiving short term treatment with hydroxychloroquine
European Society of Cardiology, September 25, 2020
[Press Release] Short-term hydroxychloroquine treatment is not associated with lethal heart rhythms in patients with COVID-19 who are risk assessed prior to receiving the drug. That’s the finding of research published today in EP Europace, a journal of the European Society of Cardiology (ESC). “This was the largest study to assess the risk of dangerous heart rhythms (arrhythmias) in COVID-19 patients treated with hydroxychloroquine,” said study author Dr. Alessio Gasperetti of Monzino Cardiology Centre, Milan, Italy and University Hospital Zurich, Switzerland. “In our cohort, there was a low rate of arrhythmias and none were associated with hydroxychloroquine.” The study began when there was very little experience using hydroxychloroquine to treat patients with COVID-19. Current evidence suggests that it is ineffective in patients with advanced disease but there is debate around its effectiveness in the early phase. This study was not designed to test the effectiveness of hydroxychloroquine in COVID-19 but rather to examine cardiac safety.
Pathological features of COVID-19-associated myocardial injury: a multicentre cardiovascular pathology study
European Heart Journal, September 24, 2020
Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features of myocardial involvement including elevated serum troponin levels and acute heart failure with reduced ejection fraction. The cardiac pathological changes in these patients with COVID-19 have yet to be well described. In this international multicentre study, cardiac tissue from the autopsies of 21 consecutive COVID-19 patients was assessed by cardiovascular pathologists. The presence of myocarditis, as defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analysed by immunohistochemistry. Other forms of acute myocyte injury and inflammation were also described, as well as coronary artery, endocardium, and pericardium involvement. Lymphocytic myocarditis was present in 3 (14%) of the cases. In two of these cases, the T lymphocytes were CD4 predominant and in one case the T lymphocytes were CD8 predominant. Increased interstitial macrophage infiltration was present in 18 (86%) of the cases. A mild pericarditis was present in four cases. Acute myocyte injury in the right ventricle, most probably due to strain/overload, was present in four cases. There was a non-significant trend toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis.
Training and Education: New Strategies For New Times
Cardiology, September 24, 2020
Much has changed this year, but one thing that remains the same is the need for training and ongoing education. Our task as physicians is to stay up to date and learn and collaborate to deliver the best patient care, and using our phones, tablets and personal computers we can do all that. While we all miss the in-person scientific meetings, there are many resources available to help us learn new techniques, innovations, devices and medications that will help our patients. Virtual education activities have evolved allowing us to continue to learn from experts in the field, and not disrupt our workflow. Here are some of the ways I’m keeping up by M. Chadi Alraies, MD, FACC, director of interventional cardiology research at Detroit Medical Center in Michigan.
Stroke occurs frequently in COVID-19, leads to ‘devastating consequences’ for patients
Helio | Neurology, September 23, 2020
Respiratory symptom severity served as the most significant indicator of in-hospital mortality among patients with COVID-19 who had a stroke, according to a systematic review published in Neurology. Older age and a greater number of cardiovascular comorbidities also correlated with in-hospital mortality in this patient population, study findings demonstrated. “To date, relatively little is known about the frequency, clinical characteristics and outcomes of acute cerebrovascular events in patients with COVID-19,” the researchers wrote. “We hypothesized that stroke is a frequent complication among COVID-19 patients, that in-hospital mortality is higher in patients with stroke and COVID-19 compared to historical non-COVID-19 cohorts, and that young patients would show a higher mortality due to a higher incidence of large vessel occlusion (LVO).” The researchers added that the burden on the health care system and other factors related to the pandemic have led the frequency of stroke events to be underestimated. The intended outcomes of the review were to estimate the proportion of COVID-19 patients who experience stroke; analyze their comorbidities, clinical characteristics and outcomes; determine clinical phenotypes; and compare in-hospital mortality between those clinical phenotypes.
Pharmacological and cardiovascular perspectives on the treatment of COVID-19 with chloroquine derivatives\
Acta Pharmacologica Sinica, September 23, 2020
Curative drugs specific for COVID-19 are currently lacking. Chloroquine phosphate and its derivative hydroxychloroquine, which have been used in the treatment and prevention of malaria and autoimmune diseases for decades, were found to inhibit SARS-CoV-2 infection with high potency in vitro and have shown clinical and virologic benefits in COVID-19 patients. Therefore, chloroquine phosphate was first used in the treatment of COVID-19 in China. Later, under a limited emergency-use authorization from the FDA, hydroxychloroquine in combination with azithromycin was used to treat COVID-19 patients in the USA, although the mechanisms of the anti-COVID-19 effects remain unclear. Preliminary outcomes from clinical trials in several countries have generated controversial results. Here, we provide pharmacological and cardiovascular perspectives on the application of chloroquine derivatives in the treatment of COVID-19. Systematic evaluations of their efficacy and safety, especially of the potential cardiovascular toxicity of chloroquine and hydroxychloroquine and combination therapies with other drugs in the treatment of COVID-19, and genetic variability in the metabolism of these drugs in patients are required to prevent lethal cardiovascular adverse events.
Routine blood test may predict mortality risk in patients with COVID-19
Helio | Primary Care, September 23, 2020
A standard test that evaluates blood cells can help identify patients hospitalized with COVID-19 who are at an elevated risk for death, according to research published in JAMA Network Open. “We were surprised to find that one standard test that quantifies the variation in size of red blood cells — called red cell distribution width, or RDW — was highly correlated with patient mortality, and the correlation persisted when controlling for other identified risk factors like patient age, some other lab tests, and some pre-existing illnesses,” Jonathan Carlson, MD, PhD, an instructor in medicine at Massachusetts General Hospital, said in a press release. In their cohort study, Carlson and colleagues retrospectively analyzed adult patients with SARS-CoV-2 infection who were admitted to one of four participating hospitals in the Boston area from March 4 through April 28. As part of standard critical care, all patients had their RDW, absolute lymphocyte count and dimerized plasmin fragment D levels collected daily. According to the researchers, RDW reflects cellular volume variation, and elevated RDW (more than 14.5%) has previously been associated with an increased risk for morbidity and mortality in a variety of diseases, including heart disease, pulmonary diseases, influenza, cancer and sepsis. A total of 1,641 patients were included in the analyses. The final discharge among these patients was June 26, and there were no COVID-19-related readmissions through July 25.
COVID Death Toll Hits 200,000 in the U.S.
WebMD, September 22, 2020
Just over 6 months after the World Health Organization declared COVID-19 a pandemic, the United States has reached a grim milestone: the novel coronavirus death toll has climbed to a staggering 200,000. “It’s sobering. It’s a large number, and clearly it tells us that everything we’re doing right now to contain it needs to continue,” says Erica Shenoy, MD, associate chief of the Infection Control Unit at Massachusetts General Hospital. “Especially heading into the fall, where we don’t know if there will be a second surge, or if this will be compounded by other respiratory illnesses.” Doctors and scientists say the number sends a clear message: Although people are itching to return to pre-pandemic life, Americans should continue to wear masks, practice hand-washing hygiene, and keep physical distance from others. While the high death toll is a bleak glimpse into how severe the illness is, there are two silver linings: The numbers seem to be trending in the right direction, and researchers have had time to discover more about a virus that at first baffled even the world’s leading scientists.
Cardiology and COVID-19
Journal of the American Medical Association, September 22, 2020
The initial reports on the epidemiology of coronavirus disease 2019 (COVID-19) emanating from Wuhan, China, offered an ominous forewarning of the risks of severe complications in elderly patients and those with underlying cardiovascular disease, including the development of acute respiratory distress syndrome, cardiogenic shock, thromboembolic events, and death. These observations have been confirmed subsequently in numerous reports from around the globe, including studies from Europe and the US. The mechanisms responsible for this vulnerability have not been fully elucidated, but there are several possibilities. In the brief timeline of the current pandemic, numerous publications highlighting the constellation of observed cardiovascular consequences have emphasized certain distinctions that appear unique to COVID-19. Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gains entry via the upper respiratory tract, its affinity and selective binding to the angiotensin-converting enzyme 2 (ACE2) receptor, which is abundant in the endothelium of arteries and veins as well as in the respiratory tract epithelium, create a scenario in which COVID-19 is as much a vascular infection as it is a respiratory infection with the potential for serious vascular-related complications.
COVID vs Head, Heart, and Heparin—Recent developments of interest in cardiovascular medicine
MedPage Today, September 22, 2020
- Heparin binds to cells at a site adjacent to ACE2, the portal for SARS-CoV-2 infection, and “potently” blocks the virus, which could open up therapy options. (Cell)
- The heightened focus on post-viral effects is what’s really novel about lingering heart damage after COVID-19, a piece in The Atlantic suggests.
- Nearly 2% of COVID-19 patients sustain a stroke, with “exceedingly high” 34% in-hospital mortality, a meta-analysis showed. (Neurology)
- Johns Hopkins Hospital turned its interactive gaming room for stroke rehabilitation into a staff decompression space during the COVID-19 lockdown.
COVID-19 mortality rates higher among men than women
Science Daily, September 22, 2020
A new review article from Beth Israel Deaconess Medical Center (BIDMC) shows people who are biologically male are dying from COVID-19 at a higher rate than people who are biologically female. In a review published in Frontiers in Immunology, researcher-clinicians at BIDMC explore the sex-based physiological differences that may affect risk and susceptibility to COVID-19, the course and clinical outcomes of the disease and response to vaccines. “The COVID-19 pandemic has revealed a striking gender bias with increased mortality rates in men compared with women across the lifespan,” said corresponding author Vaishali R. Moulton, MD, PhD, an assistant professor of medicine in the Division of Rheumatology and Clinical Immunology at BIDMC. “Apart from behavioral and lifestyle factors that differ between men and women, sex chromosome-linked genes, sex hormones and the microbiome control aspects of the immune responses to infection and are potentially important biological contributors to the sex-based differences we’re seeing in men and women in the context of COVID-19.”
ACIP Mulls Priority Groups for COVID-19 Vaccines
MedPage Today, September 22, 2020
Members of the CDC’s Advisory Committee on Immunization Practices (ACIP) meeting Tuesday appeared to agree that healthcare workers should be first in line to receive a COVID-19 vaccine when one is approved, followed by some combination of essential workers, those with high-risk medical conditions, and older adults. However, with no formal vote taken — that won’t happen until one or more vaccines are authorized or approved by the FDA for clinical use — it’s not yet official policy, and not much was settled about priorities for later rounds of immunizations. ACIP chair José Romero, MD, said once data is available from phase III clinical trials, an ACIP work group will conduct an independent review of its safety and efficacy. “If and when the FDA authorizes or approves vaccines, ACIP will have an emergency meeting and then vote on recommendations and populations for use,” he said.
Viral heart damage under scrutiny
Science, September 18, 2020
Fears that COVID-19 can cause the cardiac inflammation called myocarditis have grown, as doctors report seeing previously healthy people whose COVID-19 experience is trailed by myocarditis-induced heart failure. Mohiddin recently treated 42-year-old Abul Kashem, who had typical COVID-19 symptoms in April, including loss of smell and mild shortness of breath. A month later, he fell critically ill from severe myocarditis. “I’m just grateful to be alive,” says Kashem, who spent more than 2 weeks in an intensive care unit. Why did this happen? How the virus might damage heart muscle is just one question researchers are now probing. Other studies are following people during and after acute illness to learn how common heart inflammation is after COVID-19, how long it lingers, and whether it responds to specific treatments. Researchers also want to know whether patients fare similarly to those with myocarditis from other causes, which can include chemotherapy and other viruses. In more than half of virus-induced cases, the inflammation resolves without incident. But some cases lead to arrhythmia and impaired heart function, or, rarely, the need for a heart transplant. Because millions are now contracting the coronavirus, even a small proportion who suffer severe myocarditis would amount to a lot of people. “Are we going to have an increase of patients with heart failure secondary to this?” asks Peter Liu, a cardiologist and chief scientific officer of the University of Ottawa Heart Institute.
Virtual medical education during the COVID-19 pandemic: how to make it work
European Heart Journal, September 18, 2020
The emergence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the cause of the COVID-19 pandemic, has brought many new challenges to healthcare workers around the globe. The number of COVID-19 patients started rising in the USA after the first reported case in January 2020. Physicians in training, an essential part of the healthcare system, have found themselves to be in critical positions as a direct result of the pandemic as they continue to care for patients and work to expand their medical knowledge and skills beyond books during this uncertain time. The Centers for Disease Control and Prevention (CDC) recommended sanitary and social distancing guidelines to be followed by individuals as a measure to contain the spread of COVID-19 in the USA. These guidelines include proper handwashing techniques and maintaining at least 6 feet distance from others in social and work settings whenever possible. Therefore, many medical facilities, institutions, and societies recognized the need to cancel most of the in-person lectures and conferences to ensure compliance with the CDC and minimize the risk of exposure of medical personnel. The CDC’s social distancing guidelines have given rise to innovative ways of continuing work and study productivity via virtual meetings using online platforms including, but not limited to, Microsoft Teams, Zoom, and WebEx. In this new normal, virtual meetings have provided a solution for physicians to continue receiving education, training, and communications. Though virtual meetings attempt to resemble in-person meetings as closely as possible, these have a different dynamic as the presenter and attendees find themselves speaking to a camera rather than to a physical audience. This virtual environment takes away from the human element of immediate feedback through non-verbal cues, but in return it provides benefit of remote attendance to keep attendees safe from contagion.
Effect of COVID-19 outbreak on the treatment time of patients with acute ST-segment elevation myocardial infarction
The American Journal of Emergency Medicine, September 17, 2020
The objective was to explore the effect of COVID-19 outbreak on the treatment time of patients with ST-segment elevation myocardial infarction (STEMI) in Hangzhou, China. We retrospectively reviewed the data of STEMI patients admitted to the Hangzhou Chest Pain Center (CPC) during a COVID-19 epidemic period in 2020 (24 cases) and the same period in 2019 (29 cases). General characteristics of the patients were recorded, analyzed, and compared. Moreover, we compared the groups for the time from symptom onset to the first medical contact (SO-to-FMC), time from first medical contact to balloon expansion (FMC-to-B), time from hospital door entry to first balloon expansion (D-to-B), and catheter room activation time. The groups were also compared for postoperative cardiac color Doppler ultrasonographic left ventricular ejection fraction (LVEF), the incidence of major adverse cardiovascular and cerebrovascular events (MACCE), Kaplan-Meier survival curves during the 28 days after the operation. The times of SO-to-FMC, D-to-B, and catheter room activation in the 2020 group were significantly longer than those in the 2019 group (P < 0.05). The cumulative mortality after the surgery in the 2020 group was significantly higher than the 2019 group (P < 0.05).
Flu, COVID-19 or Both? Don’t Overlook Co-Infection, CDC Urges
MedPage Today, September 17, 2020
With overlapping signs and symptoms, surveillance, testing more important than ever. When a patient presents with acute respiratory symptoms this fall, clinicians should consider three options: influenza, COVID-19, or co-infection, CDC experts said. And given the likelihood that influenza and SARS-CoV-2 will be co-circulating in the community, clinicians should pay special attention to local surveillance data about each virus. On a CDC Clinician Outreach and Communication Activity call, CDC officials reminded clinicians that not only do influenza and COVID-19 have overlapping signs and symptoms, but co-infection with both has been documented in both case reports and case series. Co-infection, or even distinguishing SARS-CoV-2 from influenza, is particularly important because of the implications of treatment. For example, Uyeki noted that dexamethasone is recommended for severe COVID-19 infection in hospitalized patients, but corticosteroids actually prolong viral replication in influenza. Testing then becomes key in distinguishing the viruses, and Uyeki said that, as noted by Department of Health and Human Services officials, there are several kinds of “multiplex” assays that received FDA emergency use authorization (EUA), including some that received EUAs “this week,” he added.
Promising effects of exercise on the cardiovascular, metabolic and immune system during COVID-19 period
Journal of Human Hypertension, September 17, 2020
With 4 billion people in lockdown in the world, COVID-19 outbreak may result in excessive sedentary time, especially in the population of vulnerable and disabled subjects. In many chronic disorders and diseases including type 2 diabetes mellitus and hypertension, cardiovascular and immune beneficial effects of exercise interventions should be reminded. Direct metabolic and endocrine link between type 2 diabetes mellitus (T2DM), hypertension, and coronavirus SARS-CoV-2 disease (COVID-19) was recently reported. It is also important to note that with 4 billion people in lockdown in the world, COVID-19 outbreak may result in excessive sedentary time, especially in the population of vulnerable and disabled subjects. Indeed, this population is very dependent on the caregivers in charge of their rehabilitation, since the trip to the patients’ homes may be made more difficult during the outbreak. In many chronic disorders and diseases including T2DM and hypertension, cardiovascular, metabolic and immune, beneficial effects of exercise interventions have been reported. The intensity, volume, and mode of exercise may exert different activation of the hypothalamic-pituitary-adrenal axis, of the autonomous nervous system and of the resulting immunoregulatory hormones that influence immune response. Exercise interventions may affect susceptibility to infection, as they were shown to modify monocytes and lymphocytes distribution, phenotype and cytokine production.
Fabry Disease Patients Have An Increased Risk Of Stroke In The COVID-19 ERA. A Hypothesis
] Medical Hypotheses, September 17, 2020
Stroke is a severe and frequent complication of Fabry disease (FD), affecting both males and females. Cerebrovascular complications are the end result of multiple and complex pathophysiology mechanisms involving endothelial dysfunction and activation, development of chronic inflammatory cascades leading to a prothrombotic state in addition to cardioembolic stroke due to cardiomyopathy and arrhythmias. The recent coronavirus disease 2019 outbreak share many overlapping deleterious pathogenic mechanisms with those of FD and therefore we analyze the available information regarding the pathophysiology mechanisms of both disorders and hypothesize that there is a markedly increased risk of ischemic and hemorrhagic cerebrovascular complications in Fabry patients suffering from concomitant SARS-CoV-2 infections. There are 4 different pathophysiology mechanisms enhancing the risk of stroke in COVID-19 patients that overlap with those of FD including: renin angiotensin aldosterone imbalance, vasculopathy, thromboinflammation and cardiac damage.
HHS Outlines COVID Vax Distribution Strategy
MedPage Today, September 17, 2020
The Health and Human Services (HHS) department on Wednesday unveiled general outlines for how the first COVID-19 vaccine doses will be shipped and administered. Developed with the Department of Defense (DOD), the four-part strategy addresses engagement with state and local partners and other stakeholders; distribution under a “phased allocation methodology” still to be developed; safe vaccine administration and availability of auxiliary supplies; and data gathering via information technology to track distribution and administration. The strategy gives January 2021 as the target to begin distribution of an FDA-approved or authorized vaccine. Also released Wednesday was a COVID-19 Vaccination Program Interim Playbook from the CDC to assist local, state, tribal and territorial partners in rolling out their COVID-19 vaccination programs. The playbook identifies healthcare personnel and other essential workers as among the “critical populations,” although final decisions remain to be made by the CDC’s Advisory Committee on Immunization Practices.
Efforts to prevent COVID-19 led to global decline in flu
Infectious Disease News, September 17, 2020
Interventions to prevent SARS-CoV-2 transmission have led to a global decline in influenza during the COVID-19 pandemic, researchers reported in MMWR. In addition to causing a significant drop in the percentage of respiratory specimens that tested positive for influenza in the early days of the pandemic in the United States, measures such as mask wearing, social distancing, school closures and telework have kept positive tests at “historically low interseasonal levels,” the researchers said. The Southern Hemisphere has experienced a similar effect. If the measures continue through the fall, the influenza season in the U.S. “might be blunted or delayed,” according to the report. “The global decline in influenza virus circulation appears to be real and concurrent with the COVID-19 pandemic and its associated community mitigation measures,” Sonja J. Olsen, PhD, an epidemiologist in the CDC’s Influenza Division, and colleagues wrote. Olsen and colleagues reviewed data from around 300 U.S. laboratories in all 50 states, Puerto Rico, Guam and the District of Columbia. They also analyzed influenza laboratory data from surveillance platforms in Australia, Chile and South Africa to determine viral activity in the Southern Hemisphere.
Post-COVID Heart Scans Without Symptoms: Not a Good Idea
MedPage Today, September 15, 2020
Cardiac MRI (CMR) might be able to find abnormalities suggestive of myocarditis after COVID-19 recovery — or to rule them out — but it shouldn’t be used that way in the absence of symptoms, a group of cardiologists, radiologists, and others argued. “We wish to emphasize that the prevalence, clinical significance and long-term implications of CMR surrogates of myocardial injury on morbidity and mortality are unknown,” they wrote in an open letter signed by some 50 medical professionals from a range of disciplines. Until there’s better evidence, “testing asymptomatic members of the general public after COVID-19 is not indicated outside of carefully planned and approved research studies with appropriate control groups,” the group argued. The letter called on the 18 professional societies to which it was sent, including the American College of Cardiology (ACC), American Heart Association, American College of Radiology, and the Society for Cardiovascular Magnetic Resonance (SCMR) to put out clear guidance to stop people seeking CMR screening for that purpose. SCMR responded to the open letter on Tuesday, agreeing that routine CMR in asymptomatic patients after COVID-19 “is currently not justified…and it should not be encouraged.” The statement did not specifically address athletes.
Convalescent plasma treatment of severe COVID-19: a propensity score–matched control study
Nature Medicine, September 15, 2020
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new human disease with few effective treatments. Convalescent plasma, donated by persons who have recovered from COVID-19, is the acellular component of blood that contains antibodies, including those that specifically recognize SARS-CoV-2. These antibodies, when transfused into patients infected with SARS-CoV-2, are thought to exert an antiviral effect, suppressing virus replication before patients have mounted their own humoral immune responses. Virus-specific antibodies from recovered persons are often the first available therapy for an emerging infectious disease, a stopgap treatment while new antivirals and vaccines are being developed. This retrospective, propensity score–matched case–control study assessed the effectiveness of convalescent plasma therapy in 39 patients with severe or life-threatening COVID-19 at The Mount Sinai Hospital in New York City. Oxygen requirements on day 14 after transfusion worsened in 17.9% of plasma recipients versus 28.2% of propensity score–matched controls who were hospitalized with COVID-19 (adjusted odds ratio (OR), 0.86; 95% confidence interval (CI), 0.75–0.98; chi-square test P value = 0.025). Survival also improved in plasma recipients (adjusted hazard ratio (HR), 0.34; 95% CI, 0.13–0.89; chi-square test P = 0.027).
Hypertension, Obesity, and COVID-19
Journal of the American Medical Association, September 14, 2020
[Podcast] New data show unfavorable US trends in hypertension and obesity, with communities of color doing worse. Join Howard Bauchner, MD, Editor in Chief of JAMA, as he interviews National Institute of Diabetes and Digestive and Kidney Diseases Director Griffin P. Rodgers, MD, and National Heart, Lung, and Blood Institute Director Gary H. Gibbons, MD, to discuss the implications for COVID-19 outcomes and public health.
How COVID-19 can damage the brain
Nature, September 15, 2020
In the early months of the COVID-19 pandemic, doctors struggled to keep patients breathing, and focused mainly on treating damage to the lungs and circulatory system. But even then, evidence for neurological effects was accumulating. Some people hospitalized with COVID-19 were experiencing delirium: they were confused, disorientated and agitated. In April, a group in Japan published the first report of someone with COVID-19 who had swelling and inflammation in brain tissues. Another report described a patient with deterioration of myelin, a fatty coating that protects neurons and is irreversibly damaged in neurodegenerative diseases such as multiple sclerosis. “The neurological symptoms are only becoming more and more scary,” says Alysson Muotri, a neuroscientist at the University of California, San Diego, in La Jolla. The list now includes stroke, brain haemorrhage and memory loss. It is not unheard of for serious diseases to cause such effects, but the scale of the COVID-19 pandemic means that thousands or even tens of thousands of people could already have these symptoms, and some might be facing lifelong problems as a result. Yet researchers are struggling to answer key questions — including basic ones, such as how many people have these conditions, and who is at risk. Most importantly, they want to know why these particular symptoms are showing up.
Type I IFN deficiency: an immunological characteristic of severe COVID-19 patients
Signal Transduction and Targeted Therapy, September 14, 2020
Recently, a paper published in Science by Hadjadj et al. reported that type I interferon (IFN) deficiency, could be a hallmark of severe coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe COVID-19 was also associated with a lymphocytopenia, persistent blood viral load, and an exacerbated inflammatory response. These findings provide insights into the treatment of severe COVID-19 patients with type I IFN. The immunological features and mechanisms involved in COVID-19 severity are unclear. In order to test whether the severity disease can be caused by SARS-CoV-2 viral infection and hyperinflammation, Hadjadj et al. conducted a comprehensive immune analysis of grouped 50 COVID-19 patients with different disease severity. First, to identify whether the severe disease induced lymphocytopenia, Hadjadj et al. compared the peripheral blood leukocytes density of variously severe patients by combining mass cytometry with visualization of high-dimensional single-cell data based on t-distributed stochastic neighbor embedding. There is a significantly decreased density of NK cells and CD3+ T cells in severe and critical patients, while the density of B cells and monocytes was increased. The authors determined the functional status of specific T-cell subsets (CD4+/CD8+) and NK cells based on the expression of activation (CD38, HLA-DR) and exhaustion (PD-1, Tim-3) markers. They observed that the activated NK and CD4+/CD8+ T cells were increased in all infected patients, while the exhausted CD4+/CD8+ T cells and NK cells were increased in only severity patients. This result supported lymphocytopenia correlates with disease severity.
A reminder about choosing the proper code for a telehealth visit
Helio | Infectious Diseases in Children, September 14, 2020
Telehealth has helped immensely during the COVID-19 crisis. Insurance companies, although slow to approve payments, joined in to allow us to aid and interact with our patients and their families. How long this arrangement will last and how long they will waive coinsurance payments is a moving target. The AAP continues to discuss these matters with insurers. Rules have changed, confusion over which modifiers to use have been resolved and by now we are all familiar with telephone-only CPT codes 99441-3 and our old friends 99212-5 that we used for our “sick visits.” One thing has not changed, though — our fear to use 99214 and 99215, particularly when we cannot actually physically examine our patients. However, we can still use time as the main factor in choosing the proper code — 10 minutes for 99212, 15 minutes for 99213, 25 minutes for 99214 and 40 minutes for 99215. Remember, you must write down the time: For example, either 9:00 to 9:25, or 25 minutes (99214). On the other hand, do not forget that until Jan. 1, 2021, if you fulfill two-thirds of the key factors — history, physical examination and medical decision-making — you can still use 99214 with proper documentation.
The lasting misery of coronavirus long-haulers
Nature, September 14, 2020
Months after infection with SARS-CoV-2, some people are still battling crushing fatigue, lung damage and other symptoms of ‘long COVID’. People with more severe infections might experience long-term damage not just in their lungs, but in their heart, immune system, brain and elsewhere. Evidence from previous coronavirus outbreaks, especially the severe acute respiratory syndrome (SARS) epidemic, suggests that these effects can last for years. And although in some cases the most severe infections also cause the worst long-term impacts, even mild cases can have life-changing effects — notably a lingering malaise similar to chronic fatigue syndrome. Many researchers are now launching follow-up studies of people who had been infected with SARS-CoV-2, the virus that causes COVID-19. Several of these focus on damage to specific organs or systems; others plan to track a range of effects. In the United Kingdom, the Post-Hospitalisation COVID-19 Study (PHOSP-COVID) aims to follow 10,000 patients for a year, analysing clinical factors such as blood tests and scans, and collecting data on biomarkers. A similar study of hundreds of people over 2 years launched in the United States at the end of July. What they find will be crucial in treating those with lasting symptoms and trying to prevent new infections from lingering.
Home BP Monitoring Can Make Inroads During the Pandemic
MedPage Today, September 12, 2020
The rapid expansion of telemedicine due to COVID-19 presents an opportunity for home blood pressure (BP) monitoring to stake a place as a component of routine clinical practice — provided that policymakers recognize the changes needed to facilitate greater access to healthcare, according to a discussion by hypertension experts. There is increasing recognition of the importance of out-of-office confirmation of BP elevation even when white coat hypertension isn’t strongly suspected, said J. Brian Byrd, MD, of University of Michigan Medical School in Ann Arbor. It may be the right time to push for home BP measurement — a more practical alternative to ambulatory monitoring — as a standard part of patient care, several suggested during a session of the virtual Hypertension conference, hosted by the American Heart Association (AHA). In-office screening for hypertension in adults with confirmation outside of the clinical setting was tentatively given a grade A recommendation by the U.S. Preventive Services Task Force in June. Around the same time, a joint policy statement from the AHA and American Medical Association affirmed that self-measured blood pressure at home is a validated, cost-effective addition to office monitoring. “The pre-COVID status quo of the cost of care for hypertension is not sustainable. Increased utilization of telehealth has the potential to reduce the economic burden from costly hospital care attributed to poor hypertension control,” said Gbenga Ogedegbe, MD, MPH, of NYU Grossman School of Medicine in New York City.
COVID-19 Storms: Bradykinin In, Cytokine Out?
MedPage Today, September 11, 2020
In the last week, questions have been raised about whether cytokine storm is indeed a culprit in severe COVID-19, while a paper from a government lab has made an intriguing and much-discussed case for a new mechanism, bradykinin storm. While the concepts are not necessarily mutually exclusive, scientists trying to understand how COVID-19 wreaks its damage on the human body have been buzzing about the new possibilities. The theory connects many of the disparate symptoms of COVID-19, from a loss of sense of smell and taste, to a gel-like substance forming in the lungs, and abnormal coagulation. It posits that SARS-CoV-2 disrupts both the renin-angiotensin system (RAS) and the kinin-kallikrein pathways, sending bradykinin — a peptide that dilates blood vessels and makes them leaky — out of whack. The process impedes the transfer of oxygen from the lung to the blood and subsequently to all other tissues, a common abnormality in COVID-19 patients. They found the COVID-19 cases had extremely high levels (increased nearly 200-fold) of angiotensin-converting enzyme 2 (ACE2), the surface protein used by the coronavirus to enter the cell. When the virus interacts with ACE2, it triggers an abnormal response in the bradykinin pathway, Jacobson said. At the same time, levels of angiotensin-converting enzyme, which is involved in the breakdown of bradykinin, were lower in COVID-19 patients than in controls.
A big update: COVID-19 patients with hypotension may need to stop taking blood pressure medications
Cardiovascular Business, September 11, 2020
COVID-19 patients may need to stop taking angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) if they develop hypotension, according to new findings presented during the American Heart Association’s Hypertension 2020 Scientific Sessions. “Our study suggests low blood pressure in a person with a history of high blood pressure is an important and independent signal that someone with COVID-19 is developing or has acute kidney injury,” study author Paolo Manunta, MD, PhD, chair of nephrology at San Raffaele University in Milan, Italy, said in a prepared statement. “This also suggests that people with high blood pressure should carefully monitor it at home, and their kidney function should be measured when they’re first diagnosed with COVID-19. If they or their doctors notice blood pressure levels going down to the hypotensive range, their doctors may consider reducing or stopping their blood pressure medications to prevent kidney damage and possibly even death.” The role of ACE inhibitors and ARBs in the treatment of COVID-19 has been a key topic for researchers since the pandemic began. While there was an initial push from some parties for patients to stop taking antihypertensive medications if they were diagnosed with COVID-19, cardiovascular specialists pushed back, emphasizing their continued importance. For example, the AHA, Heart Failure Society of America, and American College of Cardiology released a joint statement in March that highlighted why patients should remain on ACE inhibitors and ARBs.
Ageing and atherosclerosis: vascular intrinsic and extrinsic factors and potential role of IL-6
Nature Reviews Cardiology, September 11, 2020
The number of old people (aged >65 years) is rising worldwide, and cardiovascular diseases are the largest contributor to morbidity and mortality in this population. Changes in diet and lifestyle contribute to the high cardiovascular morbidity and mortality in old individuals, but many biological processes that are altered with ageing also contribute to this increased cardiovascular risk. As a result, therapies for cardiovascular disease that are effective in young and middle-aged people might be less effective in older people. Additionally, novel therapies might be required to improve disease management specifically in old people. Deciphering the mechanisms by which ageing promotes atherosclerotic cardiovascular disease will be fundamental for the development of novel therapies to reduce the burden of atherosclerosis with ageing. The development of new therapies is especially relevant with the coronavirus disease 2019 (COVID-19) pandemic, because old people and particularly those with cardiovascular diseases are at a substantially higher risk of morbidity and death.
Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor
Nature Communications, September 11, 2020
Study of the interactions established between the viral glycoproteins and their host receptors is of critical importance for a better understanding of virus entry into cells. The novel coronavirus SARS-CoV-2 entry into host cells is mediated by its spike glycoprotein (S-glycoprotein), and the angiotensin-converting enzyme 2 (ACE2) has been identified as a cellular receptor. Here, we use atomic force microscopy to investigate the mechanisms by which the S-glycoprotein binds to the ACE2 receptor. We demonstrate, both on model surfaces and on living cells, that the receptor binding domain (RBD) serves as the binding interface within the S-glycoprotein with the ACE2 receptor and extract the kinetic and thermodynamic properties of this binding pocket. Altogether, these results provide a picture of the established interaction on living cells. Finally, we test several binding inhibitor peptides targeting the virus early attachment stages, offering new perspectives in the treatment of the SARS-CoV-2 infection.
New Recovery Programs Target COVID Long-Haulers
MedPage Today, September 10, 2020
Pulmonologists, cardiologists, neurologists, psychiatrists, and more join to get patients on their feet for good. Zijian Chen, MD, leads Mount Sinai’s COVID-19 recovery program, which is currently treating about 400 patients. At their first visit, patients are evaluated by a primary care physician for symptoms and referred to the appropriate specialists, Chen said. “Right now, we have almost every medical specialty working with the program,” Chen told MedPage Today. “We’re looking at a broad spectrum of disease. Some may have permanent lung fibrosis … that may last for the rest of their lives. Others have reactive airway or inflammatory problems that will subside over time. It’s unpredictable. It’s the same for cardiac symptoms and neurological symptoms.” At Hackensack Meridian’s COVID Recovery Center, primary care physicians develop a customized care plan and connect patients with specialists. Pulmonologists there have been treating patients with shortness of breath and exertional fatigue; cardiologists are treating heart function and rhythm disorders, and neurologists are treating comorbidities arising from strokes and clotting disorders, as well as neuropathy and cognitive impairment, according to program chair Laurie Jacobs, MD.
Single-cell transcriptomic atlas of primate cardiopulmonary aging
Cell Research, September 10, 2020
Aging is a major risk factor for many diseases, especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Disease 2019 (COVID-19). Resolving cellular and molecular mechanisms associated with aging in higher mammals is therefore urgently needed. Here, we created young and old non-human primate single-nucleus/cell transcriptomic atlases of lung, heart and artery, the top tissues targeted by SARS-CoV-2. Analysis of cell type-specific aging-associated transcriptional changes revealed increased systemic inflammation and compromised virus defense as a hallmark of cardiopulmonary aging. With age, expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) was increased in the pulmonary alveolar epithelial barrier, cardiomyocytes, and vascular endothelial cells. We found that interleukin 7 (IL7) accumulated in aged cardiopulmonary tissues and induced ACE2 expression in human vascular endothelial cells in an NF-κB-dependent manner. Furthermore, treatment with vitamin C blocked IL7-induced ACE2 expression. Altogether, our findings depict the first transcriptomic atlas of the aged primate cardiopulmonary system and provide vital insights into age-linked susceptibility to SARS-CoV-2, suggesting that geroprotective strategies may reduce COVID-19 severity in the elderly.
Aldeyra to undertake phase 2 trial of ADX-629 in patients hospitalized with COVID-19
Helio | Ocular Surgery News, September 10, 2020
Aldeyra Therapeutics has received a “study may proceed” letter from the FDA for a phase 2 clinical trial evaluating ADX-629 as a treatment for adult patients hospitalized with COVID-19, according to a press release. “What’s exciting about ADX-629 is its potential to act like a dimmer switch to modulate the aggressive immune response that is a hallmark of SARS-CoV-2, the virus that causes COVID-19,” Todd C. Brady, MD, PhD, president and CEO of Aldeyra, told Healio/OSN. “We’re still in the early innings in terms of clinical testing, but in animal models, ADX-629 has demonstrated a broad and highly statistically significant reduction in cytokine levels, which are critical mediators of inflammation in COVID-19. As a first-in-class, orally available inhibitor of RASP, ADX-629 has the potential to be clinically relevant not only for treating COVID-19 but also an array of inflammatory diseases that are not being adequately addressed by currently available therapies.” The trial will enroll about 30 patients with COVID-19. Enrollment will occur upon hospitalization, and patients will be treated for up to 28 days with orally administered ADX-629 or placebo twice daily. The trial’s key endpoints will include the National Institute of Allergy and Infectious Diseases COVID-19 scale, in addition to levels of cytokines and RASP.
AstraZeneca halts COVID-19 vaccine trial following adverse reaction in UK participant
Helio | Infectious Disease News, September 9, 2020
AstraZeneca’s phase 3 trial of a COVID-19 vaccine candidate has been put on hold because of a “suspected serious adverse reaction” in a participant from the United Kingdom, according to a report by STAT. AstraZeneca began the phase 3 trial in the United States on August 17. According to information available on clinicaltrials.gov, the trial is being held at 62 sites across the U.S., although not all locations have started enrolling participants. According to STAT, the trials were halted at all locations after a participant in the U.K. trial developed a suspected serious adverse reaction during the trial. In a statement from AstraZeneca issued to STAT, representatives said this is a “routine action” that happens whenever an unexplained illness occurs during a trial. “We are working to expedite the review of the single event to minimize any potential impact on the trial timeline,” they wrote. “We are committed to the safety of our participants and the highest standards of conduct in our trials.”
Obesity and Hypertension in the Time of COVID-19
Journal of the American Medical Association, September 9, 2020
[Editorial] In this issue of JAMA, 2 reports present cross-sectional data on the prevalence and trends for obesity and controlled hypertension from 1999 through 2018 based on data from the National Health and Nutrition Examination Survey, a federal program of nationally representative surveys designed to monitor the health and nutrition of adults and children in the US. At first glance, these 2 studies may appear to be addressing different issues. Ogden et al describe the seemingly inexorable increase in obesity prevalence among both children and adults, a condition that has few preventive strategies that have proven effective on a population basis despite recognition of its adverse effect on health. Muntner et al2 document a substantial decrease in the successful control of hypertension among US adults, a disease for which effective medical treatments exist. Hypertension increases the risk for heart disease, stroke, and chronic kidney disease, which are 3 leading causes of death for US residents, and effective treatment of hypertension can reduce the risk of these diseases. In addition to its contribution to cardiovascular and kidney diseases, obesity increases the risk for diseases affecting almost every organ system, including type 2 diabetes, nonalcoholic fatty liver disease, and certain types of cancer. The prevalence of both obesity and uncontrolled hypertension remains disturbingly high. As documented in both studies, these health indicators are moving in the wrong direction in all populations but occur disproportionately in racial and ethnic minority groups.
Abnormal Respiratory Vital Signs, ECG Findings May Predict Early Deterioration in COVID-19
Pulmonology Advisor, September 9, 2020
Abnormal respiratory vital signs coupled with electrocardiogram (ECG) findings of atrial fibrillation (AF)/flutter, right ventricular (RV) strain, or ST-segment abnormalities were found to predict early deterioration in patients with coronavirus disease 2019 (COVID-19), according to a study published in the Mayo Clinic Proceedings. Early triage is crucial for hospitalized patients with COVID-19 who require a higher level of care. In this study, researchers examined medical record data from 3 hospitals in New York City, New York to determine whether early data at emergency department presentation could predict the composite outcome of mechanical ventilation or death within the next 48 hours. The data of 1258 adults with COVID-19 (mean age, 61.6 years) who were hospitalized in March and April 2020 were examined. Electrophysiologists systematically read each patient’s ECG recordings conducted at presentation. A model adjusted for demographics, comorbidities, and vital signs was used to assess the prognostic value of ECG abnormalities. The most common comorbidities in this cohort included hypertension (57%), diabetes (37%), obesity (34%), primary lung disease (17%), and chronic kidney disease (16%). In this cohort, 73 patients (6%) died within 48 hours of presentation, and 14% of patients (n=174) were still alive at this time but were receiving mechanical ventilation. Another 277 patients (22%) died by 30 days. A total of 53% of all intubations occurred within 48 hours of presentation.
Pediatric COVID-19 cases surpass half-million
Infectious Diseases in Children, September 9, 2020
The AAP announced that a total of 513,415 pediatric cases of COVID-19 have been reported, according to an analysis of state-level data. The report found 70,630 new pediatric cases from August 20 to September 3 — a 16% increase from the total case count of 442,785 that was reported on August 19. “These numbers are a chilling reminder of why we need to take this virus seriously,” AAP President Sally Goza, MD, FAAP, said in a statement. “While much remains unknown about COVID-19, we do know that the spread among children reflects what is happening in the broader communities. A disproportionate number of cases are reported in Black and Hispanic children and in places where there is high poverty. We must work harder to address societal inequities that contribute to these disparities.” As of September 3, the total number of pediatric COVID-19 cases represents 9.8% of all reported cases.
Multimodality Imaging in Cardiovascular Complications of COVID-19
American College of Cardiology, September 9, 2020
Standard evaluation and management of the patient with suspected or proven cardiovascular complications of coronavirus disease-2019 (COVID-19), the disease caused by severe acute respiratory syndrome related-coronavirus-2 (SARS-CoV-2), is challenging. Routine history, physical examination, laboratory testing, electrocardiography, and plain x-ray imaging may often suffice for such patients, but given overlap between COVID-19 and typical cardiovascular diagnoses such as heart failure and acute myocardial infarction, need frequently arises for advanced imaging techniques to assist in differential diagnosis and management. This document provides guidance in several common scenarios among patients with confirmed or suspected COVID-19 infection and possible cardiovascular involvement, including chest discomfort with electrocardiographic changes, acute hemodynamic instability, newly recognized left ventricular dysfunction, as well as imaging during the subacute/chronic phase of COVID-19. For each, the authors consider the role of biomarker testing to guide imaging decision-making, provide differential diagnostic considerations, and offer general suggestions regarding application of various advanced imaging techniques.
The Real Reason Post-COVID Myocarditis Is a Worry
MedPage Today, September 8, 2020
It’s not often that myocarditis trends on Twitter, but cardiac MRI findings after recovery from acute COVID-19 symptoms have rocketed to public attention for their impact on decisions being made about sports. One (as yet unpublished) study found myocarditis in 15% of college athletes who tested positive, largely after mild or no symptoms. A more alarming statement by Penn State football’s team doctor put that rate at 30% to 35%, but that claim has since been walked back. Before that was a German cardiac MRI study in non-athletes that turned up lingering myocardial inflammation and other cardiac abnormalities in 78 of 100 people. While the study was subsequently corrected, the message remained the same: even a mild course of COVID-19 in relatively healthy people could leave a mark on the heart. That study, too, received an enormous amount of attention due, in part, to its use by colleges and sports programs to determine the future of the fall athletics season.
The American College of Cardiology Roundtable on Research in the Era of COVID-19
Journal of the American College of Cardiology, September 8, 2020
The onset of the SARS-CoV-2 pandemic (coronavirus disease-2019 [COVID-19]) has had a profound effect on research. It has created an impetus for change, presented a wide range of challenges, and sparked an array of initiatives. In doing so, the pandemic has revealed threats to old models of knowledge generation and openings for new approaches. It is clear there is an unprecedented need for action. To address the research challenges created by the pandemic, the American College of Cardiology (ACC) conducted a Heart House Roundtable on clinical research in the COVID-19 era. The ACC invited a range of experts to discuss the changing landscape and to identify opportunities to provide rapid research to support efforts to prevent, diagnose, and treat COVID-19 infection; to produce actionable insights about the effects of the pandemic on non–COVID-19 cardiovascular disease; and to address the need to continue and accelerate cardiovascular clinical research that remains urgently needed but that has encountered obstacles during the pandemic. The goal was to generate discussion, share insights, and produce recommendations.
The coronaviruhttps://www.nature.com/articles/d41586-020-02544-6s is mutating — does it matter?
Nature, September 8, 2020
When COVID-19 spread around the globe this year, David Montefiori wondered how the deadly virus behind the pandemic might be changing as it passed from person to person. Montefiori is a virologist who has spent much of his career studying how chance mutations in HIV help it to evade the immune system. The same thing might happen with SARS-CoV-2, he thought. In March, Montefiori, who directs an AIDS-vaccine research laboratory at Duke University in Durham, North Carolina, contacted Bette Korber, an expert in HIV evolution and a long-time collaborator. Korber, a computational biologist at the Los Alamos National Laboratory (LANL) in Sante Fe, New Mexico, had already started scouring thousands of coronavirus genetic sequences for mutations that might have changed the virus’s properties as it made its way around the world. Compared with HIV, SARS-CoV-2 is changing much more slowly as it spreads. But one mutation stood out to Korber. It was in the gene encoding the spike protein, which helps virus particles to penetrate cells. Korber saw the mutation appearing again and again in samples from people with COVID-19. At the 614th amino-acid position of the spike protein, the amino acid aspartate (D, in biochemical shorthand) was regularly being replaced by glycine (G) because of a copying fault that altered a single nucleotide in the virus’s 29,903-letter RNA code. Virologists were calling it the D614G mutation.
Developing a COVID-19 mortality risk prediction model when individual-level data are not available
Nature Communications, September 7, 2020
At the COVID-19 pandemic onset, when individual-level data of COVID-19 patients were not yet available, there was already a need for risk predictors to support prevention and treatment decisions. Here, we report a hybrid strategy to create such a predictor, combining the development of a baseline severe respiratory infection risk predictor and a post-processing method to calibrate the predictions to reported COVID-19 case-fatality rates. With the accumulation of a COVID-19 patient cohort, this predictor is validated to have good discrimination (area under the receiver-operating characteristics curve of 0.943) and calibration (markedly improved compared to that of the baseline predictor). At a 5% risk threshold, 15% of patients are marked as high-risk, achieving a sensitivity of 88%. We thus demonstrate that even at the onset of a pandemic, shrouded in epidemiologic fog of war, it is possible to provide a useful risk predictor, now widely used in a large healthcare organization.
T cells in COVID-19 — united in diversity
Nature Immunology, September 7, 2020
Comprehensive mapping reveals that functional CD4+ and CD8+ T cells targeting multiple regions of SARS-CoV-2 are maintained in the resolution phase of both mild and severe COVID-19, and their magnitude correlates with the antibody response. CD4+ and CD8+ T cells work with other constituents of a coordinated immune response to first resolve acute viral infections and then to provide protection against reinfection. Careful delineation of the frequency, specificity, functionality and durability of T cells during COVID-19 is vital to understanding how to use them as biomarkers and targets for immunotherapies or vaccines. In this issue of Nature Immunology, Peng et al. take a comprehensive approach to characterizing circulating SARS-CoV-2-specific CD4+ and CD8+ T cells following resolution of COVID-19. They report a robust and diverse T cell response targeting multiple structural and non-structural regions of SARS-CoV-2 in most resolved cases, irrespective of whether the individual had mild or severe infection. While the most frequent responses were against peptides spanning spike, membrane and nucleoprotein antigens, all eight regions tested were recognized by multiple individuals, with a maximum of 23 reactive pools in two individuals. Such multispecific T cell responses are well suited to providing a failsafe form of multilayered protection, mitigating against viral escape by mechanisms such as mutation or variable antigen presentation.
Coronavirus in Context: Can a Cholesterol Drug Fight COVID?
WebMD, September 7, 2020
[Video] Dr. John Whyte, chief medical officer at WebMD has spent a lot of episodes talking about different drug treatments for COVID-19. Watch as he interviews Dr. Yaakov Nahmias, professor of bioengineering at the Hebrew University of Jerusalem, to discuss an interesting study about the role of lipid metabolism and a strategy for some cholesterol-lowering medicines in the treatment of COVID-19.
PICS: A Serious Issue for COVID-19 Survivors
MedPage Today, September 6, 2020
Even healthcare professionals may not be aware of and prepared for a condition called post-intensive care unit (ICU) syndrome (PICS) that can occur in the aftermath of COVID-19. What about those who were hospitalized for COVID-19, treated in the ICU, and are unaware of the possible long-term impact and rehabilitation phase? There is a tendency to think that once the patient is discharged from the hospital, has tested negative, and looks well, the problem is resolved. However, the struggle of COVID-19 survivors and family members or caregivers may not end there. PICS is an ongoing challenge that may potentially present a public health crisis. PICS is a term used to describe the group of impairments faced by ICU survivors. It can persist for months or years. PICS encompasses a combination of physical, neurological, social, and psychological decline. The physical impairments include intensive care-acquired weakness, classified as critical illness myopathy, neuropathy, and neuromyopathy. Cognitive and psychological impairments involve impaired memory, language, delirium, depression, anxiety, and post-traumatic stress disorder (PTSD). During the COVID-19 pandemic, critically ill clients are considered the most vulnerable to PICS. Among these, 30% suffer from depression and 70% experience anxiety and PTSD after ICU discharge. Moreover, survivors can experience additional stress as a result of isolation and limited contact with loved ones and reduced contact with staff due to precautionary measures such as personal protective equipment.
COVID-19 and hypertension – is the HSP60 culprit for the severe course and worse outcome?
The American Journal of Physiology Heart and Circulatory Physiology, September 4, 2020
The 60 kDa heat shock protein (HSP60) is a chaperone essential for mitochondrial proteostasis ensuring thus sufficient aerobic energy production. In pathological conditions, HSP60 can be translocated from the mitochondria and excreted from the cell. In turn, the extracellular HSP60 has a strong ability to trigger and enhance inflammatory response with marked pro-inflammatory cytokine induction, which is mainly mediated by toll-like receptors binding. Previous studies have found increased circulating levels of HSP60 in hypertensive patients, as well as enhanced HSP60 expression and membrane translocation in the hypertrophic myocardium. These observations are of particular interest as they could provide a possible pathophysiological explanation of the severe course and worse outcome of SARS-CoV-2 infection in hypertensive patients, repeatedly reported during recent COVID-19 pandemic, and related to hyperinflammatory response and cytokine storm development during the third phase of the disease. In this regard, pharmacological inhibition of HSP60 could attract attention to potentially ameliorate inappropriate inflammatory reaction in severe COVID-19 patients.
CDC: Weekly COVID-19 Deaths Down, but Still Above Epidemic Threshold
Infectious Disease Special Edition, September 4, 2020
As of Sept 4, almost 190,000 people in the United States have died from COVID-19, according to the Johns Hopkins COVID-19 Dashboard, but the weekly numbers appear to be slowing. The deaths attributed to COVID-19 during the last week of August are down, but the percentage still exceeds the epidemic threshold, according to the National Center for Health Statistics (NCHS) database. Provisional data from across the United States show that based on death certificates available on Aug. 27, the percentage of deaths attributed to COVID-19, pneumonia or influenza for week 34 was 7.9%. During week 33, it was 23.3%. In addition, the statistics show that only 6% of deaths listed just COVID-19 as a cause of death. Most certificates list comorbid conditions, such as respiratory and cardiovascular conditions, as contributors to the deaths. “In 94% of deaths with COVID-19, other conditions are listed in addition to COVID-19,” the NCHS told Infectious Disease Special Edition. “These causes may include chronic conditions like diabetes or hypertension. They may also include acute conditions that occurred as a result of COVID-19, such as pneumonia or respiratory failure.”
Heart, COVID‐19, and echocardiography
Echocardiography, September 4, 2020
Although clinical manifestations of coronavirus disease of 2019 (COVID‐19) mainly consist of respiratory symptoms, a severe cardiovascular damage may occur. Moreover, previous studies reported a correlation of cardiovascular metabolic diseases with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and actually, many COVID‐19 patients show comorbidities (systemic hypertension, cardio‐cerebrovascular disease, and diabetes) and have a raised risk of death. The purpose of this review is to focus the cardiovascular effects of 2019‐nCoV on the base of the most recent specific literature and previous learnings from SARS and MERS and analyze the potential role of echocardiography during the current critical period and short‐ and long‐term follow‐up.
Invasive fungal disease common among critically ill COVID-19 patients, study finds
Helio | Infectious Disease News, September 4, 2020
Invasive fungal disease occurs often in critically ill patients with COVID-19 on mechanical ventilation, according to a study published in Clinical Infectious Diseases. “With the COVID-19 pandemic far from over, it is paramount that our understanding of the risk from associated invasive fungal disease is enhanced,” P. Lewis White, PhD, FECMM, FRCPath, consultant clinical scientist and head of the mycology reference laboratory for Public Health Wales, told Healio. White and colleagues screened 135 patients with COVID-19 for invasive fungal disease to evaluate an enhanced testing strategy. The patients were from a national, multicenter cohort in Wales. The incidence of invasive fungal disease was 26.7% — 14.1% aspergillosis and 12.6% yeast infections. The overall mortality rate was 38%, including 53% in patients with fungal disease and 31% in patients without it (P = .0387). The overall mortality rate declined when antifungal therapy was used. It was 38.5% in patients who received antifungal therapy vs. 90% in patients who did not (P = .008). White said they did not expect the high rate of invasive yeast infections.
Will Labor Day Weekend Bring Another Holiday COVID Surge?
Kaiser Health News, September 4, 2020
Hopefully, summer won’t end the way it began. Memorial Day celebrations helped set off a wave of coronavirus infections across much of the South and West. Gatherings around the Fourth of July seemed to keep those hot spots aflame. And now Labor Day arrives as those regions are cooling off from COVID-19. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, warned Wednesday that Americans should be cautious to avoid another surge in infection rates. But travelers are also weary of staying home — and tourist destinations are starved for cash. “Just getting away for an hour up the street and staying at a hotel is like a vacation, for real,” says Kimberly Michaels, who works for NASA in Huntsville, Alabama, and traveled to Nashville, Tennessee, with her boyfriend to celebrate his birthday last weekend. In time for the tail end of summer, many local governments are lifting restrictions to resuscitate tourism activity and rescue small businesses.
COVID-19 impact on treatment for chronic illness revealed
UN News, September 4, 2020
The four most common NCDs are cardiovascular disease, cancer, diabetes and chronic respiratory diseases; together, they contribute to more than 40 million deaths a year, said Dr Bente Mikkelsen, Director, WHO Division of Noncommunicable Diseases. “The most recent study shows that there is a disruption in healthcare services including NCD diagnosis and treatments in 69 per cent of cases”, she said. “In cancer, there are the highest numbers, with 55 per cent of people living with cancer (having) their health services disrupted.” Dr Mikkelsen noted that those living with one or more NCDs were among the most likely to become severely ill and die from the new coronavirus. Studies from several countries had indicated this, she said, highlighting how data on indigenous communities in Mexico, showed that diabetes was the most commonly found disease among COVID-19 fatalities. Research also found that in Italy, of those who succumbed to COVID-19 in hospital, 67 per cent suffered from hypertension and 31 per cent had type 2 diabetes.
Subtle Cardiac Troubles in MIS-C Paint a ‘Myocarditis-Like Picture’
MedPage Today, September 3, 2020
Multisystem inflammatory syndrome in children (MIS-C) caused by SARS-CoV-2 infection was often accompanied by subtle changes in myocardial function that differ from what is seen in classic Kawasaki disease, one center reported. Various strain parameters on echocardiography showed that left ventricular (LV) systolic and diastolic function were worse in MIS-C compared with Kawasaki disease and healthy controls. Myocardial injury was a common finding, in 17 out of 28 MIS-C patients, and affected patients performed particularly badly on these functional parameters, according to Anirban Banerjee, MD, of Children’s Hospital of Philadelphia (CHOP), and colleagues. Only one out of 28 MIS-C patients had coronary artery dilatation in the acute phase, which resolved over approximately 5 days, the authors reported in their study online in the Journal of the American College of Cardiology. On the other hand, four of the 20 kids with classic Kawasaki disease had coronary abnormalities (including two with aneurysms detected). “The major finding during the acute phase of MIS-C is a myocarditis-like picture, that may remain subtle and sub-clinical, particularly in the preserved EF [ejection fraction] cohort. Even in the presence of normal EF, the latter group showed distinct dysfunction in systolic and diastolic deformation parameters,” the researchers wrote. MIS-C is characterized as a hyperinflammatory syndrome with multi-organ dysfunction. The observed LV dysfunction in the study may be the result of subclinical myocarditis, which was suspected in 61% of the MIS-C group based on brain natriuretic peptide and troponin elevations, the team explained.
FDA Could Issue EUA for COVID-19 Vaccine Before Clinical Trials Are Completed
Pulmonology Advisor, September 3, 2020
Emergency use authorization (EUA) or approval for a COVID-19 vaccine before phase 3 clinical trials are complete could be considered by the U.S. Food and Drug Administration, according to the agency’s commissioner, Stephen Hahn, M.D. “It is up to the sponsor [vaccine developer] to apply for authorization or approval, and we make an adjudication of their application,” he told the Financial Times, CNN reported. “If they do that before the end of phase 3, we may find that appropriate. We may find that inappropriate, we will make a determination.” An EUA is not the same as full-fledged approval, Hahn noted. “Our emergency use authorization is not the same as a full approval,” he said. “The legal, medical, and scientific standard for that is that the benefit outweighs the risk in a public health emergency.” Two vaccines are currently in phase 3 trials in the United States and two more are expected to begin phase 3 trials by mid-September, CNN reported.
Barriers to remote care ‘unmasked at wider scale’ due to COVID-19
Helio | Cardiology Today, September 3, 2020
An interview with Khaldoun G. Tarakji, MD, MPH, a Cardiology Today Next Gen Innovator, about the data he presented at the virtual Heart Rhythm Society Annual Scientific Sessions. Tarakji, who serves as associate section head of cardiac electrophysiology and director of the Center for Digital Health at the Heart and Vascular Institute at Cleveland Clinic, also highlighted other abstracts presented at the virtual Heart Rhythm Society Annual Scientific Sessions (HRS) that gave insight into the “digital health” of patients with arrhythmias. At Heart Rhythm Society Annual Scientific Sessions (HRS), Tarakji explained about the use of virtual visits, “While there are many advantages for using virtual visits, we never thought about a pandemic as one of them. Our study was one of its kind as it provided insight about both patient experience with using this modality prior to COVID-19. Interestingly the issues highlighted in our studies as barriers were unmasked at wider scale during the pandemic. With the unprecedented demand for telemedicine, many platforms could not keep up and the technical difficulties became a major obstacle. The government was thankfully quick to respond with swift actions that included reimbursement for these visits and also allowing caregivers to use other video conferencing secured platforms at the time of the crisis. While these rules are temporary, virtual visits are here to stay, and for the right patient coupled with the right tools, they can provide effective and high-quality care.”
Technology Aids Fight Against COVID-19 — Nine innovations in health tech that help to manage the pandemic
MedPage Today, September 3, 2020
As the COVID-19 cases continue to rise across the globe, companies are working hard to develop innovative solutions to fight the coronavirus pandemic. Chinese companies such as Alibaba have led the way using artificial intelligence, data science, and technology. Startups are teaming up with clinicians, engineers, and government entities to reduce the spread of COVID-19. As we continue our fight in the management and eventual eradication of the virus, read about nine innovative ways companies are helping on the front lines.
Understanding the Association Between COVID-19, Thromboembolism, and Therapeutic Anticoagulation
Pulmonology Advisor, September 2, 2020
Among hospitalized patients with coronavirus disease 2019 (COVID-19), those who receive anticoagulation treatment have lower adjusted risk of mortality and intubation compared with in-hospital patients who do not receive anticoagulation, according to study results published in the Journal of the American College of Cardiology. A team of investigators at Icahn School of Medicine at Mount Sinai in New York, New York, expanded on previous findings that suggested an association between in-hospital anticoagulation and reduced mortality. In the present investigation, the researchers compared the effects of therapeutic and prophylactic anticoagulation treatment with the absence of such treatment. Choice of agent, survival outcomes, intubation, and major bleeding were also analyzed. In addition, the study authors also reviewed the first consecutive autopsies performed at their institution to characterize the premortem management of this patient population as it relates to anticoagulation therapy. The primary outcome was in-hospital mortality, and secondary outcomes included intubation and major bleeding. Participants were all older than 18 years, had clinically confirmed severe acute respiratory syndrome coronavirus 2 infection between March 1, 2020, and April 30, 2020, and were admitted to 1 of 5 New York City hospitals included in the study.
Kevzara fails to meet endpoints in ex-US phase 3 trial for severe COVID-19
Helio | Rheumatology, September 2, 2020
Sanofi announced that its IL-6 inhibitor Kevzara failed to meet primary and secondary endpoints in a phase 3 trial of patients outside the United States hospitalized with severe COVID-19. “Although this trial did not yield the results we hoped for, we are proud of the work that was achieved by the team to further our understanding of the potential use of Kevzara for the treatment of COVID-19,” John Reed, MD, PhD, global head of research and development at Sanofi, said in a company press release. The randomized trial included 420 patients who were severely or critically ill with COVID-19, recruited from hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia and Spain. Among the participants, 161 received 200 mg of Kevzara (sarilumab), 173 were treated with 400 mg and 86 received a placebo. According to the press release, although not statistically significant, the researchers observed numerical trends toward a decrease in hospital stay duration as well as faster time to better clinical outcomes, defined as a two-point improvement on a seven-point scale. In addition, the researchers noted a trend toward reduced mortality in the critical patient group, but not in the severe group. Lastly, the time to discharge was reduced by 2 to 3 days among patients who received sarilumab within the first 2 weeks of treatment, although, again, this was not statistically significant.
Mount Sinai identifies drugs that could prevent COVID-19 replication
Modern Healthcare, September 2, 2020
Researchers from the Icahn School of Medicine at Mount Sinai Health System in New York have developed a computational method to identify drugs that could be combat COVID-19. Unlike other research to repurpose drugs to treat infection, this effort focused on inhibiting viral uptake of SARS-CoV-2 in the first place. In a preprint paper posted to BioRxiv, the researchers explored viral sequences using PCR analysis, RNA sequencing, and bioinformatics. They identified four compounds that could block replication of the novel coronavirus, namely amlodipine, loperamide, terfenadine, and berbamine. They then validated these findings in multiple assays using primate Vero cells infected with SARS-CoV-2, A549 cells, and in human organoids. According to the paper, these compounds were found to potently reduce viral load despite having no impact on viral entry or modulation of the host antiviral response in the absence of virus. “You have a bunch of drugs that are blocking the virus in cell culture,” said lead researcher Avi Ma’ayan, director of the Mount Sinai Center for Bioinformatics and principal investigator with the academic health system’s LymeMIND team of other research into other potential COVID-19 treatments. “But this particular paper is showing a lot of details about why and which drug and … is beginning to understand the molecular mechanism.” The researchers used a collection of gene expression profiles from the National Institutes of Health’s Library of Integrated Network-based Cellular Signatures (LINCS) database that has previously been applied to identify drugs that attenuate the Ebola virus. With SARS-CoV-2, the Mount Sinai team was able to spot transcriptional irregularities by comparing changes in gene expression before and after infection or drug treatment. In this new work, the Mount Sinai team studied 50 genes that were downregulated by the virus or 50 upregulated by certain drugs. They also looked at the 100 genes most commonly coexpressed by ACE2, known to be the receptor of SARS-CoV-2.
No clinical benefit of ACE inhibitor, ARB suspension in mild to moderate COVID-19
Helio | Cardiology Today, September 1, 2020
In patients hospitalized with mild or moderate COVID-19, suspending ACE inhibitors and angiotensin receptor blockers for 30 days, compared with continued treatment, did not impact the number of days alive and out of hospital. BRACE CORONA provides the first randomized controlled trial data on continuing vs. suspending ACE inhibitors and angiotensin receptor blockers in this patient population. “Because these data indicate that there is no clinical benefit from routinely suspending these medications in hospitalized patients with mild to moderate COVID-19, they should be generally continued for those with an indication,” Renato D. Lopes, MD, MHS, PhD, professor of medicine at Duke University School of Medicine and member of the Duke Clinical Research Institute, said while presenting results of the BRACE CORONA trial at the virtual European Society of Cardiology Congress.
COVID Hypoxemia: Finally, an Explanation
MedPage Today, September 1, 2020
In the early days of the pandemic in New York City, physicians were having serious debates about whether COVID-19 patients developed typical acute respiratory distress syndrome (ARDS), or if they were suffering from a different phenomenon entirely. The main discrepancy was that patients with severe hypoxemia often had well preserved lung compliance; their lungs weren’t “stiff,” as is seen in typical ARDS. Now, a team at Mount Sinai Hospital thinks they may have an explanation for that disconnect — and it was a completely serendipitous finding, according to Alexandra Reynolds, MD, and Hooman Poor, MD, who published their findings in a letter in the American Journal of Respiratory & Critical Care Medicine. Reynolds, a neurointensivist, wondered whether her COVID-19 patients were having frequent strokes, given rising concerns about clotting being a significant feature of the disease. So she used transcranial Doppler ultrasound to assess blood flow in the brain. A robotic version of NovaSignal’s TCD system enabled the researchers to attach the scanner and leave the patient room for analysis, which was helpful during COVID quarantine, she said. “I was expecting to see microemboli given the reports of clotting, but I saw zero emboli in the patients I scanned,” Reynolds told MedPage Today.
Link found between metabolic syndrome and worse COVID-19 outcomes
Medical News Today, September 1, 2020
A new study has found that people with metabolic syndrome, which refers to a cluster of conditions that increase a person’s risk of cardiovascular issues, are more likely to have worse COVID-19 outcomes — including requiring ventilation and death. The research, which appears in the journal Diabetes Care, provides further information on the underlying risk factors that affect the severity of COVID-19. Since its emergence in Wuhan, China, in December 2019, COVID-19 has spread rapidly across the world. However, its effects are not equal. As journals started publishing the results of observational studies drawing on data from the first wave of the pandemic, it became clear that some underlying medical conditions were associated with a greater chance of a person developing severe COVID-19. According to the Centers for Disease Control and Prevention (CDC), some groups most at risk of severe disease include older adults and those with certain underlying medical conditions, such as cardiovascular diseases, obesity, and type 2 diabetes. The new research highlights that obesity, hypertension, and diabetes, in particular, are more common in people who die from COVID-19 than heart or lung conditions.
The Role of Critical Care Cardiology During the COVID-19 Pandemic
American College of Cardiology, September 1, 2020
As of August 3rd 2020, the coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2), responsible for the disease COVID-19 (coronavirus disease 2019), had infected more than 18 million people worldwide and caused nearly 700,000 deaths. After an initial wave that predominantly affected the northeastern United States, there has recently been a resurgence in cases across many states. The clinical spectrum of COVID-19 is wide, ranging from asymptomatic infection and mild upper respiratory tract illness to acute respiratory distress syndrome (ARDS), shock, and death. Critically ill patients frequently have extra-pulmonary manifestations, including myocardial injury, with elevated biomarkers, electrocardiographic changes, or echocardiographic abnormalities. Herein, we outline the central role for critical care cardiologists during this pandemic, changes to pre-pandemic practices in the cardiac intensive care unit (CICU), and the need for change at an institutional, regional, and national level in response to a surge in CICU COVID-19 patients.
Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2
Molecules, September 1, 2020
Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.
COVID-19 pandemic leads to more people with high blood pressure, research suggests
Mobi Health News, August 31, 2020
More people experienced high blood pressure in response to the COVID-19 pandemic compared to before, according to new research from chronic care management company Livongo. The study looked at the proportion of Livongo members who had high blood pressure before and during the pandemic, specifically covering the time between mid-September of 2019 and mid-August of 2020. The data does not support a direct cause-and-effect relationship between specific events related to the COVID-19 pandemic and an increased proportion of people with high blood pressure, but a correlation does exist, according to Livongo. As the pandemic progressed in the U.S., so did the percentage of Livongo members with high blood pressure, the results show. Up until January of this year, the average percentage of members with high blood pressure was 62%. However, by the end of January, when the first confirmed case of COVID-19 was announced in the U.S. and quarantining began in Wuhan, China, the average percentage of members with high blood pressure increased to 67%. By March 23, the median date of lockdown orders in the U.S., 64% of members had high blood pressure. In early April, the percentage reached a peak of 68%, which correlates with the April 3 release of COVID-19-related unemployment figures and the first time that the Centers for Disease Control and Prevention recommended that everyone wear masks in public.
Coronavirus in Context: Do Antibodies Provide Protection?
WebMD, August 31, 2020
[Video] What’s the role of antibodies against coronavirus infection? It’s one of the biggest questions over the past six months. WebMD’s Chief Medical Officer, Dr. John Whyte, speaks with Alexander Greninger, MD, PhD, Assistant Director of the UW Medicine Clinical Virology Laboratory, University of Washington, about the effectives of antibodies for COVID-19 immunity and transmission.
1st U.S. COVID-19 Reinfection Reported in Nevada Patient
WebMD, August 31, 2020
The first U.S. case of a confirmed coronavirus reinfection looks to be a patient in Nevada. The U.S. case comes a few days after the first reinfection in the world was announced in Hong Kong. The Nevada case is detailed in a new paper published in The Lancet on an online preprint server. The study has not yet been reviewed by peers. Reinfection is rare, researchers said, but people should still be cautious. “If you’ve had it, you can’t necessarily be considered invulnerable to the infection,” Mark Pandori, one of the authors and director of the Nevada State Public Health Laboratory, told NBC. According to the report, the 25-year-old man from Reno, Nevada, first tested positive for COVID-19 in mid-April after experiencing a sore throat, cough, headache, nausea, and diarrhea. He recovered but got sick again in late May, marking 48 days between two positive tests after two negative tests in between the infections. During the second round, his illness was more severe, and he was hospitalized with pneumonia. Researchers found that the genetic sequencing of the virus varied, and the patient was infected with slightly different strains of the coronavirus. They aren’t sure why he was reinfected, which could be related to the virus itself or the patient’s immune system.
Management of pneumothorax in mechanically ventilated COVID-19 patients: early experience
Interactive CardioVascular and Thoracic Surgery, August 31, 2020
Pneumothorax, a major and potential fatal complication of mechanical ventilation, can further complicate the management of COVID-19 patients, whilst chest drain insertion may increase the risk of transmission of attending staff. The rate of pneumothorax in such patients has not yet been quantified. However, previous experience from the SARS outbreak, also caused by a coronavirus, suggests a high incidence (20–34%) of pneumothorax in mechanically ventilated SARS patients. Mechanical ventilation is the most common cause of iatrogenic pneumothoraces in the ICU setting; however, it is a rare occurrence in intubated patients who have relatively normal lung parenchyma. Most pneumothoraces related to mechanical ventilation are associated with a combination of high ventilation pressures and underlying chronic lung pathology such as emphysema. Previous studies have suggested that high inspiratory airway pressures and positive end-expiratory pressure were correlated with increased incidence of barotrauma. Currently, there is limited literature on how to manage pneumothoraces in mechanically ventilated COVID-19 patients. We present a case series (nine patients) and a suggested protocol for how to manage and treat pneumothoraces in COVID-19 patients in an ICU setting.
Leaders in Cardiovascular Research: Filippo Crea
Cardiovascular Research, August 31, 2020
[Video or Article] Join Cardiovascular Research Editor-in-Chief as he interviews Professor Filippo Crea, Catholic University, Rome. Prof. He trained in Pisa Medical School in Cardiology and in Pulmonary Diseases. Crea has been a Senior Lecturer in Cardiology at RPMS-Hammersmith Hospital in London. Since 2008, he is Professor of Cardiology, Director of the Department of Cardiovascular Sciences, Director of the Postgraduate School in Cardiology, and Coordinator of the PhD programme in Cellular and Molecular Cardiology at the Catholic University in Rome. As of August 2020, he is the new Editor-in-Chief of the European Heart Journal of the European Society of Cardiology.
Fad or future? Telehealth expansion eyed beyond pandemic
Modern Healthcare, August 30, 2020
Consultations via tablets, laptops and phones linked patients and doctors when society shut down in early spring. Telehealth visits dropped with the reopening, but they’re still far more common than before and now there’s a push to make them widely available in the future. Permanently expanding access will involve striking a balance between costs and quality, dealing with privacy concerns and potential fraud, and figuring out how telehealth can reach marginalized patients, including people with mental health problems. “I don’t think it is ever going to replace in-person visits, because sometimes a doctor needs to put hands on a patient,” said CMS Administrator Seema Verma, the Trump administration’s leading advocate for telehealth. Caveats aside, “it’s almost a modern-day house call,” she added. “It’s fair to say that telemedicine was in its infancy prior to the pandemic, but it’s come of age this year,” said Murray Aitken of the data firm IQVIA, which tracks the impact. In the depths of the coronavirus shutdown, telehealth accounted for more than 40% of primary care visits for patients with traditional Medicare, up from a tiny 0.1% sliver before the public health emergency. As the government’s flagship health care program, Medicare covers more than 60 million people, including those age 65 and older, and younger disabled people.
Findings from a probability-based survey of U.S. households about prevention measures based on race, ethnicity, and age in response to SARS-CoV-2
Journal of Infectious Diseases, August 29, 2020
There are 21.7 million reported cases of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and over 776,000 deaths due to the coronavirus disease 2019 (COVID-19) worldwide through August 17, 2020. Over one-fourth of cases are in the U.S., with African American and Latinos being disproportionately impacted in case counts and death rates. Prevention control messages and efforts, such as sheltering in place and quarantining, may not have been as successful among African Americans and Latinos for numerous reasons, such as needing to work outside of the home, living in large households in close quarters, and including the effects of structural racism (i.e., access to health insurance and care, limited health literacy). Little is known about individual prevention measures that were taken in response to COVID-19 or how people may engage with surveillance/reporting strategies as we enter phase two of the pandemic. We investigated individual behaviors taken by White, African American, and Latino U.S. households in response to SARS-CoV-2, and likelihood of using digital tools for symptom surveillance/reporting. We analyzed cross-sectional week one data (April 2020) of the COVID Impact Survey in a large, nationally-representative sample of U.S. adults. In general, all groups engaged in the same prevention behaviors, but Whites reported being more likely to use digital tools to report/act on symptoms and seek testing, versus African Americans and Latinos.
Fauci on ‘Highly Specific, Direct’ Therapy for COVID-19
MedPage, August 28, 2020
Monoclonal antibodies could hold promise in COVID-19 treatment and prevention if the results bear out in clinical trials for efficacy, the nation’s leading infectious diseases expert told MedPage Today. “There’s a lot of activity and it’s a highly concentrated, highly specific, direct antiviral approach to a number of diseases. The success in Ebola was very encouraging,” said National Institute of Allergy and Infectious Diseases (NIAID) Director Anthony Fauci, MD. Most recently thrust into the spotlight as effective treatments for Ebola, monoclonal antibodies are currently being researched as a potential treatment for HIV, as well as COVID-19. This month, the NIH highlighted trials of monoclonal antibodies being conducted among several different COVID-19 patient populations: outpatients with COVID-19, patients hospitalized with the disease, and even a trial in household contacts of confirmed cases, where the therapy was used as prophylaxis. Fauci explained how the mechanism of monoclonal antibodies “is really one of a direct antiviral. It’s like getting a neutralizing antibody that’s highly, highly concentrated and highly, highly specific. So, the mechanism involved is blocking of the virus from essentially entering its target cell in the body and essentially interrupting the course of infection,” he said.
Sudden Cardiac Arrest in a Patient with Myxedema Coma and COVID-19
Journal of the Endocrine Society, August 28, 2020
SARS-CoV-2 infection is associated with significant lung and cardiac morbidity but there is a limited understanding of the endocrine manifestations of COVID-19. We present the first case of myxedema coma in COVID-19 and we discuss how SARS-CoV-2 may have precipitated multi-organ damage and sudden cardiac arrest in our patient. A 69-year-old female with a history of small cell lung cancer presented with hypothermia, hypotension, decreased respiratory rate, and a Glasgow Coma Scale score of 5. The patient was intubated and administered vasopressors. Laboratory investigation showed elevated thyroid stimulating hormone, very low free thyroxine, elevated thyroid peroxidase antibody, and markedly elevated inflammatory markers. SARS-CoV-2 test was positive. Computed tomography showed pulmonary embolism and peripheral ground glass opacities in the lungs. The patient was diagnosed with myxedema coma with concomitant COVID-19. While treatment with intravenous hydrocortisone and levothyroxine were begun the patient developed a junctional escape rhythm. Eight minutes later, the patient became pulseless and was eventually resuscitated. Echocardiogram following the arrest showed evidence of right heart dysfunction. She died two days later from multi-organ failure. This is the first report of SARS-CoV-2 infection with myxedema coma. Sudden cardiac arrest likely resulted from the presence of viral pneumonia, cardiac arrhythmia, pulmonary emboli, and myxedema coma – all of which were associated with the patient’s SARS-CoV-2 infection.
The coronavirus is most deadly if you are older and male — new data reveal the risks
Nature, August 28, 2020
For every 1,000 people infected with the coronavirus who are under the age of 50, almost none will die. For people in their fifties and early sixties, about five will die — more men than women. The risk then climbs steeply as the years accrue. For every 1,000 people in their mid-seventies or older who are infected, around 116 will die. These are the stark statistics obtained by some of the first detailed studies into the mortality risk for COVID-19. Trends in coronavirus deaths by age have been clear since early in the pandemic. Research teams looking at the presence of antibodies against SARS-CoV-2 in people in the general population — in Spain, England, Italy and Geneva in Switzerland — have now quantified that risk, says Marm Kilpatrick, an infectious-disease researcher at the University of California, Santa Cruz. The studies reveal that age is by far the strongest predictor of an infected person’s risk of dying — a metric known as the infection fatality ratio (IFR), which is the proportion of people infected with the virus, including those who didn’t get tested or show symptoms, who will die as a result. “COVID-19 is not just hazardous for elderly people, it is extremely dangerous for people in their mid-fifties, sixties and seventies,” says Andrew Levin, an economist at Dartmouth College in Hanover, New Hampshire, who has estimated that getting COVID-19 is more than 50 times more likely to be fatal for a 60-year-old than is driving a car. But “age cannot explain everything”, says Henrik Salje, an infectious-disease epidemiologist at the University of Cambridge, UK. Gender is also a strong risk factor, with men almost twice more likely to die from the coronavirus than women.
Heparin may neutralize virus that causes COVID-19
Helio | HemOnc Today, August 28, 2020
The COVID-19 pandemic has prompted a flurry of scientific studies of various potential treatments and vaccines for the novel coronavirus. One such study, conducted by researchers at Rensselaer Polytechnic Institute and published in Antiviral Research, showed the FDA-approved anticoagulant heparin may neutralize SARS-CoV-2, the virus that causes COVID-19. SARS-CoV-2 uses a surface spike protein to attach to human cells and infect them, according to the study background. However, because heparin binds tightly with the surface spike protein, it potentially could serve as a decoy and prevent infection from occurring. “We’ve known for quite some time that heparin possesses the ability to be antiviral; it has the ability to bind to very specific proteins on the surfaces of viruses,” Jonathan S. Dordick, PhD, the Howard P. Isermann Professor of Chemical and Biological Engineering at Rensselaer and one of the study authors, said in an interview with Healio. “So that wasn’t really a surprise. The other reason we studied heparin had nothing to do with its antiviral properties.”
ANMCO POSITION PAPER: Network Organization for the Treatment of Acute Coronary Syndrome Patients during the Emergency COVID-19 Pandemic
European Heart Journal Supplements, August 27, 2020
Among the risk factors associated with increased mortality from COVID-19—besides male gender and age—the following are to be considered risk factors: hypertension, diabetes mellitus, a history of cardiovascular, and cerebrovascular events. The mortality rate for acute myocardial infarction during SARS by coronavirus was 2.6%, on an overall mortality rate linked to the infection of 6.6%. In consideration of the epidemiological framework described, we have to consider all the patients that we examine for acute coronary syndrome (ACS) as potential COVID-19. This aspect is particularly important for the safety of the other hospitalized patients, of our hospitals and of our healthcare professionals (physicians, nurses, residents, social healthcare workers, and radiology technicians) who are directly involved in the management of the patient. Therefore, the cardiologist must be ready to manage any cardiac emergency by guaranteeing the adequate therapy but at the same time, must protect the healthcare professionals from the risk of infection and optimize the available individual protection resources. In a patient presenting with ST-elevation (STEMI) myocardial infarction or ‘STEMI-like’, if positive to COVID-19, the reperfusion therapeutic strategy depends on the local organization and on the possibility to access without delay a Coronary Angioplasty (PCI) COVID Center, on the basis, obviously, of the risk/benefit assessment of the individual case. However, we advise to try pursuing, in the first instance, the mechanical revascularization strategy, according to the available local possibilities.
Cardiovascular System in COVID-19: Simply a Viewer or a Leading Actor?
Life, August 27, 2020
Several studies have observed a relationship between coronavirus disease (COVID-19) infection and the cardiovascular system with the appearance of myocardial damage, myocarditis, pericarditis, heart failure and various arrhythmic manifestations, as well as an increase in thromboembolic risk. COVID-19 causes cardiovascular complications, including diffuse thrombosis, pulmonary thromboembolism, disseminated intravascular coagulation (DIC), myocarditis, pericardial effusion, both hypokinetic and hyperkinetic arrhythmias, but also cardiogenic shock. In addition, drugs currently in use for the treatment of COVID-19, such as hydroxychloroquine, azithromycin and protease inhibitors, can affect the cardiac conduction system leading to an extension of the QT interval, which in turn can predispose the onset of ventricular arrhythmias, in particular torsades de pointes. This review examines the cardiovascular involvement, direct and indirect, associated with SARS CoV-2 infection in order to manage the cardiovascular complications in the clinical practice.
Blood pressure control and adverse outcomes of COVID-19 infection in patients with concomitant hypertension in Wuhan, China
Hypertension Research, August 27, 2020
Early investigations on the clinical characteristics of patients with COVID-19 infection have found that comorbidities significantly increase the risk of severe clinical outcomes, such as mortality, ICU admission, and mechanical ventilation. One of the most common comorbidities among COVID-19 patients is hypertension, with a prevalence ranging from 16.9 to 31.2% in hospitalized patients in China. Hypertension was also the most common comorbidity in ICU patients in Lombardy, Italy (49%) and hospitalized COVID-19 patients in New York, USA (56.6%). The mechanism of exacerbation associated with underlying conditions remains unclear, and experts worldwide have called for in-depth analysis of blood pressure (BP) control in hypertension patients during the clinical course of COVID-19. The mechanisms of exacerbation of underlying cardiovascular conditions after COVID-19 infection remain unclear. One of the most cited hypotheses is the overexpression of angiotensin converting enzyme II (ACE2) in arterial endothelial and smooth muscle cells. In this retrospective cohort study, the anonymized individual medical records from February 4 (admission of the first patient) to March 31, 2020 were retrieved from the electronic database of Huoshenshan Hospital, an acute field hospital built in Wuhan in response to the COVID-19 outbreak.
The Transformational Effects of COVID-19 on Medical Education
JAMA Network, August 26, 2020
[Podcast] The onset of the COVID-19 pandemic and the public health response required to minimize the catastrophic spread of the disease required an immediate change in the traditional approach to medical education and clearly amplified the need for expanding the competencies of the US physician workforce. Medical educators responded at the local and national levels to outline concerns and offer guiding principles so that academic health systems could support a robust public health response while ensuring that physician graduates are prepared to contribute to addressing current and future threats to the health of communities. While each school approached their response somewhat differently, several common themes have emerged. Join Howard Bauchner, MD, Editor in Chief of JAMA, as he interviews Catherine Lucey, MD, FACP, Department of Medicine, University of California San Francisco School of Medicine and author of The Transformational Effects of COVID-19 on Medical Education.
Association of Troponin Levels With Mortality in Italian Patients Hospitalized With Coronavirus Disease 2019 – Results of a Multicenter Study
JAMA Cardiology, August 26, 2020
Myocardial injury, detected by elevated plasma troponin levels, has been associated with mortality in patients hospitalized with coronavirus disease 2019 (COVID-19). However, the initial data were reported from single-center or 2-center studies in Chinese populations. Compared with these patients, European and US patients are older, with more comorbidities and higher mortality rates. The objective of this study was to evaluate the prevalence and prognostic value of myocardial injury, detected by elevated plasma troponin levels, in a large population of White Italian patients with COVID-19. This is a multicenter, cross-sectional study enrolling consecutive patients with laboratory-confirmed COVID-19 who were hospitalized in 13 Italian cardiology units from March 1 to April 9, 2020. Patients admitted for acute coronary syndrome were excluded. Elevated troponin levels were defined as values greater than the 99th percentile of normal values.
Blood Thinners Again Linked to COVID-19 Survival in Hospital
MedPage Today, August 26, 2020
Anticoagulation for patients hospitalized with COVID-19 was associated with lower risk of death or intubation in an observational study from New York City’s pandemic peak. In-hospital mortality risk was a relative 50% lower with standard prophylactic dosing and 47% lower with higher therapeutic-level dosing after adjustment for other factors, both statistically significant when compared with COVID-19 patients in Mount Sinai hospitals not given an anticoagulant (mortality rates of 21.6%, 28.6%, and 25.6%, respectively). Intubation was less likely for anticoagulant-treated COVID-19 patients as well (adjusted HR 0.69 with prophylactic dosing, 95% CI 0.51-0.94, and aHR 0.72 with therapeutic dosing, 95% CI 0.58-0.89), reported Anuradha Lala, MD, of the Icahn School of Medicine at Mount Sinai in New York City, and colleagues in the Journal of the American College of Cardiology. Major bleeding events adjudicated by clinician chart review turned up a “low” rate of 1.7% (33 of 1,959) on prophylactic anticoagulation and 3% (27 of 900) on therapeutic anticoagulation compared with 1.9% (29 of 1,530) on no anticoagulant during hospitalization.
Hello? This Is Your Cardiologist
JAMA Cardiology, August 26, 2020
Read how physician Neha Yadav, MBBS, Cook County Hospital in Chicago, Illinois, was able to connect with a patient while transitioning from in-person work to telemedicine during the coronavirus disease 2019 pandemic.
Sex differences in immune responses that underlie COVID-19 disease outcomes
Nature, August 26, 2020
A growing body of evidence reveals that male sex is a risk factor for a more severe disease, including death. Globally, ~60% of deaths from COVID-19 are reported in men, and a cohort study of 17 million adults in England reported a strong association between male sex and risk of death from COVID-19 (hazard ratio 1.59, 95% confidence interval 1.53-1.65. .53-1.65). Past studies have demonstrated that sex has a significant impact on the outcome of infections and has been associated with underlying differences in immune response to infection. For example, prevalence of hepatitis A and tuberculosis are significantly higher in men compared with women. Viral loads are consistently higher in male patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Conversely, women mount a more robust immune response to vaccines. However, the mechanism by which SARS-CoV-2 causes more severe disease in male patients than in female patients remains unknown. To elucidate the immune responses against SARS-CoV-2 infection in men and women, we performed detailed analysis on the sex differences in immune phenotype via the assessment of viral loads, SARS-CoV-2 specific antibody levels, plasma cytokines/chemokines, and blood cell phenotypes.
Reverse takotsubo cardiomyopathy in fulminant COVID-19 associated with cytokine release syndrome and resolution following therapeutic plasma exchange: a case-report
BMC Cardiovascular Disorders, August 26, 2020
Fulminant (life-threatening) COVID-19 can be associated with acute respiratory failure (ARF), multi-system organ failure and cytokine release syndrome (CRS). We present a rare case of fulminant COVID-19 associated with reverse-takotsubo-cardiomyopathy (RTCC) that improved with therapeutic plasma exchange (TPE). This is a case report of a 40 year old previous healthy male presented in the emergency room with 4 days of dry cough, chest pain, myalgias and fatigue. He progressed to ARF requiring high-flow-nasal-cannula (flow: 60 L/minute, fraction of inspired oxygen: 40%). Real-Time-Polymerase-Chain-Reaction (RT-PCR) assay confirmed COVID-19 and chest X-ray showed interstitial infiltrates. Biochemistry suggested CRS: increased C-reactive protein, lactate dehydrogenase, ferritin and interleukin-6. Renal function was normal but lactate levels were elevated. Electrocardiogram demonstrated non-specific changes and troponin-I levels were slightly elevated. Echocardiography revealed left ventricular (LV) basal and midventricular akinesia with apex sparing (LV ejection fraction: 30%) and depressed cardiac output (2.8 L/min) consistent with a rare variant of stress-related cardiomyopathy: RTCC. His ratio of partial arterial pressure of oxygen to fractional inspired concentration of oxygen was < 120. He was admitted to the intensive care unit (ICU) for mechanical ventilation and vasopressors, plus antivirals (lopinavir/ritonavir), and prophylactic anticoagulation.
Professional Quality of Life and Mental Health Outcomes among Health Care Workers Exposed to Sars-Cov-2 (Covid-19)
International Journal of Environmental Research and Public Health, August 26, 2020
Healthcare workers (HCWs) facing COVID-19 pandemic represented an at-risk population for new psychosocial COVID-19 strain and consequent mental health symptoms. The aim of the present study was to identify the possible impact of working contextual and personal variables (age, gender, working position, years of experience, proximity to infected patients) on professional quality of life, represented by compassion satisfaction (CS), burnout, and secondary traumatization (ST), in HCWs facing COVID-19 emergency. Further, two multivariable linear regression analyses were fitted to explore the association of mental health selected outcomes, anxiety and depression, with some personal and working characteristics that are COVID-19-related. A sample of 265 HCWs of a major university hospital in central Italy was consecutively recruited at the outpatient service of the Occupational Health Department during the acute phase of COVID-19 pandemic. HCWs were assessed by Professional Quality of Life-5 (ProQOL-5), the Nine-Item Patient Health Questionnaire (PHQ-9), and the Seven-Item Generalized Anxiety Disorder scale (GAD-7) to evaluate, respectively, CS, burnout, ST, and symptoms of depression and anxiety. Females showed higher ST than males, while frontline staff and healthcare assistants reported higher CS rather than second-line staff and physicians, respectively. Burnout and ST, besides some work or personal variables, were associated to depressive or anxiety scores.
After Care of Survivors of COVID-19—Challenges and a Call to Action
JAMA Health Forum, August 26, 2020
For most patients with severe illness requiring hospitalization, COVID-19 has been a frightening and life-changing experience. At the peak of the pandemic, the attention of health care teams was focused on saving lives and protecting health services from being overwhelmed. Those who survived were often discharged without a robust process of follow-up. The prevalence of post–COVID-19 complications is not yet fully known and may only become apparent in the months and years to come. Data from previous coronavirus (severe acute respiratory syndrome coronavirus [SARS-CoV] and Middle East respiratory syndrome coronavirus [MERS-CoV]) outbreaks indicate that between 20% and 40% of survivors experience long-term complications. In a recent report of 143 patients with COVID-19 who were evaluated a mean of 2 months after hospital discharge at a follow-up clinic in Rome, Italy, many patients reported persistent fatigue (53.1%), dyspnea (43.4%), joint pain (27.3%), and chest pain (21.7%). Drawing on these experiences, respiratory, cardiovascular, neurologic, metabolic, and psychosocial complications may be important long-term sequelae of COVID-19. It is therefore essential that systems are in place for timely and thorough identification of such sequelae followed by appropriate interventions. We discuss the challenges we have addressed in establishing a multidisciplinary COVID-19 follow-up clinic in a secondary care setting at the University Hospital of Birmingham, England.
Malignant Ventricular Arrhythmias in Patients with Severe Acute Respiratory Distress Syndrome Due to COVID-19 without Significant Structural Heart Disease
Heart Rhythm Case Reports, August 25, 2020
Since December 2019, the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a pandemic of novel coronavirus (COVID-19) infections. Although predominantly a respiratory illness that can cause acute respiratory distress syndrome (ARDS), data suggest cardiovascular involvement contributes significantly to the disease’s mortality. Data from Wuhan, China demonstrated patients with pre-existing cardiovascular disease and elevated troponin levels had 69.44% mortality. ARDS is defined by acute hypoxemic respiratory failure of non-cardiac etiology, bilateral pulmonary infiltrates, and a decreased PaO2/FIO2 ratio with mortality rates reaching 40%. After decades of ARDS research, little has been described about any associated ventricular arrhythmias despite the potential interplay between pulmonary pathology, treatments, and malignant arrhythmias. We present a series of COVID-19 infected patients with preserved cardiac function who developed ARDS and refractory ventricular arrhythmias.
AstraZeneca starts trial of COVID-19 antibody treatment
Reuters, August 25, 2020
British drugmaker AstraZeneca has begun testing an antibody-based cocktail for the prevention and treatment of COVID-19, adding to recent signs of progress on possible medical solutions to the disease caused by the novel coronavirus. The London-listed firm, already among the leading players in the global race to develop a successful vaccine, said the study would evaluate if AZD7442, a combination of two monoclonal antibodies (mAbs), was safe and tolerable in up to 48 healthy participants between the ages of 18 and 55 years. If the UK-based early-stage trial, which has dosed its participants, shows AZD7442 is safe, AstraZeneca said it would proceed to test it as both a preventative treatment for COVID-19 and a medicine for patients who have it, in larger, mid-to-late-stage studies. Development of mAbs to target the virus, an approach already being tested by Regeneron, Eli Lilly, Roche and Molecular Partners, has been endorsed by leading scientists. mAbs mimic natural antibodies generated in the body to fight off infection and can be synthesised in the laboratory to treat diseases in patients. Current uses include treatment of some types of cancers.
Medicure Announces AGGRASTAT Shows Promise in Treating Thrombotic Complications Due to COVID-19 in Early Clinical Reports
BioSpace, August 24, 2020
Medicure, Inc., a pharmaceutical company, is reporting that early investigator sponsored clinical reports evaluating the efficacy of AGGRASTAT® (tirofiban hydrochloride) show promise for preventing and treating thrombotic complications due to COVID-19. AGGRASTAT® is not currently indicated for use in patients with COVID-19. Notably, a non-randomized, case-controlled, investigator sponsored proof of concept study (n=10) evaluating AGGRASTAT® in combination with standard of care in patients with severe COVID-19 and hypercoagulability found that enhanced platelet inhibition improves hypoxemia. Treated patients experienced a mean reduction in alveolar-arterial oxygen gradient and an increase in PaO2/FiO2 at 24h, 48h and 7 days after treatment. Seven other small clinical reports have recently been published exploring the clinical efficacy of AGGRASTAT® in patients with COVID-19. Medicure is evaluating sponsorship of further US-based randomized clinical studies to rapidly assess the efficacy and safety of using AGGRASTAT® for preventing thrombotic complications due to COVID-19. “These initial results are sufficiently positive to warrant further investigation to more clearly understand the potential role of AGGRASTAT® to reduce thrombotic effects which are observed in many COVID-19 patients”, commented Medicure’s CEO, Dr. Albert D. Friesen. “We believe there is reason to sponsor this type of clinical research due to the emerging understanding of the role of thrombosis in the pathophysiology of COVID-19.”
Outcomes of Acute Myocardial Infarction Hospitalizations During the COVID-19 Pandemic
American College of Cardiology, August 24, 2020
While hospitalization rates related to COVID-19 infection have surged, there is clear evidence that patients in the United States and around the world have less commonly sought medical attention for a number medical emergencies such as acute myocardial infarction (AMI) than they were prior to the pandemic.6 The characteristics of patients most affected by this phenomenon and its impact on complication rates and patient outcomes are yet to be elucidated. In order to examine the impact of the epidemic on patients with AMI, Dr. Gluckman and colleagues evaluated case rates and in-hospital outcomes for patients presenting with AMI to any of the 49 hospitals in the Providence St. Joseph Health (PSJH) system spread across six states. This study evaluated over 15,000 hospitalizations involving more than 14,700 patients and confirmed the concerning trends of prior studies in AMI hospitalization: case rates of AMI hospitalization across PSJH decreased during the period early in the pandemic at a rate of -19.0 (95% CI, -29.0 to -9.0) cases per week, with increasing cases at a rate of +10.5 (95% CI, +4.6 to +16.5) during the period later in the pandemic. However, case rates had not returned to baseline by the last week of the study period.
Scientists say Hong Kong man got coronavirus a second time
Modern Healthcare, August 24, 2020
University of Hong Kong scientists claim to have the first evidence of someone being reinfected with the virus that causes COVID-19. Genetic tests revealed that a 33-year-old man returning to Hong Kong from a trip to Spain in mid-August had a different strain of the coronavirus than the one he’d previously been infected with in March, said Dr. Kelvin Kai-Wang To, the microbiologist who led the work. The man had mild symptoms the first time and none the second time; his more recent infection was detected through screening and testing at the Hong Kong airport. “It shows that some people do not have lifelong immunity” to the virus if they’ve already had it, To said. “We don’t know how many people can get reinfected. There are probably more out there.” Whether people who have had COVID-19 are immune to new infections and for how long are key questions that have implications for vaccine development and decisions about returning to work, school and social activities.
Online searches for ‘chest pain’ rise, emergency visits for heart attack drop amid COVID
Newswise, August 24, 2020
A study of search engine queries addressed the question of whether online searches for chest pain symptoms correlated to reports of fewer people going to the emergency department with acute heart problems during the COVID-19 pandemic. Mayo Clinic researchers looked at Google Trends data for Italy, Spain, the U.K. and the U.S., reviewing search terms such as “chest pain” and “myocardial infarction” (heart attack). The study spanned June 1, 2019 to May 31. Prior to the pandemic, those searches had relatively similar volumes to each other. The expectation would be that the frequency of heart attacks would stay the same or even rise in this setting. However, at the onset of the COVID-19 pandemic, searches for “myocardial infarction” dropped, while searches for “chest pain” rose at least 34%. Conor Senecal, M.D., a Mayo Clinic cardiology fellow in Rochester, is first author on the study, which is published in JMIR Cardio. “Interestingly, searches for ‘heart attack’ dropped during the same period of reported reduced heart attack admissions, but surprisingly, searches for ‘chest pain’ rose,” says Dr. Senecal. “This raises concern that people may have either misconstrued chest pain as an infectious symptom or actively avoided getting care due to COVID-19 concerns.”
Not just antibodies: B cells and T cells mediate immunity to COVID-19
Nature Reviews Immunology, August 24, 2020
Recent reports that antibodies to SARS-CoV-2 are not maintained in the serum following recovery from the virus have caused alarm. However, the absence of specific antibodies in the serum does not necessarily mean an absence of immune memory. Here, we discuss our current understanding of the relative contribution of B cells and T cells to immunity to SARS-CoV-2 and the implications for the development of effective treatments and vaccines for COVID-19. The induction of SARS-CoV-2-specific memory T cells and B cells (as opposed to circulating antibodies) is important for long-term protection. In particular, T follicular helper (TFH) cells indicate maturation of the humoral immune response and the establishment of a pool of specific memory B cells ready to rapidly respond to possible reinfection. SARS-CoV-2-specific T cells are recruited from a randomly formed and pre-constituted T cell pool capable of recognizing specific viral epitopes. Specific CD4+ T cells are important for eliciting potent B cell responses that result in antibody affinity maturation, and the levels of spike-specific T cells correlate with serum IgG and IgA titres.
Effect of Renin-Angiotensin-Aldosterone System inhibitors in patients with COVID-19: a systematic review and meta-analysis of 28,872 patients
Current Atherosclerosis Reports, August 24, 2020
The role of renin-angiotensin-aldosterone system (RAAS) inhibitors, notably angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs), in the COVID-19 pandemic has not been fully evaluated. With an increasing number of COVID-19 cases worldwide, it is imperative to better understand the impact of RAAS inhibitors in hypertensive COVID patients. PubMed, Embase and the pre-print database Medrxiv were searched, and studies with data on patients on ACEi/ARB with COVID-19 were included. Random effects models were used to estimate the pooled mean difference with 95% confidence interval using Open Meta[Analyst] software. Recent Findings A total of 28,872 patients were included in this meta-analysis. The use of any RAAS inhibition for any conditions showed a trend to lower risk of death/critical events (OR 0.671, CI 0.435 to 1.034, p = 0.071). Within the hypertensive cohort, however, there was a significant lower association with deaths (OR 0.664, CI 0.458 to 0.964, p = 0.031) or the combination of death/critical outcomes (OR 0.670, CI 0.495 to 0.908, p = 0.010). There was no significant association of critical/death outcomes within ACEi vs non-ACEi (OR 1.008, CI 0.822 to 1.235, p = 0.941) and ARB vs non-ARB (OR 0.946, CI 0.735 to 1.218, p = 0.668).
An inflammatory cytokine signature predicts COVID-19 severity and survival
Nature Medicine, August 24, 2020
Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1β in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death.
FDA Authorizes Convalescent Plasma for COVID-19 Patients
MedPage Today, August 24, 2020
Convalescent plasma shows promising efficacy in hospitalized patients with COVID-19, and the benefits outweigh the risks, the FDA said in announcing emergency use authorization (EUA) for such products on Sunday. The EUA was granted to the Office of Assistant Secretary for Preparedness and Response within the Department of Health and Human Services. It is not for any particular convalescent plasma product, but rather any such preparation “collected by FDA registered blood establishments from individuals whose plasma contains anti-SARS-CoV-2 antibodies, and who meet all donor eligibility requirements,” according to a fact sheet for healthcare providers. “Independent experts at the FDA who reviewed the totality of data” including more than a dozen published studies “concluded convalescent plasma is safe and shows promising efficacy, thereby meeting criteria for an emergency use authorization,” FDA commissioner Stephen Hahn, MD, said at a press conference on Sunday night.
Sex differences underlying preexisting cardiovascular disease and cardiovascular injury in COVID-19
Journal of Molecular and Cellular Cardiology, August 22, 2020
The novel 2019 coronavirus disease (COVID-19) results from severe acute respiratory syndrome coronarvirus-2 (SARS-CoV-2) infection and typically afflicts the lungs, with severe cases leading to acute respiratory distress syndrome. Although the respiratory system is the major organ system affected by SARS-CoV-2, cardiovascular complications should not be overlooked by healthcare workers and basic scientists. In particular, acute myocardial injury, cardiac arrhythmias and microvascular dysfunction and thrombosis are reported to contribute to a large proportion of COVID-19 deaths. While there is a robust body of evidence elucidating sex differences in CVD, sex disparities in COVID-19 are becoming more apparent as well. Interestingly, mounting data also indicate that individuals with higher risk of severe COVID-19 outcome due to preexisting CVD and COVID-19-related cardiovascular injury include a disproportionate number of males. In this review, we will discuss sex differences in the interplay between preexisting CVD, COVID-19 severity, and COVID-19-related cardiac injury by providing a basic science perspective based on the current literature in this rapidly evolving field.
DARE-19: Dapagliflozin could target key mechanisms activated in COVID-19
Helio | Endocrine Today, August 22, 2020
SGLT2 inhibitors could potentially target key mechanisms activated in COVID-19, increasing lipolysis, reducing glycolysis, inflammation and oxidative stress, and improving endothelial function to reduce organ damage, according to a speaker. “We know that favorable effects on mechanisms such as endothelial function, a key driver of adverse outcomes in COVID-19, can occur very quickly after treatment with SGLT2 inhibitors,” Mikhail Kosiborod, MD, FACC, FAHA, cardiologist at Saint Luke’s Mid America Heart Institute, professor of medicine at the University of Missouri-Kansas City School of Medicine, said during an online presentation during the virtual Heart in Diabetes conference. “If you think through these mechanisms and the fact that SGLT2 inhibitors can have a positive impact on many of them, what becomes clear is that testing SGLT2 inhibitors as potential agents for organ protection in COVID-19 may be one of the key hypotheses.” The concept is relatively simple, Kosiborod said. Viral replication and spread after COVID-19 infection trigger metabolic derangements that lead to inflammatory “overdrive,” endothelial injury and, ultimately, organ damage leading to complications and death. Data suggest antiviral treatments can work in the early phase of the disease; anti-inflammatory medications show promise during the mid-phase of the disease.
Cardiovascular Risk Factors, Comorbidity Linked to COVID-19 CV Complications
Pulmonology Advisor, August 21, 2020
For patients hospitalized with COVID-19, preexisting cardiovascular comorbidities or risk factors (RFs) are associated with cardiovascular complications, which contribute to mortality, according to a meta-analysis published online in PLOS ONE. Jolanda Sabatino, M.D., from “Magna Graecia” University in Catanzaro, Italy, and colleagues conducted a meta-analysis of observational studies assessing cardiovascular complications in hospitalized COVID-19 patients. Data were included for 77,317 hospitalized patients from 21 studies. The researchers found that 12.86 percent of the patients had cardiovascular comorbidities or RFs. During hospitalization, cardiovascular complications were registered in 14.09 percent of cases. Preexisting cardiovascular comorbidities or RFs were associated significantly with cardiovascular complications in COVID-19 patients in a meta-regression analysis. Significant interactions with death were seen for preexisting cardiovascular comorbidities or RFs, older age, and the development of cardiovascular complications during hospitalization. “The association between the novel coronavirus and cardiac complications needs further exploration and clinicians should be aware of the potential impact of cardiovascular conditions and complications in COVID-19 patients, which should require more extensive and frequent monitoring,” the authors write.
Clear Link Between Heart Disease and COVID-19, But Long-Term Implications Unknown, Researchers Find in Review of Published Studies
Newswise, August 21, 2020
One of the most harrowing effects of COVID-19 is severe damage to the lungs, which makes breathing hard or impossible for those who’re severely affected. However, evidence is mounting that COVID-19 also damages the heart, damage either caused by the virus itself, from inflammation triggered by the immune system’s response to the virus or a from increased clotting in heart vessels. There is now evidence that heart damage may persist even after the patient recovers and, in some cases, that damage may be long lasting. Experts just don’t know how often the heart damage will occur at this point or whether it might affect people with only mild symptoms. The worry is so grave that it was cited by some college football conferences as one of the reasons to postpone games for the year for fear that athletes who contract COVID-19 may suffer long-term cardiovascular problems. In a prospectus review published this week in the Journal of Molecular and Cellular Cardiology, Kirk U. Knowlton MD, from the Intermountain Healthcare Heart Institute in Salt Lake City, examined more than 100 published studies related to COVID-19 and its effects on the heart. While lung disease (severe acute respiratory distress syndrome, or ARDS) has been the most consistent problem with the virus, Dr. Knowlton found that many patients also suffer significant cardiovascular damage that might also persist after they have otherwise recovered.
Utility of D-dimers and intermediate-dose prophylaxis for venous thromboembolism in critically ill patients with COVID-19
Thrombosis Research, August 21, 2020
Increasing evidence indicates that hypercoagulability plays a significant role in the pathophysiology of severe coronavirus disease 2019 (COVID-19), contributing to macro- and microvascular thrombosis. It is of practical relevance to identify adequate diagnostic and prophylactic approaches to recognize and limit these complications. We report D-dimer performance in VTE-diagnosis and the comparison of intermediate-dose versus standard-of-care prophylactic anticoagulation in VTE-prevention among critically-ill COVID-19 patients. We performed a retrospective study at Lausanne University Hospital (CHUV). We included patients aged ≥18 years admitted to ICU for severe COVID-19 with microbiologically confirmed SARS-CoV-2 infection. Until 6 April 2020, internal guidelines recommended for ICU-patients with COVID-19, in absence of contraindications, a standard-of-care prophylactic anticoagulation [enoxaparin 40 mg (60 mg for patients >120 kg) q.d. or unfractionated heparin 5′000 UI bid for those with creatinine clearance <30 ml/min]. Internal guidelines implemented intermediate-dose prophylactic anticoagulation [enoxaparin 40 mg bid (60 mg bid if >120 kg) or unfractionated heparin IV 200 UI/kg/24 h in case of impaired renal function] on 7 April 2020. D-dimers were measured irregularly prior to 29 March 2020, afterwards every other day. Primary outcome was VTE [deep venous thrombosis (DVT) assessed by compression ultrasonography, and pulmonary embolism (PE) assessed by computer tomography (CT)].
SARS-CoV-2 in cardiac tissue of a child with COVID-19-related multisystem inflammatory syndrome
The Lancet | Child and Adolescent Health, August 20, 2020
We report the case of an 11-year-old child with multisystem inflammatory syndrome in children (MIS-C) related to COVID-19 who developed cardiac failure and died after 1 day of admission to hospital for treatment. An otherwise healthy female of African descent, the patient was admitted to the paediatric intensive care unit (ICU) with cardiovascular shock and persistent fever. Her initial symptoms were fever for 7 days, odynophagia, myalgia, and abdominal pain. On admission to the ICU, the patient presented with respiratory distress, comprising tachypnoea (respiratory rate 70 breaths per min) and hypoxia, and signs of congestive heart failure, including jugular vein distention, crackles at the base of the lungs, displaced liver, hypotension (blood pressure 80/36 mm Hg), tachycardia (134 beats per min [bpm]), and cold extremities with filiform pulses. Non-exudative conjunctivitis and cracked lips were present on physical examination. The patient was promptly intubated and antibiotic treatment was started with ceftriaxone and azithromycin. Peripheral epinephrine was initiated in the emergency room before the patient was moved to paediatric ICU.
COVID-19, the heart and returning to physical exercise
Occupational Medicine, August 20, 2020
COVID-19 infection may be complicated by cardiac arrhythmias, myocarditis and other cardiovascular complications, with potentially fatal outcomes. Early reports from China suggested that 12–30% of patients admitted to hospital with SARS-CoV-2 had a raised troponin above the 99th percentile. The pathophysiological mechanisms of cardiac injury are not yet fully understood, but may include augmented metabolic demand, hypoxaemia, right ventricular pressure overload, T-cell- and cytokine-mediated hyperinflammatory reaction or direct myocardial cell infection. Cardiac involvement is likely to be potentiated by a high level of expression of angiotensin-converting enzyme 2 (ACE2). Cardiac involvement should be considered in patients presenting with a history of new-onset chest pain/pressure, palpitations, breathlessness, or exercise-induced dizziness or syncope—even in the absence of fever and other respiratory symptoms. There is concern that even ‘recovered’ patients may be at risk of adverse cardiac events.
Annual Heart in Diabetes conference offers all-virtual sessions on cardiometabolic health
Helio | Endocrine Today, August 20, 2020
Organizers behind this year’s Heart in Diabetes conference are preparing to launch a free, all-virtual platform of sessions spanning all aspects of cardiometabolic health, along with a new emphasis on the impact of the COVID-19 pandemic. Leading experts from a range of specialties will once again come together — this time online — to address the relationship between type 2 diabetes, cardiovascular and renal disease along with the latest research demonstrating their interconnectedness, according conference co-chair Yehuda Handelsman, MD, FACP, FNLA, FASCP, MACE. The now 4-day CME conference, described as where the heart, kidney and diabetes meet in clinical practice, will take place Friday through Monday. The agenda includes sessions that span the subspecialties from cardiology, lipidology and endocrinology to nephrology, hepatology and primary care, with an emphasis on the latest guidelines and data from important CV outcomes trials.
Evidence mounts for ECMO in patients with severe COVID-19 respiratory failure
Helio | Pulmonology, August 20, 2020
Two recently published studies report success with extracorporeal membrane oxygenation support in patients with acute respiratory distress syndrome associated with COVID-19. In a retrospective cohort study published in The Lancet Respiratory Medicine, researchers analyzed clinical characteristics and outcomes of 492 patients treated with ECMO for COVID-19-associated ARDS at five ICUs within the Paris-Sorbonne University Hospital Network from March 8 to May 2. The researchers reported complete day-60 follow-up for 83 patients (median age, 49 years; 73% men) who received ECMO. Before ECMO, 94% of patients were prone positioned (median driving pressure, 18 cm H2O; ratio of arterial oxygen partial pressure to fractional inspired oxygen, 60 mm Hg). Sixty days after initiation of ECMO, the researchers’ estimated probability of death was 31% and the probability of being alive and out of the ICU was 45%.
Circulating Endothelial Cells as a Marker of Endothelial Injury in Severe COVID -19
Journal of Infectious Diseases, August 19, 2020
The vascular endothelium is a dynamic organ that plays key roles in vascular homeostasis, such as maintaining vascular tone, permeability and inflammatory response, preserving the hemostatic balance. Any endothelial injury, including infections, impairs regulatory functions of the endothelium with subsequent vasoconstriction, ischemia, inflammation and activation of the coagulation cascade, ultimately leading to vessels denudation and exposure of the thrombogenic subendothelium. Circulating endothelial cells (CEC) are stressed cells detached from injured vessels. They are detectable at very low levels in healthy conditions. Increased CEC counts have been reported in various diseases of inflammatory, infectious or ischemic origin, where they evidence a profound vascular insult and are indicative of disease severity. The objective of the present study was to measure CEC in the blood of patients with COVID-19, in relation to systemic inflammation and disease severity.
Ex-CDC director Tom Frieden provides strategies for protecting HCWs amid COVID-19
Helio | Primary Care, August 19, 2020
Former CDC director Tom Frieden, MD, MPH, recently described a hierarchy of controls — elimination, substitution, engineering, administration and personal protective equipment — that may help prevent COVID-19 among health care workers. His remarks came during the National Medical Association’s Annual Meeting, held virtually due to the pandemic. Frieden said the “most effective” step is eliminating the hazard or infection. This can be accomplished by not allowing people who are ill to enter nursing homes and other congregate facilities. It can also be accomplished by ensuring that all hospitals and nursing home staffs have paid sick leave, so that there is no economic incentive to work while ill. If patients with COVID-19 cannot be separated from other patients and staff by engineering and substitution, PPE becomes necessary, Frieden said. When PPE is necessary, supply has to be ensured.
The impact of sofosbuvir/daclatasvir or ribavirin in patients with severe COVID-19
Journal of Antimicrobial Chemotherapy, August 19, 2020
Sofosbuvir and daclatasvir are direct-acting antivirals highly effective against hepatitis C virus. There is some in silico and in vitro evidence that suggests these agents may also be effective against SARS-CoV-2. This trial evaluated the effectiveness of sofosbuvir in combination with daclatasvir in treating patients with COVID-19. Patients with a positive nasopharyngeal swab for SARS-CoV-2 on RT–PCR or bilateral multi-lobar ground-glass opacity on their chest CT and signs of severe COVID-19 were included. Subjects were divided into two arms with one arm receiving ribavirin and the other receiving sofosbuvir/daclatasvir. All participants also received the recommended national standard treatment which, at that time, was lopinavir/ritonavir and single-dose hydroxychloroquine. The primary endpoint was time from starting the medication until discharge from hospital with secondary endpoints of duration of ICU stay and mortality. Sixty-two subjects met the inclusion criteria, with 35 enrolled in the sofosbuvir/daclatasvir arm and 27 in the ribavirin arm. The median duration of stay was 5 days for the sofosbuvir/daclatasvir group and 9 days for the ribavirin group. The mortality in the sofosbuvir/daclatasvir group was 2/35 (6%) and 9/27 (33%) for the ribavirin group. The relative risk of death for patients treated with sofosbuvir/daclatasvir was 0.17 (95% CI 0.04–0.73, P = 0.02) and the number needed to treat for benefit was 3.6 (95% CI 2.1–12.1, P < 0.01).
As U.S. schools reopen, concerns grow that kids spread coronavirus
Reuters, August 19, 2020
U.S. students are returning to school in person and online in the middle of a pandemic, and the stakes for educators and families are rising in the face of emerging research that shows children could be a risk for spreading the new coronavirus. Several large studies have shown that the vast majority of children who contract COVID-19, the disease caused by the virus, have milder illness than adults. And early reports did not find strong evidence of children as major contributors to the deadly virus that has killed more than 780,000 people globally. But more recent studies are starting to show how contagious infected children, even those with no symptoms, might be. “Contrary to what we believed, based on the epidemiological data, kids are not spared from this pandemic,” said Dr. Alessio Fasano, director of the Mucosal Immunology and Biology Research Center at Massachusetts General Hospital and author of a new study.
The Physicians Foundation 2020 Physician Survey
Physicians Foundation, August 18, 2020
The Physicians Foundation’s 2020 Survey of America’s Physicians finds that the majority of physicians believe COVID-19 won’t be under control until January 2021, with nearly half not seeing the virus being under control until after June 1, 2021. Furthermore, a majority of physicians believe that the virus will severely impact patient health outcomes due to delayed routine care during the pandemic. Read and download the findings. The survey, conducted in July with more than 3,500 respondents, asked physicians how the pandemic is affecting their practices and patients. Nearly three-quarters of those surveyed said COVID-19 would have serious consequences for health in their communities because many are delaying needed care. Health insurance is another problem; 76% cited changes in employment and insurance status is a primary cause of harm to patients caused by COVID-19. But 59% believed opening schools, businesses and other public places posed a greater risk to their patients than continued social isolation. “The data reveals a near-consensus among America’s physicians about COVID-19’s immediate and lasting impact on our healthcare system,” said Dr. Gary Price, president of The Physicians Foundation, in a prepared statement.
FDA flags accuracy issue with widely used coronavirus test
Associated Press, August 18, 2020
Potential accuracy issues with a widely used coronavirus test could lead to false results for patients, U.S. health officials warned. The Food and Drug Administration issued the alert Monday to doctors and laboratory technicians using Thermo Fisher’s TaqPath genetic test. Regulators said issues related to laboratory equipment and software used to run the test could lead to inaccuracies. The agency advised technicians to follow updated instructions and software developed by the company to ensure accurate results. The warning comes nearly a month after Connecticut public health officials first reported that at least 90 people had received false positive results for the coronavirus. Most of those receiving the false results were residents of nursing homes or assisted living facilities. A spokeswoman for Thermo Fisher said the company was working with FDA “to make sure that laboratory personnel understand the need for strict adherence to the instructions for use.” She added that company data shows most users “follow our workflow properly and obtain accurate results.”
Cardiac Involvement, Ongoing Myocardial Inflammation Observed After Recent COVID-19 Recovery
Pulmonology Today, August 17, 2020
A large percentage of patients who recently recover from coronavirus disease 2019 (COVID-19) were found to have cardiac involvement and ongoing myocardial inflammation, according to a study published in JAMA Cardiology. The prospective observational study included 100 patients (median age, 49 years) in the University Hospital Frankfurt COVID-19 Registry in Germany who were diagnosed with and recovered from the severe acute respiratory syndrome coronavirus 2 and identified between April and June 2020. In this cohort, cardiac magnetic resonance imaging (MRI) was performed, and levels of cardiac blood markers, including high-sensitivity C-reactive protein (CRP), high-sensitivity troponin T (hsTnT), and N-terminal pro–b-type natriuretic peptide (NT-proBNP) were measured. Data from patients recovered from COVID-19 and age- and sex-matched control normotensive healthy volunteers (n=50) and risk factor–matched patients (n=57) were compared. The overall median duration between the COVID-19 diagnosis and the performance of a cardiac MRI was 71 days. A total of 67% of the study population recovered from COVID-19 at home, and the remaining 33% of patients required hospitalization.
Assessment of COVID-19 Hospitalizations by Race/Ethnicity in 12 States
JAMA Internal Medicine, August 17, 202
Given the reported health disparities in coronavirus disease 2019 (COVID-19) infection and mortality by race/ethnicity, there is an immediate need for increased assessment of the prevalence of COVID-19 across racial/ethnic subgroups of the population in the US. We examined the racial/ethnic prevalence of cumulative COVID-19 hospitalizations in the 12 states that report such data and compared how this prevalence differs from the racial/ethnic composition of each state’s population. Using data extracted from the University of Minnesota COVID-19 Hospitalization Tracking Project, we identified the 12 states that reported the race/ethnicity of individuals hospitalized with COVID-19 between April 30 and June 24, 2020. We calculated the percentage of cumulative hospitalizations by racial/ethnic categories averaged over the study period and then calculated the difference between the percentage of cumulative hospitalizations for each subgroup and the corresponding percentage of the state’s population for each racial/ethnic subgroup as reported in the US Census. The race/ethnicity categories included were White, Black, American Indian and/or Alaskan Native, Asian, and Hispanic. Descriptive statistical analyses were conducted using Stata/MP, version 14 (Stata Corp). The University of Minnesota Institutional Review Board reviewed the study data and deemed it exempt from review and informed consent requirements because the study was not human subjects research. This analysis of COVID-19 hospitalizations in 12 US states during nearly a 2-month period represented a total of 48 788 cumulative hospitalizations among a total population of 66 796 666 individuals in 12 US states.
Cardiac Arrest Tracked Stages of Lockdown
MedPage Today, August 17, 2020
The recent uptick in out-of-hospital cardiac arrests (OHCAs) could be a consequence of heart attack patients avoiding hospitals during COVID-19, one Denver group suggested. There were significantly more OHCAs in the first 2 weeks of the local shelter-in-place order compared with the period before COVID or the early COVID period between the declaration of emergency and the statewide shelter-in-place order (46 vs 26 and 27 per week, respectively, P=0.001 and P=0.004). Despite the increase in OHCAs, there were progressively fewer average ambulance activations per week across time (P=0.007):
- 2,218 in the pre-mandate period from Jan. 1 to March 7
- 2,129 in the peri-mandate period from March 8 to 28
- 1,921 in the post-mandate period from March 29 to April 11
The report by Brian Stauffer, MD, of Denver Health Medical Center, and colleagues was published in the Aug. 24 issue of JACC: Cardiovascular Interventions. “A review at the patient level is essential to obtain a more granular understanding of these data. However, in the interim, providers should consider the unintended consequence of the pandemic response in the context of chronic and emergent cardiovascular disease,” Stauffer’s group urged. “One possibility suggested by our data is that patients with acute coronary syndromes are not presenting for care, resulting in an increase in OHCA,” they said.
AANP National Survey Reveals Progress, Challenges as Nurse Practitioners (NPs) Combat COVID-19
Cision, August 17, 2020
The findings of a second, nationwide trend survey of NPs assessing COVID-19’s impacts on NP professional practice demonstrate both significant progress and lingering challenges as health care providers work to stem the tide of the pandemic in communities nationwide. More than 80% of the profession reports their practices are better prepared to manage COVID-19 patients than at the start of the pandemic, with 35% indicating they are ready for a surge in COVID-19 cases. Despite marked progress in practice readiness and improving supplies of PPE, the number of NPs now testing positive for COVID-19 has increased three-fold since the early days of the pandemic. While acknowledging improvements in access, NPs identify testing as the most significant barrier to combatting COVID-19 in their communities, with one-third of NPs reporting patients being turned away from centralized testing sites for failure to meet pre-determined criteria, and 78% of NPs citing significant delays in receiving patients’ viral test results. Test result delays range from a low-end range of seven to 10 business days to a high-end of up to 20 days. This is the second national survey fielded by the American Association of Nurse Practitioners® (AANP), the largest national association of NPs of all specialties, aimed at understanding how COVID-19 is affecting the clinical practice of NPs across settings, specialties, and geographic location.
Highly sensitive quantification of plasma SARS-CoV-2 RNA shelds [sic] light on its potential clinical value
Clinical Infectious Diseases, August 17, 2020
Coronavirus disease 2019 (COVID-19) is a global public health problem that has already caused more than 662,000 deaths worldwide. Although the clinical manifestations of COVID-19 are dominated by respiratory symptoms, some patients present other severe damage such as cardiovascular, renal and liver injury or/and multiple organ failure, suggesting a spread of the SARS-CoV-2 in blood. Recent ultrasensitive polymerase chain reaction (PCR) technology now allows absolute quantification of nucleic acids in plasma. We herein intended to use the droplet-based digital PCR technology to obtain sensitive detection and precise quantification of plasma SARS-CoV-2 viral load (SARS-CoV-2 RNAaemia) in hospitalized COVID-19 patients. Fifty-eight consecutive COVID-19 patients with pneumonia 8 to 12 days after onset of symptoms and 12 healthy controls were analyzed. Disease severity was categorized as mild-to-moderate in 17 patients, severe in 16 patients and critical in 26 patients. Plasma SARS-CoV-2 RNAaemia was quantified by droplet digital Crystal Digital PCR™ next-generation technology. Overall, SARS-CoV-2 RNAaemia was detected in 43 (74.1%) patients. Prevalence of positive SARS-CoV-2 RNAaemia correlated with disease severity, ranging from 53% in mild-to-moderate patients to 88% in critically ill patients (p=0.036). Levels of SARS-CoV-2 RNAaemia were associated with severity (p=0.035).
CDC: Sorry, People Do Not Have COVID-19 ‘Immunity’ for 3 Months
MedPage Today, August 17, 2020
People infected with COVID-19 do not necessarily have immunity to reinfection for three months, the CDC said late Friday night, trying to squelch speculation the agency had inadvertently stimulated. While people can continue to test positive for SARS-CoV-2 for up to three months after diagnosis and not be infectious to others, that does not imply that infection confers immunity for that period, the agency said. The confusion stemmed from an August 3 update to CDC’s isolation guidance, which stated: Who needs to quarantine? People who have been in close contact with someone who has COVID-19 — excluding people who have had COVID-19 within the past 3 months. People who have tested positive for COVID-19 do not need to quarantine or get tested again for up to 3 months as long as they do not develop symptoms again. People who develop symptoms again within 3 months of their first bout of COVID-19 may need to be tested again if there is no other cause identified for their symptoms. These statements could be read as suggesting that those recovering from COVID-19 will likely be safe from reinfection for three months even with close exposure to infected people. Media reports took this as a tacit acknowledgment of immunity from the agency.
Household Transmission of SARS-CoV-2 in the United States
Clinical Infectious Diseases, August 16, 2020
Although many viral respiratory illnesses are transmitted within households, the evidence base for SARS-CoV-2 is nascent. We sought to characterize SARS-CoV-2 transmission within US households and estimate the household secondary infection rate (SIR) to inform strategies to reduce transmission. We recruited laboratory-confirmed COVID-19 patients and their household contacts in Utah and Wisconsin during March 22–April 25, 2020. We interviewed patients and all household contacts to obtain demographics and medical histories. At the initial household visit, 14 days later, and when a household contact became newly symptomatic, we collected respiratory swabs from patients and household contacts for testing by SARS-CoV-2 rRT-PCR and sera for SARS-CoV-2 antibodies testing by enzyme-linked immunosorbent assay (ELISA). We estimated SIR and odds ratios (OR) to assess risk factors for secondary infection, defined by a positive rRT-PCR or ELISA test. Thirty-two (55%) of 58 households had evidence of secondary infection among household contacts. The SIR was 29% (n = 55/188; 95% confidence interval [CI]: 23–36%) overall, 42% among children (<18 years) of the COVID-19 patient and 33% among spouses/partners. Household contacts to COVID-19 patients with immunocompromised conditions had increased odds of infection (OR: 15.9, 95% CI: 2.4–106.9). Household contacts who themselves had diabetes mellitus had increased odds of infection (OR: 7.1, 95% CI: 1.2–42.5).
The cardiac threat coronavirus poses to athletes
Axios, August 15, 2020
Cardiologists are increasingly concerned that coronavirus infections could cause heart complications that lead to sudden cardiac death in athletes. Why it matters: Even if just a tiny percentage of COVID-19 cases lead to major cardiac conditions, the sheer scope of the pandemic raises the risk for those who regularly conduct the toughest physical activity — including amateurs who might be less aware of the danger. Driving the news: Both the Big 10 and Pac-12 conferences announced this week that they wouldn’t play college football in the fall because of health concerns about the COVID-19 pandemic. According to ESPN, a major factor driving those decisions has been fear that COVID-19 could lead to a rise in myocarditis among athletes. Myocarditis is an inflammation of the heart caused by viral infections that can lead to rapid or abnormal heart rhythms and even sudden cardiac death. Myocarditis causes about 75 deaths per year in young athletes between the ages of 13 and 25, often without any warning. The 27-year-0lld Boston Celtics star Reggie Lewis collapsed at a practice and soon died from myocarditis in 1993. While research is still in its infancy, a July study of 100 adult patients in Germany had recovered from COVID-19 found that 60% had findings of ongoing myocardial inflammation.
Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization to Yale School of Public Health for SalivaDirect, Which Uses a New Method of Saliva Sample Processing
U.S. Food & Drug Administration, August 15, 2020
Today, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) to Yale School of Public Health for its SalivaDirect COVID-19 diagnostic test, which uses a new method of processing saliva samples when testing for COVID-19 infection. “The SalivaDirect test for rapid detection of SARS-CoV-2 is yet another testing innovation game changer that will reduce the demand for scarce testing resources,” said Assistant Secretary for Health and COVID-19 Testing Coordinator Admiral Brett P. Giroir, M.D. “Our current national expansion of COVID-19 testing is only possible because of FDA’s technical expertise and reduction of regulatory barriers, coupled with the private sector’s ability to innovate and their high motivation to answer complex challenges posed by this pandemic.” “Providing this type of flexibility for processing saliva samples to test for COVID-19 infection is groundbreaking in terms of efficiency and avoiding shortages of crucial test components like reagents,” said FDA Commissioner Stephen M. Hahn, M.D. “Today’s authorization is another example of the FDA working with test developers to bring the most innovative technology to market in an effort to ensure access to testing for all people in America. The FDA encourages test developers to work with the agency to create innovative, effective products to help address the COVID-19 pandemic and to increase capacity and efficiency in testing.” SalivaDirect does not require any special type of swab or collection device; a saliva sample can be collected in any sterile container. This test is also unique because it does not require a separate nucleic acid extraction step. This is significant because the extraction kits used for this step in other tests have been prone to shortages in the past. Being able to perform a test without these kits enhances the capacity for increased testing, while reducing the strain on available resources.
The Intersection Between Flu and COVID-19
Journal of the American Medical Association, August 14, 2020
[Audio Clinical Review] As the COVID-19 pandemic continues to spread throughout the world, flu season is almost upon us. This is concerning because there will be an overlap between flu and COVID-19 and patients could get both diseases. Daniel Solomon, MD, from the Division of Infectious Diseases at the Brigham and Women’s Hospital of the Harvard Medical School in Boston, discusses COVID-19 and how the flu might pan out this year.
Severe COVID-19 associated with heart issues; much yet to discover
American Heart Association, August 14, 2020
The number of people coronavirus disease 2019 (COVID-19) is rising with more cases in the U.S. (5M according to the Centers for Disease Control and Prevention, CDC) than any other country (20M confirmed cases worldwide, according to the World Health Organization, WHO). Initially thought to be an infection causing disease of the lungs, inflammation of the vascular system and injury to the heart appear to be common features of this novel coronavirus, occurring in 20% to 30% of hospitalized patients and contributing to 40% of deaths. The risk of death from COVID-19-related heart damage appears to be as or more important than other well-described risk factors for COVID-related mortality, such as age, diabetes mellitus, chronic pulmonary disease or prior history of cardiovascular disease. “Much remains to be learned about COVID-19 infection and the heart. Although we think of the lungs being the primary target, there are frequent biomarker elevations noted in infected patients that are usually associated with acute heart injury. Moreover, several devastating complications of COVID-19 are cardiac in nature and may result in lingering cardiac dysfunction beyond the course of the viral illness itself,” said Mitchell S. V. Elkind, M.D., MS, FAHA, FAAN, president of the American Heart Association, the world’s leading voluntary organization focused on heart and brain health and research, and attending neurologist at New York-Presbyterian/Columbia University Irving Medical Center. “The need for additional research remains critical. We simply don’t have enough information to provide the definitive answers people want and need.”
Arrhythmia management during COVID-19 incorporates remote monitoring, virtual visits
Cardiology Today, August 14, 2020
Since the COVID-19 pandemic started, we have learned about how it affects certain patient populations and how it can lead to complications such as arrhythmias. In a study published in JAMA in February, 44.4% of patients assessed from Wuhan, China, were treated in the ICU due to complications related to arrhythmias. Arrhythmias may also be aggravated by severe systemic inflammatory conditions associated with COVID-19. The pandemic has also affected arrhythmia management, with focus shifting to telehealth. “The pandemic and need to conduct medical care remotely at a distance supercharged the implementation of these technologies,” Jonathan P. Piccini, MD, MHS, FHRS, associate professor of medicine and director of cardiac electrophysiology at Duke University Medical Center, told Healio. “For, example in our [electrophysiology] clinic at Duke, before the pandemic, telehealth visits accounted for far less than 5% of visits. Two weeks into COVID, more than 90% of our clinic visits were telehealth encounters.”
Defining heart disease risk for death in COVID-19 infection
QJM: An International Journal of Medicine, August 13, 2020
Cardiovascular disease (CVD) was in common in Coronavirus Disease 2019 (COVID-19) patients and associated with unfavorable outcomes. We aimed to compare the clinical observations and outcomes of SARS-CoV-2-infected patients with or without CVD. Patients with laboratory-confirmed SARS-CoV-2 infection were clinically evaluated at Wuhan Seventh People’s Hospital, Wuhan, China. Demographic data, laboratory findings, comorbidities, treatments and outcomes were collected and analyzed in COVID-19 patients with and without CVD. Among 596 patients with COVID-19, 215 (36.1%) of them with CVD. Compared with patients without CVD, these patients were significantly older (66 years vs 52 years) and had higher proportion of men (52.5% vs 43.8%). Complications in the course of disease were more common in patients with CVD, included acute respiratory distress syndrome (22.8% vs 8.1%), malignant arrhythmias (3.7% vs 1.0%) including ventricular tachycardia/ventricular fibrillation, acute coagulopathy (7.9% vs 1.8%), and acute kidney injury (11.6% vs 3.4%). The rate of glucocorticoid therapy (36.7% vs 25.5%), Vitamin C (23.3% vs 11.8%), mechanical ventilation (21.9% vs 7.6%), intensive care unit admission (12.6% vs 3.7%) and mortality (16.7% vs 4.7%) were higher in patients with CVD (both p < 0.05). The multivariable Cox regression models showed that older age (≥65 years old) (HR 3.165, 95% CI 1.722-5.817) and patients with CVD (HR 2.166, 95% CI 1.189-3.948) were independent risk factors for death.
The Impact of COVID-19 on Pulmonary Hypertension
American College of Cardiology, August 13, 2020
COVID-19 has had a significant impact on all aspects of PH, from diagnosis and management to observing an increased risk of death in patients with PAH. In addition, because of the vulnerable nature of this population, the pandemic has impacted the very manner in which care is delivered in PH. The risks associated with COVID-19 in patients with PH are significant. In a US survey of 77 PAH Comprehensive Care Centers, the incidence of COVID-19 infection was 2.1 cases per 1,000 patients with PAH, which is similar to the incidence of COVID-19 infection in the general US population. But although COVID-19 did not seem to be more prevalent in patients with PAH, the mortality did appear to be higher at 12%. In addition, 33% of patients with PAH who were infected with COVID-19 ended up being hospitalized. With the outbreak of COVID-19, it became necessary to revisit the manner in which patients receive care to decrease risk of contracting the virus.
Preparing for and responding to Covid-19’s ‘second hit’
Healthcare, August 13, 2020
While already sobering, Covid-19 mortality projections only account for a portion of morbidity and mortality we should expect from the current outbreak – patients directly affected by Covid-19. Largely missing from current discussions is the indirect impact on a much broader set of patients affected the epidemic – patients who will experience greater morbidity and mortality from a wide range of clinical conditions due to disruptions in the provision of health care and other essential services – what we are describing here as the ‘second hit’ of Covid-19. Current estimates of the human health toll from the ongoing outbreak of the respiratory disease Coronavirus Disease 2019 (Covid-19) are staggering. As of July 13, 2020, there have been over 13,000,000 cases and 500,000 deaths globally, and most experts agree that the epidemic is just beginning. The second hit of Covid-19 is already well underway in the U.S. and globally, as efforts on social distancing, mitigating spread, and increasing surge capacity in hospitals are being put in place. Experts predict that health facilities will be overwhelmed for sustained periods of time, and that it is likely that social distancing measures will need to be reintroduced in subsequent epidemic waves. While necessary to mitigate Covid-19, these changes have widespread ramifications on system’s ability to manage acute, chronic, and preventive care. There are a number of major shifts happening now that can help the health system understand which parts of the system and what segments of the population will be most affected.
Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes – Interim Analysis of 2 Randomized Clinical Trials
Journal of the American Medical Association, August 13, 2020
What are the safety and immunogenicity of an inactivated vaccine against coronavirus disease 2019 (COVID-19)? This was an interim analysis of 2 randomized placebo-controlled trials. In 96 healthy adults in a phase 1 trial of patients randomized to aluminum hydroxide (alum) only and low, medium, and high vaccine doses on days 0, 28, and 56, 7-day adverse reactions occurred in 12.5%, 20.8%, 16.7%, and 25.0%, respectively; geometric mean titers of neutralizing antibodies at day 14 after the third injection were 316, 206 and 297 in the low-, medium-, and high-dose groups, respectively. In 224 healthy adults randomized to the medium dose, 7-day adverse reactions occurred in 6.0% and 14.3% of the participants who received injections on days 0 and 14 vs alum only, and 19.0% and 17.9% who received injections on days 0 and 21 vs alum only, respectively; geometric mean titers of neutralizing antibodies in the vaccine groups at day 14 after the second injection were 121 vs 247, respectively.
Researchers Strive to Recruit Hard-Hit Minorities Into COVID-19 Vaccine Trials
Journal of the American Medical Association, August 13, 2020
Seldom does a vaccine researcher’s job include calling city hall, big-box stores like Walmart and Target, and the US Postal Service. But Ann Falsey, MD, had those tasks on her to-do list in June as she prepared to recruit volunteers to test potential vaccines for coronavirus disease 2019 (COVID-19). Falsey, of the University of Rochester School of Medicine, hoped large employers in her area would publicize vaccine trials to their essential workers, many of whom are Black or Hispanic. “We are thinking very hard about not only how to get a diverse population that reflects the US population but also people at high risk—postal workers, home health workers, you name it,” she said. COVID-19’s startling toll on minorities has drawn widespread attention to the need for diversity in large-scale phase 3 vaccine trials. Two 30 000-person trials, led by Moderna and a joint effort of Pfizer and BioNTech, began on July 27. AstraZeneca was expected to start US recruitment to test its vaccine, developed with Oxford University, in August, followed by Johnson & Johnson in September and Novavax later this fall.
In-hospital Use of ACEI/ARB is associated with lower Risk of Mortality and Critic Illness in COVID-19 Patients with Hypertension: ACEI/ARB protect COVID-19 patients
Journal of Infection, August 12, 2020
[Letter to the Editor] We read with great interest the recent article published by Macro Zuin, et al. in this journal suggested the prevalence of hypertension and its contribution to increased mortality risk in COVID-19 patients. RAAS inhibitors is one of the commonly used medication for hypertension management. However, since the culprits of COVID-19, SARS-COV-2, takes advantage of membrane-bound angiotensin-converting enzyme 2 (ACE2) to infect host cells, and which were reported to be upregulated in result of treatment of RAAS inhibitors, concerns of using RAAS inhibitors in COVID-19 patients with hypertension were aroused. Nonetheless, in animal models of acute lung injury and other influenza virus infection, ACEI and ARB are protective by inhibiting the downregulation of ACE2 and further limit disease progression. Thus, RAAS inhibitors might be theoretically protective in patient with COVID-19. Despite various studies showed that RAAS inhibits were not harmful in COVID-19, more clinical data and evidence are needed for clarifying this controversial issue and developing better treatment plans for patients suffering COVID-19. Here, we present a retrospective study, analyzing use of different antihypertensive drugs and its association with various outcomes of COVID-19 patients with hypertension.
A SARS-CoV-2 Prediction Model from Standard Laboratory Tests
Clinical Infectious Diseases, August 12, 2020
With the limited availability of testing for the presence of the SARS-CoV-2 virus and concerns surrounding the accuracy of existing methods, other means of identifying patients are urgently needed. Previous studies showing a correlation between certain laboratory tests and diagnosis suggest an alternative method based on an ensemble of tests. Here, a machine learning model was trained to analyze the correlation between SARS-CoV-2 test results and 20 routine laboratory tests collected within a 2-day period around the SARS-CoV-2 test date. We used the model to compare SARS-CoV-2 positive and negative patients. In a cohort of 75,991 veteran inpatients and outpatients who tested for SARS-CoV-2 in the months of March through July, 2020, 7,335 of whom were positive by RT-PCR or antigen testing, and who had at least 15 of 20 lab results within the window period, our model predicted the results of the SARS-CoV-2 test with a specificity of 86.8%, a sensitivity of 82.4%, and an overall accuracy of 86.4% (with a 95% confidence interval of [86.0%, 86.9%]). While molecular-based and antibody tests remain the reference standard method for confirming a SARS-CoV-2 diagnosis, their clinical sensitivity is not well known. The model described herein may provide a complementary method of determining SARS-CoV-2 infection status, based on a fully independent set of indicators, that can help confirm results from other tests as well as identify positive cases missed by molecular testing.
Previous cardiovascular surgery significantly increases the risk of developing critical illness in patients with COVID-19
Journal of Infection, August 12, 2020
We read with great interest the article by Dr. Galloway JB and colleagues recently published in the Journal of Infection entitled “A clinical risk score to identify patients with COVID-19 at high risk of critical care admission or death: An observational cohort study.” Early identification of patients with high-risk of poor prognosis may facilitate the provision of timely supportive treatment in advance and reduce the mortality of patients. In this study, the authors identified several comorbidities as risk factors of worse outcomes of COVID-19 patients, including diabetes, hypertension, and chronic lung disease. However, little is known about the impact of previous surgery on COVID-19. Herein, we evaluated whether COVID-19 patients with previous surgery are at high-risk of critical illness. We conducted a multicenter study focusing on the clinical characteristics of COVID-19 patients with previous surgery in six designated hospitals in the Hubei and Guangdong provinces, China. COVID-19 was diagnosed according to the WHO interim guidance. 461 patients with COVID-19 that hospitalized from January 1 to March 31, 2020 were enrolled. We collected demographics, comorbidities, laboratory variables, and chest CT images from medical records. We defined the severity of COVID-19 according to the newest COVID-19 guidelines of China and the guidelines of American Thoracic Society for community-acquired pneumonia. Critical illness is defined as meeting at least one of the following criteria: respiratory failure requiring mechanical ventilation, shock, intensive care unit (ICU) admission, or death.
Global COVID-19 Cases Top 20 Million
WebMD, August 12, 2020
The total of number of confirmed COVID-19 cases worldwide went over the 20 million mark on Tuesday, the Johns Hopkins Coronavirus Resource Center reported. The number of us cases has grown exponentially since the virus was first reported in China about 6-and-a-half months ago. Total cases hit the 1 million mark on April 2, CNN reported. Ten million cases were recorded in late June. It took less than 6 weeks to double that figure as case counts surged in the United States and Latin America. The number of cases is probably much higher because of testing limitations and a high number of infected people who show no symptoms. Deaths have also gone up. More than 737,000 have people died worldwide, Johns Hopkins said. The nations with the most cases are the United States (almost 5.1 million with more than 163,000 deaths), Brazil (3 million cases and 101,000 deaths), India (2.2 million cases and 45,000 deaths), Russia (895,000 cases and 15,000 deaths), and South Africa (563,000 cases and 10,600 deaths). Africa recorded its 1 millionth case last week. The 7-day average of new cases has been more than 250,000 for two weeks, CNN said.
Annals On Call – Diagnosing SARS-CoV-2 Infection: Symptoms or No Symptoms?
Annals of Internal Medicine, August 12, 2020
[Podcast] In this episode of Annals On Call, Dr. Centor discusses challenges to diagnosing COVID-19 with Dr. Jeanne Marrazzo. Annals On Call focuses on a clinically influential article published in Annals of Internal Medicine. Dr. Robert Centor shares his own perspective on the material and interviews topic area experts to discuss, debate, and share diverse insights about patient care and health care delivery.
COVID-19 surge moves to Midwest, as young people fuel US case rise
Center for Infectious Disease Research and Policy, August 12, 2020
Many states initially spared from the COVID-19 pandemic is March, April, and May, are now reporting increasing transmission rates in non-metropolitan counties fueled by community spread. According to the Wall Street Journal, in Ohio, Missouri, Wisconsin, and Illinois, the weekly change in COVID-19 cases has been higher in rural regions compared to metro areas, and outbreaks are linked to social events, rather than workplace exposure or congregate living situations. A summer of waning social distancing restrictions has made bars and restaurants common COVID-19 outbreak sites, on par with nursing homes and prisons states across the country. In Louisiana, the New York Times reports bars and restaurants are linked to 25% of the state’s cases, and in Maryland, that percentage was 12%. Fueling these outbreaks are the twin forces of a national “quarantine fatigue” and young adults, who are more likely than older, more at-risk Americans, to be both patrons and employees in dining and drinking establishments. Young adults are driving outbreaks in many states, and experts worry those with mild or asymptomatic cases are spreading the disease to more vulnerable household members.
This Fall Could Be ‘Worst’ We’ve Seen
icon name=”pencil” class=”” unprefixed_class=””] WebMD, August 12, 2020
We are in a war against COVID-19, and this fall could be one of the worst from a public health standpoint that the U.S. has ever faced, says CDC Director Robert Redfield, MD. The surging coronavirus pandemic, paired with the flu season, could create the “worst fall” that “we’ve ever had,” he said during an interview on “Coronavirus in Context,” a video series hosted by John Whyte, MD, WebMD’s chief medical officer. Redfield also said the agency’s efforts to understand the virus were hampered by a lack of cooperation from China. He reached out to China CDC Director George Gao on Jan. 3 to see if the agency could work with health officials in Wuhan to better understand the outbreak. But he never received an invitation, Redfield said. “I think if we had been able to get in at that time, we probably would have learned quicker than we learned here,” Redfield said.
Having Coronavirus Disease 2019 (COVID-19): Perspective from an ICU Doc
JAMA Cardiology, August 12, 2020
Janet Shapiro, MD, an ICU physician at Mount Sinai Morningside Hospital in New York City, had just come back to work after a relatively mild course of COVID-19. She had lost her sense of smell and taste, and for a few days had a low-grade temperature and cough. But as she was rounding, she noticed she still wasn’t feeling right. She was short of breath and her heart was often pounding. She didn’t have underlying heart disease. The experience reinforced recent reports that call attention to the disease’s impact on the heart, which in many cases may be silent. Last month, two German studies published found evidence of long-lasting cardiac effects, even in patients who never developed overt cardiac disease during their infection. One, an autopsy study, found viral infection in the hearts of deceased COVID-19 patients who were never diagnosed with myocarditis during their illness. The other study found that most patients who had recovered from COVID showed abnormal cardiac MRI findings consistent with active inflammation more than 2 months after diagnosis.
Exclusive: Over 900 health workers have died of COVID-19. And the toll is rising
News Medical, August 11, 2020
More than 900 front-line health care workers have died of COVID-19, according to an interactive database unveiled Wednesday by The Guardian and KHN. Lost on the Frontline is a partnership between the two newsrooms that aims to count, verify and memorialize every U.S. health care worker who dies during the pandemic. KHN and The Guardian are tracking health care workers who died from COVID-19 and writing about their lives and what happened in their final days. It is the most comprehensive accounting of U.S. health care workers’ deaths in the country. As coronavirus cases surge — and dire shortages of lifesaving protective gear like N95 masks, gowns and gloves persist — the nation’s health care workers are again facing life-threatening conditions in Southern and Western states. A team of more than 50 journalists from the Guardian, KHN and journalism schools have spent months investigating individual deaths to make certain that they died of COVID-19, and that they were indeed working on the front lines in contact with COVID patients or working in places where they were being treated. Thus far, we have independently confirmed 167 deaths and published their names, data and stories about their lives and how they will be remembered. The tally includes doctors, nurses and paramedics, as well as crucial support staff such as hospital custodians, administrators and nursing home workers, who put their own lives at risk during the pandemic to care for others.
Cardiac surgery Enhanced Recovery Programs modified for COVID-19: key steps to preserve resources, manage caseload backlog, and improve patient outcomes
Journal of Cardiothoracic and Vascular Anesthesia, August 10, 2020
SARS-CoV-2 and the COVID-19 pandemic have turned healthcare systems worldwide upside-down, and hospitals are adjusting volume of non-urgent surgical cases according to local COVID-19 prevalence rates. In the face of active disease surges or resurgences, many hospitals are postponing all non-emergent cardiac operations to redirect scarce resources to the care of patients with severe viral illness. This includes rationing personal protective equipment (PPE), establishing additional ICU capacity often in novel spaces, sequestering ventilators, and redeploying personnel. Hospitals are at risk of being overwhelmed as demand for care exceeds available resources. In locations where infection rates are lower, the throughput of elective and semi-urgent procedures may nevertheless be maintained at a lower level in the effort to preserve reserve capacity in the event of an acute surge. In a recent survey of cardiac-surgery centers, the median reduction in case volume was between 50 to 75% over the first months of the pandemic. The forced deferral of necessary care has resulted in a backlog of patients, leading to new potential risks of increased morbidity and mortality secondary to longer wait times.
A Great Unknown: When Flu Season and COVID Collide
WebMD, August 10, 2020
For months scientists have urged the public to wear masks, wash their hands and socially distance. And as the flu season approaches, those practices have never been more crucial. Depending on whether people heed this advice, the U.S. could either see a record drop in flu cases or a dangerous viral storm, doctors say. “We just have no idea what’s going to happen. Are we going to get a second surge [of coronavirus]?” says Peter Chai, MD, an emergency physician at the Brigham and Women’s Hospital in Boston. “Hopefully, knock on wood, that won’t happen.” To get an idea of how the flu season might go, public health officials in the U.S. often look to Australia and other countries in the southern hemisphere, where they are in the winter flu season. The World Health organization reports few cases worldwide. But only time will tell whether the U.S. will follow suit. If not, the consequences could be dire, leaving people even more vulnerable to COVID-19 and potentially overwhelming hospitals, says Aubree Gordon, associate professor of epidemiology at the University of Michigan School of Public Health.
Case Rates and Outcomes in Acute MI During COVID-19 Pandemic
American College of Cardiology, August 10, 2020
The investigators conducted a retrospective cross-sectional study and analyzed AMI hospitalizations that occurred between December 30, 2018, and May 16, 2020, in 1 of the 49 hospitals in the Providence St Joseph Health system located in six states (Alaska, Washington, Montana, Oregon, California, and Texas). The cohort included patients aged ≥18 years who had a principal discharge diagnosis of AMI (ST-segment elevation myocardial infarction [STEMI] or non–STEMI [NSTEMI]). Segmented regression analysis was performed to assess changes in weekly case volumes. Cases were grouped into one of three periods: before coronavirus disease 2019 (COVID-19) (December 30, 2018-February 22, 2020), early COVID-19 (February 23-March 28, 2020), and later COVID-19 (March 29-May 16, 2020). In-hospital mortality was risk-adjusted using an observed to expected (O/E) ratio and covariate-adjusted multivariable model. The primary outcome was the weekly rate of AMI (STEMI or NSTEMI) hospitalizations. The secondary outcomes were patient characteristics, treatment approaches, and in-hospital outcomes of this patient population. Trends among the three COVID-19 periods were compared using univariate χ2, Fisher exact, or Kruskal-Wallis tests, as appropriate, for each variable.
Additional $400,000 awarded for research projects focused on cardiovascular impact of COVID-19
News Medical, August 10, 2020
The American Heart Association has awarded an additional $400,000 in research grants focused on the cardiovascular impact of COVID-19. The awards go to four more teams who submitted proposals for the COVID-19 and Its Cardiovascular Impact Rapid Response Grants during the original submission process in March. The new research projects include:
• Cleveland Clinic, led by Mina Chung, M.D., Professor of Medicine — Testing of SARS-CoV-2 Infectivity and Antiviral Drug Effects in Engineered Heart Tissue, Microglial Cell Models, and COVID-19 Patient Registries.
• Johns Hopkins University, led by Daniela Cihakova M.D., Ph.D., Associate Professor and Director of the Immune Disorders Laboratory — Pathogenesis of Cardiac Inflammation During COVID-19 Infection.
• Cedars-Sinai Board of Governors Regenerative Medicine Institute at the Cedars-Sinai Medical Center, co-led by Clive Svendsen, Ph.D., Director of the institute Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine and Professor of Biomedical Sciences and Medicine, and by Arun Sharma, Ph.D., Senior Research Fellow — Human iPSCs and Organ Chips Model SARS-CoV-2-Induced Viral Myocarditis.
• New York-Presbyterian/Columbia University Irving Medical Center, led by Emily J. Tsai, M.D., Florence Irving Assistant Professor of Medicine — Elucidating the Pathogenesis of COVID-19 Cardiac Disease Through snRNA-Seq and Histopathological Analysis of Human Myocardium.
IV High-Dose Vitamin C Success Story in COVID-19
MedPage Today, August 10, 2020
A 74-year-old white woman presents to an emergency department in Flint, Michigan, after suffering with low-grade fever, dry cough, and shortness of breath for the previous 2 days. Her medical history for the week before includes elective surgery at an¬other hospital for total replacement of the right knee. She notes that she was healthy on admission and at discharge. She stayed in a private room, and had no contact with individuals who were ill or who had traveled recently. Lung auscultation reveals bilateral rhonchi with rales, and chest radiography shows patchy air space opacity in the right upper lobe suspicious for pneumonia. Concerns about community transmission of COVID-19 prompt a nasopharyngeal swab, which is sent to the state laboratory for detection of SARS-CoV-2. The patient is admitted to the airborne-isolation unit, maintaining compliance to the CDC recommendations for contact, droplet, and airborne precautions. Results of the nasopharyngeal swab are positive for SARS-CoV-2 by reverse-transcriptase polymerase chain reaction (RT-PCR). Clinicians start treatment with oral hydroxychloroquine 400 mg once and then 200 mg twice a day, along with intravenous azithromycin 500 mg once a day, zinc sulfate 220 mg three times a day, and oral vitamin C 1 g twice a day. When blood and sputum cultures are negative for any organisms, broad-spectrum antibiotics are discontinued. The patient’s dyspnea rapidly worsens, and oxygen requirements increase to 15 liters. She is drowsy, in moderate distress, and her airways remain unprotected. On day 7, the second day of mechanical ventilation, at the request of the family when the patient develops ARDS, she is started on a continuous intravenous infusion of high-dose vita¬min C (11 g /24 hours). Two days later, her clinical condition gradually begins to improve, and the clinicians discontinue supportive treatment with norepinephrine. On day 10, the fifth day of mechanical ventilation, another chest x-ray shows that both the pneumonia and interstitial edema have improved considerably. The patient responds well to a spontaneous breathing trial with continuous positive airway pressure/pressure support, with the settings of positive end-expiratory pressure (PEEP) of 7 mm Hg, pressure support above PEEP of 10 mm Hg, and a fraction of inspired oxygen of 40%.
No End in Sight as U.S. Cases Pass 5 Million
WebMD, August 9, 2020
The U.S. logged 5 million confirmed COVID-19 cases, hitting another grim milestone in the nearly 6-month long pandemic that has devastated the country. The U.S. tally is substantially larger than the next closest country, Brazil, which has logged roughly 3 million cases. It is roughly 2.5 times the size of the outbreak in India, though the total population in that country is more than 4 times as large. Experts say the number of cases underscores the failure of our national response. In July, newly reported cases in the U.S. topped 70,000 a day. “Seventy thousand was the number of cases that they had in Wuhan, China where this started, in total. So we were having a Wuhan a day in this country,” says Carlos Del Rio, MD, an infectious disease specialist and a professor of Global Health and Epidemiology at Emory University in Atlanta. “We’re doing a crappy job.” While cases have slowed slightly in recent days, they have been rapidly accelerating in the U.S. Since the introduction of the virus, it took the U.S. more than 12 weeks to reach its first 1 million cases, 7 weeks to amass 2 million cases, 3.5 weeks to reach 3 million, and 2.5 weeks to hit 4 million, and another 2.5 weeks to reach 5 million.
Coronavirus in Context: The Impact of COVID on Digital Health
WebMD, August 7, 2020
[Video] Dr. John Whyte, Chief Medical Officer at Web MD, discusses the future of healthcare right now during COVID and post-COVID? Dr. Whyte interviews Dr. Bertalan Mesko, a self-described “geek physician” with a PhD in genomics and a medical futurist.
Acute MI fatality rate higher than expected during COVID-19 pandemic
Helio | Cardiology Today, August 7, 2020
In a cross-sectional study of patients with acute MI, there were more observed fatalities than expected during the early period of the COVID-19 pandemic. In the later period of the pandemic, there were more observed fatalities than expected for patients with STEMI but not for the overall acute MI population, researchers reported. Cardiology Today Next Gen Innovator Ty J. Gluckman, MD, FACC, FAHA, medical director of the Center for Cardiovascular Analytics, Research and Data Science (CARDS), Providence Heart Institute, Providence St. Joseph Health in Portland, Oregon, and colleagues retrospectively analyzed 15,244 patients (mean age, 68 years; 66% men; 33% with STEMI) hospitalized for acute MI at one of 49 centers in six Western states between December 30, 2018 and May 16, 2020.
Potentially fatal severe brady arrythmias related to Lopinavir-Ritonavir in a COVID 19 patient
Journal of Microbiology, Immunology and Infection, August 6, 2020
The novel coronavirus (COVID-19) outbreak was declared a global pandemic, with over 6 million people infected, and 371166 deaths worldwide. Without proven treatments for severe COVID-19, physicians have resorted to experimental therapies like Lopinavir-Ritonavir. We report the first case of potentially fatal bradyarrhythmias with long sinus pauses due to Lopinavir-Ritonavir. The patient is a 67-year-old male with a history of hypertension and coronary artery disease. He tested positive for COVID-19 on day 5 of respiratory symptoms. On day 10, he deteriorated and Lopinavir 4mg/kg / Ritonavir 1mg/kg 12-hourly was initiated. His baseline electrocardiogram showed a heart rate of 84bpm, and QTc of 496ms.
COVID-19 Breakthrough: Scientists Identify Possible “Achilles’ Heel” of SARS-CoV-2 Virus
SciTechDaily, August 6, 2020
In the case of an infection, the SARS-CoV-2 virus must overcome various defense mechanisms of the human body, including its non-specific or innate immune defense. During this process, infected body cells release messenger substances known as type 1 interferons. These attract natural killer cells, which kill the infected cells. One of the reasons the SARS-CoV-2 virus is so successful — and thus dangerous — is that it can suppress the non-specific immune response. In addition, it lets the human cell produce the viral protein PLpro (papain-like protease). PLpro has two functions: It plays a role in the maturation and release of new viral particles, and it suppresses the development of type 1 interferons. The German and Dutch researchers have now been able to monitor these processes in cell culture experiments. Moreover, if they blocked PLpro, virus production was inhibited and the innate immune response of the human cells was strengthened at the same time. Professor Ivan Dikic, Director of the Institute of Biochemistry II at University Hospital Frankfurt and last author of the paper, explains: “We used the compound GRL-0617, a non-covalent inhibitor of PLpro, and examined its mode of action very closely in terms of biochemistry, structure and function. We concluded that inhibiting PLpro is a very promising double-hit therapeutic strategy against COVID-19. The further development of PLpro-inhibiting substance classes for use in clinical trials is now a key challenge for this therapeutic approach.”
Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients With SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea
JAMA Internal Medicine, August 6, 2020
Are there viral load differences between asymptomatic and symptomatic patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection? There is limited information about the clinical course and viral load in asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this study was to quantitatively describe SARS-CoV-2 molecular viral shedding in asymptomatic and symptomatic patients. In this cohort study that included 303 patients with SARS-CoV-2 infection isolated in a community treatment center in the Republic of Korea, 110 (36.3%) were asymptomatic at the time of isolation and 21 of these (19.1%) developed symptoms during isolation. The cycle threshold values of reverse transcription–polymerase chain reaction for SARS-CoV-2 in asymptomatic patients were similar to those in symptomatic patients. Many individuals with SARS-CoV-2 infection remained asymptomatic for a prolonged period, and viral load was similar to that in symptomatic patients; therefore, isolation of infected persons should be performed.
Healthcare workers of color nearly twice as likely as whites to get COVID-19
Modern Healthcare, August 6, 2020
Healthcare workers of color were more likely to care for patients with suspected or confirmed COVID-19, more likely to report using inadequate or reused protective gear, and nearly twice as likely as white colleagues to test positive for the coronavirus, a new study found. The study from Harvard Medical School researchers also showed that healthcare workers are at least three times more likely than the general public to report a positive COVID test, with risks rising for workers treating COVID patients. Dr. Andrew Chan, a senior author and an epidemiologist at Massachusetts General Hospital, said the study further highlights the problem of structural racism, this time reflected in the front-line roles and personal protective equipment provided to people of color. “If you think to yourself, ‘healthcare workers should be on equal footing in the workplace,’ our study really showed that’s definitely not the case,” said Chan, who is also a professor at Harvard Medical School. The study was based on data from more than 2 million COVID Symptom Study app users in the U.S. and the United Kingdom from March 24 through April 23. The study, done with researchers from King’s College London, was published in the journal The Lancet Public Health.
How a Zoom forum is changing the way ICU doctors treat desperately ill Covid-19 patients
STAT, August 6, 2020
It was late April, near the height of the Covid-19 pandemic in the big cities in the northeastern U.S., and anesthesiologist Joseph Savino was puzzled. In two months, an unexpectedly high number of coronavirus patients had died in his intensive care unit at the Hospital of the University of Pennsylvania after a stroke caused by bleeding in the brain. All were among 15 Covid-19 patients at the Philadelphia hospital who had been on a life-support technology called ECMO that is a last resort for patients when mechanical ventilators fail to help their virus-ravaged lungs. ECMO, for extracorporeal membrane oxygenation — essentially an artificial lung — is high-risk, but still, the number of fatal brain bleeds seemed unusual, said Savino, a critical-care specialist. It was too low, however, “to draw any substantive conclusions” about cutting back the blood-thinning drugs they were giving other Covid-19 patients on ECMO, because blood clots, not bleeds, were seen as the major risk to survival. Swamped by overflowing ICUs and the myriad not-seen-before ways the novel coronavirus attacks the body, doctors caring for the pandemic’s sickest patients are scrambling to share their experiences with each other in real time, hoping to find ways to stanch Covid-19’s devastating toll. Some 200 physicians from several countries and dozens of states have participated in the Friday Zoom sessions.
The effects of COVID-19 on the office visit
MJH Life Sciences, August 6, 2020
[Infographic] In this State of Physician Survey, COVID-19’s effect on the office visit was the subject. With over 1,000 responses from a variety of specialties, physicians were candid about navigating a new normal with COVID-19 and the office visit. Accommodating safe distancing in the waiting room to patient compliance and education are top areas of concern highlighted on the infographic.
Association of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with risk of COVID ‐19, inflammation level, severity, and death in patients with COVID ‐19: A rapid systematic review and meta‐analysis
Clinical Cardiology, August 5, 2020
An association among the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) with the clinical outcomes of coronavirus disease 2019 (COVID-19) is unclear. PubMed, EMBASE, MedRxiv, and BioRxiv were searched for relevant studies that assessed the association between application of ACEI/ARB and risk of COVID-19, inflammation level, severity COVID-19 infection, and death in patients with COVID-19. Eleven studies were included with 33 483 patients. ACEI/ARB therapy might be associated with the reduced inflammatory factor (interleukin-6) and elevated immune cells counts (CD3, CD8). Meta-analysis showed no significant increase in the risk of COVID-19 infection (odds ratio [OR]: 0.95, 95%CI: 0.89-1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID-19 (OR: 0.75, 95%CI: 0.59-0.96) and mortality (OR: 0.52, 95%CI: 0.35-0.79). Subgroup analyses showed among the general population, ACEI/ARB therapy was associated with reduced severe COVID-19 infection (OR: 0.79, 95%CI: 0.60-1.05) and all-cause mortality (OR: 0.31, 95%CI: 0.13-0.75), and COVID-19 infection (OR: 0.85, 95% CI: 0.66-1.08) were not increased. Among patients with hypertension, the use of an ACEI/ARB was associated with a lower severity of COVID-19 (OR: 0.73, 95%CI: 0.51-1.03) and lower mortality (OR: 0.57, 95%CI: 0.37-0.87), without evidence of an increased risk of COVID-19 infection (OR: 1.00). Our results need to be interpreted with caution considering the potential for residual confounders, and more well-designed studies that control the clinical confounders are necessary to confirm our findings.
Skin Rashes a Clue to COVID-19 Vascular Disease
MedPage Today, August 5, 2020
Certain types of rashes in severe COVID-19 patients may be “a clinical clue” to an underlying thrombotic state, researchers said. Four patients with severe illness at two New York City academic medical centers had livedoid and purpuric rashes, all associated with elevated D-dimer levels and suspected pulmonary emboli, reported Joanna Harp, MD, of NewYork-Presbyterian/Weill Cornell Medical College in New York City, and colleagues, writing in a research letter in JAMA Dermatology. All had been on prophylactic anticoagulation since admission and developed those “hallmark manifestations of cutaneous thrombosis” despite escalation to therapeutic dose anticoagulation for the suspected pulmonary embolism before the rash was noted. “Clinicians caring for patients with COVID-19 should be aware of livedoid and purpuric rashes as potential manifestations of an underlying hypercoagulable state,” Harp’s group wrote. Skin biopsy in each case showed pauci-inflammatory thrombogenic vasculopathy.
Efforts Needed to Get Minorities Into Clinical Trials, Experts Say
MedPage, August 4, 2020
More work needs to be done to enroll people of color in clinical trials, Freda Lewis-Hall, MD, chief patient officer and executive vice president at Pfizer, said Sunday at the annual meeting of the National Medical Association. “One of the really interesting things the data tell us about participation in clinical trials of Black and brown people is they are much less likely to be asked,” Lewis-Hall said during the plenary session of the meeting, which was held remotely. Lewis-Hall said investigator bias against Black and brown patients is reflected in statements such as “I don’t know if they can get here; adherence might be a problem; it may take too long,” and this needs to improve. One thing that would help is having more Black and brown physicians, she added. “The numbers are woefully lagging. We need to increase our pipeline of physicians and physician-investigators, because over and over we heard that the trust issue is critical,” and that “we need to educate patients around clinical trials and their relative safety.”
Coronavirus Q&A With Anthony Fauci
JAMA Live, August 3, 2020
[Video] Anthony Fauci, MD, White House Coronavirus Task Force member and Director of the National Institutes of Allergy and Infectious Diseases, discusses latest developments in the COVID-19 pandemic with Howard Bauchner, MD, Editor in Chief, JAMA.
Trends in Emergency Department Visits and Hospital Admissions in Health Care Systems in 5 States in the First Months of the COVID-19 Pandemic in the US
JAMA Internal Medicine, August 3, 2020
In this cross-sectional study of 24 emergency departments in 5 health care systems in Colorado, Connecticut, Massachusetts, New York, and North Carolina, decreases in emergency department visits ranged from 41.5% in Colorado to 63.5% in New York, with the most rapid rates of decrease in visits occurring in early March 2020. Rates of hospital admissions from the ED were stable until new COVID-19 case rates began to increase locally, at which point relative increases in hospital admission rates ranged from 22.0% to 149.0%. To examine trends in emergency department (ED) visits and visits that led to hospitalizations covering a 4-month period leading up to and during the COVID-19 outbreak in the US. This retrospective, observational, cross-sectional study of 24 EDs in 5 large health care systems in Colorado (n = 4), Connecticut (n = 5), Massachusetts (n = 5), New York (n = 5), and North Carolina (n = 5) examined daily ED visit and hospital admission rates from January 1 to April 30, 2020, in relation to national and the 5 states’ COVID-19 case counts.
Presidential order signed expanding use of virtual doctors
The Hill, August 3, 2020
On Monday, the President signed an executive order seeking to expand the use of virtual doctors visits, as his administration looks to highlight achievements in health care. The administration waived certain regulatory barriers to video and phone calls with doctors, known as telehealth, when the coronavirus pandemic struck and many people were stuck at home. Now, the administration is looking to make some of those changes permanent, arguing the moves will provide another option for patients to talk to their doctors. The order calls on the secretary of Health and Human Services to issue rules within 60 days making some of the changes permanent.
RLF-100 (aviptadil) clinical trial showed rapid recovery from respiratory failure and inhibition of coronavirus replication in human lung cells
Cision, August 2, 2020
NeuroRx, Inc. and Relief Therapeutics Holdings AG (SIX:RLF, OTC:RLFTF) “Relief” today announced that RLF-100 (aviptadil) showed rapid recovery from respiratory failure in the most critically ill patients with COVID-19. At the same time, independent researchers have reported that aviptadil blocked replication of the SARS coronavirus in human lung cells and monocytes. RLF-100 has been granted Fast Track designation by FDA and is being developed as a Material Threat Medical Countermeasure in cooperation with the National Institutes of Health and other federal agencies. Further research will be conducted. The first report of rapid clinical recovery under emergency use IND was posted by doctors from Houston Methodist Hospital. The report describes a 54-year-old man who developed COVID-19 while being treated for rejection of a double lung transplant and who came off a ventilator within four days. Similar results were subsequently seen in more than 15 patients treated under emergency use IND and an FDA expanded access protocol which is open to patients too ill to be admitted to the ongoing Phase 2/3 FDA trial. Patients with Critical COVID-19 were seen to have a rapid clearing of classic pneumonitis findings on x-ray, accompanied by an improvement in blood oxygen and a 50% or greater average decrease in laboratory markers associated with COVID-19 inflammation.
Upping the Cardiovascular Health Game
Managed Healthcare Executive, August 1, 2020
Although it is a new disease, COVID-19 has a way of peeling back layers and bringing other medical issues to the surface. For example, research has shown that people with high blood pressure are more likely to become seriously ill. A study published in the April 22 issue of JAMA of 5,700 patients hospitalized with COVID-19 in the New York City area found that 56% had hypertension, making it the most common comorbidity. The death rate from cardiovascular disease has been declining, but it remains the leading cause of death in the United States. According to the CDC, 647,457 Americans died of heart disease and 146,383 of stroke in 2017. (Of course, this year COVID-19 has scrambled the usual list of the leading causes of death in this country.) “(Cardiovascular disease) has to be a priority of health systems and the government. We haven’t really attacked it as well as we should have,” says Martha Gulati, M.D., M.S., FACC, FAHA, division chief of cardiology at the University of Arizona College of Medicine in Phoenix and editor-in-chief at CardioSmart.org, a website run by the American College of Cardiology aimed at educating patients about heart disease. “The whole population has to be involved in this,” with a focus on preventing cardiovascular disease, Gulati says.
Stroke With COVID-19? Check the Large Vessels
MedPage, July 31, 2020
COVID-19’s excess stroke risk appeared to be largely related to large vessel strokes, an observational study showed. Among stroke code patients at one large health system in New York City during the pandemic surge there, 38.3% had COVID-19 (126 of 329 seen from March 16 to April 30, 2020). Large vessel occlusion (LVO) as a cause of the stroke was 2.4-fold more common with COVID-19 than without it after adjustment for race and ethnicity (P=0.011), Shingo Kihira, MD, of Icahn School of Medicine at Mount Sinai in New York City, and colleagues reported in the American Journal of Roentgenology. Of the stroke cases, 31.7% of those in COVID-19 patients were LVOs compared with 15.3% in those without COVID-19 (P=0.001). But there was not much difference between groups for small vessel occlusions (SVOs), at 15.9% and 13.8%, respectively (P=0.632).
Women Physicians and the COVID-19 Pandemic
Journal of the American Medical Association, July 31, 2020
Before the magnifying glass of the COVID-19 pandemic caused physicians to look more closely at many aspects of their profession, there was awareness of the general culture of overwork that affect all physicians and the expectation by some that women physicians would make adjustments in their professional roles to accommodate their personal roles. These professional adjustments were made, including part-time status, despite the known limitations on professional progression, career advancement, and economic potential. These adjustments further propagate gender inequities and the persistent compensation gap women physicians’ experience. Women physicians have diverse personal characteristics. There is no appropriate stereotype for a woman physician. Some are just starting their professional careers. Some are older, nearing retirement. Some are partnered, others are solo. Some are childless, others are parents. Family care responsibilities vary with some caring for their children, their aging parents, or both. Practice parameters and settings vary, including business owners, health care executives, academic physicians, and employees of hospitals and group practices. For partnered women physicians, a small number are the principal source of income with a partner assuming the primary role for home and family care. The increasing number of women physicians is accompanied by a rise in the number of dual physician households. This diversity of personal situations highlights the reason to avoid broad assumptions when considering the life-work preferences or professional work adjustments related to the COVID-19 epidemic for individuals or groups of physicians, by gender.
From ‘brain fog’ to heart damage, COVID-19’s lingering problems alarm scientists
Science, July 31, 2020
The list of lingering maladies from COVID-19 is longer and more varied than most doctors could have imagined. Ongoing problems include fatigue, a racing heartbeat, shortness of breath, achy joints, foggy thinking, a persistent loss of sense of smell, and damage to the heart, lungs, kidneys, and brain. The likelihood of a patient developing persistent symptoms is hard to pin down because different studies track different outcomes and follow survivors for different lengths of time. One group in Italy found that 87% of a patient cohort hospitalized for acute COVID-19 was still struggling 2 months later. Data from the COVID Symptom Study, which uses an app into which millions of people in the United States, United Kingdom, and Sweden have tapped their symptoms, suggest 10% to 15% of people—including some “mild” cases—don’t quickly recover. But with the crisis just months old, no one knows how far into the future symptoms will endure, and whether COVID-19 will prompt the onset of chronic diseases. Researchers are now facing a familiar COVID-19 narrative: trying to make sense of a mystifying illness. Distinct features of the virus, including its propensity to cause widespread inflammation and blood clotting, could play a role in the assortment of concerns now surfacing. “We’re seeing a really complex group of ongoing symptoms,” says Rachael Evans, a pulmonologist at the University of Leicester.
Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study
The Lancet | Public Health, July 31, 2020
Data for front-line health-care workers and risk of COVID-19 are limited. We sought to assess risk of COVID-19 among front-line health-care workers compared with the general community and the effect of personal protective equipment (PPE) on risk. This prospective, observational cohort study was done in the UK and the USA of the general community, including front-line health-care workers, using self-reported data from the COVID Symptom Study smartphone application (app) from March 24 (UK) and March 29 (USA) to April 23, 2020. Participants were voluntary users of the app and at first use provided information on demographic factors (including age, sex, race or ethnic background, height and weight, and occupation) and medical history, and subsequently reported any COVID-19 symptoms. We used Cox proportional hazards modelling to estimate multivariate-adjusted hazard ratios (HRs) of our primary outcome, which was a positive COVID-19 test. Among 2 035 395 community individuals and 99 795 front-line health-care workers, we recorded 5545 incident reports of a positive COVID-19 test over 34 435 272 person-days. Compared with the general community, front-line health-care workers were at increased risk for reporting a positive COVID-19 test (adjusted HR 11·61, 95% CI 10·93–12·33).
U.S. records over 25,000 coronavirus deaths in July
Reuters, July 31, 2020
U.S. coronavirus deaths rose by over 25,000 in July and cases doubled in 19 states during the month, according to a Reuters tally, dealing a crushing blow to hopes of quickly reopening the economy. The United States recorded 1.87 million new cases in July, bringing total infections to 4.5 million, for an increase of 69%. Deaths in July rose 20% to nearly 154,000 total. The biggest increases in July were in Florida, with over 310,000 new cases, followed by California and Texas with about 260,000 each. All three states saw cases double in June. Cases also more than doubled in Alabama, Alaska, Arizona, Arkansas, Georgia, Hawaii, Idaho, Mississippi, Missouri, Montana, Nevada, Oklahoma, Oregon, South Carolina, Tennessee and West Virginia, according to the tally. Connecticut, Massachusetts, New Jersey and New York had the lowest increases, with cases rising 8% or less.
Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network — United States, March–June 20
CDC Morbidity and Mortality Weekly Report, July 31, 2020
Prolonged symptom duration and disability are common in adults hospitalized with severe coronavirus disease 2019 (COVID-19). Characterizing return to baseline health among outpatients with milder COVID-19 illness is important for understanding the full spectrum of COVID-19–associated illness and tailoring public health messaging, interventions, and policy. During April 15–June 25, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had a first positive reverse transcription–polymerase chain reaction (RT-PCR) test for SARS-CoV-2, the virus that causes COVID-19, at an outpatient visit at one of 14 U.S. academic health care systems in 13 states. Interviews were conducted 14–21 days after the test date. Respondents were asked about demographic characteristics, baseline chronic medical conditions, symptoms present at the time of testing, whether those symptoms had resolved by the interview date, and whether they had returned to their usual state of health at the time of interview. Among 292 respondents, 94% (274) reported experiencing one or more symptoms at the time of testing; 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the interview (median = 16 days from testing date), including 26% among those aged 18–34 years, 32% among those aged 35–49 years, and 47% among those aged ≥50 years. Among respondents reporting cough, fatigue, or shortness of breath at the time of testing, 43%, 35%, and 29%, respectively, continued to experience these symptoms at the time of the interview.
2nd US virus surge hits plateau, but few experts celebrate
Associated Press, July 31, 2020
While deaths from the coronavirus in the U.S. are mounting rapidly, public health experts are seeing a flicker of good news: The second surge of confirmed cases appears to be leveling off. The virus has claimed over 150,000 lives in the U.S., by far the highest death toll in the world, plus more than a half-million others around the globe. Over the past week, the average number of COVID-19 deaths per day in the U.S. has climbed more than 25%, from 843 to 1,057. Florida on Thursday reported 253 more deaths, setting its third straight single-day record, while Texas had 322 new fatalities and California had 391. The number of confirmed infections nationwide has topped 4.4 million, which could be higher because of limits on testing and because some people are infected without feeling sick.
Coronary Calcium in COVID-19 Patients Linked to Worse Outcomes
tctMD, July 30, 2020
Elevated coronary artery calcium (CAC) is a marker for worse prognosis among patients hospitalized for COVID-19, according to a French analysis. “The severity of immune response, endothelial dysfunction, and myocardial stress due to COVID-19 could be exacerbated in patients with subclinical coronary atherosclerosis,” write Jean Guillaume Dillinger, MD, PhD (Lariboisiere Hospital, Paris, France), and colleagues. Although small, the study supports the practice of analyzing CAC in every COVID-19 patient, since it is a “freebie” that can help plan appropriate management, said Harvey Hecht, MD (Mount Sinai Medical Center, New York, NY), who was not involved in the study. “You’re getting a CT scan of the lungs on every COVID patient and that information is just there. You simply can’t miss it. So it takes virtually no additional time to do the measurements,” he told TCTMD, acknowledging that this information is not always reported on a routine basis despite guideline recommendations. In those patients with COVID-19 and elevated CAC, Hecht advised physicians to “follow that patient more carefully and perhaps be more aggressive at the first signs of worsening of their COVID status and their pneumonia. You should be more aggressive in treating that with all available tools.”
Treatment Options for COVID-19
Helio | Infectious Disease News, July 30, 2020
[Podcast] Research and data on potential treatment modalities continue to emerge at a rapid pace. This episode explores the IDSA and NIH guidelines for the treatment and management of COVID-19, as well as available evidence on antivirals, glucocorticoids and antibodies. Gitanjali Pai, MD, is an infectious disease physician at Memorial Hospital and Physicians’ Clinic in Stilwell, Oklahoma. She is a member of the Infectious Disease News Editorial Board and host of Healio’s podcast Unmasking COVID-19.
Systematic review of the role of renin-angiotensin system inhibitors in late studies on Covid-19: A new challenge overcome?
International Journal of Cardiology, July 30, 2020
A role for the renin-angiotensin-aldosterone-system in Severe Acute Respiratory Syndrome-Coronavirus-2 infection and in the development of COronaVIrus Disease-19 disease has generated remarkable concerns among physicians and patients. Even though a suggestive pathophysiological link between renin-angiotensin-aldosterone-system and the virus has been proposed, its pathogenic role remains very difficult to be defined. Although COronaVIrus Disease-19 targets preferentially older people with high prevalence of hypertension and extensive use of renin-angiotensin-aldosterone-system inhibitors, an independent role for hypertension and its therapies is not defined. In this article, we scrutinize evidence from the most representative available studies in which the potential role of renin-angiotensin system inhibitors, specifically angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, was evaluated in the COronaVIrus Disease-19 disease course, with regard to severity of the disease and mortality.
The toll that COVID-19 takes on the heart
NewsMedical, July 29, 2020
The coronavirus disease (COVID-19) has ravaged across the globe, with more than 16.95 million people infected. Early in the pandemic, the disease was described as a respiratory condition as it usually attacks the lungs first. As the disease progressed, other vital organs have been affected, including the heart and the kidneys. Now, two new studies describe the toll that COVID-19 takes on the heart, increasing the risk of long-term damage even after patients recover. These studies also show that heart damage can even occur in people who did not have severe illness that required hospitalization.
Cardiac Endotheliitis and Multisystem Inflammatory Syndrome After COVID-19
Annals of Internal Medicine, July 29, 2020
Endotheliitis and microangiopathy have been identified as key features of the pathophysiology of severe coronavirus disease 2019 (COVID-19). In addition, a multisystem inflammatory syndrome (MIS) similar to Kawasaki disease has been increasingly reported in association with COVID-19 in children and young adults. Although vascular damage seems to be a component of both of these presentations, the pathologic features of MIS remain elusive. This report is meant to provide what we believe to be the first report on the pathologic findings of vasculitis of the small vessels of the heart, which likely represents MIS, leading to death in a young adult after presumed resolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The patient was a 31-year-old African American woman with a body mass index of 36.1 kg/m2, hypertension controlled with lisinopril, and diabetes with poor adherence to metformin and glipizide (hemoglobin A1c level, 13.9%). She was admitted for fever, dry cough, and abdominal discomfort of 5 days. She was positive for SARS-CoV-2 by reverse transcriptase polymerase chain reaction testing of a nasopharyngeal swab specimen and was treated with a course of azithromycin and 2 days of hydroxychloroquine. At discharge, she was afebrile and her oxygen saturation was 95% on room air.
Phase 3 Trial of COVID-19 Vaccine Candidate mRNA-1273 Begins
Pulmonology Advisor, July 29, 2020
Moderna and the National Institutes of Allergy and Infectious Diseases have initiated a phase 3 trial evaluating the vaccine candidate mRNA-1273 against coronavirus disease 2019 (COVID-19). The trial, which is the first to be implemented under Operation Warp Speed, is expected to enroll around 30,000 adults and will be conducted at multiple clinical research sites across the US. In addition, the National Institutes of Health (NIH) Coronavirus Prevention Network will participate in conducting the trial. Testing sites in areas with emerging cases or high incidence rates will be prioritized for enrollment. Participants will be randomized to receive 2 intramuscular injections of either mRNA-1273 or saline placebo approximately 28 days apart. The study’s primary aim will be to assess whether the vaccine is able to prevent symptomatic COVID-19 after the administration of 2 doses; prevention after 1 dose will also be investigated as a secondary goal. Moreover, researchers will look at whether vaccination with mRNA-1273 prevents severe COVID-19 or laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with or without disease symptoms, as well as death.
Evaluation of Stress Cardiac Magnetic Resonance Imaging in Risk Reclassification of Patients With Suspected Coronary Artery Disease
JAMA Cardiology, July 29, 2020
The role of stress cardiac magnetic resonance (CMR) imaging in clinical decision-making by reclassification of risk across American College of Cardiology/American Heart Association guideline–recommended categories has not been established. In a multicenter cohort study of 1698 consecutive patients (median follow-up, 5.4 years) without a history of coronary artery disease, stress cardiac magnetic resonance imaging was performed for evaluation of suspected coronary artery disease. Stress cardiac magnetic resonance imaging significantly reclassified patient risk for cardiovascular death and myocardial infarction across American College of Cardiology/American Heart Association guideline–based risk categories. The findings of this study suggest that, in patients with suspected coronary artery disease, stress cardiac magnetic resonance imaging may provide incremental prognostic value for cardiovascular death and myocardial infarction and aid in clinical decision-making by reclassifying a substantial proportion of patients at intermediate risk.
U.S. records a coronavirus death every minute as total surpasses 150,000
Reuters, July 29, 2020
One person in the United States died about every minute from COVID-19 on Wednesday as the national death toll surpassed 150,000, the highest in the world. The United States recorded 1,461 new deaths on Wednesday, the highest one-day increase since 1,484 on May 27, according to a Reuters tally. U.S. coronavirus deaths are rising at their fastest rate in two months and have increased by 10,000 in the past 11 days. Nationally, COVID-19 deaths have risen for three weeks in a row while the number of new cases week-over-week recently fell for the first time since June. A spike in infections in Arizona, California, Florida and Texas this month has overwhelmed hospitals. The rise has forced states to make a U-turn on reopening economies that were restricted by lockdowns in March and April to slow the spread of the virus. Texas leads the nation with nearly 4,300 deaths so far this month, followed by Florida with 2,900 and California, the most populous state, with 2,700. The Texas figure includes a backlog of hundreds of deaths after the state changed the way it counted COVID-19 fatalities.
Eagle’s Eye View: COVID-19 Tip of the Week – Elevated Troponin Levels
American College of Cardiology, July 29, 2020
[Video] Watch Dr. Kim Eagle as he provides a weekly tip for clinicians on the front lines of the COVID-19 pandemic. This week, he discussed elevated troponin levels and outcomes in patients diagnosed with COVID-19. (See full article, Myocardial Injury in Patients Hospitalized With COVID-19, below.)
As pandemic rages, PPE supply remains a problem
Center for Infectious Disease Research and Policy, July 29, 2020
On top of being overwhelmed with severely ill people, healthcare workers are dealing with shortages of the personal protective equipment (PPE) that they need to keep from getting infected themselves. N95 respirators, surgical masks, gowns, and gloves were all were in short supply, forcing hospitals to ration them. At the root of the issue were several problems: a global surge in demand for protective gear that was outstripping supply, a lack of adequate supplies in the Strategic National Stockpile, which is intended to supplement state and local supplies during public health emergencies, and a response that lacked any federal coordination. A nationwide scrum for available PPE ensued, pitting state governments, healthcare systems, and individual hospitals against each other as they fought to outbid each other for adequate supplies for the pandemic response. Four months later, many hospitals have a better supply of PPE than they did in March and April. But with the dramatic nationwide rise in coronavirus cases that began in mid-June and shows no signs of slowing, concerns about PPE supplies remain. And demand is now coming not only from the hospitals that are treating COVID-19 patients, but also from nursing homes, primary care doctors who want to ensure a safe environment as they begin welcoming back patients for routine primary care, and other frontline healthcare workers.
Impact of Cardiac CT During COVID-19
Diagnostic and Interventional Cardiology, July 28, 2020
The use of cardiovascular computer tomography angiography (CCTA) is one of the areas that has seen a sudden increase in use and value since the start of the ongoing COVIF-19 pandemic. While SARS-CoV-2 has had significantly impacted cardiovascular care delivery, with a large reduction in elective diagnostic testing and face-to-face patient care, it also resulted a necessary re-examination of how cardiac care is delivered. Alternative approaches, beyond traditional, entrenched clinical practice for cardiac imaging are discussed in a recent paper published in Radiology: Cardiothoracic Imaging. “In many ways, the COVID crisis has been like a crucible,” the authors of the paper wrote. “Anything that is extraneous or unnecessary, anything that has gone on ‘just because’ gets melted away, leaving only that which is inherently of value and worth keeping.” The authors said telemedicine is showing cardiologists that not every patient needs to present in-person in order to have meaningful interactions for care. They said the same is true for an expanded clinical role of CCTA in ambulatory and acute care settings has been equally beneficial. However, they argue neither approach will be sustainable in the future unless the regulatory and reimbursement systems for care delivery can adapt to these innovative approaches.
Myocardial Injury in Patients Hospitalized With COVID-19
American College of Cardiology, July 27, 2020
Data were obtained retrospectively from the electronic medical record (EMR) of patients admitted with COVID-19 to one of five Mount Sinai Health System hospitals in New York City between February and April 2020. Patients with a troponin I drawn within 24 hours of admission were included. These levels were stratified into normal (0.00-0.03 ng/ml), mildly elevated (>0.03-0.09 ng/ml), and elevated (>0.09 ng/ml). Variables collected included demographics, laboratory values, and comorbidities based on International Classification of Diseases, Tenth Revision (ICD-10) billing codes. A CURB-65 score was computed on admission to reflect illness severity, reported as an integer between 0-5. The primary outcome was mortality, with a composite secondary outcome of mortality or mechanical ventilation. Of patients admitted with COVID-19, 2,736 (89.1%) of 3,069 had ≥1 troponin I measurement within 24 hours of admission. The median age was 66.4 years, 59.6% were male, and 40.7% of patients were ages >70 years; 27.6% of patients self-identified as African American, and 27.6% as Hispanic or Latino. Mean body mass index (BMI) was 29.8 ± 6 kg/m2. Cardiovascular disease (CVD), comprised of either coronary artery disease (CAD), atrial fibrillation (AF), or heart failure (HF) was present in 24% of patients. The risk factors of hypertension (HTN) and diabetes (DM) were present in another 25.8% of the cohort. Statins were used in 36% of patients and angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) in 22%. Regarding troponin levels, 1,751 (64%) patients had an initial troponin in the normal range, while 455 (17%) had mild elevation and 530 (19%) had an elevated troponin; 173 (6.3%) patients had a troponin elevation over 1 ng/ml at any point during their hospital stay.
Cleaner data confirm severe COVID-19 link to diabetes, hypertension
The Hospitalist, July 27, 2020
Further refinement of data from patients hospitalized worldwide for COVID-19 disease showed a 12% prevalence rate of patients with diabetes in this population and a 17% prevalence rate for hypertension. These are lower rates than previously reported for COVID-19 patients with either of these two comorbidities, yet the findings still document important epidemiologic links between diabetes, hypertension, and COVID-19, said the study’s authors. A meta-analysis of data from 15,794 patients hospitalized because of COVID-19 disease that was drawn from 65 carefully curated reports published from December 1, 2019, to April 6, 2020, also showed that, among the hospitalized COVID-19 patients with diabetes (either type 1 or type 2), the rate of patients who required ICU admission was 96% higher than among those without diabetes and mortality was 2.78-fold higher, both statistically significant differences. The rate of ICU admissions among those hospitalized with COVID-19 who also had hypertension was 2.95-fold above those without hypertension, and mortality was 2.39-fold higher, also statistically significant differences, reported a team of researchers in the recently published report.
Longitudinal analyses reveal immunological misfiring in severe COVID-19
Nature, July 27, 2020
Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19). Yet, longitudinal immunological correlates of disease outcome remain unclear. Here, we serially analysed immune responses in 113 COVID-19 patients with moderate (non-ICU) and severe (ICU) disease. Immune profiling revealed an overall increase in innate cell lineages with a concomitant reduction in T cell number. We identify an association between early, elevated cytokines and worse disease outcomes. Following an early increase in cytokines, COVID-19 patients with moderate disease displayed a progressive reduction in type-1 (antiviral) and type-3 (antifungal) responses. In contrast, patients with severe disease maintained these elevated responses throughout the course of disease. Moreover, severe disease was accompanied by an increase in multiple type 2 (anti-helminths) effectors including, IL-5, IL-13, IgE and eosinophils.
COVID-19 fears would keep most Hispanics with stroke, MI symptoms home
The Hospitalist, July 27, 2020
More than half of Hispanic adults would be afraid to go to a hospital for a possible heart attack or stroke because they might get infected with SARS-CoV-2, according to a new survey from the American Heart Association. Compared with Hispanic respondents, 55% of whom said they feared COVID-19, significantly fewer Blacks (45%) and Whites (40%) would be scared to go to the hospital if they thought they were having a heart attack or stroke, the AHA said based on the survey of 2,050 adults, which was conducted May 29 to June 2, 2020, by the Harris Poll. Hispanics also were significantly more likely to stay home if they thought they were experiencing a heart attack or stroke (41%), rather than risk getting infected at the hospital, than were Blacks (33%), who were significantly more likely than Whites (24%) to stay home, the AHA reported.
Covid-19 and the cardiovascular system: a comprehensive review
Journal of Human Hypertension, July 27, 2020
The main clinical manifestations of COVID-19 are respiratory, varying from a mild presentation to acute respiratory distress syndrome (ARDS), being potentially fatal. Moreover, as in other respiratory infections, pre-existing CV diseases and risk factors can increase the severity of COVID-19, leading to the aggravation and decompensation of chronic underlying cardiac pathologies as well as acute-onset of new cardiac complications [3], highlighting that myocardial injury can be present in approximately 12% of hospitalized patients with SARS-CoV-2 infection. Within the CV manifestations of COVID-19, we can highlight four different aspects: (a) CV risk factors and established CV disease is associated with a worse prognosis, (b) appearance of acute CV complications in previously healthy individuals, (c) promising therapies with antimalarials and antivirals present important CV side effects, and (d) questioning the safety of the use of renin–angiotensin–aldosterone system (RAAS) inhibitors regarding an increased risk of COVID-19. Thus, the need to elucidate the potential pathophysiological mechanisms caused by COVID-19 and its CV repercussions becomes evident.
Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19)
JAMA Cardiology, July 27, 2020
Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown. The objective of the study was to evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness. In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020. Exposure included recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription–polymerase chain reaction on swab test of the upper respiratory tract. Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained. Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor–matched patients (n = 57).
Ischemic Stroke Risk May Be Higher in COVID-19 vs Influenza
Pulmonary Advisor, July 27, 2020
Patients hospitalized with coronavirus disease 2019 (COVID-19) had higher rates of ischemic stroke those of patients with influenza, according to study results published in JAMA Neurology. The rates of ischemic stroke were compared between patients who presented to the emergency room or who were admitted to 2hospitals in New York City for either COVID-19 or influenza. Patients were aged ≥18 years with laboratory-confirmed influenza A/B or COVID-19 infection as confirmed by evidence of severe acute respiratory syndrome coronavirus 2 in the nasopharynx by polymerase chain reaction. Of the 3402 patients with either COVID-19 or influenza in the emergency room or admitted to the hospital, 1916 had COVID-19 while 1486 had influenza. The rates of ischemic stroke were 1.6% in patients with COVID-19, while ischemic stroke occurred in 0.2% of patients with influenza. After adjustment for age, sex, and race, the likelihood of stroke remained higher with COVID-19 infection than with influenza infection (odds ratio, 7.6; 95% CI, 2.3-25.2).
Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases
JAMA Cardiology, July 27, 2020
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be documented in various tissues, but the frequency of cardiac involvement as well as possible consequences are unknown. The objective of the study was to evaluate the presence of SARS-CoV-2 in the myocardial tissue from autopsy cases and to document a possible cardiac response to that infection. This cohort study used data from consecutive autopsy cases from Germany between April 8 and April 18, 2020. All patients had tested positive for SARS-CoV-2 in pharyngeal swab tests. Cardiac tissue from 39 consecutive autopsy cases were included. The median (interquartile range) age of patients was 85 (78-89) years, and 23 (59.0%) were women. SARS-CoV-2 could be documented in 24 of 39 patients (61.5%). Viral load above 1000 copies per μg RNA could be documented in 16 of 39 patients (41.0%). A cytokine response panel consisting of 6 proinflammatory genes was increased in those 16 patients compared with 15 patients without any SARS-CoV-2 in the heart. Comparison of 15 patients without cardiac infection with 16 patients with more than 1000 copies revealed no inflammatory cell infiltrates or differences in leukocyte numbers per high power field.
The Color of COVID: Will Vaccine Trials Reflect America’s Diversity?
Kaiser Health News, July 27, 2020
Black and Latino people have been three times as likely as white people to become infected with COVID-19 and twice as likely to die, according to federal data obtained via a lawsuit by The New York Times. Asian Americans appear to account for fewer cases but have higher rates of death. Eight out of 10 COVID deaths reported in the U.S. have been of people ages 65 and older. And the Centers for Disease Control and Prevention warns that chronic kidney disease is among the top risk factors for serious infection. Historically, however, those groups have been less likely to be included in clinical trials for disease treatment, despite federal rules requiring minority and elder participation and the ongoing efforts of patient advocates to diversify these crucial medical studies. In a summer dominated by COVID-19 and protests against racial injustice, there are growing demands that drugmakers and investigators ensure that vaccine trials reflect the entire community.
Coronavirus Disease 2019 (COVID-19) and the Heart—Is Heart Failure the Next Chapter?
JAMA Cardiology, July 27, 2020
[Editorial] Multiple data sets now confirm the increased risk for morbid and mortal complications due to coronavirus disease 2019 (COVID-19) in individuals with preexisting cardiovascular diseases including hypertension, coronary artery disease, and heart failure. These salient observations have strengthened preventive strategies and undoubtedly have resulted in lives saved. Although episodes of clinical myocarditis have been suspected and a few cases have been reported in the literature, direct cardiac involvement due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been difficult to confirm. In this issue of JAMA Cardiology, Linder and colleagues report on 39 autopsy cases of patients with COVID-19 in whom pneumonia was the clinical cause of death in 35 of 39 (89.7%). While histopathologic evaluation did not meet criteria seen in acute myocarditis, there was evidence of virus present in the heart in 24 of 39 patients (61.5%) with a viral load more than 1000 copies per microgram of RNA in 16 of 24 patients (66.7%). Evidence of active viral replication was also noted. In situ hybridization suggested that the most likely localization of the viral infection was in interstitial cells or macrophages infiltrating the myocardial tissue rather than localization in the myocytes themselves. Further using a panel of 6 proinflammatory genes, the investigators demonstrated increased activity among hearts with evidence of viral infection compared with hearts with no SARS-CoV-2 viral infection detected. These new findings provide intriguing evidence that COVID-19 is associated with at least some component of myocardial injury, perhaps as the result of direct viral infection of the heart.
Florida records 9,300 new coronavirus cases, blows past New York
Reuters, July 26, 2020
Florida on Sunday became the second state after California to overtake New York, the worst-hit state at the start of the U.S. novel coronavirus outbreak, according to a Reuters tally. Total COVID-19 cases in the Sunshine State rose by 9,300 to 423,855 on Sunday, just one place behind California, which now leads the country with 448,497 cases. New York is in third place with 415,827 cases. Still, New York has recorded the most deaths of any U.S. state at more than 32,000 with Florida in eighth place with nearly 6,000 deaths. On average, Florida has added more than 10,000 cases a day in July while California has been adding 8,300 cases a day and New York has been adding 700 cases.
U.S .agency vows steps to address COVID-19 inequalities
Modern Healthcare, July 25, 2020
If Black, Hispanic and Native Americans are hospitalized and killed by the coronavirus at far higher rates than others, shouldn’t the government count them as high risk for serious illness? That seemingly simple question has been mulled by federal health officials for months. And so far the answer is no. But federal public health officials have released a new strategy that vows to improve data collection and take steps to address stark inequalities in how the disease is affecting Americans. Officials at the Centers for Disease Control and Prevention stress that the disproportionately high impact on certain minority groups is not driven by genetics. Rather, it’s social conditions that make people of color more likely to be exposed to the virus and — if they catch it — more likely to get seriously ill. “To just name racial and ethnic groups without contextualizing what contributes to the risk has the potential to be stigmatizing and victimizing,” said the CDC’s Leandris Liburd, who two months ago was named chief health equity officer in the agency’s coronavirus response. Outside experts agreed that there’s a lot of potential downside to labeling certain racial and ethnic groups as high risk.
US surpasses 1,000 COVID-19 deaths for fourth straight day
The Hill, July 25, 2020
The U.S. tallied over 1,000 coronavirus-related deaths Friday for the fourth straight day this week, yet another sign of the alarming spike in COVID-19 cases across the country. There were 1,178 new deaths Friday alone, according to the COVID Tracking project, compared with 1,038 Tuesday, 1,117 Wednesday, and 1,039 Thursday. Over 137,000 people have died in the U.S. and over 4 million people have contracted the virus in the country since the outbreak began. The alarming figures are largely driven by a surge in cases across the South and West, particularly in Arizona, California, Florida and Texas. The spikes have led to urgent calls from public health officials for Americans, particularly young people, to heed health guidance such as wearing masks and socially distancing.
COVID-19 pandemic may play critical role in increased CTA use
Cardiology Today, July 24, 2020
The COVID-19 pandemic poses several challenges for cardiac care but may be an opportunity for coronary CTA to be more widely used, according to presentations at the Society of Cardiovascular Computed Tomography Annual Scientific Meeting. The role of coronary CTA during the COVID-19 pandemic depends on the stage of disease. For the acute stage of the disease, clinicians will ask whether patients have ACS or myocardial injury. “This is an important question because 10% to 30% of patients with COVID who are admitted have elevated troponin markers,” Ron Blankstein, MD, MSCCT, FASNC, FACC, FASPC, director of cardiac computed tomography, associate director of the cardiovascular imaging program and associate physician of preventive cardiology at Brigham and Women’s Hospital, associate professor of medicine and radiology at Harvard Medical School and president of the Society of Cardiovascular Computed Tomography (SCCT), said during the presentation. In the chronic stage of the disease, coronary CTA may be used to evaluate patients who have chest pain, potentially new left ventricular dysfunction or new arrhythmias.
Cardiac CT may be safer vs. TEE during COVID-19 pandemic
Cardiology Today, July 23, 2020
Cardiac CT may be the ideal imaging technique during the COVID-19 pandemic compared with transesophageal echocardiography, according to a presentation at the Society of Cardiovascular Computed Tomography Annual Scientific Meeting. “The COVID-19 pandemic has affected and upended everything that we do in delivering cardiovascular care,” Andrew D. Choi, MD, FSCCT, co-director of cardiac CT and MRI, interventional echocardiographer and associate professor of medicine and radiology at George Washington University School of Medicine, said during the presentation.
Time to Address Race-Ethnic COVID Disparities in Seniors, Senate Panel Told
MedPage Today, July 23, 2020
Enhancing data collection, investing in research, and building trust can help mitigate the disparate impacts of the COVID-19 pandemic on Black and Latinx seniors, witnesses told members of the Senate Special Committee on Aging during a hearing on Tuesday. The pandemic’s impact on minority and ethnic groups appears most acute in young people and seems to taper off among community-dwelling older adults, Mercedes Carnethon, PhD, an epidemiologist and preventive medicine specialist at Northwestern University in Chicago, told the committee. Nevertheless, disparities persist for seniors living in congregate care settings such as nursing homes. In fact, nursing homes with a higher proportion of Black and Latinx residents have double the rates of COVID-19 infections than facilities with a greater share of non-Hispanic whites, Carnethon said. Current policies don’t require universal reporting of race or ethnicities of individuals affected by COVID-19, she said.
Association of Interleukin 7 Immunotherapy With Lymphocyte Counts Among Patients With Severe Coronavirus Disease 2019 (COVID-19)
JAMA Network Open, July 22, 2020
[Research Letter] Cytokine storm–mediated organ injury continues to dominate current thinking as the primary mechanism for coronavirus disease 2019 (COVID-19). Although there is an initial hyper-inflammatory phase, mounting evidence suggests that virus-induced defective host immunity may be the real cause of death in many patients. COVID-19 has been called a serial lymphocyte killer because profound and protracted lymphopenia is a near uniform finding among patients with severe COVID-19 and correlates with morbidity and mortality. Autopsies demonstrate a devastating depletion of lymphocytes in the spleen and other organs. CD4, CD8, and natural killer cells, which play important antiviral roles, are depleted and have reduced function, leading to immune collapse. Clinical and pathological findings in patients with COVID-19 indicate that immunosuppression is a critical determinant of outcomes.
Trends in US Heart Transplant Waitlist Activity and Volume During the Coronavirus Disease 2019 (COVID-19) Pandemic
JAMA Cardiology, July 22, 2020
How have heart transplant listings and volumes in the US changed during the coronavirus disease 2019 (COVID-19) pandemic? In this cross-sectional analysis of heart transplant data from the United Network for Organ Sharing and the US Centers for Disease Control and Prevention, compared with the pre–COVID-19 era, the total number of waitlist inactivations has increased while new waitlist additions, deceased donor recoveries, and heart transplants have decreased across the US. During the COVID-19 era, there was significant regional variation in these practices. Solid organ transplants have declined significantly during the coronavirus disease (COVID-19) pandemic in the US. Limited data exist regarding changes in heart transplant (HT). The objective of the study was to describe national and regional trends in waitlist inactivations, waitlist additions, donor recovery, and HT volume during COVID-19.
Financial Impact of COVID-19 on physicians and their practices
MJH Life Sciences, July 22, 2020
[Infographic] With over 1,600 responses from a variety of specialties, physicians weighed in on the financial impact of COVID-19 and how they are navigating the decrease in patient volume, telehealth reimbursements and financial relief. These results convey the challenges and concerns of physicians as they transition to the new normal with COVID-19. From anticipated loss in revenue to influence on headcount, the Financial Impact survey reveals the lasting repercussions COVID-19 will have practices for the remainder of 2020 and beyond.
Autopsies reveal surprising cardiac changes in COVID-19 patients
Medical Xpress, July 21, 2020
A series of autopsies conducted by LSU Health New Orleans pathologists shows the damage to the hearts of COVID-19 patients is not the expected typical inflammation of the heart muscle associated with myocarditis, but rather a unique pattern of cell death in scattered individual heart muscle cells. They report the findings of a detailed study of hearts from 22 deaths confirmed due to COVID-19 in a Research Letter published in Circulation, available here. “We identified key gross and microscopic changes that challenge the notion that typical myocarditis is present in severe SARS-CoV-2 infection,” says Richard Vander Heide, M.D., Ph.D., Professor and Director of Pathology Research at LSU Health New Orleans School of Medicine. “While the mechanism of cardiac injury in COVID-19 is unknown, we propose several theories that bear further investigation that will lead to greater understanding and potential treatment interventions.” The team of LSU Health pathologists led by Dr. Vander Heide, an experienced cardiovascular pathologist, also found that unlike the first SARS coronavirus, SARS-CoV-2 was not present in heart muscle cells. Nor were there occluding blood clots in the coronary arteries.
Seroprevalence of Antibodies to SARS-CoV-2 in 10 Sites in the United States, March 23-May 12, 2020
JAMA Internal Medicine, July 21, 2020
In this cross-sectional study of 16 025 residual clinical specimens, estimates of the proportion of persons with detectable SARS-CoV-2 antibodies ranged from 1.0% in the San Francisco Bay area (collected April 23-27) to 6.9% of persons in New York City (collected March 23-April 1). Six to 24 times more infections were estimated per site with seroprevalence than with coronavirus disease 2019 (COVID-19) case report data. For most sites, it is likely that greater than 10 times more SARS-CoV-2 infections occurred than the number of reported COVID-19 cases; most persons in each site, however, likely had no detectable SARS-CoV-2 antibodies.
Higher SARS-CoV-2 Viral Load Associated With Shorter Symptom Duration
Pulmonary Advisor, July 21, 2020
Viral load (VL) of severe acute respiratory syndrome coronavirus 2 is lower in hospitalized patients, and higher VL is associated with a shorter duration of symptoms and hospital stay, according to a study published online July 2 in The American Journal of Pathology. Kimon V. Argyropoulos, M.D., from NYU Langone Health in New York City, and colleagues examined the associations between VL and parameters such as symptom severity, disposition, length of hospitalization, and admission to the intensive care unit in a cohort of 205 patients from a tertiary care center. The researchers found that after adjustment for age, sex, race, body mass index, and comorbidities, diagnostic VL was significantly lower in hospitalized than nonhospitalized patients (log10 VL, 3.3 versus 4.0). In all patients and hospitalized patients only, higher VL was associated with a shorter duration of symptoms and shorter hospital stay. There was no significant association noted between VL, intensive care unit admission, length of oxygen support, and overall survival.
HHS Rolls Out New COVID-19 Data Dashboard
MedPage Today, July 21, 2020
The Department of Health and Human Services (HHS) debuted its new COVID-19 dashboard on Monday, and the department’s data chief said it will provide even more data than the CDC’s old one did. Called the Coronavirus Data Hub, the HHS dashboard replaces the CDC’s National Healthcare Safety Network (NHSN), to which states and hospitals had previously been submitting COVID-19 data such as intensive care unit capacity, ventilator use, personal protective equipment (PPE) levels, and staffing shortages. But in guidance to hospitals, updated July 10 and published with little fanfare, HHS ordered hospitals to stop submitting such data to the NHSN and instead submit it either to HHS or to their state health department, which would then submit it to HHS. The data would then be put on the dashboard via the department’s new HHS Protect data system. The dashboard’s public-facing side allows users to see the overall number of confirmed coronavirus cases in the U.S. as well as the overall number of reported deaths. It also includes data on inpatient and ICU bed utilization.
As Coronavirus Patients Skew Younger, Tracing Task Seems All But Impossible
Kaiser Health News, July 20, 2020
Younger people are less likely to be hospitalized or die of COVID-19 than their elders, but they circulate more freely while carrying the disease, and their cases are harder to trace. Together, these facts terrify California hospital officials. People under 50 make up 73% of those testing positive for the disease in the state since the beginning of June, compared with 52% before April 30. That shift isn’t comforting to Dr. Alan Williamson, chief medical officer of Eisenhower Health in Riverside County’s Coachella Valley. “It honestly worries me more because it means that this is now established in the community,” he said. As the virus spreads throughout the United States, figuring out how patients were exposed becomes increasingly difficult, which makes it nearly impossible to stop viral transmission. Younger people with COVID-19 are also less likely to pick up the phone when a contact tracer calls, health officials say.
Synairgen’s Inhaled COVID-19 Treatment Appears to Decrease Disease Risk by 79%
BioSpace, July 20, 2020
A small biotech company in Southampton, UK, Synairgen, announced positive results from a clinical trial of its wholly-owned inhaled formulation of interferon beta in COVID-19 patients. Company shares exploded 373% at the news. The company indicated its nebulizer treatment resulted in a 79% lower risk of patients developing severe disease compared to those receiving a placebo. And the patients receiving the treatment “were more than twice as likely to recover (defined as ‘no limitation of activities’ or ‘no clinical or virological evidence of infection’) over the course of the treatment period compared to those receiving placebo.” It’s worth noting that the p-value of the 79% figure was 0.046, which only provides a narrow margin for being statistically significant. P-value, or probability value, is a determination of statistical value.
As Coronavirus Patients Skew Younger, Tracing Task Seems All But Impossible
Kaiser Health News, July 20, 2020
Younger people are less likely to be hospitalized or die of COVID-19 than their elders, but they circulate more freely while carrying the disease, and their cases are harder to trace. Together, these facts terrify California hospital officials. People under 50 make up 73% of those testing positive for the disease in the state since the beginning of June, compared with 52% before April 30. That shift isn’t comforting to Dr. Alan Williamson, chief medical officer of Eisenhower Health in Riverside County’s Coachella Valley. “It honestly worries me more because it means that this is now established in the community,” he said. As the virus spreads throughout the United States, figuring out how patients were exposed becomes increasingly difficult, which makes it nearly impossible to stop viral transmission. Younger people with COVID-19 are also less likely to pick up the phone when a contact tracer calls, health officials say.
Key Points About Myocardial Injury and Cardiac Troponin in COVID-19
American College of Cardiology, July 17, 2020
The coronavirus disease 2019 (COVID-19) pandemic has affected >8 million patients and caused >400 thousand deaths to date.1 Recent reports indicate that myocardial injury is frequent among patients with COVID-19. Here we summarize 10 key points about myocardial injury and COVID-19.
Mavrilimumab Improves Clinical Outcomes in Severe COVID-19 Pneumonia
Pulmonology Advisor, July 17, 2020
Treatment with mavrilimumab is associated with improved clinical outcomes compared with standard care in non-mechanically ventilated patients with severe coronavirus disease 2019 (COVID-19) pneumonia and systemic hyperinflammation, according to the results of a single-center prospective cohort study published in The Lancet Rheumatology. Hyperinflammation, with its excessive cytokine production (known as a cytokine storm), has been identified as a key factor of poor prognosis in patients with COVID-19-related severe pneumonia, leading to high frequencies of respiratory failure and mortality. Therefore, researchers investigated whether mavrilimumab, an anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor-α monoclonal antibody, added to standard management, improves clinical outcomes in patients with COVID-19 pneumonia and systemic hyperinflammation.
Coronary Artery Calcification and Complications in COVID-19 Patients
American College of Cardiology, July 17, 2020
This cross-sectional study was conducted from March 15-May 3, 2020 in consecutive patients 40-80 years of age without cardiovascular disease (CVD) who were hospitalized with COVID-19 and had a noncontrast chest computed tomography (CT) on the day of admission. The presence or absence of CAC (CAC+ and CAC-, respectively) was defined as any area ≥1 mm2 with a density >130 Hounsfield units along the known coronary tract. There was no ECG gating. Primary outcome segmented by median age was the first occurrence of mechanical noninvasive or invasive ventilation, extracorporeal membrane oxygenation (ECMO), or death within 30 days of admission. The presence and extent of CAC is associated with a worse prognosis in hospitalized COVID-19 patients. The severity of immune response, endothelial dysfunction, and myocardial stress due to COVID-19 could be exacerbated in patients with subclinical coronary atherosclerosis.
WHO reports record total of new coronavirus cases worldwide
The Hill, July 17, 2020
The World Health Organization (WHO) on Friday reported a record number of daily coronavirus cases worldwide with the U.S. leading other nations in the spike. In a daily report, WHO reported 237,743 new COVID-19 cases in the last 24 hours, surpassing the previous single-day record of 230,370 on July 12. There were 5,682 more deaths in the past day. There have been more than 13.6 million confirmed coronavirus cases around the globe since the pandemic began. The U.S. had the highest number of new cases out of any other country with more than 67,000, almost doubling the nearly 35,000 new cases in India, which had the second-most cases in the last 24 hours. The record-breaking total comes as states across the U.S., particularly in the South and West, see alarming spikes in COVID-19 cases. Texas reported roughly 10,000 new cases Thursday for the third day in a row, while California tallied nearly 20,000 new cases over the last two days. Florida also saw nearly 14,000 new cases Thursday.
Evidence used to update the list of underlying medical conditions that increase a person’s risk of severe illness from COVID-19
Centers for Disease Control and Prevention, July 17, 2020
Updates to the list of underlying medical conditions that put individuals at increased risk for severe illness from COVID-19 were based on published reports, articles in press, unreviewed pre-prints, and internal data available between December 1, 2019 and May 29, 2020. This list is a living document that will be periodically updated by CDC, and it could rapidly change as the science evolves. Severe illness from COVID-19 was defined as hospitalization, admission to the ICU, intubation or mechanical ventilation, or death. The level of evidence for each condition was determined by CDC reviewers based on available information about COVID-19. Conditions were added to the list (if not already on the previous underlying medical conditions list [originally released in March 2020]) if evidence for an association with severe illness from COVID-19 met any of the criteria listed.
Racial/Ethnic Disparities in Disease Severity on Admission Chest Radiographs among Patients Admitted with Confirmed COVID-19: A Retrospective Cohort Study
Radiology, July 16, 2020
Disease severity on chest radiographs (CXR) has been associated with higher risk of disease progression and adverse outcomes from COVID-19. Few studies have evaluated COVID-19-related racial/ethnic disparities in radiology. This study evaluated whether Non-White minority patients hospitalized with confirmed COVID-19 infection presented with increased severity on admission CXR compared with White/Non-Hispanic patients. This single-institution, retrospective cohort study was approved by the IRB. Patients hospitalized with confirmed COVID-19 infection (3/27/20-4/10/20) were identified using the electronic medical record (EMR) (n=326, mean age: 59 years (SD: 17 years), M:F (188:138). Primary outcome was severity of lung disease on admission CXR, measured by modified Radiographic Assessment of Lung Edema (mRALE) score. Secondary outcome was a composite adverse clinical outcome of intubation, ICU admission, or death. Primary exposure was racial/ethnic category: White/Non-Hispanic versus Non-White [i.e., Hispanic, Black, Asian, Other]. Multivariable linear regression analyses were performed to evaluate the association between mRALE scores and race/ethnicity. Read the results.
As Coronavirus Patients Skew Younger, Tracing Task Seems All But Impossible
Kaiser Health News, July 20, 2020
Younger people are less likely to be hospitalized or die of COVID-19 than their elders, but they circulate more freely while carrying the disease, and their cases are harder to trace. Together, these facts terrify California hospital officials. People under 50 make up 73% of those testing positive for the disease in the state since the beginning of June, compared with 52% before April 30. That shift isn’t comforting to Dr. Alan Williamson, chief medical officer of Eisenhower Health in Riverside County’s Coachella Valley. “It honestly worries me more because it means that this is now established in the community,” he said. As the virus spreads throughout the United States, figuring out how patients were exposed becomes increasingly difficult, which makes it nearly impossible to stop viral transmission. Younger people with COVID-19 are also less likely to pick up the phone when a contact tracer calls, health officials say.
SARS-CoV-2 and the cardiovascular system
Clinica Chimica Acta, July 19, 2020
The coronavirus disease COVID-19 is a public health emergency caused by a novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 infection uses the angiotensin-converting enzyme 2 (ACE2) receptor, and typically spreads through the respiratory tract. Invading viruses can elicit an exaggerated host immune response, frequently leading to a cytokine storm that may be fueling some COVID-19 death. This response contributes to multi-organ dysfunction. Accumulating data points to an increased cardiovascular disease morbidity, and mortality in COVID-19 patients. This brief review explores potential available evidence regarding the association between COVID-19, and cardiovascular complications.
Coagulopathy in COVID-19: Focus on vascular thrombotic events
Journal of Molecular and Cellular Cardiology, July 19, 2020
SARS-CoV-2 causes a phenotype of pneumonia with diverse manifestation, which is termed as coronavirus disease 2019 (COVID-19). An impressive high transmission rate allows COVID-19 conferring enormous challenge for clinicians worldwide, and developing to a pandemic level. Combined with a series of complications, a part of COVID-19 patients progress into severe cases, which critically contributes to the risk of fatality. To date, coagulopathy has been found as a prominent feature of COVID-19 and severe coagulation dysfunction may be associated with poor prognosis. Coagulopathy in COVID-19 may predispose patients to hypercoagulability-related disorders including thrombosis and even fatal vascular events. Inflammatory storm, uncontrolled inflammation-mediated endothelial injury and renin angiotensin system (RAS) dysregulation are the potential mechanisms. Ongoing efforts made to develop promising therapies provide several potential strategies for hypercoagulability in COVID-19. In this review, we introduce the clinical features of coagulation and the increased vascular thrombotic risk conferred by coagulopathy according to present reports about COVID-19. The potential underlying mechanisms and emerging therapeutic avenues are discussed, emphasizing an urgent need for effective interventions.
WHO reports record total of new coronavirus cases worldwide
The Hill, July 17, 2020
The World Health Organization (WHO) on Friday reported a record number of daily coronavirus cases worldwide with the U.S. leading other nations in the spike. In a daily report, WHO reported 237,743 new COVID-19 cases in the last 24 hours, surpassing the previous single-day record of 230,370 on July 12. There were 5,682 more deaths in the past day. There have been more than 13.6 million confirmed coronavirus cases around the globe since the pandemic began. The U.S. had the highest number of new cases out of any other country with more than 67,000, almost doubling the nearly 35,000 new cases in India, which had the second-most cases in the last 24 hours. The record-breaking total comes as states across the U.S., particularly in the South and West, see alarming spikes in COVID-19 cases. Texas reported roughly 10,000 new cases Thursday for the third day in a row, while California tallied nearly 20,000 new cases over the last two days. Florida also saw nearly 14,000 new cases Thursday.
Evidence used to update the list of underlying medical conditions that increase a person’s risk of severe illness from COVID-19
Centers for Disease Control and Prevention, July 17, 2020
Updates to the list of underlying medical conditions that put individuals at increased risk for severe illness from COVID-19 were based on published reports, articles in press, unreviewed pre-prints, and internal data available between December 1, 2019 and May 29, 2020. This list is a living document that will be periodically updated by CDC, and it could rapidly change as the science evolves. Severe illness from COVID-19 was defined as hospitalization, admission to the ICU, intubation or mechanical ventilation, or death. The level of evidence for each condition was determined by CDC reviewers based on available information about COVID-19. Conditions were added to the list (if not already on the previous underlying medical conditions list [originally released in March 2020]) if evidence for an association with severe illness from COVID-19 met any of the criteria listed.
Racial/Ethnic Disparities in Disease Severity on Admission Chest Radiographs among Patients Admitted with Confirmed COVID-19: A Retrospective Cohort Study
Radiology, July 16, 2020
Disease severity on chest radiographs (CXR) has been associated with higher risk of disease progression and adverse outcomes from COVID-19. Few studies have evaluated COVID-19-related racial/ethnic disparities in radiology. This study evaluated whether Non-White minority patients hospitalized with confirmed COVID-19 infection presented with increased severity on admission CXR compared with White/Non-Hispanic patients. This single-institution, retrospective cohort study was approved by the IRB. Patients hospitalized with confirmed COVID-19 infection (3/27/20-4/10/20) were identified using the electronic medical record (EMR) (n=326, mean age: 59 years (SD: 17 years), M:F (188:138). Primary outcome was severity of lung disease on admission CXR, measured by modified Radiographic Assessment of Lung Edema (mRALE) score. Secondary outcome was a composite adverse clinical outcome of intubation, ICU admission, or death. Primary exposure was racial/ethnic category: White/Non-Hispanic versus Non-White [i.e., Hispanic, Black, Asian, Other]. Multivariable linear regression analyses were performed to evaluate the association between mRALE scores and race/ethnicity. Read the results.
COVID-19 and high blood pressure: Why hypertension patients can be severely affected by the disease
Firstpost, July 16, 2020
COVID-19 was first reported in Wuhan, Hubei Province, China on the 31 December 2019. Since then, much research has been done into establishing who is the most vulnerable to this new disease and how can the disease’s impact be reduced for these at-risk populations. COVID-19 patients who have other underlying conditions or comorbidities are one of the groups which are most vulnerable to having complications if they contract the infection. As per some reports, the most common comorbidities are hypertension (30 percent), diabetes (19 percent) and coronary heart disease (8 percent). About 99 percent of COVID-19 patients who died in Italy had either hypertension or other diseases like cancer, diabetes or other lung diseases. About 76 percent of these were patients who were suffering from high BP. What needs to be noted is that nearly two-thirds of the world population above the age of 60 have hypertension. Another possible reason why people with hypertension are at a higher risk is the drugs they use to treat the disease and not the disease itself. Hypertension and other cardiovascular diseases which are often found in COVID-19 patients are treated with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). Both these drugs increase the level of ACE2 in the body and COVID-19 viruses attach themselves to this enzyme to infect the cells.
Among patients with stroke, outcomes worse in those with COVID-19
Helio | Cardiology Today, July 16, 2020
Ischemic stroke in patients with COVID-19 conferred greater mortality and worse functional outcomes than stroke in patients without COVID-19, according to a report published in Stroke. “The association between COVID-19 and severe stroke highlights the urgent need for studies aiming to uncover the underlying mechanisms and is relevant for prehospital stroke awareness and in-hospital acute stroke pathways during the current and future pandemics, since severe strokes have typically poor prognosis and can potentially be treated with recanalization techniques,” George Ntaios, MD, MSc, PhD, from the department of internal medicine of the School of Health Sciences at the University of Thessaly in Larissa, Greece, and colleagues wrote. For this analysis, researchers pooled consecutive patients hospitalized with COVID-19 and stroke from 28 sites in 16 countries (n = 174; median age, 71 years; 38% women) and performed a 1-to-1 propensity score matching analyses with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne project from 2003 to 2019. Researchers observed that the median NIH Stroke Scale score was higher in patients with COVID-19 (OR = 1.69; 95% CI, 1.08-2.65) compared with patients without COVID-19.
COVID-19 and the heart: Searching for the location of the SARS-CoV-2 receptor
Medical Xpress, July 15, 2020
Nearly 20% of all COVID-19-associated deaths are from cardiac complications, yet the mechanisms from which these complications arise have remained a topic of debate in the cardiology community. One hypothesis centers on the infection of the heart itself, but the understanding of which cells may be infected is unclear. To address this, MMRI Assistant Professor Dr. Nathan Tucker, in collaboration with the Broad Institute, the University of Pennsylvania, and Bayer US, report the distribution of the SARS-CoV-2 receptor in a manuscript titled, “Myocyte upregulation of ACE2 in cardiovascular disease” published in the journal, Circulation. COVID-19 (SARS-CoV-2) infects cells through a particular cellular molecule, termed ACE2. To assess levels of this molecule in different patient populations and in response to common hypertension medications (ACE inhibitors), the group applied state-of-the-art single nucleus sequencing technologies in human heart samples.
COVID19 and increased mortality in African Americans: socioeconomic differences or does the renin angiotensin system also contribute?
Journal of Human Hypertension, July 15, 2020
The dawn of the new decade is marked by the emergence of the novel coronavirus SARS-CoV-2, whose spread has resulted in the COVID-19 pandemic, having already affected millions of individuals and resulted in hundreds of thousands of deaths worldwide. While the pandemic situation is constantly evolving, alarming signals have arisen during the past few weeks from the United States of America, which now represents the world’s most affected country, as disproportionally higher infection and mortality rates in African–Americans compared to other races were reported in some states. After these initial reports that raised public awareness, most states gradually started sharing data regarding confirmed cases and deaths by race. Most of them have reported higher infection rates in African–Americans, although data regarding confirmed COVID-19 cases by race are largely incomplete. Furthermore, based on current estimates, it is calculated that overall African–Americans suffer from a 2.4 and 2.2 times higher mortality rate when compared to Whites and Asians or Latinos, respectively. The higher mortality rate in African–Americans raises questions about the underlying mechanisms behind these racial disparities. Several known mechanisms might be implicated, including increased comorbidities, inequalities in healthcare access, and socioeconomic factors. However, we propose that another mechanism might be also implicated: the renin-angiotensin system.
UTHealth physicians investigate blood pressure drug’s effect on improving COVID-19 outcomes
News Medical, July 14, 2020
An interventional therapy aimed at improving survival chances and reducing the need for critical care treatment due to COVID-19 is being investigated by physicians at The University of Texas Health Science Center at Houston (UTHealth). The clinical trial is underway at Memorial Hermann and Harris Health System’s Lyndon B. Johnson Hospital. The randomized, double-blind, placebo-controlled study is evaluating the effectiveness of the drug ramipril, an angiotensin-converting enzyme (ACE) inhibitor approved to treat high blood pressure, heart failure, and diabetic kidney disease. The yearlong trial aims to enroll up to 560 patients across the nation with COVID-19. A positive COVID-19 test is required before the medication is administered. Experts are investigating whether ACE inhibitors can reduce the severity of COVID-19 by ensuring the renin-angiotensin-aldosterone system (RAAS) functions properly. RAAS is the hormone system responsible for regulating blood pressure, electrolyte and fluid balance, and overall circulatory system flow.
FDA Fast-Tracks Two mRNA-Based COVID-19 Vaccine Candidates
Monthly Prescribing Reference, July 13, 2020
The Food and Drug Administration (FDA) has granted Fast Track designation to 2 of Pfizer and BioNTech’s vaccine candidates against coronavirus disease 2019 (COVID-19). The vaccine candidates, BNT162b1 and BNT162b2, are both nucleoside-modified messenger RNA (modRNA) vaccines. BNT162b1 encodes an optimized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein receptor binding domain (RBD) antigen, while BNT162b2 encodes an optimized SARS-CoV-2 full-length spike protein antigen. The Companies recently announced positive preliminary results from a phase 1/2 study evaluating BNT162b1. Initial findings from the US trial showed the vaccine candidate produced neutralizing antibody responses similar to those seen in convalescent human serology samples obtained from patients with confirmed SARS-CoV-2 infection. Data from a similar trial in Germany is expected to be released in July. If regulatory approval is granted, a phase 2b/3 trial, which may include upwards of 30,000 individuals, could begin this July after an appropriate dose level is determined.
Considerations on cardiac patients during Covid‐19 outbreak
Echocardiography, July 12, 2020
[Letter to the Editor] The ongoing coronavirus disease (Covid‐19) pandemic has challenged globalized society to cope with the adoption of revolutionary healthcare measures. The severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) not only causes viral pneumonia but also acute myocardial injury and chronic damage to the cardiovascular system. Currently, treating patients with cardiovascular disease (CVD) has become more challenging. A network of “hub ” and “spoke ” centers based on a system of specialized Covid‐19 referral hospitals has been organized, in order to guarantee optimal medical care for patients with cardiac and noncardiac emergencies. Indeed, in Lombardy, Italy (the epicenter of the European outbreak), the ST‐elevation myocardial infarction (STEMI) regional network has been rearranged, reducing by more than 75% the number of previous “hub ” centers with 24 hours a day—7 days a week capacity to perform primary percutaneous coronary interventions (PCI), with 13 hospitals acting as “hubs ” and other 42 acting as “spokes. ” The most vulnerable Covid‐19‐free subjects, such as patients with chronic cardiac disorders (ie, heart failure), have not routinely been followed‐up in the hospital facilities during the pandemic. A rapid reorganization of cardiac services and practical guidance on how to manage chronic patients are needed in the shortest time. Telemedicine and telecardiology, integrated with the traditional management, appear to be precious tools for this emergent medical model, focused on the interplay between social, economic, environmental, and clinical factors.
COVID-19, coagulopathy and venous thromboembolism: more questions than answers
Internal and Emergency Medicine, July 11, 2020
The acute respiratory illnesses caused by severe acquired respiratory syndrome corona Virus-2 (SARS-CoV-2) is a global health emergency, involving more than 8.6 million people worldwide with more than 450,000 deaths. Among the clinical manifestations of COVID-19, the disease that results from SARS-CoV-2 infection in humans, a prominent feature is a pro-thrombotic derangement of the hemostatic system, possibly representing a peculiar clinicopathologic manifestation of viral sepsis. The severity of the derangement of coagulation parameters in COVID-19 patients has been associated with a poor prognosis, and the use of low molecular weight heparin (LMWH) at doses registered for prevention of venous thromboembolism (VTE) has been endorsed by the World Health Organization and by Several Scientific societies. This review is particularly focused on four clinical questions: What is the incidence of VTE in COVID-19 patients? How do we frame the COVID-19 associated coagulopathy? Which role, if any, do antiphospolipid antibodies have? How do we tackle COVID-19 coagulopathy? In the complex scenario of an overwhelming pandemic, most everyday clinical decisions have to be taken without delay, although not yet supported by a sound scientific evidence.
SARS-CoV-2 a dagger to the aging heart
News Medical, July 9, 2020
Researchers in Europe have shown that genes involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are expressed to a higher degree in older heart muscle cells (cardiomyocytes) than they are in younger cardiomyocytes. The team found that genes encoding the proteins involved in host cell viral entry, including angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) were upregulated in aged cardiomyocytes compared to young adult cardiomyocytes. Risk factors for adverse outcomes following SARS-CoV-2 infection include age over 70 years and comorbidity, particularly cardiovascular disease. Anthony Davenport (University of Cambridge) and colleagues say their findings could inform studies investigating experimental or currently available compounds to understand further how the protein pathways in cardiomyocytes contribute to disease outcomes in older patients with coronavirus disease 2019 (COVID-19). NOTE: This report by bioRxiv is published as a preliminary scientific report that is not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Stroke risk higher in COVID-19 vs. influenza
Cardiology Today, July 9, 2020
Patients who visited the ED or were hospitalized for COVID-19 had a higher risk for ischemic stroke compared with those with ED visits or hospitalizations for influenza, researchers found. “We found that COVID-19 was associated with a far greater risk for stroke than the flu and stress the importance of combating this deadly disease,” Alexander E. Merkler, MD, assistant professor of neurology and neuroscience at Weill Cornell Medicine, told Healio. “Our findings highlight the fact that COVID is not the same as the flu. COVID is far more serious, as we found that COVID is associated with an almost eightfold higher risk for stroke than the flu.” In this retrospective cohort study published in JAMA Neurology, researchers analyzed data from 1,916 patients who visited the ED or were hospitalized for COVID-19 between March 4 and May 2. This group was compared with 1,486 patients who visited the ED or were hospitalized for influenza between January 2016 and May 2018.
U.S. sets one-day record with more than 60,500 COVID cases; Americans divided
Reuters, July 9, 2020
More than 60,500 new COVID-19 infections were reported across the United States on Thursday, according to a Reuters tally, setting a one-day record as weary Americans were told to take new precautions and the pandemic becomes increasingly politicized. The total represents a slight rise from Wednesday, when there were 60,000 new cases, and marks the largest one-day increase by any country since the pandemic emerged in China last year. As infections rose in 41 of the 50 states over the last two weeks, Americans have become increasingly divided on issues such as the reopening of schools and businesses. Orders by governors and local leaders mandating face masks have become particularly divisive. “It’s just disheartening because the selfishness of (not wearing a mask) versus the selflessness of my staff and the people in this hospital who are putting themselves at risk, and I got COVID from this,” said Dr. Andrew Pastewski, ICU medical director at Jackson South Medical Center in Miami.
Incidence of Stress Cardiomyopathy During the Coronavirus Disease 2019 Pandemic
JAMA Network Open, July 9, 2020
The coronavirus disease 2019 (COVID-19) pandemic has resulted in severe psychological, social, and economic stress in people’s lives. It is not known whether the stress of the pandemic is associated with an increase in the incidence of stress cardiomyopathy. The objective of the study was to determine the incidence and outcomes of stress cardiomyopathy during the COVID-19 pandemic compared with before the pandemic. This retrospective cohort study at cardiac catheterization laboratories with primary percutaneous coronary intervention capability at 2 hospitals in the Cleveland Clinic health system in Northeast Ohio examined the incidence of stress cardiomyopathy (also known as Takotsubo syndrome) in patients presenting with acute coronary syndrome who underwent coronary arteriography. Patients presenting during the COVID-19 pandemic, between March 1 and April 30, 2020, were compared with 4 control groups of patients with acute coronary syndrome presenting prior to the pandemic across 4 distinct timelines: March to April 2018, January to February 2019, March to April 2019, and January to February 2020.
COVID‐19 and hypertension—evidence and practical management: Guidance from the HOPE Asia Network
The Journal of Clinical Hypertension, July 9, 2020
There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID‐19). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin‐angiotensin system (RAS) inhibitors due to a key role of angiotensin‐converting enzyme 2 receptors in the entry of the SARS‐CoV‐2 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS‐CoV‐2 virus infection or worsens the course of COVID‐19. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID‐19 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N‐terminal pro‐B‐type natriuretic peptide, D‐dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID‐19 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well‐being.
Late Coronary Stent Thrombosis in a Patient With Coronavirus Disease 2019
JAMA Cardiology | Research Letter, July 8, 2020
The excessive inflammatory response and hypercoaguable state associated with coronavirus disease 2019 (COVID-19) might trigger acute coronary events or stent thrombosis. However, cases of stent thrombosis directly associated with COVID-19 have not been reported. We describe a patient with COVID-19 developing late drug-eluting stent thrombosis. Academic ethics committee approval was waived because this was a single-case report; written informed consent was obtained from the patient. An 81-year-old man with hypertension, coronary artery disease, and recent COVID-19 infection presented in April 2020 with an anterior ST-segment elevation myocardial infarction. Five years prior to admission, following a myocardial infarction, drug-eluting stents were implanted in his left main to left anterior descending coronary artery (LAD), circumflex coronary artery, and right coronary artery. Three months prior to admission, an exercise test with a positive result led to the implantation of a durable-polymer ridaforolimus drug-eluting stent (3 × 15 mm) in a de novo lesion in the proximal left anterior descending coronary artery, overlapping with the stent coming from the left main coronary artery. He was compliant with a dual antiplatelet regimen of aspirin and clopidogrel. Ten days prior to admission, he was admitted to another hospital for dyspnea and fever, with a final diagnosis of COVID-19 with bilateral pneumonia.
Cardiac Arrhythmias Seen in Critically Ill Patients With COVID-19
Pulmonary Advisor, July 8, 2020
Critically ill patients with COVID-19 are more likely to develop heart rhythm disorders than other hospitalized patients, according to a study published online June 22 in Heart Rhythm. Anjali Bhatla, from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues reviewed the incidence of cardiac arrests, arrhythmias, and inpatient mortality among 700 COVID-19 patients (mean age 50 years; 45 percent male) admitted to one center over a nine-week period. The researchers found that 11 percent of patients received care in the intensive care unit (ICU), and there were nine cardiac arrests (all occurring in ICU patients), 25 incident atrial fibrillation (AF) events, nine clinically significant bradyarrhythmias, and 10 nonsustained ventricular tachycardias (NSVTs). Admission to the ICU was associated with incident AF (odds ratio, 4.68) and NSVT (odds ratio, 8.92) in adjusted analysis. There were also independent associations seen between age and incident AF (odds ratio, 1.05) and between prevalent heart failure and bradyarrhythmias (odds ratio, 9.75). In-hospital mortality was only associated with cardiac arrest.
Changes in Blood Platelets Triggered by COVID-19 Could Trigger Heart Attacks, Strokes
Journal of Invasive Cardiology, July 6, 2020
Changes in blood platelets triggered by COVID-19 could contribute to the onset of heart attacks, strokes, and other serious complications in some patients who have the disease, according to University of Utah Health scientists. The researchers found that inflammatory proteins produced during infection significantly alter the function of platelets, making them “hyperactive” and more prone to form dangerous and potentially deadly blood clots. They say better understanding the underlying causes of these changes could possibly lead to treatments that prevent them from happening in COVID-19 patients. Their report appears in Blood, an American Society of Hematology journal. “Our finding adds an important piece to the jigsaw puzzle that we call COVID-19,” says Robert A. Campbell, Ph.D., senior author of the study and an assistant professor in the Department of Internal Medicine. “We found that inflammation and systemic changes, due to the infection, are influencing how platelets function, leading them to aggregate faster, which could explain why we are seeing increased numbers of blood clots in COVID patients.”
Effect of hypertension on outcomes of adult inpatients with COVID-19 in Wuhan, China: a propensity score–matching analysis
Respiratory Research, July 6, 2020
Participants enrolled in this study were patients with COVID-19 who had been hospitalized at the Central Hospital of Wuhan, China. Chronic comorbidities and laboratory and radiological data were reviewed; patient outcomes and lengths of stay were obtained from discharge records. We used the Cox proportional-hazard model (CPHM) to analyze the effect of hypertension on these patients’ outcomes and PSM analysis to further validate the abovementioned effect. A total of 226 patients with COVID-19 were enrolled in this study, of whom 176 survived and 50 died. The proportion of patients with hypertension among non-survivors was higher than that among survivors (26.70% vs. 74.00%; P < 0.001). Results obtained via CPHM showed that hypertension could increase risk of mortality in COVID-19 patients (hazard ratio 3.317; 95% CI [1.709–6.440]; P < 0.001). Increased D-dimer levels and higher ratio of neutrophils to lymphocytes (N/L) were also found to increase these patients’ mortality risk. After matching on propensity score, we still came to similar conclusions. After we applied the same method in critically ill patients, we found that hypertension also increased risk of death in patients with severe COVID-19.
Guidelines for Family Presence Policies During the COVID-19 Pandemic
JAMA Health Forum, July 6, 2020
Active engagement of patients and their families in decisions about their own care is a foundation of a high-quality, person-centered health care system. Expanding the acceptance and participation of family care partners at the bedside has been an ongoing effort by patient advocacy communities over the past several decades. In this context, family refers to any support person defined by the patient or resident as family, including friends, neighbors, relatives, and/or professional support persons. Great progress has been made to invite partners into the labor and delivery room, to welcome parents to stay at their child’s side throughout a hospitalization, and to honor the wishes of terminally ill individuals to have family with them during end-of-life care. Significant clinical, psychological, and emotional benefits of these practices have been well documented for patients, family, and health care professionals. The National Academy of Medicine has asserted the importance that “family and/or care partners are not kept an arm’s length away as spectators but participate as integral members of their loved one’s care team.”
Q&A: With or without COVID-19, we will transform the care delivery system
Modern Healthcare, July 6, 2020
Dr. Sanjay Doddamani is chief operating officer and chief physician executive at Southwestern Health Resources, a clinically integrated network comprising independent community practices together with Texas Health Resources and the University of Texas Southwestern Medical Center in the Dallas-Fort Worth area. He started in his role in mid-March, just weeks before a national emergency was declared due to the COVID-19 outbreak. He previously served as senior physician adviser at the Center for Medicare and Medicaid Innovation and was chief medical officer for the accountable care organization and the home-based program at Geisinger Health. Read this Q&A session with Dr. Doddamani about Southwestern’s experience and the network’s approach to dealing with the pandemic and the organization’s emphasis on value-based care.
Hundreds of scientists say coronavirus is airborne, ask WHO to revise recommendations: NYT
Reuters, July 5, 2020
Hundreds of scientists say there is evidence that the novel coronavirus in smaller particles in the air can infect people and are calling for the World Health Organization to revise recommendations, the New York Times reported on Saturday. The WHO has said the coronavirus disease spreads primarily from person to person through small droplets from the nose or mouth, which are expelled when a person with COVID-19 coughs, sneezes or speaks. In an open letter to the agency, which the researchers plan to publish in a scientific journal next week, 239 scientists in 32 countries outlined the evidence showing smaller particles can infect people, the NYT said.
Potential effective treatment for COVID-19: systematic review and meta-analysis of the severe infectious disease with convalescent plasma therapy
International Journal of Infectious Diseases, July 4, 2020
Convalescent plasma (CP) has been used successfully to treat many types of infectious diseases, and it has shown initial effects in the treatment of the emerging 2019 coronavirus disease (COVID-19). However, its curative effect and feasibility have yet to be confirmed by formal evaluation and well-designed clinical trials. To explore the effectiveness of treatment and predict the potential effect of CP for COVID-19, studies of different types of infectious diseases treated with CP were included in this systematic review and meta-analysis. Related studies were obtained from databases and screened based on the inclusion criteria. The data quality was assessed, and the data were extracted and pooled for analysis.
Coronavirus Update With Anthony Fauci
JAMA Network, July 2, 2020
Editor in Chief of JAMA, Howard Bauchner, MD, interviews Anthony Fauci, MD, White House Coronavirus Task Force member and Director of the National Institutes of Allergy and Infectious Diseases. The two discuss latest developments in the COVID-19 pandemic, including latest developments, protecting the elderly, genetic shift and mutations, vaccine durability and more.
Moving From The Five Whys To Five Hows: Addressing Racial Inequities In COVID-19 Infection And Death
Health Affairs, July 2, 2020
In recent months, states and municipalities have begun releasing data on COVID-19 infections and death that reveal profound racial disparities. In Louisiana, Black patients account for 57 percent of COVID-19 deaths, while making up only 33 percent of the total population. In Wisconsin, Hispanic patients constitute 12 percent of confirmed COVID-19 cases, but only 7 percent of the total population. In New York City, the epicenter of the pandemic in the US, age-adjusted mortality rates are more than double for Black and Hispanic patients (243.6 and 237.7 per 100,000) compared to white and Asian patients (121.5 and 109.4 per 100,000). Studies of patients hospitalized across New York have found that hypertension, diabetes, and obesity are associated with an elevated risk for COVID-19 morbidity and mortality. But why are there higher rates of hypertension, diabetes, and obesity in communities of color? The answer does not lie in biology. Here again, structural and environmental factors such as resource deprivation, poor access to health care, discrimination, and racism have driven a higher burden of these diseases in communities of color.
US posts largest single-day jump in new COVID-19 cases
Center for Infectious Disease and Research Policy (CIDRAP) News, July 2, 2020
The Centers for Disease Control and Prevention (CDC) today reported a record of 54,357 new coronavirus cases over yesterday—a record single-day jump that presses the United States further than what some thought was the peak this spring. For reference, as CNN reported, it took the United States a little more than 2 months to report its first 50,000 cases. Total US cases were at 2,679,230, including 128,024 deaths, according to the CDC. The infection curve is rising in 40 of 50 states, and 36 states are seeing an increase in the percentage of positive coronavirus tests, AP reported today. Some public health officials and governors are blaming bars for the increase in cases, the New York Times reported today, while others are pointing to hasty business reopenings, according to Politico.
Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza
JAMA Neurology, July 2, 2020
It is uncertain whether coronavirus disease 2019 (COVID-19) is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection. The objective was to compare the rate of ischemic stroke between patients with COVID-19 and patients with influenza, a respiratory viral illness previously associated with stroke. This retrospective cohort study was conducted at 2 academic hospitals in New York City, New York, and included adult patients with emergency department visits or hospitalizations with COVID-19 from March 4, 2020, through May 2, 2020.
Treatment with ACE inhibitors or ARBs and risk of severe/lethal COVID-19: a meta-analysis
Heart, July 1, 2020
It has been hypothesised that the use of ACE inhibitors and angiotensin receptor blockers (ARBs) might either increase or reduce the risk of severe or lethal COVID-19. The findings from the available observational studies varied, and summary estimates are urgently needed to elucidate whether these drugs should be suspended during the pandemic, or patients and physicians should be definitely reassured. This meta-analysis of adjusted observational data aimed to summarise the existing evidence on the association between these medications and severe/lethal COVID-19. Ten studies, enrolling 9890 hypertensive subjects were included in the analyses. Compared with untreated subjects, those using either ACE inhibitors or ARBs showed a similar risk of severe or lethal COVID-19 (summary OR: 0.90; 95%CI 0.65 to 1.26 for ACE inhibitors; 0.92; 95% CI 0.75 to 1.12 for ARBs).
Emergency transfers for STEMI, stroke reduced during pandemic
Helio | Cardiology Today, July 1, 2020
Daily emergency transfers for STEMI and stroke within the Cleveland Clinic regional health system dropped significantly after the onset of the COVID-19 pandemic, researchers reported. In an analysis of the Cleveland Clinic critical care transport system published in Circulation: Cardiovascular Quality and Outcomes, investigators compared emergency transfer data for STEMI, stroke and abdominal aortic aneurysm from 2019 to March 8, 2020 (baseline), with data collected from March 9 and May 6, 2020 (pandemic period). “The Cleveland Clinic has a long-established ‘auto-launch’ process that clinicians can activate to bypass the need for an accepting provider or available bed and to initiate the immediate emergency transfer for patients experiencing STEMI, acute stroke and aortic emergencies,” Umesh N. Khot, MD, vice chairman of the Robert and Suzanne Tomsich Department of Cardiovascular Medicine and a staff cardiologist in the Section of Clinical Cardiology in the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic, and colleagues wrote.Guidelines: Cardiovascular risks in COVID-19 infection
Blood type may contribute to likelihood of acquiring COVID-19
Helio | Primary Care, July 1, 2020
A patient’s blood type plays a role in the likelihood of developing COVID-19, data from two genetic studies show. An infectious disease expert unaffiliated with the studies told Healio Primary Care that the results are possible, but with some important caveats. In the first study, which appeared in The New England Journal of Medicine, David Ellinghaus, a scientist at the Institute of Clinical Molecular Biology in Germany, and colleagues analyzed nearly 8.6 million single nucleotide polymorphisms from 1,610 Spanish and Italian patients with COVID-19 and respiratory failure. Another 2,205 uninfected participants served as controls. Participants’ age, ethnicity and sex were also part of the analysis.
Recommendations for the Management of ACS in COVID-19
Cardiology Advisor, June 30, 2020
A comprehensive protocol-based triaging and decision making at the point of care in patients with COVID-19 presenting with acute myocardial injury is necessary to reduce provider anxiety and confusion, offer a pathway for streamlined management of these challenging patients, while simultaneously minimizing the exposure of medical personnel to this highly contagious virus, according to a report published in Atherosclerosis. COVID-19 has forced the healthcare system to reconsider its approach to even the most basic practices. Recent reports show that acute myocardial injury and subsequent troponin and/or ST-segment elevation are common findings and risk predictors among patients with COVID-19.
Coronavirus (COVID-19) Update: FDA Takes Action to Help Facilitate Timely Development of Safe, Effective COVID-19 Vaccines
FDA.gov, June 30, 2020
Today, the U.S. Food and Drug Administration took important action to help facilitate the timely development of safe and effective vaccines to prevent COVID-19 by providing guidance with recommendations for those developing COVID-19 vaccines for the ultimate purpose of licensure. The guidance, which reflects advice the FDA has been providing over the past several months to companies, researchers, and others, describes the agency’s current recommendations regarding the data needed to facilitate the manufacturing, clinical development, and approval of a COVID-19 vaccine. The guidance also discusses the importance of ensuring that the sizes of clinical trials are large enough to demonstrate the safety and effectiveness of a vaccine. It conveys that the FDA would expect that a COVID-19 vaccine would prevent disease or decrease its severity in at least 50% of people who are vaccinated.
How to maintain momentum on telehealth after COVID-19 crisis ends
American Medical Association, June 30, 2020
The use of telehealth has exploded as many regulatory barriers to its use have been temporarily lowered during the COVID-19 pandemic. The AMA is advocating for making many of these emergency policy changes permanent. “The expansion of telehealth and the offering of new telehealth services that were not previously covered really enabled physicians to care for their patients in the midst of this crisis,” Todd Askew, the AMA’s senior vice president of advocacy, said during a recent “AMA COVID-19 Update” video. “We have moved forward a decade in the use of telemedicine in this country and it’s going to become, and will remain, an increasingly important part of physician practices going forward.”
Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study
The Lancet, June 30, 2020
An important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19-associated coagulopathy, characterised by increased thrombotic and microvascular complications. Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy. To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19. Our findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death. Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19.
COVID-19 sparks increased telehealth use for arrhythmia management
Helio | Cardiology Today, June 30, 2020
The COVID-19 pandemic has been a catalyst for rapid adoption of telehealth to remotely manage and monitor patients with arrhythmias, which will continue even after the pandemic passes, the authors of a multi-society practice update wrote. The practice update, which was published in the Journal of the American College of Cardiology, was prepared by arrhythmia experts and representatives from the American Heart Association, American College of Cardiology, Heart Rhythm Society and several other organizations from Europe, Asia Pacific and Latin America. “These technologies are here to stay,” Niraj Varma, MD, PhD, professor of medicine and cardiac electrophysiologist at Cleveland Clinic and chair of the writing group, told Healio. “Patients and doctors have found them very useful. We would like the accessibility to these technologies to increase on a worldwide basis because we think it’s going to be integrated with general medical practice in the future.”
U.S. coronavirus cases rise by 47,000, biggest one-day spike of pandemic
Reuters, June 30, 2020
New U.S. COVID-19 cases rose by more than 47,000 on Tuesday according to a Reuters tally, the biggest one-day spike since the start of the pandemic, as the government’s top infectious disease expert warned that number could soon double. California, Texas and Arizona have emerged as new U.S. epicenters of the pandemic, reporting record increases in COVID-19 cases. “Clearly we are not in total control right now,” Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, told a U.S. Senate committee. “I am very concerned because it could get very bad.”
HHS will renew public health emergency
Modern Healthcare, June 29, 2020
HHS spokesman Michael Caputo on Monday tweeted that HHS intends to extend the COVID-19 public health emergency that is set to expire July 25. The extension would prolong the emergency designation by 90 days. Several payment policies and regulatory adjustments are attached to the public health emergency, so the extension is welcome news for healthcare providers. HHS “expects to renew the Public Health Emergency due to COVID-19 before it expires. We have already renewed this PHE once,” Caputo said. Provider groups including the American Hospital Association have urged HHS to renew the distinction.
Global coronavirus deaths top half a million
Reuters, June 28, 2020
The death toll from COVID-19 surpassed half a million people on Sunday, according to a Reuters tally, a grim milestone for the global pandemic that seems to be resurgent in some countries even as other regions are still grappling with the first wave. The respiratory illness caused by the new coronavirus has been particularly dangerous for the elderly, although other adults and children are also among the 501,000 fatalities and 10.1 million reported cases. While the overall rate of death has flattened in recent weeks, health experts have expressed concerns about record numbers of new cases in countries like the United States, India and Brazil, as well as new outbreaks in parts of Asia.
Who Is Most At-Risk for Severe COVID-19?
MedPage Today, June 27, 2020
[Quiz] New information is posted daily, but keeping up can be a challenge. As an aid for readers and for a little amusement, here is a 10-question quiz based on the news of the week. Topics include COVID-19 risk factors, future pandemic preparation, and effects on kids from parents’ mental illness. After taking the quiz, scroll down in your browser window to find the correct answers and explanations, as well as links to the original articles.
Myocarditis in a 16-year-old boy positive for SARS-CoV-2
The Lancet | Clinical Picture, June 27, 2020
A 16-year-old boy was admitted to our emergency department, in Lombardy, complaining of intense pain in his chest—radiating to his left arm—which had started 1 h earlier. The day before he had a fever of 38·3°C that decreased after 100 mg of nimesulide. He reported no other symptoms, no medical history, and no contact with anyone with confirmed COVID-19. We found his vital signs to be normal apart from his temperature which was raised at 38·5°C. On auscultation of the patient’s chest, we heard normal heart sounds, no pericardial rub, and no abnormal respiratory signs. We found no lymphadenopathy, no rash, and no areas of localised tenderness on the chest wall. An electrocardiogram (ECG) showed inferolateral ST-segment elevation and a transthoracic echocardiography showed hypokinesia of the inferior and inferolateral segments of the left ventricle, with a preserved ejection fraction of 52%; no pericardial effusion was seen. Investigations showed raised high-sensitivity cardiac troponin I (9449 ng/L), creatine phosphokinase (671·0 U/L), C-reactive protein (32·5 mg/L), and lactate dehydrogenase (276·0 U/L) concentrations. The leucocyte count was 12·75 × 109 per L, the neutrophil count was 10·04 × 109 per L, and the lymphocyte count was 0·78 × 109 per L.
Colchicine for COVID-19; Metabolic Syndrome Prevalence
MedPage Today, June 27, 2020
[Podcast] Topics include colchicine for heart complications of COVID, black versus white patients with COVID-19 hospitalization, prevalence of metabolic syndrome in the U.S., and ACE inhibitors and ARBs and COVID. TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.
COVID-19 Practice Financial Assistance
American College of Physicians, Updated June 26, 2020
The ACP provides resources to help guide practices in plans for re-opening. Resources include guides, checklists, staffing and workflow modifications, and materials for communicating with patients. The ACP also offers clinical and public policy guidance on how to resume some economic, social and medical care activities to mitigate COVID-19 and allow expansion of healthcare capacity. For more information, the CDC offers a framework for providing non-COVID-19 care during the pandemic.
CMS Announces Additional QPP, MIPS Flexibilities for 2020
American College of Cardiology, Jun 25, 2020
The Centers for Medicare and Medicaid Services (CMS) continues to provide flexibilities to clinicians participating in the Quality Payment Program (QPP) Merit-based Incentive Payment System (MIPS) in 2020 as a result of the COVID-19 pandemic. Clinicians significantly impacted by the public health emergency may submit an Extreme & Uncontrollable Circumstances Application to reweight any or all of the MIPS performance categories for performance year 2020. Clinicians requesting relief will need to provide a justification of the impacts to their practice as a result of the public health emergency.
Stroke increases mortality risk in younger patients with COVID-19
Helio | Cardiology Today, June 23, 2020
Acute ischemic stroke increased the risk for all-cause mortality in young adults with COVID-19 despite a low prevalence in this patient group, according to a study published in The American Journal of Cardiology. “To our knowledge, this is the first study to report the incidence and outcomes of acute ischemic stroke in young adults with COVID-19 infection,” Frank Annie, PhD, research scientist at Charleston Area Medical Center Institute for Academic Medicine in West Virginia, and colleagues wrote. “We found a low overall incidence but a grim prognosis of acute ischemic stroke among unselected young adults with COVID-19.”
Home BP Monitoring ‘More Important Than Ever’ During Pandemic
MedPage Today, June 23, 2020
The USPSTF, AHA, AMA re-up support for out-of-office measurement. Keep screening for hypertension, the U.S. Preventive Services Task Force (USPSTF) reiterated in draft guidelines, while other groups urged home blood pressure monitoring as well. The USPSTF gave a grade A recommendation to in-office screening for hypertension in adults with confirmation outside of the clinical setting before starting treatment. The draft recommendations — open for public comment until July 20 — match the group’s 2015 final recommendations, but buttressed with additional research from the past 5 years. A separate joint policy statement from the American Heart Association and American Medical Association (AHA/AMA) affirmed that self-measured blood pressure (SMBP) at home is a validated approach and cost effective when added to office monitoring.
Cardiologists shed new light on COVID-19 and cardiac arrhythmias
Cardiovascular Business, June 23, 2020
A higher rate of cardiac arrhythmias has been observed in hospitalized COVID-19 patients, but new research suggests there’s more behind that trend than the virus itself. The study, published in Heart Rhythm Journal, explored data from 700 COVID-19 patients admitted to a single facility in Pennsylvania from March 6 to May 19, 2020. Eleven percent of the cohort was admitted to the ICU, and all nine cardiac arrests occurred among those patients. In addition, ICU admission was specifically associated with atrial fibrillation (AF) and nonsustained ventricular tachycardia; cardiac arrests were associated with “acute, in-hospital mortality.” These findings, the authors explained, highlight why cardiac arrests and arrhythmias “are likely the consequence of systemic illness and not solely the direct effect of COVID-19 infection.”
Targeting the Immune System for Pulmonary Inflammation and Cardiovascular Complications in COVID-19 Patients
Frontiers in Immunology, June 23, 2020
In December 2019, following a cluster of pneumonia cases in China caused by a novel coronavirus (CoV), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infection disseminated worldwide and, on March 11th, 2020, the World Health Organization officially declared the pandemic of the relevant disease named coronavirus disease 2019 (COVID-19). In Europe, Italy was the first country facing a true health policy emergency, and, as at 6.00 p.m. on May 2nd, 2020, there have been more than 209,300 confirmed cases of COVID-19. Due to the increasing number of patients experiencing a severe outcome, global scientific efforts are ongoing to find the most appropriate treatment. The usefulness of specific anti-rheumatic drugs came out as a promising treatment option together with antiviral drugs, anticoagulants, and symptomatic and respiratory support. For this reason, the authors share their experience and knowledge on the use of these drugs in the immune-rheumatologic field, providing in this review the rationale for their use in the COVID-19 pandemic.
Stroke increases mortality risk in younger patients with COVID-19
Helio | Cardiology Today, June 23, 2020
Acute ischemic stroke increased the risk for all-cause mortality in young adults with COVID-19 despite a low prevalence in this patient group, according to a study published in The American Journal of Cardiology. “To our knowledge, this is the first study to report the incidence and outcomes of acute ischemic stroke in young adults with COVID-19 infection,” Frank Annie, PhD, research scientist at Charleston Area Medical Center Institute for Academic Medicine in West Virginia, and colleagues wrote. “We found a low overall incidence but a grim prognosis of acute ischemic stroke among unselected young adults with COVID-19.”
Could Extended Anticoagulation Help After COVID-19?
MedPage Today, June 22, 2020
After hospitalization for medical illness, an extended course of low-dose anticoagulation reduced arterial and venous thromboembolic events combined, secondary analysis of a randomized trial suggested — a finding with implications for post-COVID care. Taking 10-mg rivaroxaban (Xarelto) for 45 days post-discharge reduced fatal and major events by a relative 28% in patients with additional risk factors for venous thromboembolism (VTE) in a prespecified secondary analysis of the MARINER trial.
Self-Measured Blood Pressure Monitoring at Home: A Joint Policy Statement From the American Heart Association and American Medical Association
Circulation, June 22, 2020
The diagnosis and management of hypertension, a common cardiovascular risk factor among the general population, have been based primarily on the measurement of blood pressure (BP) in the office. BP may differ considerably when measured in the office and when measured outside of the office setting, and higher out-of-office BP is associated with increased cardiovascular risk independent of office BP. Self-measured BP monitoring, the measurement of BP by an individual outside of the office at home, is a validated approach for out-of-office BP measurement. Several national and international hypertension guidelines endorse selfmeasured BP monitoring. Indications include the diagnosis of white-coat hypertension and masked hypertension and the identification of whitecoat effect and masked uncontrolled hypertension.
Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality
Journal of the American Medical Association, June 19, 2020
Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major threat to global health. Research on modifiable risk factors potentially linked to increased susceptibility to infection or to worse outcomes among those who have the disease has focused on cardiovascular comorbidity, hypertension, and diabetes. Interest has been directed to the use of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) because these drugs may affect the ability of SARS-CoV-2 to infect cells through upregulation of angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2 cell entry. Based on this suggested mechanism, media reports have raised questions about ACEI/ARB treatment in the setting of COVID-19.
Coronavirus and Health Inequities
JAMA Medical News, June 19, 2020
Recorded today, Linda Rae Murray, MD, MPH discusses topics in health equity with JAMA Medical News Associate Managing Editor Jennifer Abbasi.
Characteristics Associated With Out-of-Hospital Cardiac Arrests and Resuscitations During the Novel Coronavirus Disease 2019 Pandemic in New York City
JAMA Cardiology, June 19, 2020
Risk factors for out-of-hospital death due to novel coronavirus disease 2019 (COVID-19) are poorly defined. From March 1 to April 25, 2020, New York City, New York (NYC), reported 17 118 COVID-19–related deaths. On April 6, 2020, out-of-hospital cardiac arrests peaked at 305 cases, nearly a 10-fold increase from the prior year. This study describes the characteristics (race/ethnicity, comorbidities, and emergency medical services [EMS] response) associated with outpatient cardiac arrests and death during the COVID-19 pandemic in NYC.
Degree of myocardial injury severity may affect survival in COVID-19
Helio | Cardiology Today, June 19, 2020
The prevalence of myocardial injury in acute COVID-19 is approximately 36%, but its presence was significantly associated with worse outcomes, researchers reported. Elevated troponin levels, an indicator of myocardial injury, conferred a higher risk for death among patients hospitalized with COVID-19. According to a report published in the Journal of the American College of Cardiology, patients with confirmed COVID-19 (mean age, 66 years; 60% men; 35% with history of CVD) admitted between Feb. 27 and April 12 who had troponin levels measured within 24 hours of admission were assessed to determine the effect of myocardial injury.
Steroid treatment for COVID-19 has NYC doctors cautiously optimistic
Modern Healthcare, June 19, 2020
Local physicians said a U.K. study of the use of the steroid dexamethasone in treating severe COVID-19 patients showed promising results, but they’re reserving judgment until more data from the study is published. Initial results were announced Tuesday in a press release. The randomized trial, supported by the University of Oxford, tested dexamethasone in about 2,100 patients with an additional 4,300 receiving only usual care. The study found that the drug reduced the number of deaths by one-third in patients using mechanical ventilators and one-fifth in patients receiving only oxygen. There was no benefit among patients who didn’t require respiratory support.
Lifting COVID-19 “Lockdown” Restrictions May Cause Infection Resurgence
Pulmonary Advisor, June 18, 2020
Data from multiple countries demonstrate that lifting restrictions imposed to reduce the spread of coronavirus disease 2019 (COVID-19) would result in a resurgence of infections, according to provisional analyses published in the European Respiratory Journal. Most countries with significant COVID-19 outbreaks have introduced social distancing or “lockdown” measures to reduce viral transmission, however, the question of when, how, and to what extent these measures can be lifted remains.
Telehealth visits during COVID-19 may exacerbate inequities in cardiology care
Helio | Cardiology Today, June 18, 2020
Inequities persist in telehealth during the COVID-19 pandemic, as patients who completed telehealth visits at cardiology clinics were more likely to be older men who spoke English, according to a study published in Circulation. “We have seen how COVID-19 has been the great unequalizer,” Lauren A. Eberly, MD, MPH, cardiology fellow at the University of Pennsylvania, told Healio. “The findings of this study demonstrate significant inequities are also present among non-COVID patients in accessing necessary telemedicine care. … These results call for immediate implementation of strategies to ensure more equitable access to telemedicine care.”
Chicago has a unique COVID strain: research
Modern Healthcare, June 18, 2020
Chicagoans are being infected with a unique strain of COVID-19 that’s linked to the early coronavirus outbreak in China, according to new research. Northwestern Medicine scientists have determined that the Chicago area “is a melting pot for different versions of the virus because it is such a transportation hub,” Dr. Egon Ozer, an assistant professor at Northwestern University’s Feinberg School of Medicine and a Northwestern Medicine physician, said in a statement today. Ozer’s team is learning how variations of the severe acute respiratory syndrome that causes COVID-19 infects people differently. It’s a finding they say could help shape a potential vaccine.
Accelerated COVID-19 vaccine effort should not mean compromises, experts say
Helio | Infectious Disease, June 18, 2020
Public-private partnerships, collaboration among researchers and knowledge of existing coronaviruses have all contributed to the accelerated development of COVID-19 vaccine candidates, according to Infectious Disease News Editorial Board Member Kathleen M. Neuzil, MD, MPH, FIDSA. Neuzil, a professor of vaccinology and director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine, said vaccine development overall is a “continuum” from the discovery phase to “delivery and impact.” Neuzil and other presenters opened the National Foundation for Infectious Diseases’ Annual Conference on Vaccinology Research with a discussion on the current state of vaccine development for COVID-19.
R-107 Shows Promise in Early Study for PAH Linked to COVID-19
Pulmonary Hypertension News, June 17, 2020
Kalytera Therapeutics has announced positive early results for R-107, a liquid form of nitric oxide designed to treat pulmonary arterial hypertension (PAH) associated with COVID-19. Nitric oxide, known as NO, is a gas naturally present in the lungs. It facilitates oxygenation by relaxing, or dilating, the blood vessels, allowing blood to flow smoothly. R-107 is a liquid prodrug of nitric oxide, meaning that the compound is a precursor to its pharmacologically active form. Once injected into the body, R-107 is converted into its active form, called R-100, which steadily releases NO into lung tissues over the course of several days.
COVID-19 Anticoagulation Trial; Kids’ Healthy Vessels; Rebooting EP
MedPage Today, June 16, 2020
As the SARS-CoV-2 virus’s endothelial effects emerge as important in its clotting complications, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) trial is preparing to launch to compare low-dose thromboprophylaxis versus full anticoagulation. (NIH Director’s Blog) Implantable loop recorders could be used to monitor for fever as a sign of COVID-19 infection, a case report in HeartRhythm Case Reports showed. Conscious sedation for transcatheter aortic valve replacement was associated with a small reduction in mortality and more discharge to home than seen with those procedures done under general anesthesia in an instrumental variable analysis in JACC: Cardiovascular Interventions.
US taking ‘wrong approach’ to COVID-19 testing, expert warns
Helio | Infectious Diseases, June 16, 2020
The American Lung Association recently held a virtual Town Hall meeting to debunk widespread misperceptions in the United States about which populations should be prioritized for COVID-19 testing and how to interpret the results. “Far too many people have misinterpreted testing,” Michael T. Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota, said during the meeting. “While we need to greatly expand our SARS-CoV-2 testing as a critical component of our response to COVID-19, the pandemic messaging to date needs to move beyond the ‘Test, test, test!’ mantras. That is the wrong approach.”
China’s COVID-19 vaccine candidate shows promise in human trials, CNBG says
Reuters, June 16, 2020
China National Biotec Group (CNBG) said on Tuesday its experimental coronavirus vaccine has triggered antibodies in clinical trials and the company plans late-stage human trials in foreign countries. No vaccines have been solidly proven to be able to effectively protect people from the virus that has killed more than 400,000 people, while multiple candidates are in various stages of development globally. The vaccine, developed by a Wuhan-based research institute affiliated to CNBG’s parent company Sinopharm, was found to have induced high-level antibodies in all inoculated people without serious adverse reaction, according to the preliminary data from a clinical trial initiated in April involving 1,120 healthy participants aged between 18 and 59.
Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19
Oxford University, June 16, 2020
In March 2020, the RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial was established as a randomised clinical trial to test a range of potential treatments for COVID-19, including low-dose dexamethasone (a steroid treatment). Over 11,500 patients have been enrolled from over 175 NHS hospitals in the UK. On 8 June, recruitment to the dexamethasone arm was halted since, in the view of the trial Steering Committee, sufficient patients had been enrolled to establish whether or not the drug had a meaningful benefit. A total of 2104 patients were randomised to receive dexamethasone 6 mg once per day (either by mouth or by intravenous injection) for ten days and were compared with 4321 patients randomised to usual care alone. Among the patients who received usual care alone, 28-day mortality was highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%).
Coronavirus death rate is higher for those with chronic ills
Associated Press, June 15, 2020
Death rates are 12 times higher for coronavirus patients with chronic illnesses than for others who become infected, a new U.S. government report says. The Centers for Disease Control and Prevention report released Monday highlights the dangers posed by heart disease, diabetes and lung ailments. These are the top three health problems found in COVID-19 patients, the report suggests. The report is based on 1.3 million laboratory-confirmed coronavirus cases reported to the agency from January 22 through the end of May. Information on health conditions was available for just 22% of the patients. It shows that 32% had heart-related disease, 30% had diabetes and 18% had chronic lung disease, which includes asthma and emphysema.
Is Hypertension a Real Risk Factor for Poor Prognosis in the COVID-19 Pandemic?
Current Hypertension Reports (via Springer Link), June 13, 2020
There is increasing evidence indicating an association between several risk factors and worse prognosis in patients with coronavirus disease 2019 (COVID-19), including older age, hypertension, heart failure, diabetes, and pulmonary disease. Hypertension is of particular interest because it is common in adults and there are concerns related to the use of renin-angiotensin system (RAS) inhibitors in patients with hypertension infected with COVID-19. In this review, we provide a critical review to the following questions: (1) Does hypertension influence immunity or ACE2 expression favoring viral infections? (2) Are the risks of complications in hypertension mediated by its treatment? (3) Is aging a major factor associated with worse prognosis in patients with COVID-19 and hypertension?
Cardiac sequelae of novel coronavirus disease 2019 (COVID-19): a clinical case series
European Heart Journal (Case Reports), June 13, 2020
The pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spreading worldwide, exhausting resources across health systems. First appearing in Wuhan, China, it commonly manifested with respiratory symptoms of cough, dyspnoea, fever, chills, and myalgias. Individuals with history of cardiovascular disease are predisposed to infection and are at increased risk of adverse outcomes. Previous beta-coronavirus infections, such as severe acute respiratory syndrome, were associated with tachyarrhythmias and heart failure. Cardiac manifestations of COVID-19 were later reported, typically from viral myocarditis and treatment side effects.5 Given the increased incidence and saturation of resources, COVID-19 has had indirect effects on care, impacting timing and optimal treatment of acute cardiovascular disease. The objective of this clinical case series is to highlight cardiac complications of COVID-19.
Anti-contagion interventions prevented up to 62 million confirmed
Helio | Infectious Disease News, June 12, 2020
Anti-contagion policies have prevented or delayed as many as 62 million confirmed COVID-19 infections, which corresponded with the prevention of an estimated 530 million cases in six countries, according to a study published in Nature. “We found that in the absence of policy intervention, the number of COVID-19 infections doubled approximately every 2 days,” Esther Rolf, a PhD candidate in the computer science department at University of California, Berkeley, told Healio. “In all six countries we studied, we found that the anti-contagion policies put in place significantly slowed the spread of the disease, resulting in an estimated 500 million infections prevented or delayed, across the six countries in the time frame that we studied.”
HRS/EHRA/APHRS/LAHRS/ACC/AHA worldwide practice update for telehealth and arrhythmia monitoring during and after a pandemic
Heart Rhythm, June 11, 2020
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started in the city of Wuhan late in 2019. Within a few months, the disease spread toward all parts of the world and was declared a pandemic on March 11, 2020. The current health care dilemma worldwide is how to sustain the capacity for quality services not only for those suffering from COVID-19 but also for non-COVID-19 patients, all while protecting physicians, nurses, and other allied health care workers. The pandemic poses challenges to electrophysiologists at several levels. Hospitalized COVID-19-positive patients may have preexisting arrhythmias, develop new arrhythmias, or be placed at increased arrhythmic risk from therapies for COVID-19.
More Calls for Routine VTE Prophylaxis in Severe COVID-19
MedPage Today, June 11, 2020
Given the coagulopathy that often complicates severe COVID-19 illness, certain best practices should be followed for venous thromboembolism (VTE) prevention and treatment, even if data to inform these decisions are scarce, experts said. Critically or acutely ill COVID-19 patients should receive anticoagulant thromboprophylaxis (unless contraindicated), according to recent guidance from the American College of Chest Physicians.
U.S. Coronavirus Cases Hit 2 Million as New Hotspots Surface
HealthDay News, June 11, 2020
The number of confirmed U.S. coronavirus cases passed 2 million on Thursday, as public health experts warned of the emergence of new COVID-19 hotspots across the country. Just three weeks after Arizona Gov. Doug Ducey lifted the state’s stay-at-home order, there has been a significant spike in coronavirus cases, with lawmakers and medical professionals warning that hospitals might not be able to handle a big influx of new cases. Already, hospitals in the state are at 83 percent capacity, the Associated Press reported. But Arizona is not alone in seeing increases in hospitalizations: new U.S. data shows at least eight other states with spikes since Memorial Day. In Texas, North and South Carolina, California, Oregon, Arkansas, Mississippi and Utah, increasing numbers of COVID-19 patients are showing up at hospitals.
COVID-19 may impair certain kinds of ventricular function
Cardiology Today, June 10, 2020
Patients with COVID-19 had impaired left ventricular diastolic and right ventricular function despite most patients having preserved LV systolic function, researchers found in a study published in Circulation. Yishay Szekely, MD, a cardiologist at Tel Aviv Sourasky Medical Center and Tel Aviv University Sackler School of Medicine, and colleagues analyzed data from 100 patients (mean age, 66 years; 63% men) with COVID-19 who were admitted to Tel Aviv Medical Center between March 21 and April 16. All patients underwent an echocardiographic evaluation within 24 hours of hospital admission. The assessment was repeated in patients with clinical deterioration, defined as death or hemodynamic, respiratory or cardiac deterioration.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Induced Cardiovascular Syndrome: Etiology, Outcomes, and Management
Cureus, June 10, 2020
As the number of coronavirus disease 2019 (COVID-19) cases grows, more complications associated with the disease become apparent. One of the more concerning complications affects the cardiovascular system. Thus far, there is limited information available on the etiology, clinical outcomes, and management options for cardiovascular complications caused by COVID-19. The more common cardiovascular sequalae are acute coronary syndrome, cardiomyopathy, arrythmia, myocarditis, cardiogenic shock, and cardiac arrest. Interestingly, the observed cardiovascular injury is similar to that caused by Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), and influenza.
Lack of Health Literacy a Barrier to Grasping COVID-19
MedPage Today, June 10, 2020
A lack of health literacy is preventing people from having a good understanding of the novel coronavirus, two speakers said Wednesday at an online briefing sponsored by the National Academies of Sciences, Engineering, and Medicine. “So many people are confused about the symptoms” of COVID-19, said Lisa Fitzpatrick, MD, MPH, founder of Grapevine Health, a nonprofit organization in Washington that helps design culturally appropriate health information campaigns targeted at underserved populations. When Grapevine Health sent workers out to talk to people about the pandemic, “So many told us they didn’t know the symptoms,” said Fitzpatrick.
The Variety of Cardiovascular Presentations of COVID-19
Circulation, June 9, 2020
The global pandemic caused by coronavirus disease 2019 (COVID-19) has affected more than 880,000 people in over 180 countries or regions worldwide. COVID-19 is the clinical manifestation of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and most frequently presents with respiratory symptoms that can progress to pneumonia and, in severe cases, acute respiratory distress syndrome and shock. However, there is increasing awareness of the cardiovascular manifestations of COVID-19 disease and the adverse impact that cardiovascular involvement has on prognosis. Discriminating between a cardiac or respiratory etiology of symptoms can be challenging since each may present predominantly with dyspnea. It is also critical to recognize when cardiac and pulmonary involvement coexist. In this paper, we present 4 cases that illustrate a variety of cardiovascular presentations of COVID-19 infection. In addition to discussing the basic clinical physiology, we also discuss clinical decision making in the current environment, while considering resource allocation and the welfare of healthcare professionals.
Cholesterol and COVID-19; Novel HFpEF Drug; Full Speed on CV Surgery?
MedPage Today, June 9, 2020
High cholesterol in tissue may increase entry points into cells for SARS CoV-2, the virus that causes COVID-19, such that rapidly dropping cholesterol in the blood could increase risk, researchers found in preclinical experiments reported on the preprint server bioRxiv, which is not peer reviewed. The Pittsburgh Post-Gazette has an explainer. ST-segment-elevation MI admissions have dropped by an average 50%, with about half presenting later than usual, according to an international survey by the European Society of Cardiology. The first molecular profile comparing blood samples of people with and without COVID-19 showed that differences fell into two groups – those related to the immune system and those related to platelet function.
Out of the lab and into people’s arms: A list of COVID-19 vaccines that are being studied in clinical trials
ABC News, June 9, 2020
The world’s leading drug companies, universities and governments are racing to develop a vaccine for COVID-19, the disease that has taken more than 400,000 lives globally. Of the 133 candidates being explored, ten have been approved for human trials, according to the World Health Organization. Companies and research groups in China, the early epicenter of the coronavirus outbreak, are testing five of those vaccines in human trials. Meanwhile, U.S.-based companies are involved in the development of four additional vaccines, including one that has NIAID Director Anthony Fauci “cautiously optimistic.”
Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome
Circulation, June 9, 2020
[White Paper] Coronavirus disease 2019 (COVID-19) is a rapidly expanding global pandemic caused by severe acute respiratory syndrome coronavirus 2, resulting in significant morbidity and mortality. A substantial minority of patients hospitalized develop an acute COVID-19 cardiovascular syndrome, which can manifest with a variety of clinical presentations but often presents as an acute cardiac injury with cardiomyopathy, ventricular arrhythmias, and hemodynamic instability in the absence of obstructive coronary artery disease. The cause of this injury is uncertain but is suspected to be related to myocarditis, microvascular injury, systemic cytokine-mediated injury, or stress-related cardiomyopathy. Although histologically unproven, severe acute respiratory syndrome coronavirus 2 has the potential to directly replicate within cardiomyocytes and pericytes, leading to viral myocarditis.
When the Dust Settles: Preventing a Mental Health Crisis in COVID-19 Clinicians
Annals of Internal Medicine, June 9, 2020
On 26 April, after spending weeks caring for patients with coronavirus disease 2019 (COVID-19) in New York City, emergency room physician Lorna Breen took her own life. Her grieving family recounts days of helplessness leading up to this as Dr. Breen described how COVID-19 upended her emergency department and left her feeling inadequate despite years of training and expertise. The clinical experience of Dr. Breen during this pandemic has not been unique. During the past 5 months, COVID-19 has caused an upheaval of medical systems around the world, with more than 4 million cases and 300 000 deaths worldwide so far. Unfortunately, we’ve also seen that the experience in caring for patients with the virus may have profound effects on clinicians’ mental health. A recent study conducted at the center of the outbreak in China reported that more than 70% of frontline health workers had psychological distress after caring for patients with COVID-19.
Coronavirus: What We Know Now
WebMD, June 8, 2020
The first confirmed cases of coronavirus in the U.S. appeared in January. At the time, the world knew almost nothing about how the virus spreads or how to treat it. Six months later, our knowledge has grown, but researchers continue to make discoveries almost daily. At first, health experts believed COVID-19, the disease caused by the new coronavirus, primarily affected patients’ lungs. While it’s still primarily a lung disease, other symptoms have appeared often, and they’ve been added to the list of signs of COVID.
Heart injury among hospitalized COVID-19 patients associated with higher risk of death
Medical Express, June 8, 2020
Mount Sinai researchers have found that myocardial injury (heart damage) is prevalent among patients hospitalized with COVID-19 and is associated with higher risk of mortality. More specifically, a serious myocardial injury can triple the risk of death. “There has been a lot of speculation about how COVID-19 affects the heart and blood vessels, and with what frequency. Our observational study may help to shed some light on this. We found that 36 percent of patients who were hospitalized with COVID-19 had elevated troponin levels—which represents heart injury—and were at higher risk of death,” says lead author Anu Lala, MD, Assistant Professor of Medicine (Cardiology) at the Icahn School of Medicine at Mount Sinai.
Risk of Dying Doubled in Wuhan COVID-19 Patients With Hypertension
tctMD | The Heart Beat (by the Cardiovascular Research Foundation, June 8, 2020
New observational data from Wuhan, China, suggest that hypertensive patients hospitalized with COVID-19 had a twofold increased risk of dying compared to those without hypertension, and that not being on medication for hypertension at the time of hospitalization worsens outcomes. The study also provides additional reassurance about the use of antihypertensives that target the renin-angiotensin-aldosterone system (RAAS). “Patients with RAAS inhibitors were not exposed to a higher risk of mortality in our study and, after pooling previously published data in a study-level meta-analysis, the use of RAAS inhibitors was shown to be possibly associated with lower risk of mortality,” write Chao Gao, MD (Xijing Hospital, Xi’an, China), and colleagues. Nevertheless, they urge caution in interpreting the results due to the observational nature of the study.
High Fatality Rate in Heart Transplant Recipients With COVID-19
Cardiology Advisor, June 8, 2020
Novel coronavirus disease 2019 (COVID-19) was found to be associated with a higher fatality rate in recipients of heart transplant, according to a case series published in JAMA Cardiology. Heart transplant recipients may be at increased risk for complications of COVID-19 due to a high burden of comorbidities and treatment with immunosuppressive agents. However, immunosuppression has also been proposed as a possible option for treatment of COVID-19, as it may curb the “cytokine storm” that has been observed in severe cases. With this retrospective review of adult heart transplant recipients at a large academic center in New York, New York, investigators aimed to determine the outcomes of heart transplant recipients with COVID-19 while receiving chronic immunosuppression.
Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2
Journal of the American Medical Association, June 8, 2020
This case series included 58 hospitalized children, a subset of whom required intensive care, and met definitional criteria for pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS), including fever, inflammation, and organ dysfunction. Of these children, all had fever and nonspecific symptoms, such as abdominal pain (31 [53%]), rash (30 [52%]), and conjunctival injection (26 [45%]); 29 (50%) developed shock and required inotropic support or fluid resuscitation; 13 (22%) met diagnostic criteria for Kawasaki disease; and 8 (14%) had coronary artery dilatation or aneurysms. Some clinical and laboratory characteristics had important differences compared with Kawasaki disease, Kawasaki disease shock syndrome, and toxic shock syndrome.
COVID-19 Critical Care Update
View this COVID-19 Critical Care Update with Howard Bauchner, MD, Editor in Chief, JAMA, talks with Maurizio Cecconi, MD of Humanitas University in Milan and Derek C. Angus, MD, MPH of the University of Pittsburgh.
First Study Investigating Antibody Treatment for COVID-19 Begins
Pulmonology Advisor, June 8, 2020
The first patients have been dosed in a phase 1 trial evaluating a potential antibody therapy designed to treat coronavirus disease 2019 (COVID-19). These patients received treatment at major medical centers in the US, including NYU Grossman School of Medicine and Cedars-Sinai in Los Angeles. The investigational agent, LY-CoV555, is a potent, neutralizing lgG1 monoclonal antibody directed against the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The randomized, double-blind, placebo-controlled study is investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of 1 dose of LY-CoV555 in patients hospitalized with COVID-19; those requiring mechanical ventilation or who have received convalescent COVID-19 plasma treatment prior to enrollment were excluded from the study.
Coronavirus Cases in the U.S.
Center for Disease Control and Prevention, June 8, 2020
The U.S. Centers for Disease Control and Prevention (CDC) on Sunday reported 1,920,904 cases of new coronavirus, an increase of 29,214 cases from its previous count, and said COVID-19 deaths in the United States had risen by 709 to 109,901. The CDC reported its tally of cases of COVID-19, the respiratory illness caused by the new coronavirus, as of 4 p.m. EDT on June 6. Its previous tally was released on Friday.
Blood Test May Predict Clot Risk in Severe COVID-19
MedPage Today, June 7, 2020
Hypercoagulability on thromboelastography (TEG) was a good predictor of thrombotic events among COVID-19 patients entering the ICU, according to a single-center study. The clinically significant thrombosis that developed in 13 of 21 PCR-test-positive patients (62%) seen at Baylor St. Luke’s Medical Center ICU from March 15 to April 9 was associated with hypercoagulable TEG parameters in all cases. Maximum amplitude on that test was elevated in all 10 patients with two or more thrombotic complications compared with 45% of those with no more than one such event (nearly all arterial, central venous, or dialysis catheter or filter thromboses).
COVID-19 vaccine development pipeline gears up
The Lancet, June 6, 2020
Vaccine makers are racing to develop COVID-19 vaccines, and have advanced ten candidates into clinical trials. But challenges remain. Vaccine development is typically a long game. The US Food and Drug Administration only approved a first vaccine against Ebola virus last year, 43 years after the deadly virus was discovered. Vaccinologists have made little headway with HIV or respiratory syncytial virus, despite huge investments. On average, it takes 10 years to develop a vaccine. With the COVID-19 crisis looming, everyone is hoping that this time will be different. Already, ten vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) are in clinical trials, and researchers at the University of Oxford and AstraZeneca hope to have the first phase 3 data in hand this summer.
ACC Roundtable Convenes Stakeholders to Better Understand COVID-19 Implications on CV Research
American College of Cardiology, June 4, 2020
The emergence of COVID-19 has forced clinical researchers to endure major setbacks related to existing academic and industry-sponsored clinical trials. Recognizing these constraints, the ACC convened a focused Heart House Roundtable on May 29 to better understand the pandemic’s implications for ongoing and future cardiovascular research. “Because of the global COVID-19 pandemic, we are facing unprecedented times in clinical research,” said James L. Januzzi, Jr., MD, FACC, who co-chaired the Roundtable along with Harlan M. Krumholz, MD, SM, FACC. “Unforeseen obstacles are now present in all types of clinical investigation, from observational research to clinical trials. This meeting reflects the ACC’s commitment to facilitating generation of actionable knowledge to improve heart health even in these challenging times.”
Telehealth in the era of COVID-19: Concerns for patients with cancer, heart disease
Helio | Cardiology Today, June 4, 2020
Many physicians are now at the front lines of the COVID-19 pandemic. Those who do not have direct COVID-19 roles, including those in cardio-oncology, are trying to maintain normalcy in medicine as much as possible amid the chaos. About 1.8 million people will be diagnosed with cancer in the U.S. in 2020, 5% of whom have elevated risk for heart disease, according to estimates from the American Cancer Society. Unfortunately, this same population — our clinic patients with heart disease and cancer — are also at highest risk for infection, complications and death from COVID-19 due to their cancer, heart disease or a combination of both.
Retraction of Two Published Studies Related to COVID-19 From Lancet, NEJM
American College of Cardiology, June 4, 2020
Two studies of drug therapy and COVID-19 have been retracted from two different journals, a day after each issued an expression of concern about the quality of the data. Both studies used data from an international database held by Surgisphere Corporation which included electronic health records from 169 hospitals on three continents. The Lancet has retracted the paper titled Hydroxychloroquine or Chloroquine With or Without a Macrolide for Treatment of COVID-19: A Multinational Registry Analysis. The New England Journal of Medicine has retracted the paper titled Cardiovascular Disease, Drug Therapy, and Mortality in COVID-19.
Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study
European Heart Journal, June 4, 2020
This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital. The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China. Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension. After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs. 1.1%, adjusted HR 2.12, 95% CI 1.17–3.82, P = 0.013]. While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19.
Impact of the COVID-19 Pandemic on Emergency Department Visits — United States, January 1, 2019–May 30, 2020
Center for Disease Control and Prevention, June 3, 2020
As the number of persons hospitalized with COVID-19 increased, early reports from Austria (1), Hong Kong (2), Italy (3), and California (4) suggested sharp drops in the numbers of persons seeking emergency medical care for other reasons. To quantify the effect of COVID-19 on U.S. emergency department (ED) visits, CDC compared the volume of ED visits during four weeks early in the pandemic March 29–April 25, 2020 (weeks 14 to 17; the early pandemic period) to that during March 31–April 27, 2019 (the comparison period). During the early pandemic period, the total number of U.S. ED visits was 42% lower than during the same period a year earlier, with the largest declines in visits in persons aged ≤14 years, females, and the Northeast region.
Pediatric Acute Heart Failure and SARS-CoV-2 Infection
American College of Cardiology, June 3, 2020
Although it initially appeared that school-aged children are not greatly impacted by SARS-CoV-2 infection, there have been increasing concerns about a related multisystem inflammatory condition. This multicenter report with predominantly French centers (one center in Switzerland) describes experience with cardiac involvement of this disease process. Pro-BNP was often severely elevated in affected patients, and participating centers ultimately employed pro-BNP in the assessment of children in the emergency room with prolonged and unexplained fever.
Coronavirus in Context: The Latest Update on COVID-19 and the Heart
WebMD, June 3, 2020
[Video] Deepak L. Bhatt, MD, MPH, Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital Heart & Vascular Center, and Professor of Medicine at Harvard Medical School, is interviewed by WebMD’s Chief Medical Officer to talk about the relations between COVID-19 and the heart.
The Collision of COVID-19 and the U.S. Health System
Annals of Internal Medicine, June 2, 2020
The coronavirus disease 2019 (COVID-19) pandemic is wreaking havoc and causing fear, illness, suffering, and death across the world. This outbreak lays bare the fault lines in our society and highlights that the United States could have been better prepared for the pandemic had we a more equitable and just health care system. As leaders in the American College of Physicians (ACP), we have helped develop ACP’s wide-ranging policies on health care in the United States. The College has adopted a “health in all policies” approach, integrating health considerations into policymaking across sectors to improve the health and health care of all communities and people, which we believe, if enacted, would have enabled the United States to more effectively respond to the COVID-19 pandemic.
Heart pump authorized for emergency use for right HF, decompensation from COVID-19
Helio | Cardiology Today, June 2, 2020
Abiomed announced that the FDA issued an emergency use authorization for a temporary heart pump for patients with COVID-19 with right HF or decompensation including pulmonary embolism. The emergency use authorization indicates that the heart pump (Impella RP) can be used in the hospital for temporary right ventricular support for up to 14 days for the treatment of patients with acute right HF or decompensation associated with COVID-19 complications, according to a press release from the company.
Frailty Score Joins the COVID-19 Battle
MedPage Today, June 2, 2020
A clinical frailty scale (CFS) developed at Nova Scotia’s Dalhousie University is helping doctors predict outcomes of older COVID-19 patients in urgent care settings and decide who gets more aggressive treatments. Because the CFS quickly offers a quantitative number, it avoids age bias when it comes to treatment decisions, said Kenneth Rockwood, MD, of the Division of Geriatric Medicine, Department of Community Health and Epidemiology, School of Health Administration, whose team developed the scale.
Mass gatherings, erosion of trust upend coronavirus control
Associated Press, June 1, 2020
Protests erupting across the nation over the past week — and law enforcement’s response to them — are threatening to upend efforts by health officials to track and contain the spread of coronavirus just as those efforts were finally getting underway. Health experts need newly infected people to remember and recount everyone they’ve interacted with over several days in order to alert others who may have been exposed, and prevent them from spreading the disease further. But that process, known as contact tracing, relies on people knowing who they’ve been in contact with — a daunting task if they’ve been to a mass gathering.
Drop in type A aortic dissection surgeries during COVID-19 pandemic raises concerns
Helio | Cardiology Today, June 1, 2020
During the height of the COVID-19 pandemic in New York, cases requiring surgical repair of acute type A aortic dissection dropped dramatically in the city, according to a new report. The decline may be due to an increase in patients dying at home and/or not wanting to present to the ED because of fear of acquiring COVID-19 at the hospital, the researchers wrote in the Journal of the American College of Cardiology. “From conversations with other aortic surgeons in New York City and posts on social media, we noticed we were all seeing fewer and fewer acute cases, whether aortic dissections or STEMIs,” Ismail El-Hamamsy, MD, PhD, FRCSC, system director of aortic surgery and Randall B. Griepp Professor of Cardiovascular Surgery at The Mount Sinai Health System, told Healio.
Learning Through Rapid Change: Summer COVID-19 Education Series
American College of Cardiology, June 1, 2020
The COVID-19 pandemic has and will continue to take its toll on clinicians and the health care system. Each day brings new discoveries — provoking more unanswered questions and posing unprecedented challenges. The Summer COVID-19 Education Series will present weekly episodes of targeted and easy-to-consume education to address current and evolving knowledge and practice gaps to help you manage your patients with COVID-19 and heart disease both now and into the future. No registration is required. Join us June 6, 2020, 9:00 a.m. – 12:15 p.m. ET.
COVID-19: ACE2centric infective disease?
Hypertension, June 1, 2020
Diffuse pulmonary inflammation, endothelial inflammation and enhanced thrombosis are cardinal features of COVID-19, the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These features are reminiscent of several adverse reactions triggered by angiotensin II, and opposed by angiotensin, in many experimental models. Experimental and clinical data suggest that the imbalance between angiotensin II and angiotensin1-7 resulting from the ACE2 down-regulation and deficiency induced by the virus might play an important role in conditioning some clinical features of COVID-19. Thus, from a mechanistic standpoint, this novel disease could be considered a sort of ‘ACE2centric’ infective disease. Some potential therapeutic implications including recombinant ACE2, angiotensin1-7 and angiotensin II type 1 receptor blockers are under clinical testing.
Did Volunteers Tolerate This Coronavirus Vax?
MedPage Today, May 30, 2020
24-hour news cycle is just as important to medicine as it is to politics, finance, or sports. New information is posted daily, but keeping up can be a challenge. As an aid for readers and for a little amusement, here is a 10-question quiz based on the news of the week. Topics include coronavirus vaccine research, LGBTQ deaths by suicide, and hypertension. After taking the quiz, scroll down in your browser window to find the correct answers and explanations, as well as links to the original articles.
Coronavirus May Be a Blood Vessel Disease, Which Explains Everything
Elemental, May 29, 2020
In April, blood clots emerged as one of the many mysterious symptoms attributed to Covid-19, a disease that had initially been thought to largely affect the lungs in the form of pneumonia. Quickly after came reports of young people dying due to coronavirus-related strokes. Next it was Covid toes — painful red or purple digits. What do all of these symptoms have in common? An impairment in blood circulation. Add in the fact that 40% of deaths from Covid-19 are related to cardiovascular complications, and the disease starts to look like a vascular infection instead of a purely respiratory one.
The COVID-19 Rehabilitation Pandemic
Age and Aging, May 29, 2020
The COVID-19 pandemic and the response to the pandemic are combining to produce a tidal wave of need for rehabilitation. Rehabilitation will be needed for survivors of COVID-19, many of whom are older, with underlying health problems. In addition, rehabilitation will be needed for those who have become deconditioned as a result of movement restrictions, social isolation, and inability to access healthcare for pre-existing or new non-COVID-19 illnesses. Delivering rehabilitation in the same way as before the pandemic will not be practical, nor will this approach meet the likely scale of need for rehabilitation. This commentary reviews the likely rehabilitation needs of older people both with and without COVID-19 and discusses how strategies to deliver effective rehabilitation at scale can be designed and implemented in a world living with COVID-19.
COVID-19: An ACP Physician’s Guide
American College of Physicians, Updated May 28, 2020
This ACP Physician’s Guide and its collected national resources support physicians as they respond to the Covid-19 pandemic. The ACP-produced resource can be easily accessed on handheld devices and other computers to provide a clinical overview of infection control and patient care guidance. CME credit and MOC points available.
Admission of patients with STEMI since the outbreak of the COVID-19 pandemic. A survey by the European Society of Cardiology
European Heart Journal – Quality of Care and Clinical Outcomes, May 28, 2020
COVID-19, caused by the SARS-CoV2 virus, is a highly contagious condition which may lead to severe respiratory failure and premature mortality. The present pandemic has required the rapid redeployment and mobilization of substantial healthcare resources worldwide, along with widespread “lockdown”, with estimates suggesting that by April over a third of the global population was under some form of restrictive measure. 3 Over the same time, a reduction in hospital admissions for acute non-communicable conditions, such as myocardial infarction and stroke has been reported in several countries. Presented here are the results of a survey conducted by the ESC probing the perception of cardiologists and cardiovascular nurses with regards to ST-elevation myocardial infarction (STEMI) admissions to their hospitals.
ED visits for suspected MI, stroke down during COVID-19 pandemic
Helio | Cardiology Today, May 28, 2020
Many U.S. institutions have reported significant declines in the volume of patients presenting to the ED with potential MI or stroke due to fears associated with COVID-19. Some health care professionals have noticed a dropoff in acute MI and stroke cases since the United States began taking stringent measures to combat the pandemic in mid-March, likely caused by patients delaying their presentation to the ED with MI or stroke or not seeking medical attention at all.
Asymptomatic transmission during the COVID-19 pandemic and implications for public health strategies
Clinical Infectious Diseases, May 28, 2020
SARS-CoV-2 spread rapidly within months despite global public health strategies to curb transmission by testing symptomatic patients and encouraging social distancing. Here, we summarize rapidly emerging evidence highlighting transmission by asymptomatic and pre-symptomatic individuals. Viral load of asymptomatic carriers is comparable to symptomatic patients, viral shedding is highest before symptom onset suggesting high transmissibility before symptoms. Within universally tested subgroups, surprisingly high percentages of COVID-19 positive asymptomatic individuals were found. Asymptomatic transmission was reported in several clusters.
Researchers scramble to meet ‘urgent need’ for COVID-19 vaccine
Helio | Infectious Disease News, May 28, 2020
As deaths from COVID-19 increase to more than 100,000 in the United States, institutions around the world are working to develop an effective vaccine. Kaiser Permanente Washington Health Research Institute in Seattle is conducting a phase 1 clinical trial to assess an investigational vaccine, while Johnson & Johnson plans to initiate human clinical studies for its potential candidate by September. According to WHO, there are 10 COVID-19 vaccine candidates under clinical evaluation and an additional 115 candidates in preclinical evaluation. In a remote hearing of the U.S. Senate Committee on Health, Education, Labor & Pensions earlier this month, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said an NIH-directed trial is expected to enter phase 2/3 in late spring or early summer.
Biomedical scientist to explore how COVID-19 and cardiovascular disease are linked
University of California Riverside, May 27, 2020
Changcheng Zhou, a professor of biomedical sciences at the UCR School of Medicine, will join colleagues in studying the potential impact of COVID-19 on the cardiovascular system. Recent data shows COVID-19 patients with hypertension and cardiovascular disease are highly susceptible to their more severe effects, with mortality rates up to three times higher than the general population. In collaboration with the American Heart Association COVID-19 Coordinating Center, the team will aim to address unanswered questions following the long-term effects of the coronavirus crisis on cardiovascular and cerebrovascular health.
Seniors with COVID-19 taking ACE inhibitors have lower hospitalization risk
Yale News, May 27, 2020
A Yale-led study suggests that older COVID-19 patients taking ACE inhibitors for hypertension have a lower risk of hospitalization for the novel coronavirus. The study is posted on the medical pre-print website medRxiv and has been submitted for peer-reviewed publication. Researchers analyzed retrospective data from about 10,000 patients with hypertension who tested positive for SARS-CoV-2, the virus that causes COVID-19. All patients were enrolled in either Medicare Advantage or a commercially insured health care plan and had a prescription for at least one hypertension medication, such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB).
ASPC: Telehealth, fast response to CV symptoms crucial during COVID-19 pandemic
Helio | Cardiology Today, May 27, 2020
During the COVID-19 pandemic, cardiologists can utilize telehealth to reach out to their patients without disruption and should encourage them to get CV symptoms addressed immediately, according to a scientific statement. The statement by the American Society for Preventive Cardiology (ASPC), published in the American Journal of Preventive Cardiology, also focused on emphasizing the importance of CV health and continued care. “The COVID-19 pandemic has created several disruptions in outpatient care for patients at higher risk of cardiovascular disease, and we are concerned about future waves of preventable cardiovascular events that will follow,” Amit Khera, MD, MSc, FACC, FAHA, professor of internal medicine at UT Southwestern Medical Center, director of the UT Southwestern Preventive Cardiology Program and president of the ASPC, said in a press release.
Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review
Annals of Internal Medicine, May 27, 2020
Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). This article summarizes evidence (from Four randomized controlled trials, 10 cohort studies, and 9 case series) about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19).
Management of hypertension in COVID-19
World Journal of Cardiology | May 26, 2020
The ACE2 receptor plays a central role in severe acute respiratory syndrome coronavirus 2 host cell entry and propagation. It has therefore been postulated that angiotensin converting enzyme inhibitors and angiotensin receptor blockers may upregulate ACE2 expression and thus increase susceptibility to infection. We suggest that alternative anti-hypertensive agents should be preferred among individuals who may be exposed to this increasingly common and potentially lethal virus.
Could the D614 G substitution in the SARS-CoV-2 spike (S) protein be associated with higher COVID-19 mortality?
International Journal of Infectious Diseases |May 26, 2020
Increasing number of deaths due to COVID-19 pandemic has raised serious global concerns. Higher testing capacity and ample intensive care availability could explain lower mortality in some countries compared to others. Nevertheless, it is also plausible that the SARS-CoV-2 mutations giving rise to different phylogenetic clades are responsible for the obvious death disparities around the world. Current research literature linking the genetic make-up of SARS-CoV-2 with fatality is lacking. Here, we suggest that this disparity in fatality rates may be attributed to SARS-CoV-2 evolving mutations and urge the international community to begin addressing the phylogenetic clade classification of SARS-CoV-2 in relation to clinical outcomes.
UN virus therapy trial pauses hydroxychloroquine testing
Associated Press | May 25, 2020
The World Health Organization said Monday that it will temporarily drop hydroxychloroquine — the anti-malarial drug U.S. President Trump says he is taking — from its global study into experimental COVID-19 treatments, saying that its experts need to review all available evidence to date. In a press briefing, WHO director-general Tedros Adhanom Ghebreyesus said that in light of a paper published last week in the Lancet that showed people taking hydroxychloroquine were at higher risk of death and heart problems, there would be “a temporary pause” on the hydroxychloroquine arm of its global clinical trial.
Cost-Related Antihypertensive Medication Nonadherence: Action in the Time of COVID-19 and Beyond
American Journal of Hypertension | May 25, 2020
In this issue of the American Journal of Hypertension, Dr. Jing Fang and colleagues add to the existing literature on cost-related medication nonadherence (CRMN) with their study, “Association between cost-related medication nonadherence and hypertension management among US adults.”7 In their study, they examined the percentage of US adults who experienced CRMN using data from the 2017 National Health Interview Survey (NHIS). The authors also investigated the association of CRMN with current antihypertensive medication use and self-reporting having normal blood pressure. The NHIS is a nationally representative study of non-institutionalized US adults conducted annually by the National Center for Health Statistics and the 2017 NHIS included 78,132 participants.
Has the curve flattened?
Johns Hopkins University & Medicine | May 25, 2020
Countries around the world are working to “flatten the curve” of the coronavirus pandemic. Flattening the curve involves reducing the number of new COVID-19 cases from one day to the next. This helps prevent healthcare systems from becoming overwhelmed. When a country has fewer new COVID-19 cases emerging today than it did on a previous day, that’s a sign that the country is flattening the curve. On a trend line of total cases, a flattened curve looks how it sounds: flat. On the charts on this page, which show new cases per day, a flattened curve will show a downward trend in the number of daily new cases. This analysis uses a 5-day moving average to visualize the number of new COVID-19 cases and calculate the rate of change.
Op-Ed: Is coronavirus infectivity linked to blood pressure medication?
Digital Journal | May 23, 2020
As part of the review into why some people are more prone to contracting a coronavirus infection, some scientists are finding a connection with high blood pressure medication. Other researchers, however, have yet to find evidence. As part of considering why some people are more prone to contracting the SARS-CoV-2 coronavirus than others, it is important to factor in how the virus spreads. The primary way is through water or mucus droplets, which are passed from person to person. Second to this is direct contact – from hand to infected surface, and then to the nose, mouth or eyes. Viral RNA can be recovered from a variety of surfaces, including plastic and steel several days after it was originally deposited
Co-infections among patients with COVID-19: the need for combination therapy with non-anti-SARS-CoV-2 agents?
Journal of Microbiology, Immunology and Infection | May 23, 2020
Co-infection has been reported in patients with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, but there is limited knowledge on co-infection among patients with coronavirus disease 2019 (COVID-19). The prevalence of co-infection was variable among COVID-19 patients in different studies, however, it could be up to 50% among non-survivors. Co-pathogens included bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumonia, Legionella pneumophila and Acinetobacter baumannii; Candida species and Aspergillus flavus; and viruses such as influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus.
Rethinking the role of blood pressure drugs in COVID-19
Chemical and Engineering News | May 22, 2020
Once thought to boost levels of ACE2, the novel coronavirus’s doorway into human cells, these widely used medicines are now contenders to treat the respiratory disease. All it takes is a simple cough: a sharp intake of breath, the compression of air in the lungs, and the throat flying open to spew air, spit, and mucus. If the person coughing is infected with the novel coronavirus, it comes along for the ride on droplets, which can travel up to 50 miles per hour. When someone breathes those droplets in, the virus can get into the lungs. Once inside, it uses a spike protein on its surface to target an enzyme—ACE2—scattered over the outsides of the airway’s cells. If the spike protein connects with its target, the coronavirus uses ACE2 as a door to slip inside the cell. Thus begins an infection.
Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis
The Lancet | May 22, 2020
In this large multinational real-world analysis, we did not observe any benefit of hydroxychloroquine or chloroquine (when used alone or in combination with a macrolide) on in-hospital outcomes, when initiated early after diagnosis of COVID-19. Each of the drug regimens of chloroquine or hydroxychloroquine alone or in combination with a macrolide was associated with an increased hazard for clinically significant occurrence of ventricular arrhythmias and increased risk of in-hospital death with COVID-19. The use of hydroxychloroquine or chloroquine in COVID-19 is based on widespread publicity of small, uncontrolled studies, which suggested that the combination of hydroxychloroquine with the macrolide azithromycin was successful in clearing viral replication.
CDC Releases Tips For Managing Workplace Fatigue During COVID-19
American College of Cardiology | May 20, 2020
Health care workers are working longer hours and more shifts with stressful and physically demanding work due to the COVID-19 pandemic. This has left health care teams with less time to sleep and care for their own well-being, increasing the risk for extreme fatigue. Workplace fatigue can increase the risk for injury, infections, illnesses and mental health disorders.
How to Discover Antiviral Drugs Quickly
New England Journal of Medicine | May 20, 2020
We urgently need effective drugs for coronavirus disease 2019 (Covid-19), but what is the quickest way to find them? One approach that sometimes seems akin to a “Hail Mary” pass in American football is to hope that drugs that have worked against a different virus (such as hepatitis C or Ebola) will also work against Covid-19. Alternatively, we can be rational and specifically target proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) so as to interrupt its life cycle.
COVID-19 Tip of the Week
American College of Cardiology | May 20, 2020
Dr. Kim Eagle provides a weekly tip for clinicians on the front lines of the COVID-19 pandemic. Dr. Eagle explains a recent Annals of Internal Medicine article, which examines false-negative rates according to time since exposure.
Study Finds Seniors with COVID-19 Taking Hypertension Medication at Lower Risk of Hospitalization, Clinical Trial to Follow Immediately
Business Wire | May 19, 2020
A study completed by UnitedHealth Group (NYSE: UNH) with the Yale School of Medicine found that older COVID-19 patients with hypertension taking angiotensin-converting enzyme (ACE) inhibitors had a lower risk of COVID-19 hospitalization. A pragmatic clinical trial will be a critical next step. The study, which was recently submitted for peer-reviewed publication, analyzed retrospective data from about 10,000 patients testing positive for SARS-CoV-2 who were enrolled in Medicare Advantage or commercially insured plans, and had a prescription for one or more anti-hypertensive medications. The use of ACE inhibitors was associated with an almost 40% lower risk of COVID-19 hospitalization for Medicare Advantage patients.
Study projects US COVID-19 deaths to triple by end of year
The Hill, May 19 | 2020
A new study suggests the number of Americans who will die after contracting the novel coronavirus is likely to more than triple by the end of the year, even if current social distancing habits continue for months on end. The study, conducted by the Comparative Health Outcomes, Policy and Economics Institute at the University of Washington’s School of Pharmacy, found that 1.3 percent of those who show symptoms of COVID-19 die, an infection fatality rate that is 13 times higher than a bad influenza season.
The Covid-19 Pandemic and the Incidence of Acute Myocardial Infarction
New England Journal of Medicine | May 19, 2020
During the Covid-19 pandemic, reports have suggested a decrease in the number of patients presenting to hospitals because of emergency conditions such as acute myocardial infarction. We examined this issue using data from Kaiser Permanente Northern California, a large integrated health care delivery system with 21 medical centers and 255 clinics that provides comprehensive care for more than 4.4 million persons throughout Northern California. We examined patient characteristics and weekly incidence rates of hospitalization for acute myocardial infarction STEMI or NSTEMI among adults in the Kaiser Permanente system before and after the first reported death from Covid-19 in Northern California on March 4, 2020.
Right Heart Problems Spell Trouble for COVID-19 Patients
MedPageToday | May 18, 2020
Right ventricular (RV) dilation was linked to in-hospital mortality among COVID-19 patients at one New York City hospital, researchers reported. That abnormal echocardiographic finding was observed in 31% of the 110 people hospitalized with the infection from March 26 to April 22 of this year, according to a group led by Edgar Argulian, MD, MPH, of Mount Sinai Morningside Hospital in New York City. Rates of in-hospital mortality were 41% for this subset with RV dilation compared with 11% among other patients.
Cardiac dysfunction and thrombocytopenia-associated multiple organ failure inflammation phenotype in a severe paediatric case of COVID-19
The Lancet | May 18, 2020
A 16-year-old male with chromosome 18q deletion and well controlled epilepsy presented to the Children’s National Hospital (Washington, DC, USA) with haemodynamic shock after 4 days of fever and one generalised seizure at home. Although he had no respiratory symptoms, his mother was ill with a cough. Upon arrival (hospital day 0), he was intubated and resuscitated with intravenous crystalloid fluids (>40 mL/kg), an intravenous epinephrine infusion (0·4 μg/kg per min), and intravenous stress-dose hydrocortisone (100 mg). His initial infectious disease evaluation, including testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), did not detect an infectious aetiology; however, a second test for SARS-CoV-2 on day 3 after hospital admission was positive.
Moderna posts ‘positive’ early data for COVID-19 vaccine
FiercePharma | May 18, 2020
With eyes on a phase 3 study this summer, Moderna posted promising early data for its COVID-19 vaccine. The jab prompted an immune response similar to those seen in patients who have recovered from the disease. The study, being run by the National Institute of Allergy and Infectious Diseases (NIAID), is testing three dose levels of the vaccine, mRNA-1273, given in two injections a month apart. Eight patients who received the two lowest dose levels—25 micrograms and 100 micrograms—developed neutralizing antibodies against SARS-CoV-2, the virus that causes COVID-19, two weeks after receiving their second dose.
Cardiac Surgery during the COVID‐19 Pandemic: Perioperative Considerations and Triage Recommendations
Journal of the American Heart Association | May 16, 2020
The epidemic caused by the SARS-CoV-2 virus, the etiologic agent of Coronavirus Disease 2019 (COVID-19), represents the third introduction of the highly pathogenic coronavirus into the population. COVID-19 and the previous iterations, SARS-CoV-1 in 2002 and Middle East Respiratory Syndrome (MERS-CoV) in 2012, are RNA viruses transmitted from animals to humans that can cause a spectrum of respiratory symptoms, ranging from mild symptoms (cough, fever, malaise, anosmia, fatigue, loss of appetite) to acute respiratory distress syndrome (ARDS). Due to the highly contagious nature of COVID-19, the unprecedented rate of spread on a global scale, and lack of effective treatment, healthcare systems around the world are already overwhelmed and their infrastructure strained. Accordingly, several societies have offered guidelines and recommendations on how to conserve resources and triage patients that need more urgent care.
Impact of the COVID-19 pandemic on ongoing cardiovascular research projects: considerations and adaptations
European Journal of Cardiovascular Nursing |May 16, 2020
COVID-19, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was initially identified in December 2019 as a case of pneumonia in Wuhan, China. The World Health Organization declared the outbreak a public health emergency of international concern on 30 January 2020, and a pandemic on 11 March 2020. This outbreak is considered the biggest global health crisis of our times, leading to severe socioeconomic disruption, closures of educational institutions, significant mortality, shortages of medical supplies and major unprecedented challenges for healthcare systems around the world. The impact on healthcare extends beyond COVID-19 management and entails important considerations for clinical services, research and education across primary care and most medical subspecialties; the deferral of activities deemed non-essential (i.e. unrelated to COVID-19 planning and management) are commonplace during this pandemic.
CMS issues more rule changes to cope with COVID-19 — are they enough?
Healio | Primary Care | May 15, 2020
CMS recently announced a second round of regulatory waivers and rule changes to expand care to the nation’s seniors and provide health care systems flexibility. Though physicians applauded the new measures, they also said that CMS could do more to help primary care physicians recover from the financial toll of COVID-19.
Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults
Annals of Internal Medicine | May 15, 2020
The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in COVID-19 disease susceptibility, severity, and treatment is unclear. Two retrospective cohort studies found that ACEI and ARB use was not associated with a higher likelihood of receiving a positive SARS-CoV-2 test result, and 1 case–control study found no association with COVID-19 illness in a large community (moderate-certainty evidence). Fourteen observational studies, involving a total of 23 565 adults with COVID-19, showed consistent evidence that neither medication was associated with more severe COVID-19 illness (high-certainty evidence). Four registered randomized trials plan to evaluate ACEIs and ARBs for treatment of COVID-19.
Coronavirus May Pose a New Risk to Younger Patients: Strokes
New York Times | May 14, 2020
Doctors have reported a flurry of cases in Covid-19 patients — including a healthy 27-year-old emergency medical technician in Queens. After a month in the hospital, he is learning to walk again. Ravi Sharma was doubled over on his bed when his father found him. He’d had a bad cough for a week and had self-quarantined in his bedroom. As an emergency medical technician, he knew he was probably infected with the coronavirus. Now, Mr. Sharma, 27, could not move the right side of his body, and could only grunt in his father’s direction. His sister, Bina Yamin, on the phone from her home in Fort Wayne, Ind., could hear the sounds. “Call 911,” she told her father. “I think Ravi’s having a stroke.” She was right.
The New Normal: Key Considerations for Effective Serious Illness Communication Over Video or Telephone During the Coronavirus Disease 2019 (COVID-19) Pandemic
Annals of Internal Medicine | May 14, 2020
On 4 March 2019, a year before the coronavirus disease 2019 (COVID-19) pandemic descended on the United States, a doctor delivered difficult news to a 78-year-old man who was in the intensive care unit with advanced chronic obstructive pulmonary disease. His granddaughter, sitting beside him, recorded the interaction on her cellphone. First, we see the nurse roll in a piece of equipment with a screen. She attends to other tasks in the patient’s room while a man on the screen—the doctor—begins to speak. We hear only parts of what he says: damage to the man’s lungs cannot be fixed; morphine may help him feel better. The granddaughter asks her grandfather if he understands; we cannot hear his response. The clip ends. The man died the next day. His family, deeply dissatisfied with the interaction, released the video to the press, and articles with titles like “Doctor delivers end-of-life news via robot” were broadly disseminated.
Assessment of Deaths From COVID-19 and From Seasonal Influenza
JAMA Internal Medicine | May 14, 2020
As of early May 2020, approximately 65 000 people in the US had died of coronavirus disease 2019 (COVID-19),1 the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This number appears to be similar to the estimated number of seasonal influenza deaths reported annually by the Centers for Disease Control and Prevention (CDC). This apparent equivalence of deaths from COVID-19 and seasonal influenza does not match frontline clinical conditions, especially in some hot zones of the pandemic where ventilators have been in short supply and many hospitals have been stretched beyond their limits. The demand on hospital resources during the COVID-19 crisis has not occurred before in the US, even during the worst of influenza seasons. Yet public officials continue to draw comparisons between seasonal influenza and SARS-CoV-2 mortality, often in an attempt to minimize the effects of the unfolding pandemic.
COVID-19, hypertension and cardiovascular diseases: Should we change the therapy?
Pharmacological Research | May 13, 2020
The coronavirus disease (COVID-19) has spread all around the world in a very short period of time. Recent data are showing significant prevalence of arterial hypertension and cardiovascular diseases (CVD) among patients with COVID-19, which raised many questions about higher susceptibility of patients with these comorbidities to the novel coronavirus, as well as the role of hypertension and CVD in progression and the prognosis of COVID-19 patients.
Inequity in Crisis Standards of Care
New England Journal of Medicine | May 13, 2020
In Racism without Racists, Eduardo Bonilla-Silva articulates why “color blindness,” an ethos based on the belief that race is no longer relevant, is contradictory and harmful. Color-blind policies, such as race-neutral mortgage practices and Medicare and Medicaid rules, have resulted in discrimination against black people and greater burdens on communities of color. To insist on color blindness is to deny the experience of people of color in a highly racialized society and to absolve oneself of any role in the process. Many clinicians and policymakers are therefore alarmed by recent state-based crisis standards of care (CSCs) that provide a color-blind process for determining whether a patient with Covid-19 respiratory failure lives or dies.
Preventing a Parallel Pandemic — A National Strategy to Protect Clinicians’ Well-Being
New England Journal of Medicine | May 13, 2020
The Covid-19 pandemic, which had killed more than 60,000 Americans by May 1, has been compared with Pearl Harbor and September 11 — cataclysmic events that left indelible imprints on the U.S. national psyche. Like the volunteers who flooded into Manhattan after the World Trade Center attacks, the health care providers working on the front lines of the Covid-19 pandemic will be remembered by history as heroes. These courageous people are risking their lives, threatened not only by exposure to the virus but also by pervasive and deleterious effects on their mental health.
‘No Intubation’: Seniors Fearful Of COVID-19 Are Changing Their Living Wills
Kaiser Health News | May 12, 2020
Last month, Minna Buck revised a document specifying her wishes should she become critically ill. “No intubation,” she wrote in large letters on the form, making sure to include the date and her initials. Buck, 91, had been following the news about COVID-19. She knew her chances of surviving a serious bout of the illness were slim. And she wanted to make sure she wouldn’t be put on a ventilator under any circumstances. “I don’t want to put everybody through the anguish,” said Buck, who lives in a continuing care retirement community in Denver. For older adults contemplating what might happen to them during this pandemic, ventilators are a fraught symbol, representing a terrifying lack of personal control as well as the fearsome power of technology.
With little data, doctors struggle to decide which Covid-19 patients should get remdesivir
STAT | May 12, 2020
Now that the federal government has begun distributing the experimental Covid-19 drug remdesivir, hospitals are in a bind. So far, it’s the only medication that has shown benefit for coronavirus patients in rigorous studies. But there isn’t enough for everyone who’s eligible. That leaves doctors with a wrenching ethical decision: Who gets the drug, and who doesn’t? As if the question wasn’t hard enough on moral grounds alone, it’s made even trickier by a dearth of data: Clinicians still don’t have the fine-grained study results showing which patients are most likely to benefit from the medication.
How COVID-19’s egregious impact on minorities can trigger change
American Medical Association, May 12, 2020
There have been more than 1 million cases of COVID-19 in the U.S., leading to tens of thousands of deaths. Since the start of the pandemic, tens of millions have lost their jobs with many losing their health insurance too. The impact on the nation’s minorities has been particularly harsh. So severe, in fact, that one physician suggested in a JAMA Viewpoint essay that the enormity of the pandemic’s impact on African Americans and other racial and ethnic minorities may create the will that finally leads to meaningful action on health inequity.
ACE2: the molecule that helps coronavirus invade your cells
The Conversation, May 12, 2020
The more we learn about the science behind COVID-19, the more we are beginning to understand the vital role a single molecule in our bodies plays in how we contract the disease. That molecule, angiotensin-converting enzyme 2, or ACE2, essentially acts as a port of entry that allows the coronavirus to invade our cells and replicate. It occurs in our lungs, but also in our heart, intestines, blood vessels and muscles. And it may be behind the vastly different death rates we are seeing between men and women.
COVID-19 Update
American Medical Association | May 11, 2020
AMA experts and health professionals discuss how senior physicians are contributing their experience and expertise during the COVID-19 pandemic.
Men’s blood contains greater concentrations of enzyme that helps COVID-19 infect cells
European Society of Cardiology | May 11, 2020
This finding may explain why men with heart failure suffer more from the coronavirus than women. Evidence from a large study of several thousand patients shows that men have higher concentrations of angiotensin-converting enzyme 2 (ACE2) in their blood than women. Since ACE2 enables the coronavirus to infect healthy cells, this may help to explain why men are more vulnerable to COVID-19 than women. The study, published in the European Heart Journal, also found that heart failure patients taking drugs targeting the renin-angiotensin-aldosterone system (RAAS), such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), did not have higher concentrations of ACE2 in their blood.
Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic
Journal of the American College of Cardiology | May 2020
The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients. First, those with COVID-19 and pre-existing cardiovascular disease have an increased risk of severe disease and death. Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism. Third, therapies under investigation for COVID-19 may have cardiovascular side effects. Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions. Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become hosts or vectors of virus transmission.
Collateral Effect of Covid-19 on Stroke Evaluation in the United States
The New England Journal of Medicine | May 8, 2020
The effect of the Covid-19 pandemic on medical care for conditions other than Covid-19 has been difficult to quantify. Any decrease in care for patients with acute conditions such as ischemic stroke may be consequential because timely treatment may decrease the incidence of disability. We used the numbers of patients in a commercial neuroimaging database associated with the RAPID software platform (iSchemaView) as a surrogate for the quantity of care that hospitals provided to patients with acute ischemic stroke. This software system is typically used to select patients who may benefit from endovascular thrombectomy by identifying occlusions of major brain arteries or regions of the brain with potentially reversible ischemia that have not become infarcted. Imaging data with demographic information are uploaded in real time to a data repository.
100 Days Into COVID-19, Where Do We Stand?
WebMD | May 7, 2020
The United States saw its first confirmed case of COVID-19 on Jan. 20. By the end of February, we had our first American death. We’ve now passed the 100-day mark, and the numbers are alarming, with 1.2 million confirmed cases here. More than 70,000 people have died here. And because testing has been limited, experts say those numbers are really much larger. So obviously, it’s bad. But is it getting better? “We’re not doing well at all,” says Jeffrey Shaman, PhD, a professor of environmental health sciences at Columbia University Mailman School of Public Health, who has led work to model national projections. “We had our first confirmed case the same day as South Korea. We have six times as many people, but 100 times as many cases.”
Results from 11 AHA-funded COVID-19 studies expected within months
Cardiology News | May 7, 2020
The American Heart Association (AHA) has awarded $1.2 million in grants to teams at 11 institutions to study COVID-19 effects on the cardiovascular and cerebrovascular systems. Work is set to start in June, with findings reported in as few as 6 months. The Cleveland Clinic will coordinate the efforts, collecting and disseminating the findings. There were more than 750 research proposals in less than a month after the association announced its COVID-19 and its Cardiovascular Impact Rapid Response Grant initiative.
Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past
Journal of Clinical Virology | June 2020
Coronavirus disease 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus strain disease, has recently emerged in China and rapidly spread worldwide. This novel strain is highly transmittable and severe disease has been reported in up to 16% of hospitalized cases. More than 600,000 cases have been confirmed and the number of deaths is constantly increasing. COVID-19 hospitalized patients, especially those suffering from severe respiratory or systemic manifestations, fall under the spectrum of the acutely ill medical population, which is at increased venous thromboembolism risk. Thrombotic complications seem to emerge as an important issue in patients infected with COVID-19.
Eagle’s Eye View: COVID-19 Tip of the Week [Podcast]
🎧 American College of Cardiology | May 6, 2020
Dr. Kim Eagle provides a weekly tip for clinicians on the front lines of the COVID-19 pandemic. This week highlights remdesivir, an antiviral drug that appears to have some benefit in COVID-19 patients.
New angiotensin studies in COVID-19 give more reassurance
Cardiology News, May 6 | 2020
Four more studies of the relationship of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) with COVID-19 have been published in the past few days in top-tier peer-reviewed journals, and on the whole, the data are reassuring. Although all the studies are observational in design and have some confounding factors, overall, the results do not suggest that continued use of ACE inhibitors and ARBs causes harm. However, there are some contradictory findings in secondary analyses regarding possible differences in the effects of the two drug classes.
ACE2, COVID-19, and ACE Inhibitor and ARB Use during the Pandemic: The Pediatric Perspective
Hypertension | May 5, 2020
Potential but unconfirmed risk factors for coronavirus disease 2019 in adults and children may include hypertension, cardiovascular disease, and chronic kidney disease, as well as the medications commonly prescribed for these conditions, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Coronavirus binding to angiotensin-converting enzyme 2, a crucial component of the renin-angiotensin-aldosterone system, underlies much of this concern. Children are uniquely impacted by the coronavirus but the reasons are unclear. This review will highlight the relationship of coronavirus disease 2019 with hypertension, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, and lifetime risk of cardiovascular disease from the pediatric perspective.
Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19)
JAMA Cardiology | May 5, 2020
What is the association of use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) with testing positive for coronavirus disease 2019 (COVID-19)? In this cohort study of 18 472 patients, 1322 (7.2%) were taking ACEIs and 982 (5.3%) were taking ARBs. A positive COVID-19 test result was observed in 1735 (9.4%) tested patients, and among all patients with positive test results, 116 (6.7%) were taking ACEIs, and 98 (5.6%) were taking ARBs; there was no association between ACEI/ARB use and testing positive for COVID-19 (overlap propensity score–weighted odds ratio, 0.97; 95% CI, 0.81-1.15).
Study to determine incidence of novel coronavirus infection in U.S. children begins
National Institutes of Health | May 4, 2020
A study to help determine the rate of novel coronavirus infection in children and their family members in the United States has begun enrolling participants. The study, called Human Epidemiology and Response to SARS-CoV-2 (HEROS), also will help determine what percentage of children infected with SARS-CoV-2, the virus that causes COVID-19, develop symptoms of the disease. In addition, the HEROS study will examine whether rates of SARS-CoV-2 infection differ between children who have asthma or other allergic conditions and children who do not.
RAAS Inhibitors Not Linked to Higher COVID-19 Risks
Renal & Urology News | May 4, 2020
Inhibitors of the renin-angiotensin-aldosterone system (RAAS) do not appear to increase the risk of COVID-19 or its severity, according to the findings of 3 studies published on May 1 in the New England Journal of Medicine. Physicians have been concerned about a potential increased risk of COVID-19 related to medications that act on the RAAS because the viral receptor is angiotensin-converting enzyme 2 (ACE2).
ACC, Other CV Societies Issue Guide to Safely Resume Cardiovascular Procedures, Diagnostic Tests
American College of Cardiology | May 4, 2020
American College of Cardiology together with other North American cardiovascular societies has issued a framework for ethically and safely reintroducing invasive cardiovascular procedures and diagnostic tests after the initial peak of the COVID-19 pandemic. The COVID-19 pandemic has forced appropriate, but significant, restrictions on routine medical care, including invasive procedures to treat heart disease and diagnostic tests to diagnose heart disease.
Renin–Angiotensin–Aldosterone System Inhibitors and Risk of Covid-19
New England Journal of Medicine | May 1, 2020
There is concern about the potential of an increased risk related to medications that act on the renin–angiotensin–aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). The study assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference.
COVID-19 Practice Management Resource
American College of Physicians | May 1, 2020
The ACP provides this toolkit intended to help practices now and in the coming weeks make adjustments due to COVID-19. Any new clinical guidance for physicians will be posted on this ACP page including telehealth coding and billing information, state and private payer policies, practice financial assistance and more.
Patients With Familial Hypercholesterolemia at Higher Risk for Cardiac Complications From COVID-19
Endocrinology Advisor | May 1, 2020
Individuals with novel coronavirus disease 2019 (COVID-19) who have familial hypercholesterolemia (FH) may be at higher risk for cardiac complications and atherosclerotic cardiovascular disease (ASCVD) in the long-term, according to study results published in the Journal of Internal Medicine. FH is characterized by a lifelong a 2- to 3-fold increase in plasma low-density lipoprotein-cholesterol concentration. If left untreated, FH may lead to premature ASCVD and a higher risk for acute coronary events during middle age.
COVID-19: Caring for Patients With Cardiovascular Disease in the Outpatient Setting
Pharmacy Times | May 1, 2020
It has been just over 2 months since the first United States reported case of coronavirus disease 2019 (COVID-19), a viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Everyday life has been subject to many, previously inconceivable changes over the past several weeks. Each day, there are new data pouring in from around the globe and it is becoming more difficult to stay on top of the information. The number of cases just surpassed 1 million in the United States, putting the global total at just more than 3 million, as of the writing of this article on April 29, 2020. The Centers for Disease Control and Prevention and the Johns Hopkins Coronavirus Resource Center both point to 1 million cases by this day.
Trial To Determine if Hypertension Drug Reduces COVID-19 Severity
Technology Networks | May 1, 2020
Researchers at University of California San Diego School of Medicine have launched a clinical trial to investigate whether a drug approved for treating high blood pressure, heart failure and diabetic kidney disease might also reduce the severity of COVID-19 infections, lowering rates for intensive care unit admissions, the use of mechanical ventilators and all-cause mortality. The trial will be randomized, double-blind and placebo-controlled, the gold standard for clinical trials. It will involve multiple sites, with the University of California San Diego as coordinating institution. Up to 560 participants will be recruited, either presenting with COVID-19 symptoms at emergency departments or currently hospitalized with the disease caused by the novel coronavirus, SARS-CoV-2. The trial is expected to run one year.
Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19
New England Journal of Medicine | May 1, 2020
Coronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context. Using an observational database from 169 hospitals, the 8910 patients with Covid-19 for whom discharge status was available at the time of the analysis, a total of 515 died in the hospital and 8395 survived to discharge. The factors we found to be independently associated with an increased risk of in-hospital death were an age greater than 65 years, coronary artery disease, heart failure, cardiac arrhythmia, chronic obstructive pulmonary disease, and current smoking.
Covid-prompted 400% rise in engagement led this home health startup to emerge from stealth
MedCity News | April 30, 2020
Tomorrow Health, a home health medical equipment and supplies startup founded in 2018, was planning to fly under the radar until August but huge demand and interest since Covid-19 hit led it to emerge from stealth this week. Startups come out of stealth for a variety of reasons but what’s common to the unveiling is that they always follow a predetermined calendar. A pandemic, of course, can wreak havoc on the best-laid plans. But for New York based Tomorrow Health Covid-19 is a crisis that equals a great opportunity.
Nearly 6 in 10 Oregonians Who Died of COVID-19 Had Heart Disease, State Says
Willamette Week | April 30, 2020
Oregon passed a bleak milestone today, announcing deaths 100 and 101 from the novel coronavirus. But the more significant data about COVID-19 was released without fanfare Tuesday afternoon: The Oregon Health Authority disclosed comorbidity data, or underlying conditions, for COVID-19 deaths in the state. The data show that nearly 6 in 10 of the victims of COVID-19 suffered from heart disease. Nearly 1 in 3 had diabetes. Almost a quarter of the deaths are of former smokers, but just one out of the 73 cases the OHA reviewed was a current smoker at the time they contracted the virus.
Remdesivir shows success in large COVID-19 trial. Will become ‘new standard of care,’ Fauci says.
LiveScience | April 29, 2020
The drug remdesivir significantly reduces the time it takes for COVID-19 patients to recover, as compared with a placebo treatment, according to a large, international study. “The data shows that remdesivir has a clear-cut, significant, positive effect in diminishing the time to recovery,” Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), said in an interview with NBC News today (April 29). Patients treated with remdesivir took an average of 11 days to recover as compared with 15 days for those who received a placebo, he said.
Rare inflammatory syndrome seen in US child with Covid-19
CNN | April 29, 2020
US doctors say they may have seen a possible complication of coronavirus infection in a young child: a rare inflammatory condition called Kawasaki disease. National Health Service England sent an alert to doctors and on Sunday the Paediatric Intensive Care Society tweeted it out to members. It warned about a small increase in cases of critically ill children with “common overlapping features of toxic shock syndrome and atypical Kawasaki disease with blood parameters” with some children testing positive for COVID-19.
Widely Used Surgical Masks Are Putting Health Care Workers At Serious Risk
Kaiser Health News | April 29, 2020
With medical supplies in high demand, federal authorities say health workers can wear surgical masks for protection while treating COVID-19 patients — but growing evidence suggests the practice is putting workers in jeopardy. The Centers for Disease Control and Prevention recently said lower-grade surgical masks are “an acceptable alternative” to N95 masks unless workers are performing an intubation or another procedure on a COVID patient that could unleash a high volume of virus particles.
US hits 1 million COVID-19 cases as states take on testing
CIDRAP News (Center for Infectious Disease Research and Policy) | April 28, 2020
The US case count for COVID-19 topped 1 million cases today, meaning the country has accounts for a third of all reported cases of the novel coronavirus in the world. In total, a tracker maintained by Johns Hopkins University shows 1,002,498 cases, including 57,533 fatalities. The milestone comes a day after the world surpassed 3 million cases in the 4 months since the virus was first detected in Wuhan, China. Less than 1 month ago—on April 2—the global total hit 1 million cases.
CDC Adds Six Symptoms to COVID-19 List
WebMD | April 28, 2020
The CDC has added several new symptoms to its list for the coronavirus: chills, muscle pain, headache, sore throat, repeated shaking with chills and a loss of taste or smell. The six new symptoms join the existing list with fever, cough and shortness of breath or difficulty breathing. The expanded list could help those who are trying to identify whether they have symptoms related to COVID-19. With a limited number of test kits available, those who want to take a test typically must show symptoms first.
Infectious Diseases Society of America Guidelines on Infection Prevention in Patients with Suspected or Known COVID-19
Infectious Diseases Society of America (ISDA) | April 27, 2020
IDSA formed a multidisciplinary guideline panel including front-line clinicians, infectious disease specialists, experts in infection control and guideline methodologists with representation from the disciplines of preventive care, public health, medical microbiology, pediatrics, critical care medicine and gastroenterology. The process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and grey literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. The IDSA guideline panel agreed on eight recommendations and provided narrative summaries of other interventions undergoing evaluations.
Discussing COVID-19 and hypertension
Medical News Today | April 26, 2020
Hypertension, or high blood pressure, is highly prevalent in the United States and beyond. As the COVID-19 pandemic continues, researchers are keen to understand whether hypertension or the drugs that treat it might interact with the virus. To date, the novel coronavirus, SARS-CoV-2, has reached every continent on Earth other than Antarctica. The disease that it causes —COVID-19—has led to the deaths of thousands of people. Risk factors are of particular interest to both scientists and the public alike.
COVID-19 Quick Notes From FDA, CMS, HHS and Others
Cardiology | April 25, 2020
An overview of recent information from the FDA, CMS, HHS and more to help guide addressing COVID-19.
Report Proposes COVID-19 National Surveillance Plan
JAMA Health Forum | April 24, 2020
As state governments continue to focus on mitigating further spread of the SARS-CoV-2 coronavirus through stay-in-place orders, building a national COVID-19 surveillance system is crucial for containing transmission of the virus now and preparing for future waves of the infection, according to a new report issued by the Duke-Margolis Center for Health Policy.
ACEI/ARB Use in COVID-19 Patients With Hypertension
American College of Cardiology | April 24, 2020
What is the association between in-hospital use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) and all-cause mortality in COVID-19 patients with hypertension? The authors concluded that among hospitalized COVID-19 patients with hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers.
Child Abuse Awareness Month During the Coronavirus Disease 2019 Pandemic
JAMA Pediatrics | April 24, 2020
April is Child Abuse Awareness month, even during the coronavirus disease 2019 (COVID-19) pandemic. Social isolation, the public health measure now in place across the world, is also a proven risk factor for child abuse. Other risks include stress, uncertain access to food and housing, and worries about making ends meet. Owing to the current COVID-19 pandemic, we recognize that parents and caregivers feel overwhelmed with these stresses. They may be experiencing job loss, childcare struggles, and schedule changes.
Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area
Journal of the American Medical Association | April 22, 2020
In this case series that included 5700 patients hospitalized with COVID-19 in the New York City area, the most common comorbidities were hypertension, obesity, and diabetes. A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%).
Thrombosis and COVID-19: FAQs for Current Practice
Cardiology | April 22, 2020
An FAQ on the potential impact of COVID-19 on thrombotic and/or bleeding risk from ACC’s Science and Quality Committee summarize the current data on the risk, potential need for hemostasis/coagulation testing, VTE prophylaxis, and therapeutic anticoagulation in patients with COVID-19 without confirmed/suspected thrombosis.
The New Pandemic Threat: People May Die Because They’re Not Calling 911
American Heart Association | April 22, 2020
Leaders of major national organizations – dedicated to saving people from heart disease and stroke – speak out. Reports from the front lines of hospitals indicate a marked drop in the number of heart attacks and strokes nationally. But, COVID-19 is definitely not stopping people from having heart attacks, strokes and cardiac arrests. We fear it is stopping people from going to the hospital and that can be devastating. You might think a hospital is the last place you should go now. That’s why we – the leaders of major national organizations dedicated to saving people from heart disease and stroke – feel it’s necessary to say this loud and clear: Calling 911 immediately is still your best chance of surviving or saving a life.
Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection
Journal of the American Medical Association | April 22, 2020
Since December 2019, a pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally. A spectrum of disease severity has been reported, with main symptoms that include fever, fatigue, dry cough, myalgia, and dyspnea. Previous strains of coronavirus have been demonstrated to invade the central nervous system through the olfactory neuroepithelium and propagate from within the olfactory bulb. Furthermore, nasal epithelial cells display the highest expression of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2, in the respiratory tree. This study evaluated prevalence, intensity, and timing of an altered sense of smell or taste in patients with SARS-CoV-2 infections.
Lost on the Frontline
Kaiser Health News | April 22, 2020
America’s health care workers are dying. In some states, medical staff account for as many as 20% of known coronavirus cases. They tend to patients in hospitals, treating them, serving them food and cleaning their rooms. Others at risk work in nursing homes or are employed as home health aides. Some of them do not survive the encounter. Many hospitals are overwhelmed and some workers lack protective equipment or suffer from underlying health conditions that make them vulnerable to the highly infectious virus. Many cases are shrouded in secrecy. “Lost on the Frontline” is a collaboration between The Guardian and Kaiser Health News that aims to document the lives of health care workers in the U.S. who die from COVID-19, and to understand why so many are falling victim to the pandemic.
Thrombosis and COVID-19: FAQs for Current Practic
Cardiology Magazine | April 22, 2020
An FAQ on the potential impact of COVID-19 on thrombotic and/or bleeding risk from ACC’s Science and Quality Committee summarize the current data on the risk, potential need for hemostasis/coagulation testing, VTE prophylaxis, and therapeutic anticoagulation in patients with COVID-19 without confirmed/suspected thrombosis.
Managing the Patient with AMI and COVID-19 – JACC Consensus Statement
emDocs.net | April 21, 2020
In the midst of the current COVID-19 pandemic, we often focus on pulmonary complications including hypoxemic respiratory failure. However, patients with COVID-19 are at risk of cardiac complications including heart failure, myocarditis, acute myocardial infarction (AMI), and several others. Even more challenging is that many patients with cardiovascular disease and AMI may not be infected with COVID-19. Fortunately, the American College of Cardiology, the American College of Emergency Physicians, and the Society for Cardiovascular Angiography and Interventions published a joint statement in the Journal of the American College of Cardiology, detailing personal protective equipment (PPE), ST elevation myocardial infarction (STEMI) and NSTEMI management, emergency medical systems (EMS), and systems of care.
Health Care Workers Are Scared, Sad, Exhausted—and Angry
Scientific American | April 21, 2020
Front line health care professionals, particularly nurses, physician assistants and doctors, are experiencing a range of complex emotions during the COVID-19 pandemic. They risk their lives to save others. They place their loved ones at risk because of their exposure. This makes them fearful. They are forced to make hard decisions concerning life and death, and witness and support those patients die alone and often painfully. This makes them sad. This is the state of affairs in a number of hot spots within the United States and around the world. But there is another common emotion they may be experiencing that is less talked about: anger.
ST-Segment Elevation in Patients With COVID-19
American College of Cardiology | April 20, 2020
The investigators included patients with confirmed COVID-19 who had ST-segment elevation on electrocardiography from six New York hospitals in this case series. Patients with COVID-19 who had nonobstructive disease on coronary angiography or had normal wall motion on echocardiography in the absence of angiography were presumed to have noncoronary myocardial injury.
CDC’s Failed Coronavirus Tests Were Tainted With Coronavirus, Feds Confirm
Ars Technica | April 20, 2020
A federal investigation found CDC researchers not following protocol. As the new coronavirus took root across America, the US Centers for Disease Control and Prevention sent states tainted test kits in early February that were themselves seeded with the virus, federal officials have confirmed. The contamination made the tests uninterpretable, and—because testing is crucial for containment efforts—it lost the country invaluable time to get ahead of the advancing pandemic.
AHA calls for more hospital support in next COVID-19 bill
Modern Healthcare | April 19, 2020
The American Hospital Association on Sunday said hospitals still need more funding to provide care and ensure they have adequate supplies for their workforce. In a letter to House Minority Leader Kevin McCarthy (R-Calif.), the association thanked him for supporting additional hospital funding and said they still must be a priority as their finances take a hit from the pandemic.
US coronavirus death toll tops 40,000 as researchers call for more testing before reopening economy
CNN | April 19, 2020
The United States’ coronavirus death toll topped 40,000 on Sunday afternoon, according to data from Johns Hopkins University. The 40,461 deaths are among more than 755,533 coronavirus cases, the university’s Covid-19 tracker says.
The grim milestone was reached as Harvard researchers warned that if the country wants the economy to open back up — and stay that way — testing must go up to at least 500,000 people per day.
How does coronavirus kill? Clinicians trace a ferocious rampage through the body, from brain to toes
Science | April 17, 2020
On rounds in a 20-bed intensive care unit (ICU) one recent day, physician Joshua Denson assessed two patients with seizures, many with respiratory failure and others whose kidneys were on a dangerous downhill slide. Days earlier, his rounds had been interrupted as his team tried, and failed, to resuscitate a young woman whose heart had stopped. All shared one thing, says Denson, a pulmonary and critical care physician at the Tulane University School of Medicine. “They are all COVID positive.” As the number of confirmed cases of COVID-19 surges past 2.2 million globally and deaths surpass 150,000, clinicians and pathologists are struggling to understand the damage wrought by the coronavirus as it tears through the body. They are realizing that although the lungs are ground zero, its reach can extend to many organs including the heart and blood vessels, kidneys, gut, and brain.
JACC Paper Outlines Implications, Considerations For Thrombotic Disease Patients During COVID-19 Pandemic
Journal of the American College of Cardiology | April 17, 2020
The COVID-19 pandemic has implications in the prevention and management of patients with thrombotic and thromboembolic disease, according to a state-of-the-art review published April 17 in the Journal of the American College of Cardiology. Behnood Bikdeli, MD, MS, et al., summarize the pathogenesis, epidemiology, treatment and available outcomes data related to thrombotic disease in COVID-19 patients, as well as management of thrombotic events in patients without COVID-19, providing clinical guidance when possible. The authors outline investigational therapies for COVID-19 and their interactions, as well as other considerations, when used in patients taking antiplatelet agents or anticoagulants.
How to Obtain a Nasopharyngeal Swab Specimen
New England Journal of Medicine | April 17, 2020
Collection of specimens from the surface of the respiratory mucosa with nasopharyngeal swabs is a procedure used for the diagnosis of Covid-19 in adults and children. The procedure is also commonly used to evaluate patients with suspected respiratory infection caused by other viruses and some bacteria. This video describes the collection of nasopharyngeal specimens for detection of Covid-19, the illness caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Those with High Blood Pressure Are at a Greater Risk for COVID-19
CNN Health | April 17, 2020
As the novel coronavirus sweeps the globe, people with high blood pressure are among those who are at heightened risk for more severe complications should they contract Covid-19. “If you get an extraordinary viral disease that will damage your lungs, you need a heart that can work with how your body responds to the virus,” said Dr. Maria Carolina Delgado-Lelievre, an assistant professor of medicine at the University of Miami’s Miller School of Medicine.
Audio Interview: Caring for Patients with Covid-19
New England Journal of Medicine | April 16, 2020
The rapid spread of SARS-CoV-2, a novel coronavirus that emerged in late 2019, and the resulting Covid-19 disease has been labeled a Public Health Emergency of International Concern by the World Health Organization. What physicians need to know about transmission, diagnosis, and treatment is the subject of ongoing updates from infectious disease experts at the Journal. In this audio interview conducted on April 15, 2020, the editors discuss making clinical decisions for patients with Covid-19 as we await evidence from randomized trials.
Early peek at data on Gilead coronavirus drug suggests patients are responding to treatment
STAT | April 16, 2020
Chicago hospital treating severe Covid-19 patients with Gilead Sciences’ antiviral medicine remdesivir in a closely watched clinical trial is seeing rapid recoveries in fever and respiratory symptoms, with nearly all patients discharged in less than a week, STAT has learned. Remdesivir was one of the first medicines identified as having the potential to impact SARS-CoV-2, the novel coronavirus that causes Covid-19, in lab tests. The entire world has been waiting for results from Gilead’s clinical trials, and positive results would likely lead to fast approvals by the Food and Drug Administration and other regulatory agencies. If safe and effective, it could become the first approved treatment against the disease.
Thanks to COVID-19, Cardiology Fellows Gain Unexpected Skills but Risk Losing Others
tctMD/the heart beat | April 16, 2020
Trading catheters for central lines, many fellows are stepping into roles they’d never imagined, while programs adapt. For fellows, this time of year is usually filled with planning solo cases, finalizing contracts, and looking forward to the next stages of their careers. This year is not like other years. The COVID-19 pandemic has swept through cardiology training programs across the country, sending program directors scrambling to maintain some sense of a normal curriculum through virtual platforms. Fellows, on the other hand, are trading their planned education for shifts in ICU wards, all while doing their best to ensure safety and sanity.
Healthcare Workers With COVID-19 Relatively Young, Mostly Female: CDC
tctMD/the heart beat | April 15, 2020
Although the majority did not require hospitalization, severe disease and death were reported across age groups. The Centers for Disease Control and Prevention (CDC) has released its first report on US healthcare personnel (HCP) who’ve developed COVID-19, with details published in Morbidity and Mortality Weekly Report. Fully three-quarters of these providers were women, and the median age was 42 years. Less than half had an underlying medical condition. Although most healthcare workers did not require hospitalization, severe disease and death were reported across age groups.
An Age/Old Dilemma? Pulling Senior Cardiologists From the Front During COVID-19
tctMD/the heart beat | April 14, 2020
Some US hospitals have asked doctors over a certain age to work from home, but surge situations may mean all hands on deck. Around the United States, hospital leaders either preparing for or already coping with an influx of patients with COVID-19 are facing a difficult dilemma: how do you protect your most senior—and most vulnerable—physicians from infection without losing their decades of knowledge and experience? In many places, that means asking older cardiologists to work from home or otherwise away from the front lines to lessen their risk of contracting SARS-CoV-2 but still contribute to the fight.
Children With COVID-19 May Not Show Symptoms, Still Spread Disease to Others
American College of Cardiology | Apr 13, 2020
Some children with COVID-19 may experience mild illness and may not show symptoms, but they can still spread the disease to others, according to the first report from the Centers for Disease Control and Prevention (CDC) that examines data on the disease in children and published in Morbidity and Mortality Weekly Report. The report analyzed data from 149,760 laboratory-confirmed COVID-19 cases in the U.S. occurring between Feb. 12 and April 2. Among the 149,082 (99.6%) reported cases for which age was known, 2,572 (1.7%) were among children <18 years.
Cardiac Rehab During COVID-19: Telehealth, Unpaid Heroes Step Up to Help at Home
tctMD/the heart beat | April 10, 2020
Experts say there’s no better time than now to keep preventive CV care going and forge a new path for outpatient cardiac rehab. Although patients across the United States can no longer physically go to cardiac rehab facilities, advocates are working behind the scenes to make sure patients in need do not fall between the cracks while the COVID-19 crisis rages on. “In speaking with program directors and being involved with various forums, it is clear that the majority of cardiac rehab programs across the country right now are at a standstill,” Laurence Sperling, MD (Emory University School of Medicine, Atlanta, GA), told TCTMD. The scope of the problem is large, with 2,685 cardiac rehab programs and 1,758 pulmonary rehab programs across the United States that typically provide services to hundreds of thousands of patients.
Structural Heart Interventions in the Midst of COVID-19: Today’s Advice, Tomorrow’s Unknowns
tctMD/the heart beat | April 13,2020
Which TAVR can be deferred, which MV should be repaired? Advice from ACC, SCAI, and the heart of the US pandemic. Many transcatheter interventions for structural heart disease have been cancelled or postponed indefinitely amid the COVID-19 pandemic, but some patients can’t wait, according to a new consensus statement. The joint document issued last week by the American College of Cardiology (ACC) and the Society for Cardiovascular Angiography and Interventions (SCAI) proposes triage considerations to help heart teams decide which procedures should happen ASAP.
Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization to Decontaminate Millions of N95 Respirators
FDA | April 12, 2020
The U.S. Food and Drug Administration issued an emergency use authorization (EUA) that has the potential to decontaminate approximately 4 million N95 or N95-equivalent respirators per day in the U.S. for reuse by health care workers in hospital settings. “Our nation’s health care workers are among the many heroes of this pandemic and we need to do everything we can to increase the availability of the critical medical devices they need, like N95 respirators,” said FDA Commissioner Stephen M. Hahn, M.D. “FDA staff continue to work around the clock, across government and with the private sector to find solutions. This authorization will help provide access to millions of respirators so our health care workers on the front lines can be better protected and provide the best care to patients with COVID-19.”
Why African-Americans may be especially vulnerable to COVID-19
Science News | April 10, 2020
COVID-19 was called the great equalizer. Nobody was immune; anybody could succumb. But the virus’ spread across the United States is exposing racial fault lines, with early data showing that African-Americans are more likely to die from the disease than white Americans.
Don’t Overlook COVID-19’s Cardiovascular Footprint, Say NYC Physicians
tctMD/the heart beat | April 9,2020
A case series from this United States hot spot shows the diversity of CV presentations and the care individual patients may require. Cardiovascular risks sparked by COVID-19—and their diverse presentations—are becoming ever more apparent as the disease spreads worldwide. Clinicians are faced with developing unique diagnostic algorithms and treatment pathways to help these patients as patterns emerge.
Reinventing Cardiovascular Care in Two Weeks: An Industry Adapts to a Pandemic
MedAxiom | April 9, 2020
Healthcare as an industry is not known for its speed in making changes, instead being identified as steady and traditional. This is particularly true when considering the patient encounter or office visit; the experience today would largely mirror its corollary from 1980. However, when a worldwide pandemic came crashing down the U.S. provider community – in particular the cardiovascular community – responded in lightning speed. Within a matter of weeks, cardiovascular patient visits using telemedicine went from near zero to 75 percent. This is disruptive change that would make even a startup technology company proud. More importantly, it allowed critical patient care to continue and afforded providers a much-needed reduction in exposure. The reaction by the medical community thus far has been nothing short of heroic and provides a strong reason for optimism at a time when the world needs it most.
Guidance on treating COVID-19 patients with signs of acute heart attack
Science Daily, April 9 | 2020
Much remains unknown about COVID-19, but many studies already have indicated that people with cardiovascular disease are at greater risk of COVID-19. There also have been reports of ST-segment elevation (STE), a signal of obstructive coronary artery disease, in patients with COVID-19 who after invasive coronary angiography show no sign of the disease.
COVID-19 and Cardiology
European Society of Cardiology | April 9, 2020
The ESC is a vast, diverse community. We learn from each other so that we can give our patients the best possible care. Never has this been more important than during a pandemic. This page is designed to provide you with an array of useful resources, updated regularly.
AHA, ACC, HRS Caution Use of COVID-19 Therapies Hydroxychloroquine and Azithromycin in Cardiac Patients
Diagnostic and Interventional Cardiology | April 8, 2020
The scientific community is learning more about the impact and interaction of cardiovascular diseases with novel coronavirus (COVID-19, SARS-CoV-2), including the impact of drug therapies being used and their negative cardiovascular impact. Together, the American Heart Association (AHA), the American College of Cardiology (ACC) and the Heart Rhythm Society (HRS) April 8 jointly published a new guidance, “Considerations for Drug Interactions on QTc in Exploratory COVID-19 (Coronavirus Disease 19) Treatment,” to detail critical cardiovascular considerations in the use of hydroxychloroquine and azithromycin for the treatment of COVID-19.
French Hospital Stops Hydroxychloroquine Treatment for Covid-19 Patient Over Major Cardiac Risk
Newsweek | April 8, 2020
A hospital in France has had to stop an experimental treatment using hydroxychloroquine on at least one coronavirus patient after it became a “major risk” to their cardiac health.
The University Hospital Center of Nice (CHU de Nice) is one of many hospitals trialing hydroxychloroquine in COVID-19 patients. It announced it had been selected for the trial on March 22. A statement from the hospital said it was testing four experimental treatments, one of which included hydroxychloroquine. It hoped to establish its effectiveness and side effects of this and the other treatments being tested.
C.D.C. Releases Early Demographic Snapshot of Worst Coronavirus Cases
The New York Times | April 8, 2020
The agency’s study of hospitalizations for Covid-19 in March shows heightened numbers for those with underlying conditions, men and African-Americans. On March 1, there were 88 confirmed cases of the coronavirus in the United States. By month’s end, there were more than 170,000. The Centers for Disease Control and Prevention has compiled data on people who were hospitalized from the virus during that month to get a clearer demographic picture of infected patients who have required the most serious medical care.
Novel Coronavirus Information Center
Elsevier | Updated April 8, 2020
Elsevier’s free health and medical research on the novel coronavirus (SARS-CoV-2) and COVID-19. Under the Clinical information tab, you will find evidence-based skill guides and care
Hypertension and COVID-19
American Journal of Hypertension | April 6, 2020
The world is currently suffering from the outbreak of a pandemic caused by the severe acute respiratory syndrome coronavirus SARS-CoV-2 that causes the disease called COVID-19, first reported in Wuhan, Hubei Province, China on December 31, 2019. As of March 29, 2020, there have been 732153 confirmed cases of COVID-19 reported worldwide, with 34686 deaths. The clinical and epidemiological features of COVID-19 have been repeatedly published in the last few weeks. Interestingly, specific comorbidities associated with increased risk of infection and worse outcomes with development of increased severity of lung injury and mortality have been reported. The most common comorbidities in one report were hypertension (30%), diabetes (19%), and coronary heart disease (8%).
Heart Damage in COVID-19 Patients Puzzles Doctors
Scientific American | April 6, 2020
While the focus of the COVID-19 pandemic has been on respiratory problems and securing enough ventilators, doctors on the front lines are grappling with a new medical mystery. In addition to lung damage, many COVID-19 patients are also developing heart problems—and dying of cardiac arrest.
COVID-19: AHA Guidance on Hypertension, Latest on Angiotensin Link
Medscape | April 1, 2020
The American Heart Association (AHA) has issued new guidance for patients with hypertension during the COVID-19 outbreak. At the same time, several new review articles have been published further exploring the possible relationship between the renin-angiotensin system (RAS) and the virus.
Renin-Angiotensin System Blockers and the COVID-19 Pandemic
American Heart Association | March 25, 2020
During the spread of the severe acute respiratory syndrome coronavirus-2, some reports of data still emerging and in need of full analysis indicate that certain groups of patients are at risk of COVID-19. This includes patients with hypertension, heart disease, diabetes mellitus, and clearly the elderly. Many of those patients are treated with reninangiotensin system blockers.
ESC Council on Hypertension Says ACE-I and ARBs Do Not Increase COVID-19 Mortality
Diagnositc and Interventional Cardiology | March 16, 2020
The European Society of Cardiology (ESC) issued a statement March 13 recommending in novel coronavirus (COVID-19, and now clinically referred to as SARS‐CoV‐2) patients not discontinuing angiotensin converting enzyme inhibitors (ACE-i) or angiotensin receptor blockers (ARBs) used to control hypertension.
Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?
The Lancet | March 11, 2020
The most distinctive comorbidities of 32 non-survivors from a group of 52 intensive care unit patients with novel coronavirus disease 2019 (COVID-19) in the study by Xiaobo Yang and colleagues1 were cerebrovascular diseases (22%) and diabetes (22%).
Post–COVID 2021Conditions Among Adult COVID-19 Survivors Aged 18–64 and ≥65 Years — United States, March 2020–November
MMWR CDD | May 27, 2022
As more persons are exposed to and infected by SARS-CoV-2, reports of patients who experience persistent symptoms or organ dysfunction after acute COVID-19 and develop post-COVID conditions have increased. COVID-19 survivors have twice the risk for developing pulmonary embolism or respiratory conditions; one in five COVID-19 survivors aged 18–64 years and one in four survivors aged ≥65 years experienced at least one incident condition that might be attributable to previous COVID-19. Implementation of COVID-19 prevention strategies, as well as routine assessment for post-COVID conditions among persons who survive COVID-19, is critical to reducing the incidence and impact of post-COVID conditions, particularly among adults aged ≥65 years.
Diagnostic Accuracy of Chest Digital Tomosynthesis in Patients Recovering after COVID-19 Pneumonia
Tomography, April 24, 2022
Our purpose was to assess the diagnostic accuracy of traditional chest X-ray (CXR) and digital tomosynthesis (DTS) compared to computed tomography (CT) in detecting pulmonary interstitial changes in patients having recovered from severe COVID-19. This was a retrospective observational study, and received local ethics committee approval. Patients suspected of having COVID-19 pneumonia upon emergency department admission between 1 March and 31 August 2020, and who underwent CXR followed by DTS and CT, were considered. Inclusion criteria were as follows: (1) patients with previous SARS-CoV-2 infection proven by a positive RT-PCR on nasopharyngeal swabs performed upon admission to the hospital, and with complete clinical recovery; (2) a diagnosis of SARS-CoV-2-related ARDS, according to the Berlin criteria, during hospitalization; (3) no recent history of other lung disease; and (4) complete imaging follow-up by CXR, DTS, and CT for at least 6 months and up to one year. Analysis of DTS images was carried out independently by two radiologists with 16 and 10 years of experience in chest imaging, respectively. The following findings were evaluated: (1) ground-glass opacities (GGOs); (2) air-space consolidations with or without air bronchogram; (3) reticulations; and (4) linear consolidation. Indicators of diagnostic performance of RX and digital tomosynthesis were calculated using CT as a reference. All data were analyzed using R statistical software (version 4.0.2, 2020). Out of 44 patients initially included, 25 patients (17 M/8 F), with a mean age of 64 years (standard deviation (SD): 12), met the criteria and were included. The overall average numbers of findings confirmed by CT were GGOs in 11 patients, lung consolidations in 8 patients, 7 lung interstitial reticulations, and linear consolidation in 20 patients. DTS showed a significantly higher diagnostic accuracy compared to CXR in recognizing interstitial lung abnormalities—especially GGOs (p = 0.0412) and linear consolidations (p = 0.0009). The average dose for chest X-ray was 0.10 mSv (0.07–0.32), for DTS was 1.03 mSv (0.74–2.00), and for CT scan was 3 mSv. Conclusions: According to our results, DTS possesses a high diagnostic accuracy, compared with CXR, in revealing lung fibrotic changes in patients who have recovered from COVID-19 pneumonia.
Fewer children hospitalized with asthma exacerbations during early days of COVID-19
Healio | Allergy/Asthma, April 22, 2022
Fewer children with asthma were hospitalized for exacerbations during the first few months of the COVID-19 pandemic compared with the previous year, although they presented with more severe symptoms, according to a recent study. Nada Alabdulkarim, MBBS, a pediatric resident at Children’s National Hospital in Washington, D.C., and colleagues examined 50 cases between April 1 and Sept. 30, 2020, as well as 243 controls from the same period in 2019, in the study published in Annals of Allergy, Asthma & Immunology. The children in the pandemic cases were significantly older compared with those in the control cases (9.8 ± 4.3 years vs. 6.7 ± 3.8 years; P < .0001). There also was a trend toward fewer Hispanic children among the pandemic cases compared with the controls. The control cases had a greater proportion of children with eczema (32.1% vs. 16%; P = .02) and food allergies (18.5% vs. 6%; P = .03), although the researchers did not find any significant differences in the prevalence of other comorbidities. Considering its use an objective measure of increased severity of asthma exacerbations at presentation, the researchers said that intravenous magnesium sulfate was more frequently administered during the pandemic compared with the control period (84% vs. 63%; P = .001). In fact, there was a 16% higher likelihood of patients receiving magnesium sulfate with each year increase in age. African American and Hispanic patients had higher odds of receiving magnesium sulfate in the ED as well.
Exercise Limitation 3 Months Post Severe COVID-19 Lung Infection
Pulmonology Advisor, April 22, 2022
At 3 months following a severe COVID-19 pulmonary infection, a third of patients enrolled in a cohort study report a limitation in exercise capacity, which is associated with decreased pulmonary function, reduced skeletal muscle mass and function, but no significant impairment in cardiac function. The ongoing prospective, monocentric COVulnerability study was conducted at Henri Mondor Hospital, APHP, Creteil, France. Results of the analysis were published in the journal Respiratory Research. The researchers sought to establish the frequency of long-term exercise capacity limitation among survivors of COVID-19 pulmonary infection and the factors that are associated with the impairment. Patients were enrolled between March 2020 and July 2021 who had been diagnosed with a severe COVID-19 pulmonary infection, hospitalized at an intensive care unit or at a conventional care unit for more than 7 days, and had received oxygen therapy during hospitalization (>3 L/min). Of the 220 survivors of a severe COVID-19 pulmonary infection included in the COVulnerability cohort, 105 agreed to undergo a follow-up assessment at 3 months following hospital discharge. The participants underwent cardiopulmonary exercise testing, pulmonary function tests, echocardiography, and skeletal muscle mass evaluation. Results of the study showed that among the 105 participants, 35% had a reduced exercise capacity (peak oxygen uptake [VO2peak] <80% predicted). Patients with reduced exercise capacity, compared with those with normal exercise capacity, were more often men (89.2% vs 67.6%, respectively; P =.015), were significantly more likely to have been diagnosed with diabetes (45.9% vs 17.6%, respectively; P =.002), were significantly more likely to have been diagnosed with renal dysfunction (21.6% vs 17.6%, respectively; P =.006), and had a significantly lower body mass index (25.79±3.68 kg/m2 vs 29.07±5.24 kg/m2, respectively; P =.001). The participants did not differ, however, with respect to initial acute disease severity. Altered exercise capacity was associated with impaired pulmonary function, as evaluated by a significant decrease in forced vital capacity (FVC; P <.0001), forced expiratory volume in 1 second (FEV1; P <.0001), total lung capacity (P <.0001), and diffusing capacity of the lung for carbon monoxide (DLCO; P =.015).
Assessing clinical applicability of COVID-19 detection in chest radiography with deep learning
Scientific Reports, April 21, 2022
The coronavirus disease 2019 (COVID-19) pandemic has impacted healthcare systems across the world. Chest radiography (CXR) can be used as a complementary method for diagnosing/following COVID-19 patients. However, experience level and workload of technicians and radiologists may affect the decision process. Recent studies suggest that deep learning can be used to assess CXRs, providing an important second opinion for radiologists and technicians in the decision process, and super-human performance in detection of COVID-19 has been reported in multiple studies. In this study, the clinical applicability of deep learning systems for COVID-19 screening was assessed by testing the performance of deep learning systems for the detection of COVID-19. Specifically, four datasets were used: (1) a collection of multiple public datasets (284.793 CXRs); (2) BIMCV dataset (16.631 CXRs); (3) COVIDGR (852 CXRs) and 4) a private dataset (6.361 CXRs). All datasets were collected retrospectively and consist of only frontal CXR views. A ResNet-18 was trained on each of the datasets for the detection of COVID-19. It is shown that a high dataset bias was present, leading to high performance in intradataset train-test scenarios (area under the curve 0.55–0.84 on the collection of public datasets). Significantly lower performances were obtained in interdataset train-test scenarios however (area under the curve > 0.98). A subset of the data was then assessed by radiologists for comparison to the automatic systems. Finetuning with radiologist annotations significantly increased performance across datasets (area under the curve 0.61–0.88) and improved the attention on clinical findings in positive COVID-19 CXRs. Nevertheless, tests on CXRs from different hospital services indicate that the screening performance of CXR and automatic systems is limited (area under the curve < 0.6 on emergency service CXRs). However, COVID-19 manifestations can be accurately detected when present, motivating the use of these tools for evaluating disease progression on mild to severe COVID-19 patients.
Acute Upper Airway Disease Up in Children During Omicron Surge
Medical Professionals Reference | April 21, 2022
SARS-CoV-2-positive rates of acute pediatric upper airway infection (UAI) increased during the omicron surge, according to a research letter published online April 15 in JAMA Pediatrics. Blake Martin, MD, from University of Colorado in Aurora, and colleagues used data from the US National COVID Cohort Collaborative to assess whether cases of UAI among children increased when omicron became the dominant SARS-CoV-2 variant in the US. The analysis included children (younger than 19 years) with a positive SARS-CoV-2 test result in both the pre-omicron (March 1, 2020, to December 25, 2021) and omicron (December 26, 2021, to February17, 2022) periods. The researchers found that SARS-CoV-2-positive UAI rates increased with progression from the pre-omicron to omicron periods (1.5 vs 4.1%), with 46% of the 384 cases occurring during the omicron period. During this period, children with UAIs were more likely to be younger and Hispanic or Latino and less likely to receive dexamethasone or develop severe disease versus those in the pre-omicron period. More than 1 in 5 children hospitalized with SARS-CoV-2 and UAI developed severe disease. The proportion of children with a pediatric complex chronic condition was similar between the two periods. “While the rate of SARS-CoV-2 pediatric UAI is not overwhelmingly high, understanding this new clinical phenotype and the potential for acute upper airway obstruction may help guide therapeutic decision making,” the authors write.
Angiotensin receptor blockers tied to less ventilation, vasopressors in men with COVID-19
Healio | Pulmonology, April 21, 2022
Use of angiotensin receptor blockers (ARBs) was associated with less need for ventilation and vasopressors among men hospitalized with COVID-19, but not in women, according to research presented at the Society of Critical Care Medicine Congress. Research to date has demonstrated that men have worse COVID-19 outcomes than women, with a similar number of cases and no difference in mortality between sexes, but more hospitalizations and ICU admissions in men, Genevieve Rocheleau, MSc, summer research student at the University of British Columbia Centre for Health Lung Innovation in Critical Care Medicine and second-year medical student at the University of Limerick in Ireland, said during a presentation. The ARBs CORONA I study was conducted at 10 sites in Canada and enrolled 1,686 patients admitted to the hospital for acute COVID-19 (median age, 67 years; 61% men). Upon enrollment, 18% of patients were taking an ARB), 18% an angiotensin-converting enzyme (ACE) inhibitor and 64% neither an ARB nor ACE inhibitor. Patients presented with comorbidities known to increase risk for severe COVID-19, including hypertension in 53%, diabetes in 33%, chronic cardiac disease in 25% and chronic kidney disease in 14%. In this cohort, overall outcomes were worse in men than women. There was no difference in in-hospital or 28-day mortality, use of renal replacement therapy or time to hospital discharge. However, men had significantly greater odds of ICU admission (adjusted OR = 1.42; P = .008), need for invasive ventilation (aOR = 1.45; P = .006) and need for vasopressors (aOR = 1.46; P = .005), according to the abstract published in Critical Care Medicine. When the researchers evaluated outcomes based on ARB use, they found a different need for organ support with ARBs according to sex, Rocheleau said. Men taking ARBs were less likely to need ventilation (P = .006) or vasopressors (P = .044) compared with men not on ARBs, Rocheleau said.
Follow-Up CT Patterns of Residual Lung Abnormalities in Severe COVID-19 Pneumonia Survivors: A Multicenter Retrospective Study
Tomography, April 20, 2022
Prior studies variably reported residual chest CT abnormalities after COVID-19. This study evaluates the CT patterns of residual abnormalities in severe COVID-19 pneumonia survivors. All consecutive COVID-19 survivors who received a CT scan 5–7 months after severe pneumonia in two Italian hospitals (Reggio Emilia and Parma) were enrolled. Individual CT findings were retrospectively collected and follow-up CT scans were categorized as: resolution, residual non-fibrotic abnormalities, or residual fibrotic abnormalities according to CT patterns classified following standard definitions and international guidelines. In 225/405 (55.6%) patients, follow-up CT scans were normal or barely normal, whereas in 152/405 (37.5%) and 18/405 (4.4%) patients, non-fibrotic and fibrotic abnormalities were respectively found, and 10/405 (2.5%) had post-ventilatory changes (cicatricial emphysema and bronchiectasis in the anterior regions of upper lobes). Among non-fibrotic changes, either barely visible (n = 110/152) or overt (n = 20/152) ground-glass opacities (GGO), resembling non-fibrotic nonspecific interstitial pneumonia (NSIP) with or without organizing pneumonia features, represented the most common findings. The most frequent fibrotic abnormalities were subpleural reticulation (15/18), traction bronchiectasis (16/18) and GGO (14/18), resembling a fibrotic NSIP pattern. When multiple timepoints were available until 12 months (n = 65), residual abnormalities extension decreased over time. NSIP, more frequently without fibrotic features, represents the most common CT appearance of post-severe COVID-19 pneumonia.
How delivering cardiopulmonary resuscitation and basic life support skills training through places of worship can help save lives and address health inequalities
European Heart Journal, April 20, 2022
Early delivery of high-quality cardiopulmonary resuscitation (CPR) and rapid defibrillation strengthen the initial links of the chain of survival and can help improve out-of-hospital cardiac arrest (OHCA) outcomes. However, health inequalities exist in OHCA survival at regional and global levels, which reduces the chances of survival, with disproportionately lower CPR delivery rates seen in areas of socio-economic deprivation and ethnic minority groups. In the United Kingdom for example, the British Muslim and South Asian communities also have higher levels of health disparities in cardiovascular disease, diabetes, and physical activity, which can predispose them to poorer outcomes from OHCA. Thus, when developing and delivering training for the public, it is important to ensure that there is equitable access.
Effectiveness of Tocilizumab in Patients with Severe or Critical Lung Involvement in COVID-19: A Retrospective Study
Journal of Clinical Medicine, April 20, 2022
Acute lung injury is associated with dysfunctional immune response to SARS-CoV-2. This leads to CRS, which require immunomodulatory treatments aiming to limit the excessive production of cytokines. The literature so far indicates the effectiveness of tocilizumab in patients with COVID-19-associated pneumonia, but there is no clear evidence of its effectiveness in patients with at least 50% lung involvement; therefore, we aimed to bridge this gap in knowledge. Longitudinal data for 4287 patients with confirmed COVID-19 infection were collected. In total, 182 cases with lung involvement >50% and biochemical indicators of cytokine release storm (Il-6 >100 pg/mL) were selected and analyzed using non-parametric statistics and multivariate Cox models. Among the 182 included patients, 100 (55%) were treated with TCZ, while 82 (45%) did not receive TCZ. The groups were balanced regarding demographics, lung involvement and biochemical markers. Overall mortality in the group was 63.1%. Mortality in the TCZ group was 58.0% compared to 69.5% (n = 57) in the non-TCZ group (p = 0.023). In multivariate Cox proportional hazards models, intravenous administration of tocilizumab was associated with lower probability of ICU admission (HR: 0333 (CI: 0.159–0.700, p = 0.004)) and lower mortality (HR: 0.57306 (CI: 0.354–0.927, p = 0.023)). Tocilizumab is effective as a treatment in the most severely ill patients, in whom the level of lung involvement by the inflammatory process can exceed 50% with coexisting biochemical indices of cytokine storm (Il-6 > 100 pg/mL).
Bacterial Ventilator-Associated Pneumonia in COVID-19 Patients: Data from the Second and Third Waves of the Pandemic
Journal of Clinical Medicine, February 19, 2022
During the coronavirus disease 2019 (COVID-19) pandemic, many patients requiring invasive mechanical ventilation were admitted to intensive care units (ICU) for COVID-19-related severe respiratory failure. As a matter of fact, ICU admission and invasive ventilation increased the risk of ventilator-associated pneumonia (VAP), which is associated with high mortality rate and a considerable burden on length of ICU stay and healthcare costs. The objective of this review was to evaluate data about VAP in COVID-19 patients admitted to ICU that developed VAP, including their etiology (limiting to bacteria), clinical characteristics, and outcomes. The analysis was limited to the most recent waves of the epidemic. The main conclusions of this review are the following: (i) P. aeruginosa, Enterobacterales, and S. aureus are more frequently involved as etiology of VAP; (ii) obesity is an important risk factor for the development of VAP; and (iii) data are still scarce and increasing efforts should be put in place to optimize the clinical management and preventative strategies for this complex and life-threatening disease.
Matrix Metalloproteinases on Severe COVID-19 Lung Disease Pathogenesis: Cooperative Actions of MMP-8/MMP-2 Axis on Immune Response through HLA-G Shedding and Oxidative Stress
Biomolecules, April 19, 2022
Patients with COVID-19 predominantly have a respiratory tract infection and acute lung failure is the most severe complication. While the molecular basis of SARS-CoV-2 immunopathology is still unknown, it is well established that lung infection is associated with hyper-inflammation and tissue damage. Matrix metalloproteinases (MMPs) contribute to tissue destruction in many pathological situations, and the activity of MMPs in the lung leads to the release of bioactive mediators with inflammatory properties. We sought to characterize a scenario in which MMPs could influence the lung pathogenesis of COVID-19. Although we observed high diversity of MMPs in lung tissue from COVID-19 patients by proteomics, we specified the expression and enzyme activity of MMP-2 in tracheal-aspirate fluid (TAF) samples from intubated COVID-19 and non-COVID-19 patients. Moreover, the expression of MMP-8 was positively correlated with MMP-2 levels and possible shedding of the immunosuppression mediator sHLA-G and sTREM-1. Together, overexpression of the MMP-2/MMP-8 axis, in addition to neutrophil infiltration and products, such as reactive oxygen species (ROS), increased lipid peroxidation that could promote intensive destruction of lung tissue in severe COVID-19. Thus, the inhibition of MMPs can be a novel target and promising treatment strategy in severe COVID-19.
Assessment of Awake Prone Positioning in Hospitalized Adults With COVID-19—A Nonrandomized Controlled Trial
JAMA Internal Medicine, April 18, 2022
Awake prone positioning may improve hypoxemia among patients with COVID-19, but whether it is associated with improved clinical outcomes remains unknown. To determine whether the recommendation of awake prone positioning is associated with improved outcomes among patients with COVID-19–related hypoxemia who have not received mechanical ventilation. This pragmatic nonrandomized controlled trial was conducted at two academic medical centers (Vanderbilt University Medical Center and NorthShore University HealthSystem) during the COVID-19 pandemic. A total of 501 adult patients with COVID-19–associated hypoxemia who had not received mechanical ventilation were enrolled from May 13 to December 11, 2020. Patients were assigned 1:1 to receive either the practitioner-recommended awake prone positioning intervention (intervention group) or usual care (usual care group). Primary outcome analyses were performed using a bayesian proportional odds model with covariate adjustment for clinical severity ranking based on the World Health Organization ordinal outcome scale, which was modified to highlight the worst level of hypoxemia on study day 5. A total of 501 patients (mean [SD] age, 61.0 [15.3] years; 284 [56.7%] were male; and most [417 (83.2%)] were self-reported non-Hispanic or non-Latinx) were included. Baseline severity was comparable between the intervention vs usual care groups, with 170 patients (65.9%) vs 162 patients (66.7%) receiving oxygen via standard low-flow nasal cannula, 71 patients (27.5%) vs 62 patients (25.5%) receiving oxygen via high-flow nasal cannula, and 16 patients (6.2%) vs 19 patients (7.8%) receiving noninvasive positive-pressure ventilation. Nursing observations estimated that patients in the intervention group spent a median of 4.2 hours (IQR, 1.8-6.7 hours) in the prone position per day compared with 0 hours (IQR, 0-0.7 hours) per day in the usual care group. On study day 5, the bayesian posterior probability of the intervention group having worse outcomes than the usual care group on the modified World Health Organization ordinal outcome scale was 0.998 (posterior median adjusted odds ratio [aOR], 1.63; 95% credibility interval [CrI], 1.16-2.31). However, on study days 14 and 28, the posterior probabilities of harm were 0.874 (aOR, 1.29; 95% CrI, 0.84-1.99) and 0.673 (aOR, 1.12; 95% CrI, 0.67-1.86), respectively. Exploratory outcomes (progression to mechanical ventilation, length of stay, and 28-day mortality) did not differ between groups.
Invasive Respiratory Fungal Infections in COVID-19 Critically Ill Patients
Journal of Fungi, April 17, 2021
Patients with coronavirus disease 19 (COVID-19) admitted to the intensive care unit (ICU) often develop respiratory fungal infections. The most frequent diseases are the COVID-19 associated pulmonary aspergillosis (CAPA), COVID-19 associated pulmonary mucormycosis (CAPM) and the Pneumocystis jirovecii pneumonia (PCP), the latter mostly found in patients with both COVID-19 and underlying HIV infection. Furthermore, co-infections due to less common mold pathogens have been also described. Respiratory fungal infections in critically ill patients are promoted by multiple risk factors, including epithelial damage caused by COVID-19 infection, mechanical ventilation and immunosuppression, mainly induced by corticosteroids and immunomodulators. In COVID-19 patients, a correct discrimination between fungal colonization and infection is challenging, further hampered by sampling difficulties and by the low reliability of diagnostic approaches, frequently needing an integration of clinical, radiological and microbiological features. Several antifungal drugs are currently available, but the development of new molecules with reduced toxicity, less drug-interactions and potentially active on difficult to treat strains, is highly warranted. Finally, the role of prophylaxis in certain COVID-19 populations is still controversial and must be further investigated.
Residual lesions on chest-Xray after SARS-CoV-2 pneumonia: Identification of risk factors
Medicina Clínica, April 14, 2022
COVID-19 pneumonia is the most frequent clinical manifestation of this disease, and its long-term sequelae and possible progression to pulmonary fibrosis are still unknown. The aim of this study is a mid-term review of the sequelae on plain chest radiography (CXR) in patients with a previous diagnosis of COVID-19 pneumonia. Retrospective review of patients with a diagnosis of COVID-19 pneumonia, assessing the persistence of residual lesions in the control CXR and analysing their possible relationship with epidemiological factors, risk factors, treatments received and initial radiological patterns. A total of 143 patients (52 women and 91 men) were analysed. Mean age was 64 years. Radiological complete resolution (CR) was observed in 104 (73%) and partial resolution (PR) in 39 (27%). Of the risk factors only age was significantly related to persistence of residual lesions (OR 1.06 CI95% (1.02,1.10). In relation to treatments, significant differences were found with tocilizumab and glucocorticoids, where treated patients had a higher risk of residual lesions (OR 2.44 (1.03,5.80) and 3.05(1.43,6.51) respectively. In the analysis of radiological patterns, significant differences were observed in patients with peripheral condensations in the acute course and a pattern of early radiological worsening. A clinical-radiological dissociation was evident: 83% of patients with residual lesions had no respiratory symptoms. COVID19 pneumonias may have a slower radiological resolution in older patients with certain initial radiological patterns, but the development of pulmonary fibrosis in these patients is still questionable.
Modeling the disruption of respiratory disease clinical trials by non-pharmaceutical COVID-19 interventions
Nature Communications, April 13, 2022
Respiratory disease trials are profoundly affected by non-pharmaceutical interventions (NPIs) against COVID-19 because they perturb existing regular patterns of all seasonal viral epidemics. To address trial design with such uncertainty, we developed an epidemiological model of respiratory tract infection (RTI) coupled to a mechanistic description of viral RTI episodes. We explored the impact of reduced viral transmission (mimicking NPIs) using a virtual population and in silico trials for the bacterial lysate OM-85 as prophylaxis for RTI. Ratio-based efficacy metrics are only impacted under strict lockdown whereas absolute benefit already is with intermediate NPIs (eg. mask-wearing). Consequently, despite NPI, trials may meet their relative efficacy endpoints (provided recruitment hurdles can be overcome) but are difficult to assess with respect to clinical relevance. These results advocate to report a variety of metrics for benefit assessment, to use adaptive trial design and adapted statistical analyses. They also question eligibility criteria misaligned with the actual disease burden.
Fourth Dose of BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting
New England Journal of Medicine, April 13, 2022
With large waves of infection driven by the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), alongside evidence of waning immunity after the booster dose of coronavirus disease 2019 (Covid-19) vaccine, several countries have begun giving at-risk persons a fourth vaccine dose. To evaluate the early effectiveness of a fourth dose of the BNT162b2 vaccine for the prevention of Covid-19–related outcomes, we analyzed data recorded by the largest health care organization in Israel from January 3 to February 18, 2022. We evaluated the relative effectiveness of a fourth vaccine dose as compared with that of a third dose given at least 4 months earlier among persons 60 years of age or older. We compared outcomes in persons who had received a fourth dose with those in persons who had not, individually matching persons from these two groups with respect to multiple sociodemographic and clinical variables. A sensitivity analysis was performed with the use of parametric Poisson regression. The primary analysis included 182,122 matched pairs. Relative vaccine effectiveness in days 7 to 30 after the fourth dose was estimated to be 45% (95% confidence interval [CI], 44 to 47) against polymerase-chain-reaction–confirmed SARS-CoV-2 infection, 55% (95% CI, 53 to 58) against symptomatic Covid-19, 68% (95% CI, 59 to 74) against Covid-19–related hospitalization, 62% (95% CI, 50 to 74) against severe Covid-19, and 74% (95% CI, 50 to 90) against Covid-19–related death. The corresponding estimates in days 14 to 30 after the fourth dose were 52% (95% CI, 49 to 54), 61% (95% CI, 58 to 64), 72% (95% CI, 63 to 79), 64% (95% CI, 48 to 77), and 76% (95% CI, 48 to 91). In days 7 to 30 after a fourth vaccine dose, the difference in the absolute risk (three doses vs. four doses) was 180.1 cases per 100,000 persons (95% CI, 142.8 to 211.9) for Covid-19–related hospitalization and 68.8 cases per 100,000 persons (95% CI, 48.5 to 91.9) for severe Covid-19. In sensitivity analyses, estimates of relative effectiveness against documented infection were similar to those in the primary analysis. A fourth dose of the BNT162b2 vaccine was effective in reducing the short-term risk of Covid-19–related outcomes among persons who had received a third dose at least 4 months earlier.
Patients with allergic disorders have greater risk of high blood pressure and coronary heart disease
News Medical, April 11, 2022
Data from the National Health Interview Survey demonstrated adults with a history of allergic disorders have an increased risk of high blood pressure and coronary heart disease, with the highest risk seen in Black male adults. The study is being presented at ACC Asia 2022 Together with the Korean Society of Cardiology Spring Conference on April 15-16, 2022. Previous studies reported an association between allergic disorders and cardiovascular disease, which remain controversial findings, Guo said. The current study aimed to determine whether adults with allergic disorders have increased cardiovascular risk. The study used 2012 data from the National Health Interview Survey (NHIS), which is a cross-sectional survey of the United States population. The allergic group included adults with at least one allergic disorder, including asthma, respiratory allergy, digestive allergy, skin allergy and other allergy. Overall, the study included 34,417 adults, over half of whom were women and averaged 48.5 years old. The allergic group included 10,045 adults. The researchers adjusted for age, sex, race, smoking, alcohol drinking and body mass index; they also examined subgroups stratified by demographic factors. The researchers found a history of allergic disorders was associated with increased risk of developing high blood pressure and coronary heart disease. In further analyses, individuals with a history of allergic disorders between ages 18 and 57 had a higher risk of high blood pressure. A higher risk of coronary heart disease was seen in study participants who were between ages 39-57, male and Black/African American. Asthma contributed most to the risk of high blood pressure and coronary heart disease.
Bronchopleural fistula due to cavitary pneumonia after SARS-CoV-2 infection treated with open thoracostomy
Journal of Surgical Case Reports, April 11, 2022
Severe coronavirus disease of 2019 (COVID-19) disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes substantial parenchymal damage in some patients. There is a paucity of literature describing the surgical management COVID-19 associated bronchopleural fistula after failure of medical therapy. We present the case of a 59-year-old woman with SARS-CoV-2 pneumonia, secondary bacterial pneumonia with bronchopleural fistula and radiographic and clinical evidence of disease refractory to medical therapy. After a course of culture-driven antimicrobial therapy and failure to improve following drainage with tube thoracostomy, she was treated successfully with Clagett open thoracostomy. After resolution of the bronchopleural fistula, the thoracostomy was closed and she was discharged home. In cases of severe COVID-19 complicated by bronchopleural fistula with parenchymal destruction, a tailored approach involving surgical management when indicated can lead to acceptable outcomes without significant morbidity.
Venovenous ECMO Shows Promise in COVID-19 Patients
Anesthesiology News, April 7, 2022
New research has highlighted the important role that venovenous extracorporeal membrane oxygenation (VV ECMO) can play in critically ill COVID-19 patients who do not respond to conventional respiratory therapy. The chart review found that the overwhelming majority of these patients were successfully discharged to long-term acute rehabilitation or home, leading the researchers to recommend use of the therapeutic strategy in this otherwise fragile patient population. “At the beginning of the COVID-19 pandemic in early 2020, we weren’t really sure of the best way to treat the disease,” said Sarah Sun, BS, a medical student at Rush Medical College, in Chicago. “While several international organizations suggested the use of ECMO to help with these patients, we didn’t have enough data at the time to see if it actually worked.” To help answer this question, the investigators reviewed the charts of 21 patients (median age, 45 years; 15 males) with confirmed COVID-19 who had presented to the institution during the surge of cases between late March and early August 2020. Almost all patients (95%) had at least one pre-ECMO comorbidity, including 12 (57.1%) with a medical history of obesity, 11 (52.4%) with hypertension, four (19%) with asthma, four (19%) with diabetes, three (14.3%) with a history of tobacco use and one (4.8%) with liver disease. Analysis of patient outcomes found that all 21 patients reported the occurrence of at least one complication, either during or after ECMO support. The most common among these were bleeding (n=18; 85.7%), pneumonia (n=17; 81.0%) and pneumothorax (n=5; 23.8%). Other less common complications included cardiac arrest (n=2; 9.5%), cholecystitis (n=2; 9.5%), hemothorax (n=2; 9.5%), rhabdomyolysis (n=1; 4.8%) and encephalopathy (n=1; 4.8%). Four patients (28.6%) developed renal failure while on ECMO. “We cannot say with conviction that these complications were caused by ECMO,” Sun said in an interview with Anesthesiology News. “They could be due to the ECMO or simply a product of the COVID-19 itself.”
Early Th2 inflammation in the upper respiratory mucosa as a predictor of severe COVID-19 and modulation by early treatment with inhaled corticosteroids: a mechanistic analysis
The Lancet | Respiratory Medicine, April 7, 2022
Community-based clinical trials of the inhaled corticosteroid budesonide in early COVID-19 have shown improved patient outcomes. We aimed to understand the inflammatory mechanism of budesonide in the treatment of early COVID-19. The STOIC trial was a randomised, open label, parallel group, phase 2 clinical intervention trial where patients were randomly assigned (1:1) to receive usual care (as needed antipyretics were only available treatment) or inhaled budesonide at a dose of 800 μg twice a day plus usual care. For this experimental analysis, we investigated the nasal mucosal inflammatory response in patients recruited to the STOIC trial and in a cohort of SARS-CoV-2-negative healthy controls, recruited from a long-term observational data collection study at the University of Oxford. In patients with SARS-CoV-2 who entered the STOIC study, nasal epithelial lining fluid was sampled at day of randomisation (day 0) and at day 14 following randomisation, blood samples were also collected at day 28 after randomisation. Nasal epithelial lining fluid and blood samples were collected from the SARS-CoV-2 negative control cohort. Inflammatory mediators in the nasal epithelial lining fluid and blood were assessed for a range of viral response proteins, and innate and adaptive response markers using Meso Scale Discovery enzyme linked immunoassay panels. 146 participants were recruited in the STOIC trial (n=73 in the usual care group; n=73 in the budesonide group). 140 nasal mucosal samples were available at day 0 (randomisation) and 122 samples at day 14. At day 28, whole blood was collected from 123 participants (62 in the budesonide group and 61 in the usual care group). 20 blood or nasal samples were collected from healthy controls. In early COVID-19 disease, there was an enhanced inflammatory airway response with the induction of an anti-viral and T-helper 1 and 2 (Th1/2) inflammatory response compared with healthy individuals. Individuals with COVID-19 who clinically deteriorated (ie, who met the primary outcome) showed an early blunted respiratory interferon response and pronounced and persistent Th2 inflammation, mediated by CC chemokine ligand (CCL)-24, compared with those with COVID-19 who did not clinically deteriorate. Over time, the natural course of COVID-19 showed persistently high respiratory interferon concentrations and elevated concentrations of the eosinophil chemokine, CCL-11, despite clinical symptom improvement. There was persistent systemic inflammation after 28 days following COVID-19, including elevated concentrations of interleukin (IL)-6, tumour necrosis factor-α, and CCL-11. Budesonide treatment modulated inflammation in the nose and blood and was shown to decrease IL-33 and increase CCL17.
Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study
British Medical Journal, April 6, 2022
Our objective was to quantify the risk of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19. This self-controlled case series and matched cohort study was performed at the National registries in Sweden. Participants included 1,057,174 people who tested positive for SARS-CoV-2 between 1 February 2020 and 25 May 2021 in Sweden, matched on age, sex, and county of residence to 4,076,342 control participants. Self-controlled case series and conditional Poisson regression were used to determine the incidence rate ratio and risk ratio with corresponding 95% confidence intervals for a first deep vein thrombosis, pulmonary embolism, or bleeding event. In the self-controlled case series, the incidence rate ratios for first time outcomes after covid-19 were determined using set time intervals and the spline model. The risk ratios for first time and all events were determined during days 1-30 after covid-19 or index date using the matched cohort study, and adjusting for potential confounders (comorbidities, cancer, surgery, long-term anticoagulation treatment, previous venous thromboembolism, or previous bleeding event). Compared with the control period, incidence rate ratios were significantly increased 70 days after covid-19 for deep vein thrombosis, 110 days for pulmonary embolism, and 60 days for bleeding. In particular, incidence rate ratios for a first pulmonary embolism were 36.17 (95% confidence interval 31.55 to 41.47) during the first week after covid-19 and 46.40 (40.61 to 53.02) during the second week. Incidence rate ratios during days 1-30 after covid-19 were 5.90 (5.12 to 6.80) for deep vein thrombosis, 31.59 (27.99 to 35.63) for pulmonary embolism, and 2.48 (2.30 to 2.68) for bleeding. Similarly, the risk ratios during days 1-30 after covid-19 were 4.98 (4.96 to 5.01) for deep vein thrombosis, 33.05 (32.8 to 33.3) for pulmonary embolism, and 1.88 (1.71 to 2.07) for bleeding, after adjusting for the effect of potential confounders. The rate ratios were highest in patients with critical covid-19 and highest during the first pandemic wave in Sweden compared with the second and third waves. In the same period, the absolute risk among patients with covid-19 was 0.039% (401 events) for deep vein thrombosis, 0.17% (1761 events) for pulmonary embolism, and 0.101% (1002 events) for bleeding. The findings of this study suggest that covid-19 is a risk factor for deep vein thrombosis, pulmonary embolism, and bleeding. These results could impact recommendations on diagnostic and prophylactic strategies against venous thromboembolism after covid-19.
Q&A: IL-13 protects patients with allergic asthma against effects of SARS-CoV-2 infection
Healio | Allergy/Asthma, April 5, 2022
The Th2 cytokine IL-13 appeared to play a significant role in protecting people with allergic asthma against the damaging effects of SARS-CoV-2 infection, according to a study published in Proceedings of the National Academy of Sciences. After infecting human airway epithelial cell cultures with the virus, the researchers found that the protein angiotensin-converting enzyme 2 (ACE2) governed which cell types were infected and the viral load found in this cell population. Further examination revealed the virus left ciliated cells and severe cytopathogenesis, culminating in ciliated cells packed with virions shedding away from the airway surface. This shedding created a viral reservoir that spread the virus and increased the potential for infected cells to relocate to deeper lung tissue, the researchers wrote. Noting that IL-13 significantly affects viral entry into cells, replication inside cells and virus spread, Healio spoke with Camille Ehre, PhD, assistant professor of pediatrics at the University of North Carolina School of Medicine, to find out more about how this cytokine protects patients with allergic asthma and others from SARS-CoV-2.
Very late intubation in COVID-19 patients: a forgotten prognosis factor?
Critical Care, April 2, 2022
[Letter to the Editor] Description of all consecutive critically ill COVID 19 patients hospitalized in ICU in University Hospital of Guadeloupe and outcome according to delay between steroid therapy initiation and mechanical ventilation onset. Very late mechanical ventilation defined as intubation after day 7 of dexamethasone therapy was associated with grim prognosis and a high mortality rate of 87%. Here, we aimed to describe the characteristics and outcome of COVID-19 patients who were intubated very late after the onset of a severe form of the disease.
Willingness to Treat with Therapies of Unknown Effectiveness in Severe COVID-19: A Survey of Intensivist Physicians
Annals of the American Thoracic Society, April 1, 2022
Little is known about how physicians develop their beliefs about new treatments or update their beliefs in the face of new clinical evidence. These issues are particularly salient in the context of the coronavirus disease (COVID-19) pandemic, which created rapid demand for novel therapies in the absence of robust evidence. Our objective was to identify psychological traits associated with physicians’ willingness to treat with unproven therapies and willingness to update their treatment preferences in the setting of new evidence in the context of COVID-19. We administered a longitudinal e-mail survey to United States physicians board certified in intensive care medicine in April and May 2020 (phase one) and October and November 2020 (phase two). We assessed five psychological traits potentially related to evidence uptake: need for cognition, evidence skepticism, need for closure, risk tolerance, and research engagement. We then examined the relationship between these traits and physician preferences for pharmacological treatment for a hypothetical patient with severe COVID-19 pneumonia. There were 592 responses to the phase one survey, conducted prior to publication of trial data. At this time physicians were most willing to treat with macrolide antibiotics (50.5%), followed by antimalaria agents (36.1%), corticosteroids (24.5%), antiretroviral agents (22.6%), and angiotensin inhibitors (4.4%). Greater evidence skepticism (relative risk [RR], 1.40; 95% confidence interval [CI], 1.30–1.52; P < 0.001), greater need for closure (RR, 1.19; 95% CI, 1.06–1.34; P = 0.003), and greater risk tolerance (RR, 1.17; 95% CI, 1.08–1.26; P < 0.001) were associated with an increased willingness to treat, whereas greater need for cognition (RR, 0.85; 95% CI, 0.75–0.96, P = 0.010) and greater research engagement (RR, 0.91; 95% CI, 0.88–0.95; P < 0.0001) were associated with decreased willingness to treat. In phase two, most physicians updated their beliefs after publication of trial data about antimalarial agents and corticosteroids. Physicians with greater evidence skepticism were more likely to persist in their beliefs.
Recovery From Mechanical Ventilation in Patients With vs Without COVID-19
Pulmonology Advisor, March 30, 2022
Among patients in the ICU who require mechanical ventilation and tracheostomy, those with COVID-19 have a higher chance for recovery than other patients. This was among the findings of research recently published in CHEST. Investigators for the current study sought to determine potential reasons for successful ventilator liberation among patients admitted to long-term acute care hospitals with and without COVID-19-related respiratory failure. Toward that end, researchers conducted a retrospective cohort study of 165 patients discharged from 2020 to 2021 at Barlow Respiratory Hospital in Los Angeles. Of these patients, 37 were admitted for COVID-19. The researchers found that the adjusted ventilatory liberation rate was higher among patients with COVID-19 compared with those without (91.4% vs 56%, respectively). Functional status was also higher in those with COVID-19. Furthermore, patients with COVID-19 had shorter lengths of stay, and a trend was observed reflecting lower levels of care for these patients. The investigators hypothesized that increased rates of ventilator liberation in COVID patients is due to their enhanced recovery potential. COVID-19 patients spent more time at short-term acute care hospitals before transfer to long-term acute care hospitals (LTACH) and were already starting to recover. Of note, shock, thrombocytopenia, and hemodialysis did not vary among patients with and without COVID-19, although those with COVID-19 had more comorbidities.
FDA authorizes second COVID-19 booster shot for adults aged 50 years or older
Healio | Infectious Disease, March 29, 2022
The FDA on Tuesday authorized a second booster dose of COVID-19 vaccine for people aged 50 years or older and certain immunocompromised patients, citing evidence that it improves protection against severe disease. The authorization applies to the messenger RNA vaccines made by Pfizer-BioNTech and Moderna. The FDA previously authorized a booster shot for older adults in September. They are now eligible for a fourth shot. Immunocompromised adults who received a recommended three-dose primary series of either vaccine have been eligible for a fourth dose since October and may now receive a fifth dose. Following the authorization, the CDC updated its recommendations to include an additional dose for these populations, adding that adults who received a primary vaccine and booster dose of Johnson & Johnson’s vaccine at least 4 months ago may now receive a second booster dose of an mRNA vaccine. The FDA specified that a second booster dose of either mRNA vaccine may be administered to people aged 50 years or older at least 4 months after they received their first booster dose of any authorized or approved COVID-19 vaccine.
COVID-19 Severity in Patients With Asthma: Impact of Atopy and Other Factors
Clinical Advisor, March 29, 2022
Among patients with asthma who contract COVID-19, those with allergic and eosinophilic phenotypes have less severe outcomes from COVID-19 infection and a lower risk of hospital admissions; in contrast, patients with asthma who are older or have cardiovascular comorbidities, aspirin exacerbated respiratory disease (AERD), or eosinopenia tend to have more severe outcomes, according to a retrospective study of Spanish patients published in the Journal of Asthma and Allergy. Asthma is characterized by chronic airway inflammation and a poor antiviral immune response; however, most studies do not include asthma as a comorbidity associated with the risk of severity of COVID-19 infection. Therefore, researchers in Spain aimed to determine the relationship between COVID-19 severity and asthma, specifically examining the effects of atopy, certain clinical and demographic characteristics, phenotypes, and laboratory data. The analysis was conducted using medical records data collected from March 2020 to April 2021on a cohort of 201 adults with asthma who contracted COVID-19. All patients were being followed for asthma at 13 allergy departments in Spain. The researchers analyzed lung function test and asthma control test (ACT) results from before and after patients contracted COVID-19. Approximately 30% of these patients were admitted for bilateral pneumonia. “Our study reinforces the hypothesis about the protector factor of eosinophils and T2 cytokines in COVID-19,” concluded the researchers. “Our study also shows that severe disease with poorer lung function and poor control, old age and cardiovascular comorbidities are associated with a more severe course of COVID-19,” the researchers added.
COVID-19 symptoms are reduced by targeted hydration of the nose, larynx and trachea
Scientific Reports, March 29, 2022
Dehydration of the upper airways increases risks of respiratory diseases from COVID-19 to asthma and COPD. We find in human volunteer studies involving 464 human subjects in Germany, the US, and India that respiratory droplet generation increases by up to 4 orders of magnitude in dehydration-associated states of advanced age (n = 357), elevated BMI-age (n = 148), strenuous exercise (n = 20) and SARS-CoV-2 infection (n = 87), and falls with hydration of the nose, larynx and trachea by calcium-rich hypertonic salts. We also find in a protocol of exercise-induced airway dehydration that hydration of the airways by calcium-rich salts increases oxygenation relative to a non-treatment control (P < 0.05). In a random control study of COVID-19 positive subjects (n = 40), thrice-a-day delivery of the calcium-rich hypertonic salts (active) suppressed respiratory droplet generation by 51% ± 11% and increased oxygen saturation over three days of treatment by 48.08% ± 9.61% (P < 0.001), while no changes were observed in the nasal-saline control group. Self-reported symptoms significantly declined in the active group and did not decline in the control group. Hydration of the upper airways appears promising as a non-drug approach for reducing risks of respiratory diseases such as COVID-19.
COVID-19 and Long-Term Outcomes: Lessons from Other Critical Care Illnesses and Potential Mechanisms
American Journal of Respiratory Cell and Molecular Biology, March 29, 2022
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that is currently causing a pandemic and has been termed Coronavirus disease 2019 (COVID-19). The elderly or those with preexisting conditions like diabetes, hypertension, coronary heart disease, chronic obstructive pulmonary disease, cerebrovascular disease, or kidney dysfunction are more likely to develop severe cases when infected. COVID-19 patients admitted to the intensive care unit (ICU) have higher mortality than non-ICU patients. Critical illness has consistently posed a challenge not only in terms of mortality, but also in regard to long-term outcomes of survivors. Patients who survive acute critical illness including, but not limited to, pulmonary and systemic insults associated with ARDS, pneumonia, systemic inflammation, and mechanical ventilation, will likely suffer from Post-ICU Syndrome (PICS), a phenomenon of cognitive, psychiatric, and/or physical disability following treatment in the ICU. Post-ICU morbidity and mortality continues to be a cause for concern when considering large-scale studies showing 12-month mortality risks of 11.8% to 21%. Previous studies have demonstrated that multiple mechanisms, including cytokine release, mitochondrial dysfunction and even amyloids may lead to end-organ dysfunction in patients. We hypothesize that COVID-19 infection will lead to PICS via potentially similar mechanisms as other chronic critical illness and cause long-term morbidity and mortality in patients. We consider a variety of mechanisms and questions that not only consider the short-term impact of the COVID-19 pandemic, but its long-term effects that may not yet be imagined.
Ultrastructural insight into SARS-CoV-2 entry and budding in human airway epithelium
Nature Communications, March 25, 2022
Ultrastructural studies of SARS-CoV-2 infected cells are crucial to better understand the mechanisms of viral entry and budding within host cells. Here, we examined human airway epithelium infected with three different isolates of SARS-CoV-2 including the B.1.1.7 variant by transmission electron microscopy and tomography. For all isolates, the virus infected ciliated but not goblet epithelial cells. Key SARS-CoV-2 entry molecules, ACE2 and TMPRSS2, were found to be localised to the plasma membrane including microvilli but excluded from cilia. Consistently, extracellular virions were seen associated with microvilli and the apical plasma membrane but rarely with ciliary membranes. Profiles indicative of viral fusion where tomography showed that the viral membrane was continuous with the apical plasma membrane and the nucleocapsids diluted, compared with unfused virus, demonstrate that the plasma membrane is one site of entry where direct fusion releasing the nucleoprotein-encapsidated genome occurs. Intact intracellular virions were found within ciliated cells in compartments with a single membrane bearing S glycoprotein. Tomography showed concentration of nucleocapsids round the periphery of profiles strongly suggestive of viral budding into these compartments and this may explain how virions gain their S glycoprotein containing envelope.
CD4+ T Cell Dysfunction in Severe COVID-19 Disease is TNFα/TNFRI-Dependent
American Journal of Respiratory and Critical Care Medicine, March 24, 2022
Lymphopenia is common in severe COVID-19 disease, yet the immune mechanisms are poorly understood. As inflammatory cytokines are increased in severe SARS-CoV-2 infection, we hypothesized a role in contributing to reduced T-cell numbers. We sought to characterize the functional SARS-CoV-2 T-cell responses in severe versus recovered, mild COVID-19 patients to determine whether differences were detectable. Using flow cytometry and single cell RNA sequence analyses we assessed SARS-CoV-2-specific responses in our cohort. In 148 patients with severe COVID-19, we found lymphopenia was associated with worse survival. CD4+ lymphopenia predominated, with lower CD4+/CD8+ ratios in severe COVID-19 compared to patients with mild disease (p<0.0001). In severe disease, immunodominant CD4+ T-cell responses to Spike-1(S1) produced increased in vitro TNF-α, but demonstrated impaired S1-specific proliferation and increased susceptibility to activation-induced cell-death (AICD) following antigen exposure. CD4+TNF-α+ T-cell responses inversely correlated with absolute CD4+ counts from severe COVID-19 patients (n=76; R=-0.797, P<0.0001). In vitro TNF-α blockade including infliximab or anti-TNFRI antibodies strikingly rescued S1-specific CD4+ T-cell proliferation and abrogated S1-specific AICD in PBMC from severe COVID-19 patients (P<0.001). Single-cell RNAseq demonstrated marked downregulation of Type-1 cytokines and NFkB signaling in S1-stimulated CD4+ cells with infliximab treatment. We also evaluated bronchoalveolar lavage (BAL) and lung explant CD4+ T-cells recovered from severe COVID-19 patients and observed that lung T-cells produced higher TNF-α compared to PBMC. Together, our findings show CD4+ dysfunction in severe COVID-19 is TNF-α/TNFRI-dependent through immune mechanisms that may contribute to lymphopenia. TNF-α blockade may be beneficial in severe COVID-19.
Antiplatelets Don’t Get Critically Ill COVID Patients Off Ventilation Sooner
MedPage Today, March 22, 2022
Antiplatelet therapy didn’t appear to help critically ill COVID-19 patients recover quicker, the randomized REMAP-CAP platform trial showed. The aspirin and P2Y12 inhibitor arms were stopped early for futility, due to greater than 95% posterior probability of less than a 20% relative benefit in days alive and free of respiratory or cardiovascular organ support in the ICU to 21 days. The number of organ support-free days didn’t suggest a benefit for either type of antiplatelet alone or when pooled (median 7 in both groups, adjusted OR [aOR] 1.02, 95% credible interval [CrI] 0.86-1.23), reported Charlotte Bradbury, MD, PhD, of the University of Bristol in England, and colleagues in JAMA in conjunction with a presentation at the International Symposium on Intensive Care and Emergency Medicine in Brussels. However, survival to hospital discharge was numerically more common with the antiplatelet agents considered together (71.5% vs 67.9% among controls, aOR 1.27, 95% CrI 0.99-1.62). While not statistically significant, it did have a 97% posterior probability of efficacy in the Bayesian analysis, which rose to 99.7% when considering 90-day survival. The number of patients on short durations of organ support counterbalanced that survival difference, yielding the neutral results, they pointed out. “It is possible that antiplatelet therapy may reduce fatal complications of COVID-19 in critically ill patients while potentially increasing the need for organ support, possibly through bleeding that may or may not be clinically evident, such as alveolar hemorrhage,” Bradbury’s group suggested.
Monitoring respiratory mechanics by oscillometry in COVID-19 patients receiving non-invasive respiratory support
PLOS ONE, March 21, 2022
Non-invasive ventilation (NIV) has been increasingly used in COVID-19 patients. The limited physiological monitoring and the unavailability of respiratory mechanic measures, usually obtainable during invasive ventilation, is a limitation of NIV for ARDS and COVID-19 patients management. This pilot study was aimed to evaluate the feasibility of non-invasively monitoring respiratory mechanics by oscillometry in COVID-19 patients with moderate-severe acute respiratory distress syndrome (ARDS) receiving NIV. Fifteen COVID-19 patients affected by moderate-severe ARDS at the RICU (Respiratory Intensive Care Unit) of the University hospital of Cattinara, Trieste, Italy were recruited. Patients underwent oscillometry tests during short periods of spontaneous breathing between NIV sessions. Oscillometry proved to be feasible, reproducible and well-tolerated by patients. At admission, 8 of the 15 patients showed oscillometry parameters within the normal range which further slightly improved before discharge. At discharge, four patients had still abnormal respiratory mechanics, not exclusively linked to pre-existing respiratory comorbidities. Lung mechanics parameters were not correlated with oxygenation. Our results suggest that lung mechanics provide complementary information for improving patients phenotyping and personalisation of treatments during NIV in COVID 19 patients, especially in the presence of respiratory comorbidities where deterioration of lung mechanics may be less coupled with changes in oxygenation and more difficult to identify. Oscillometry may provide a valuable tool for monitoring lung mechanics in COVID 19 patients receiving NIV.
Profile of Clinical and Analytical Parameters in Bronchiectasis Patients during the COVID-19 Pandemic: A One-Year Follow-Up Pilot Study
Journal of Clinical Medicine, March 21, 2022
Whether the COVID-19 pandemic may have modified the clinical planning and course in bronchiectasis patients remains to be fully elucidated. We hypothesized that the COVID-19 pandemic may have influenced the management and clinical outcomes of bronchiectasis patients who were followed up for 12 months. In bronchiectasis patients (n = 30, 23 females, 66 years), lung function testing, disease severity [FEV1, age, colonization, radiological extension, dyspnea (FACED), exacerbation (EFACED)] and dyspnea scores, exacerbation numbers and hospitalizations, body composition, sputum microbiology, and blood analytical biomarkers were determined at baseline and after a one-year follow-up. Compared to baseline (n = 27, three patients dropped out), in bronchiectasis patients, a significant increase in FACED and EFACED scores, number of exacerbations, and erythrocyte sedimentation rate (ESR) was observed, while FEV1, ceruloplasmin, IgE, IgG, IgG aspergillus, IgM, and IgA significantly decreased. Patients presenting colonization by Pseudomonas aeruginosa (PA) remained unchanged (27%) during follow-up. In bronchiectasis patients, FEV1 declined only after a one-year follow-up along with increased exacerbation numbers and disease severity scores, but not hospitalizations. However, a significant decrease in acute phase-reactants and immunoglobulins was observed at the one-year follow-up compared to baseline. Despite the relatively small cohort, the reported findings suggest that lung function impairment may not rely entirely on the patients’ inflammatory status.
Spontaneous Post-COVID-19 Pneumothorax in a Patient with No Prior Respiratory Tract Pathology: A Case Report
Reports, March 21, 2022
Spontaneous pneumothorax in the setting of coronavirus disease 19 (COVID-19) has been first described as an unlikely complication, mainly occurring in critically ill patients or as a consequence of mechanical ventilation. We report a case with COVID-19 pneumonia followed by a spontaneous pneumothorax in a young non-smoker without any predisposing pathology. Approximately 1% of patients with COVID-19 pneumonia develop pneumothorax, presumably due to the barotrauma caused by positive pressure ventilation. In the case presented, no such trauma could be suspected. Other possible “culprits” (emphysema, cystic fibrosis, necrotizing pneumonia, severe asthma, lung inflammation/malignancy, as well as Marfan syndrome and alpha 1-antitrypsin deficiency) also cannot be taken in consideration. The patient is a non-smoker and in good physical condition (could walk for 5 km prior to the COVID-19 infection); he was tested for alpha 1-antitripsin deficiency (negative). The control CT scan before the discharge did not show any bulla or emphysema. The patient denies having significant cough—thus, the so-called Maclin effect (occurs due to extensive cough in an area that the alveolar walls are weakened) should also be excluded. It is obvious that there is only a thin burden between the mild course of the disease and full-blown respiratory failure (with life-threatening consequences), as well as between the “really recovered” patient after the discharge and the patient with unsuspected risk for ulterior complications. Increasing evidence of spontaneous pneumothorax in non-ventilated patients after COVID-19 should make clinicians aware of the “rare” possibility for a spontaneous pneumothorax to cause acute worsening dyspnea or acute clinical deterioration in patients with a recent COVID-19 history.
Prone positioning during veno-venous or veno-arterial extracorporeal membrane oxygenation: feasibility and complications after cardiothoracic surgery
Critical Care, March 21, 2022
Extracorporeal membrane oxygenation (ECMO) is a standard treatment for refractory hypoxaemia (veno-venous ECMO, VV-ECMO) and cardiogenic shock (veno-arterial ECMO, VA-ECMO). Severe hypoxaemia may persist despite ECMO. Prone positioning (PP) can improve outcomes of acute respiratory distress syndrome (ARDS). However, few data exist on PP in hypoxaemic patients receiving VV-ECMO or VA-ECMO, particularly after cardiothoracic surgery. Here, we evaluated oxygenation and complications seen with PP during ECMO. We retrospectively studied consecutive patients managed with PP and ECMO between August 2014 and December 2020. PP was used in patients with either refractory hypoxaemia (PaO2/FiO2 < 80 despite 100% FiO2 on ECMO) or persistent hypoxaemia (FiO2 requirement ≥ 80% with ECMO and lung condensations by CT). PP was chosen in patients on VA-ECMO because an additional venous cannula would have decreased arterial flow, potentially causing intolerance and, in the event of posterior basal pulmonary condensation, inducing adverse effects. We recorded ventilation and ECMO parameters, reason for PP, and complications. FiO2 ECMO, FiO2ventilator, and PaO2 were collected before, during, and 6–12 h after PP. Of 556 patients managed with ECMO, 34 (6.1%) (25 VV-ECMO, 9 VA-ECMO) received PP during ECMO. PP significantly improved oxygenation. Of the 87 PP sessions, six (6.9%) were followed by severe complications requiring emergent treatment. No patient experienced ECMO decannulation. Grade 3 or 4 pressure sores developed on the face or trunk in six (18%) patients. Of the 34 patients, nine (26%) died in the ICU. No patient died after ICU discharge. Of the 522 patients who received ECMO without PP, 237 (45.4%) died in the ICU, and median ECMO duration was 7 days [4–12].
COVID-19 Patients Presenting with Post-Intubation Upper Airway Complications: A Parallel Epidemic?
Journal of Clinical Medicine, March 20, 2022
During the current pandemic, we witnessed a rise of post-intubation tracheal stenosis (PITS) in patients intubated due to COVID-19. We prospectively analyzed data from patients referred to our institution during the last 18 months for severe symptomatic post-intubation upper airway complications. Interdisciplinary bronchoscopic and/or surgical management was offered. Twenty-three patients with PITS and/or tracheoesophageal fistulae were included. They had undergone 31.85 (±22.7) days of ICU hospitalization and 17.35 (±7.4) days of intubation. Tracheal stenoses were mostly complex, located in the subglottic or mid-tracheal area. A total of 83% of patients had fracture and distortion of the tracheal wall. Fifteen patients were initially treated with rigid bronchoscopic modalities and/or stent placement and eight patients with tracheal resection-anastomosis. Post-treatment relapse in two of the bronchoscopically treated patients required surgery, while two of the surgically treated patients required rigid bronchoscopy and stent placement. Transient, non-life-threatening post-treatment complications developed in 60% of patients and were all managed successfully. The histopathology of the resected tracheal specimens didn’t reveal specific alterations in comparison to pre-COVID-era PITS cases. Prolonged intubation, pronation maneuvers, oversized tubes or cuffs, and patient- or disease-specific factors may be pathogenically implicated. An increase of post-COVID PITS is anticipated. Careful prevention, early detection and effective management of these iatrogenic complications are warranted.
Different Methods to Improve the Monitoring of Noninvasive Respiratory Support of Patients with Severe Pneumonia/ARDS Due to COVID-19: An Update
Journal of Clinical Medicine, March 19, 2022
The latest guidelines for the hospital care of patients affected by coronavirus disease 2019 (COVID-19)-related acute respiratory failure have moved towards the widely accepted use of noninvasive respiratory support (NIRS) as opposed to early intubation at the pandemic onset. The establishment of severe COVID-19 pneumonia goes through different pathophysiological phases that partially resemble typical acute respiratory distress syndrome (ARDS) and have been categorized into different clinical–radiological phenotypes. These can variably benefit on the application of external positive end-expiratory pressure (PEEP) during noninvasive mechanical ventilation, mainly due to variable levels of lung recruitment ability and lung compliance during different phases of the disease. A growing body of evidence suggests that intense respiratory effort producing excessive negative pleural pressure swings (Ppl) plays a critical role in the onset and progression of lung and diaphragm damage in patients treated with noninvasive respiratory support. Routine respiratory monitoring is mandatory to avoid the nasty continuation of NIRS in patients who are at higher risk for respiratory deterioration and could benefit from early initiation of invasive mechanical ventilation instead. Here we propose different monitoring methods both in the clinical and experimental settings adapted for this purpose, although further research is required to allow their extensive application in clinical practice. We reviewed the needs and available tools for clinical–physiological monitoring that aims at optimizing the ventilatory management of patients affected by acute respiratory distress syndrome due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.
Can Lung Ultrasound Be the Ideal Monitoring Tool to Predict the Clinical Outcome of Mechanically Ventilated COVID-19 Patients? An Observational Study
Healthcare, March 18, 2022
During the COVID-19 pandemic, lung ultrasound (LUS) has been widely used since it can be performed at the patient’s bedside, does not produce ionizing radiation, and is sufficiently accurate. The LUS score allows for quantifying lung involvement; however, its clinical prognostic role is still controversial. A retrospective observational study on 103 COVID-19 patients with respiratory failure that were assessed with an LUS score at intensive care unit (ICU) admission and discharge in a tertiary university COVID-19 referral center. The deceased patients had a higher LUS score at admission than the survivors (25.7 vs. 23.5; p-value = 0.02; cut-off value of 25; Odds Ratio (OR) 1.1; Interquartile Range (IQR) 1.0−1.2). The predictive regression model shows that the value of LUSt0 (OR 1.1; IQR 1.0–1.3), age (OR 1.1; IQR 1.0−1.2), sex (OR 0.7; IQR 0.2−3.6), and days in spontaneous breathing (OR 0.2; IQR 0.1–0.5) predict the risk of death for COVID-19 patients (Area under the Curve (AUC) 0.92). Furthermore, the surviving patients showed a significantly lower difference between LUS scores at admission and discharge (mean difference of 1.75, p-value = 0.03). Upon entry into the ICU, the LUS score may play a prognostic role in COVID-19 patients with ARDS. Furthermore, employing the LUS score as a monitoring tool allows for evaluating the patients with a higher probability of survival.
Frailty as a predictor of mortality in COVID-19 patients receiving CPAP for respiratory insufficiency
Aging Clinical and Experimental Research, March 17, 2022
Exploring the association between frailty and mortality in a cohort of patients with COVID-19 respiratory insufficiency treated with continuous positive airway pressure. Frailty was measured using a Frailty Index (FI) created by using the baseline assessment data on comorbidities and body mass index and baseline blood test results (including pH, lactate dehydrogenase, renal and liver function, inflammatory indexes and anemia). FI > 0.25 identified frail individuals. Among the 159 included individuals (81% men, median age of 68) frailty was detected in 69% of the patients (median FI score 0.3 ± 0.08). Frailty was associated to an increased mortality (adjusted HR 1.99, 95% CI 1.02–3.88, p = 0.04). Frailty is highly prevalent among patients with COVID-19, predicts poorer outcomes independently of age. A personalization of care balancing the risk and benefit of treatments (especially the invasive ones) in such complex patients is pivotal.
Awake prone positioning for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure: a systematic review and meta-analysis
The Lancet | Respiratory Medicine, March 17, 2022
Awake prone positioning has been broadly utilised for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure, but the results from published randomised controlled trials (RCTs) in the past year are contradictory. We aimed to systematically synthesise the outcomes associated with awake prone positioning, and evaluate these outcomes in relevant subpopulations. In this systematic review and meta-analysis, two independent groups of researchers searched MEDLINE, Embase, PubMed, Web of Science, Scopus, MedRxiv, BioRxiv, and ClinicalTrials.gov for RCTs and observational studies (with a control group) of awake prone positioning in patients with COVID-19-related acute hypoxaemic respiratory failure. The primary outcome was the reported cumulative intubation risk across RCTs, and effect estimates were calculated as risk ratios (RR;95% CI). The analysis was primarily conducted on RCTs, and observational studies were used for sensitivity analyses. No serious adverse events associated with awake prone positioning were reported. A total of 1243 studies were identified, we assessed 138 full-text articles and received the aggregated results of three unpublished RCTs; therefore, after exclusions, 29 studies were included in the study. Ten were RCTs (1985 patients) and 19 were observational studies (2669 patients). In ten RCTs, awake prone positioning compared with the supine position significantly reduced the need for intubation in the overall population (RR 0·84 [95% CI 0·72–0·97]). A reduced need for intubation was shown among patients who received advanced respiratory support (ie, high-flow nasal cannula or non-invasive ventilation) at enrolment (RR 0·83 [0·71–0·97]) and in intensive care unit (ICU) settings (RR 0·83 [0·71–0·97]) but not in patients receiving conventional oxygen therapy (RR 0·87 [0·45–1·69]) or in non-ICU settings (RR 0·88 [0·44–1·76]). No obvious risk of bias and publication bias was found among the included RCTs for the primary outcome.
Efficacy of Losartan in Hospitalized Patients With COVID-19–Induced Lung Injury: A Randomized Clinical Trial
JAMA Network Open, March 16, 2022
SARS-CoV-2 viral entry may disrupt angiotensin II (AII) homeostasis, contributing to COVID-19 induced lung injury. AII type 1 receptor blockade mitigates lung injury in preclinical models, although data in humans with COVID-19 remain mixed. The objective was to test the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19. This blinded, placebo-controlled randomized clinical trial was conducted in 13 hospitals in the United States from April 2020 to February 2021. Hospitalized patients with COVID-19 and a respiratory sequential organ failure assessment score of at least 1 and not already using a renin-angiotensin-aldosterone system (RAAS) inhibitor were eligible for participation. Data were analyzed from April 19 to August 24, 2021. Losartan 50 mg orally twice daily vs equivalent placebo for 10 days or until hospital discharge. The primary outcome was the imputed arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2:FiO2) ratio at 7 days. Secondary outcomes included ordinal COVID-19 severity; days without supplemental O2, ventilation, or vasopressors; and mortality. Losartan pharmacokinetics and RAAS components were measured in a subgroup of participants. A total of 205 participants (mean [SD] age, 55.2 [15.7] years; 123 [60.0%] men) were randomized, with 101 participants assigned to losartan and 104 participants assigned to placebo. Compared with placebo, losartan did not significantly affect PaO2:FiO2 ratio at 7 days (difference, −24.8 [95%, −55.6 to 6.1]; P = .12). Compared with placebo, losartan did not improve any secondary clinical outcomes and led to fewer vasopressor-free days than placebo (median [IQR], 9.4 [9.1-9.8] vasopressor-free days vs 8.7 [8.2-9.3] vasopressor-free days). This randomized clinical trial found that initiation of orally administered losartan to hospitalized patients with COVID-19 and acute lung injury did not improve PaO2:FiO2 ratio at 7 days. These data may have implications for ongoing clinical trials.
Quantitative Chest CT Assessment of Small Airways Disease in Post-Acute SARS-CoV-2 Infection
Radiology, March 15, 2022
The long-term effects of SARS-CoV-2 infection on pulmonary structure and function remain incompletely characterized. Our objective was to test whether SARS-CoV-2 infection leads to small airways disease in patients with persistent symptoms. In this single center study at a university teaching hospital, adults with confirmed COVID-19 who remained symptomatic >30 days following diagnosis were prospectively enrolled and compared to healthy participants (controls). Participants with post-acute sequelae of COVID-19 (PASC) were classified as ambulatory, hospitalized, or requiring the intensive care unit (ICU) based on the highest level of care received during acute infection. Symptoms, pulmonary function tests, and chest CT images were collected, and quantitative CT analysis was performed using supervised machine-learning to measure regional ground glass opacities (GGO) and inspiratory and expiratory image-matching to measure regional air trapping. Univariable analyses and multivariable linear regression were used to compare groups. One hundred participants with PASC (median age, 48 years; 66 women) were evaluated and compared with 106 matched healthy controls. Sixty-seven percent (67/100) of the participants with PASC were classified as ambulatory, 17% (17/100) were hospitalized and 16% (16/100) required care in the ICU. Among the hospitalized and ICU groups, the mean percent of total lung classified as GGO was 13.2% and 28.7%, respectively, and was higher than in the ambulatory group (3.7%, p<.001 for both comparisons). The mean percentage of total lung affected by air trapping was 25.4%, 34.6%, and 27.3% in the ambulatory, hospitalized, and ICU groups and 7.2% in healthy controls (p<.001). Air trapping correlated with the residual volume to total lung capacity ratio (RV/TLC; r=0.6, p<.001). In survivors of COVID-19, small airways disease occurred independently of initial infection severity. The long-term consequences are unknown.
Rapid-Onset Cystic Bronchiectasis in a Mechanically Ventilated Patient with COVID-19
American Journal of Respiratory and Critical Care Medicine, March 15, 2022
A 40-year-old man presented to the ICU after intubation due to respiratory failure secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonitis. Past medical history revealed a history of intravenous drug use (heroin). Early blood and sputum cultures also grew a Panton-Valentine leukocidin–positive Staphylococcus aureus. Dexamethasone and antibiotics were administered and lung-protective ventilation and proning were instituted. Imaging during the first and second week of illness revealed rapid progression from pneumonitis to severe cystic bronchiectasis. The patient developed persistent hypercapnic acidosis, despite high VE. Bedside calculations revealed dead space ventilation ranging from 5.14 L/min to 5.92 L/min. The patient received a tracheostomy in his third week of stay to facilitate weaning of mechanical ventilation. After ICU discharge, he received rehabilitation for critical illness myopathy and developed a mild persistent productive cough. He was discharged to a step-down facility for ongoing rehabilitation 5 months after admission.
Patients with severe COVID-19 have reduced circulating levels of angiotensin-(1–7): A cohort study
Health Science Reports, March 14, 2022
Angiotensin-converting enzyme 2 (ACE2) acts as a functional receptor for the entry of severe acute respiratory syndrome coronavirus 2 into host cells. Angiotensin (1–7) (Ang (1–7)) obtained from the function of ACE2 improves heart and lung function. We investigated the relationship between Ang (1–7) level and disease severity in patients with coronavirus disease 2019 (COVID-19). This cohort study was carried out at Masih Daneshvari Hospital in Tehran, Iran from September 2020 to October 2020. To do so, the Ang (1–7) levels of 331 hospitalized COVID-19 patients with and without underlying disease were measured by ELISA kit. The need for oxygen, intubation, and mechanical ventilation were recorded for all the patients. Results showed a significant inverse relationship between the levels of Ang 1–7 and the severity of the disease (needed oxygen, intubation, and mechanical ventilation). According to the results, median (interquartile range) of Ang (1–7) levels was significantly lower in patients who needed oxygen versus those who needed no oxygen (44.50 (91) vs. 82.25 (68), p = 0.002), patients who needed intubation and mechanical ventilation versus those who did not (9.80 (62) vs. 68.70 (102), p < 0.000) and patients hospitalized in an intensive care unit (ICU) than people hospitalized in other wards. We also found that the older patients were more in need of ICU and mechanical ventilation than younger patients. Higher levels of Ang (1–7) have been associated with decreased disease severity. Besides this, we perceived that synthetic Ang 1–7 peptides may be useful to treat and reduce the complications of COVID-19.
Inflammatory burden and persistent CT lung abnormalities in COVID-19 patients
Scientific Reports, March 11, 2022
Inflammatory burden is associated with COVID-19 severity and outcomes. Residual computed tomography (CT) lung abnormalities have been reported after COVID-19. The aim was to evaluate the association between inflammatory burden during COVID-19 and residual lung CT abnormalities collected on follow-up CT scans performed 2–3 and 6–7 months after COVID-19, in severe COVID-19 pneumonia survivors. C-reactive protein (CRP) curves describing inflammatory burden during the clinical course were built, and CRP peaks, velocities of increase, and integrals were calculated. Other putative determinants were age, sex, mechanical ventilation, lowest PaO2/FiO2 ratio, D-dimer peak, and length of hospital stay (LOS). Of the 259 included patients (median age 65 years; 30.5% females), 202 (78%) and 100 (38.6%) had residual, predominantly non-fibrotic, abnormalities at 2–3 and 6–7 months, respectively. In age- and sex-adjusted models, best CRP predictors for residual abnormalities were CRP peak (odds ratio [OR] for one standard deviation [SD] increase = 1.79; 95% confidence interval [CI] = 1.23–2.62) at 2–3 months and CRP integral (OR for one SD increase = 2.24; 95%CI = 1.53–3.28) at 6–7 months. Hence, inflammation is associated with short- and medium-term lung damage in COVID-19. Other severity measures, including mechanical ventilation and LOS, but not D-dimer, were mediators of the relationship between CRP and residual abnormalities.
Reduced levels of pulmonary surfactant in COVID-19 ARDS
Scientific Reports, March 8, 2022
To provide novel data on surfactant levels in adult COVID-19 patients, we collected bronchoalveolar lavage fluid less than 72 h after intubation and used Fourier Transform Infrared Spectroscopy to measure levels of dipalmitoylphosphatidylcholine (DPPC). A total of eleven COVID-19 patients with moderate-to-severe ARDS (CARDS) and 15 healthy controls were included. CARDS patients had lower DPPC levels than healthy controls. Moreover, a principal component analysis was able to separate patient groups into distinguishable subgroups. Our findings indicate markedly impaired pulmonary surfactant levels in COVID-19 patients, justifying further studies and clinical trials of exogenous surfactant.
ACE2 protein expression in lung tissues of severe COVID-19 infection
Scientific Reports, March 8, 2022
Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COrona VIrus Disease 2019 (COVID-19). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-19 patients for other indications. IHC for CD61 and CD163 was performed for the assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. In a total of 55, 44 COVID-19 post-mortem lung samples were tested for ACE2, 36 for CD163, and 26 for CD61, compared to 15 non-covid 19 control lung sections. Quantification of immunostaining, random sampling, and correlation analysis were used to substantiate the morphologic findings. Our results show that ACE2 protein expression was significantly higher in COVID-19 post-mortem lung tissues than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels were positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity.
COVID-19 Mortality and Obstructive Airway Diseases
Pulmonology Advisor, March 3, 2022
Patients hospitalized with COVID-19 who have comorbid asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) have a significantly lower survival probability than patients without these comorbidities, according to research presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2022 Annual Meeting, held in Phoenix, Arizona, February 25 to 28. Seeking to determine the effects of obstructive airway diseases on COVID-19 outcomes, researchers in Korea conducted a study involving 5625 patients hospitalized for COVID-19, who were divided into asthma, COPD, ACO, and control groups. Patient data was analyzed to determine probability of survival as well as factors affecting COVID-19 mortality, disease severity, and oxygen demand. The investigators found that mortality rates among patients in the asthma, COPD, and ACO groups were 2.3, 4.8, and 5.5 times higher, respectively, than among patients in the control group. The investigators further noted that patients in the asthma, COPD, and ACO groups were more likely to require oxygen and mechanical ventilation.
Long-Haul COVID-19 and T-Cell Activation
Pulmonology Advisor, March 3, 2022
Survivors of severe COVID-19 with long-haul respiratory symptoms display activated T-cell signatures and marked immune perturbations. A cohort study was conducted among a group of patients who had survived severe SARS-CoV-2 infection. Results of the study were presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2022 Annual Meeting, held in Phoenix, Arizona, February 25 to 28. The investigators sought to explore the long-term evolution of T cells following COVID-19 infection among patients with long-haul symptoms. They tracked circulating T cells in a group of 88 individuals who had been hospitalized with COVID-19 and subsequently experienced persistent respiratory symptoms. The T cells were obtained during severe acute COVID-19, at 6 weeks after hospital discharge, and between 6 and 11 months following hospital discharge. High-dimensional immunophenotyping with spectral flow cytometry was used to analyze the participants’ T cells. The Tracking Responders Expanding (T-REX) algorithm was used to identify longitudinal changes in complex T-cell signatures. ImmunoCAP assay was utilized to evaluate patients for antibodies to SARS-CoV-2 proteins. Participants with long-haul respiratory symptoms who were sampled at 6 weeks following hospital discharge had higher rates of activated and tissue-homing CD4+ and CD8+ T cells, compared with healthy individuals and patients who had experienced a mild acute COVID-19 infection. A higher number of terminally differentiated CD8+ T cells were also detected in these individuals. The T-REX algorithm identified multiple CD4+ and CD8+ T-cell signatures that expanded or contracted by 95% or more up to 6 months following acute infection, including highly activated subtypes. Fluctuations in T-cell signatures were observed several months following acute infection, even in the presence of decreasing antibodies to SARS-CoV-2 proteins.
Alveolar, Endothelial, and Organ Injury Marker Dynamics in Severe COVID-19
American Journal of Respiratory and Critical Care Medicine, March 1, 2022
Alveolar and endothelial injury may be differentially associated with coronavirus disease (COVID-19) severity over time. The objective was to describe alveolar and endothelial injury dynamics and associations with COVID-19 severity, cardiorenovascular injury, and outcomes. This single-center observational study enrolled patients with COVID-19 requiring respiratory support at emergency department presentation. More than 40 markers of alveolar (including receptor for advanced glycation endproducts [RAGE]), endothelial (including angiopoietin-2), and cardiorenovascular injury (including renin, kidney injury molecule-1, and troponin-I) were serially compared between invasively and spontaneously ventilated patients using mixed-effects repeated-measures models. Ventilatory ratios were calculated for intubated patients. Associations of biomarkers with modified World Health Organization scale at Day 28 were determined with multivariable proportional-odds regression. Of 225 patients, 74 (33%) received invasive ventilation at Day 0. RAGE was 1.80-fold higher in invasive ventilation patients at Day 0 (95% confidence interval [CI], 1.50–2.17) versus spontaneous ventilation, but decreased over time in all patients. Changes in alveolar markers did not correlate with changes in endothelial, cardiac, or renal injury markers. In contrast, endothelial markers were similar to lower at Day 0 for invasive ventilation versus spontaneous ventilation, but then increased over time only among intubated patients. In intubated patients, angiopoietin-2 was similar (fold difference, 1.02; 95% CI, 0.89–1.17) to nonintubated patients at Day 0 but 1.80-fold higher (95% CI, 1.56–2.06) at Day 3; cardiorenovascular injury markers showed similar patterns. Endothelial markers were not consistently associated with ventilatory ratios. Endothelial markers were more often significantly associated with 28-day outcomes than alveolar markers. Alveolar injury markers increase early. Endothelial injury markers increase later and are associated with cardiorenovascular injury and 28-day outcome.
Effects of Trunk Inclination on Respiratory Mechanics in Patients with COVID-19–associated Acute Respiratory Distress Syndrome: Let’s Always Report the Angle!
American Journal of Respiratory and Critical Care Medicine, March 1, 2022
The role of trunk inclination on respiratory function has been explored in patients with “typical” acute respiratory distress syndrome (ARDS) (1–3). Data regarding patients with coronavirus disease (COVID-19)–associated ARDS (C-ARDS) are currently lacking. The aim of our study was to assess the effects of changes in trunk inclination on lung mechanics and gas exchange in mechanically ventilated patients with C-ARDS. Methods This single-center physiological crossover study was conducted on adult patients admitted to our COVID-ICU. Diagnosis of C-ARDS, deep sedation, paralysis, and volume-controlled mechanical ventilation were the inclusion criteria. Contraindications to mobilization (e.g., intracranial hypertension, spinal cord injury, tracheal lesions) and pregnancy constituted exclusion criteria. Patients were enrolled according to study personnel availability. A 5-F esophageal balloon (CooperSurgical) was inserted. The balloon was inflated with 1 ml of air, and the correct position/function was verified before each measurement. Mechanical ventilation parameters, kept constant throughout the study, were set by the attending physician. Usually, positive endexpiratory pressure (PEEP) is set according to the best respiratory system compliance (CRS) assessed with a recruitment maneuver followed by a decremental PEEP trial. Of note, trunk inclination during PEEP selection is not standardized. Patients underwent three 15-minute steps in which trunk inclination was changed from 40° (semirecumbent, baseline) to 0° (supine-flat), and back to 40° during the last step. At the end of each step, partitioned respiratory mechanics, arterial/central venous blood gas analysis, and basic hemodynamics were recorded. Ventilatory ratio was calculated. Twenty patients were enrolled (11 male; 67 [59–70] years; body mass index, 30 [28–35] kg/m2; Simplified Acute Physiology Score-II, 36 [32–45]). ARDS was mild in 1, moderate in 9, and severe in 10 patients. Patients were studied 2.5 (2.0–4.5) days after intubation. VT was 5.9 (5.7–6.3) ml/kg of predicted body weight, and PEEP was 14 (12–14) cm H2O. A significant reduction in both PaCO2 (52 [47–57] vs. 50 [46–54] mm Hg; P < 0.001) and ventilatory ratio (1.81 [1.47–2.02] vs. 1.68 [1.43–1.96]; P < 0.001) was recorded when patients were placed supine-flat. Moreover, a positive correlation (r = 0.66; P = 0.002) between the drop of driving pressure and the reduction of PaCO2 was observed. Oxygenation was not significantly affected by changes in trunk inclination. Changes in respiratory mechanics and PaCO2 were rapidly reversed once patients were repositioned in the semirecumbent position.
Is Asthma an Independent Risk Factor for COVID-19?
Medical Professionals Reference, February 25, 2022
Asthma may be a risk factor for severe COVID-19, according to a recent study conducted at Kaiser Permanente Northern California that examined the incidence of COVID-19 infection, hospitalization, and severity in asthma patients during 2020. Results of the study are being presented at the American Association of Allergy, Asthma & Immunology (AAAAI) 2022 Annual Meeting, held in Phoenix, Arizona, from February 25 to 28. To address the limited knowledge about asthma as a risk factor for COVID-19, the researchers conducted a retrospective cohort study that enrolled a cohort of asthma patients (n = 41,282) and a matched control cohort of adults (n = 41,282) of corresponding age, sex, and race/ethnicity (mean age 55 [±16] years; 63% female; 55% White individuals). Using electronic health records, the researchers collected data on demographics, clinical factors, comorbidities, polymerase chain reaction COVID-19 testing, hospitalization, and inpatient COVID-19 treatment. The investigators found that asthma was inversely associated with having a positive COVID-19 test (8.7% vs 9.4% positive among those tested; OR, 0.90; 95% CI, 0.82-0.99; P =.03) after adjustment for age, sex, race or ethnicity, BMI, smoking, the Neighborhood Deprivation Index, and comorbidities. Asthma was not related to COVID-19 hospitalization (2.9 vs 1.4 per 1000 persons; OR, 1.04; 95% CI, 0.96-1.12; P =.32) after adjustment for the same covariates. Asthma was positively associated with a composite outcome that included COVID-19-related intensive care unit (ICU) admission, intubation, or remdesivir treatment (2.5 vs 1.0 per 1000 persons; OR, 1.89; 95% CI, 1.28-2.81; P =.001) after adjustment for the same covariates.
Atopy Status of Patients With Asthma and Exacerbation Rates Post COVID-19
Pulmonology Advisor, February 24, 2022
Asthma exacerbations occur at a significantly lower rate for patients with asthma who have COVID-19 when those patients also have allergic rhinitis vs when they do not have allergic rhinitis. These were among study findings being presented at the American Association of Allergy, Asthma & Immunology (AAAAI) 2022 Annual Meeting, held in Phoenix, Arizona, from February 25 to 28. Asthma symptoms may be exacerbated and prolonged by COVID-19 in some but not all patients with asthma. Researchers sought to examine the effect of the allergic status of patients with asthma on asthma exacerbation rates and outcomes following COVID-19. In this prospective cohort study, conducted at a tertiary care medical center in 2020 between February and April, 193 patients with COVID-19 who also had asthma were followed for asthma exacerbation symptoms for 4 to 8 months (mean duration 211 days) following their positive COVID-19 test. Researchers utilized logistic regression to compare asthma patients with and without allergic rhinitis for asthma outcomes after experiencing COVID-19. Statistics were adjusted for use of inhaled-corticosteroids, BMI, and demographics. Of the patients studied, 55 (28.5%) had asthma with allergic rhinitis and 138 (71.5%) had asthma without allergic rhinitis. Gender distribution, BMI, and age were similar between cohorts, but the asthma exacerbation rate was significantly lower in patients with vs without allergic rhinitis (54.5% vs 68.1%, respectively; adjusted P =.046). No difference was observed between cohorts for use of oral steroids after COVID-19, frequency of specialist visits, uncontrolled asthma duration, or step-up therapy.
ECMO During Respiratory Pandemics: Past, Present, and Future
American Journal of Respiratory and Critical Care Medicine, February 24, 2022
The role of extracorporeal membrane oxygenation (ECMO) in the management of severe acute respiratory failure, including the acute respiratory distress syndrome, has become better defined in recent years in light of emerging high-quality evidence and technological advances. Utilization of ECMO has consequently increased throughout many parts of the world. The coronavirus disease 2019 (COVID-19) pandemic, however, has highlighted deficiencies in organizational capacity, research capability, knowledge sharing and resource utilization. While governments, medical societies, hospital systems and clinicians were collectively unprepared for the scope of this pandemic, the use of ECMO – a highly resource-intensive and specialized form of life support – presented specific logistical and ethical challenges. As the pandemic has evolved, there has been greater collaboration in the use of ECMO across centers and regions, along with more robust data-reporting through international registries and observational studies. Nevertheless, centralization of ECMO capacity is lacking in many regions of the world and equitable use of ECMO resources remains uneven. There are no widely available mechanisms to conduct large-scale, rigorous clinical trials in real-time. In this Critical Care Perspective, we outline lessons learned during COVID-19 and prior respiratory pandemics in which ECMO was used, and how we might apply these lessons going forward both during the ongoing COVID-19 pandemic as well as in the future.
Major cardiovascular risk factors common yet undertreated in patients with COPD
Healio | Pulmonology, February 17, 2022
Among patients with COPD, major cardiovascular risk factors were common but inadequately monitored, treated and controlled, researchers reported in the Annals of the American Thoracic Society. “COPD inherently conveys high cardiovascular risk due to cumulative smoking burden, advanced population age and clustering of additional risk factors, intertwined with socioeconomic deprivation, impaired health literacy and reduced physical activity,” Nathaniel M. Hawkins, MD, MPH, assistant professor in the division of cardiology at the University of British Columbia, Vancouver, and colleagues wrote. “Risk factors were very common in our cohort, with one-quarter having diabetes, > 50% hypertension, > 60% dyslipidemia, > 70% overweight and > 80% smoking history.” The cross-sectional analysis evaluated medical records of 32,695 patients with COPD (mean age, 68.4 years; 50.7% women) in the Canadian Primary Care Sentinel Surveillance Network from 2013 to 2018. These patients were matched for age, sex and rural residence with 32,638 control participants (mean age, 68.4 years; 50.7% women). Researchers identified five CV risk factors in the cohort: hypertension, dyslipidemia, diabetes, obesity and smoking. The mean Framingham Risk Score was 20.6% among patients with COPD compared with 18.6% among controls. Nearly 54% of patients with COPD were categorized as having high CV risk. All five CVD risk factors were more common among patients with COPD compared with controls: hypertension (52.3% vs. 44.9%); dyslipidemia (62% vs. 57.8%); diabetes (25% vs. 20.2%); obesity (40.8% vs. 36.8%); and smoking (40.9% vs. 11.4%). In addition, CV therapies were underutilized in patients with COPD. Angiotensin-converting enzyme inhibitors were used in 69%, statins in 69% and smoking-cessation therapies in 27%.
OxVent: Design and evaluation of a rapidly-manufactured Covid-19 ventilator
eBioMedicine, February 13, 2022
The manufacturing of any standard mechanical ventilator cannot rapidly be upscaled to several thousand units per week, largely due to supply chain limitations. The aim of this study was to design, verify and perform a pre-clinical evaluation of a mechanical ventilator based on components not required for standard ventilators, and that met the specifications provided by the Medicines and Healthcare Products Regulatory Agency (MHRA) for rapidly-manufactured ventilator systems (RMVS). The design utilises closed-loop negative feedback control, with real-time monitoring and alarms. Using a standard test lung, we determined the difference between delivered and target tidal volume (VT) at respiratory rates between 20 and 29 breaths per minute, and the ventilator’s ability to deliver consistent VT during continuous operation for >14 days (RMVS specification). Additionally, four anaesthetised domestic pigs (3 male-1 female) were studied before and after lung injury to provide evidence of the ventilator’s functionality, and ability to support spontaneous breathing. Continuous operation lasted 23 days, when the greatest difference between delivered and target VT was 10% at inspiratory flow rates >825 mL/s. In the pre-clinical evaluation, the VT difference was -1 (-90 to 88) mL [mean (LoA)], and positive end-expiratory pressure (PEEP) difference was -2 (-8 to 4) cmH2O. VT delivery being triggered by pressures below PEEP demonstrated spontaneous ventilation support.
Study finds high mortality burden, premature deaths with mild pulmonary hypertension
Healio | Pulmonology, February 11, 2022
Individuals with mildly elevated estimated right ventricular systolic pressure had a high burden of mortality and consequential premature deaths, researchers reported in the European Respiratory Journal. “Our findings support the contention that even subclinical pulmonary hypertension has an extensive clinical impact,” Simon Stewart, MD, professor and senior principal research fellow in the Centre for Cardiopulmonary Health at Torrens University Australia, Adelaide, and the School of Medicine, Dentistry and Nursing at the University of Glasgow, U.K., and colleagues wrote. The researchers aimed to determine the impact of pulmonary hypertension on premature mortality by conducting a large real-world echocardiographic database study. The study included 70,826 men (mean age, 61.3 years) and 84,130 women (mean age, 61.4 years) with no evidence of left heart disease assessed by echocardiography. Researchers studied the distribution of estimated right ventricular systolic pressure (eRVSP) and examined individually linked mortality, premature mortality and associated life-years lost based on eRVSP levels. Fifty-five percent of participants had eRVSP levels indicative of no pulmonary hypertension (< 30 mm Hg), 31.8% mild pulmonary hypertension (30-39.9 mm Hg), 8.4% moderate pulmonary hypertension (40-49.9 mm Hg) and 4.8% severe pulmonary hypertension (50 mm Hg). Premature mortality, as a proportion of all deaths, increased from 46.7% to 79.2% among participants with an eRVSP less than 30 mm Hg compared with participants with an eRVSP of 60 mm Hg or more.
COVID-19 and Moral Injury: a Mental Health Pandemic for Frontline Health Care Workers
Pulmonology Advisor, February 11, 2022
More than 2 years ago, the alarm and first warnings of a global pandemic sounded. Now with over 830,000 deaths caused by COVID-19 in the US, there looms on the horizon a second underlying curve with equally serious long-term consequences: a mental health pandemic. The mental health fallout from the COVID-19 pandemic demands recognition, intervention, and mitigation strategies. Among the many at-risk populations are frontline health care workers who have been at the epicenter of the global pandemic, working long shifts with at times a tenuous safety net and limited support, and caring for COVID-19 patients with limited resources, mixed messaging, and uncertainty with regards to an end to the crisis. The psychological effects in some health care providers are akin to the moral trauma or moral injury that is recognized in combat veterans with post-traumatic stress disorder (PTSD). Mental health professionals and other health care providers caring for frontline health care workers who present with insomnia, depression, anxiety, panic attacks, PTSD, and suicidal thoughts should recognize and validate their experiences and moral injury. Intervention strategies including health promotion, resilience training, and ongoing multilevel support will play an important role in flattening the moral injury curve. Leaders in health care have the opportunity to create and foster a culture of open, nonjudgmental communication. In the face of unpredictable events such as the COVID-19 pandemic, natural disasters, and social and political unrest that impact health care delivery, strategies are available to promote mental health recovery and return to stability and wellness among frontline health care workers.
Critically ill patients with COVID-19 show lung fungal dysbiosis with reduced microbial diversity in Candida spp colonized patients
International Journal of Infectious Diseases, February 9, 2022
The COVID-19 pandemic has intensified interest in how the infection impacts the lung microbiome of critically ill patients and contributes to acute respiratory distress syndrome (ARDS). We aimed to characterize the lower respiratory tract mycobiome of COVID-19 critically ill patients in comparison to COVID-19-negative patients. We performed an Internal transcribed spacer 2 (ITS2) profiling, with the Illumina MiSeq platform, on 26 respiratory specimens from COVID-19 positive patients as well as from 26 patients with non-COVID-19 pneumonia.COVID-19+ patients were more likely to be colonized with Candida spp. and ARDS was associated with lung dysbiosis characterised by a shift to Candida species colonisation and a decrease of fungal diversity. We also observed higher bacterial phylogenetic distance among taxa in COVID-19+ colonized patients. In COVID-19+ patients non-colonized with Candida spp, ITS2 amplicon sequencing revealed an increase of Ascomycota unassigned spp. and one Aspergillus spp positive specimen. Then, we found that corticosteroid therapy was frequently associated with positive Galactomannan cell wall component of Aspergillus spp among COVID-19+ patients. Our study underpins that ARDS in COVID-19+ patients is associated with lung dysbiosis and that an increased density of Ascomycota unassigned spp. is present in patients not colonized with Candida spp.
https://www.atsjournals.org/doi/pdf/10.1164/rccm.202109-2025LE”> Ventilation is not Depressed in Hypoxemic Patients with Acute COVID-19 Infection
American Journal of Respiratory and Critical Care Medicine, February 7, 2022
Early reports of hypoxemic patients with COVID-19 pneumonia exhibiting little respiratory distress have prompted the suggestion that SARS COV-2 infection results in a unique respiratory pathophysiology. One hypothesis to explain the apparent disconnect between severe hypoxemia and the reported absence of dyspnea is a blunted hypoxic ventilatory response (HVR). We therefore sought to test the hypothesis that hypoxemic patients with COVID-19 have a reduced ventilation compared to healthy controls. As part of a cross- sectional study of gas exchange in early COVID-19 pneumonia patients on presentation to hospital, we measured mean alveolar partial pressure for CO2 (PACO2), which represents the inverse of alveolar ventilation (⩒A), and related it to the severity of hypoxemia, as measured by the arterial partial pressure for oxygen (PaO2). Published normal subject data relating PACO2 to PaO2 under normoxic and acute hypoxic conditions were used to assess whether COVID-19 patient ⩒A levels were in the expected range for the severity of hypoxemia, thus inferring the ventilatory response of these patients. Data were collected from 22 males and 8 females, aged 23-85 years (50.7±15 years (mean±SD)). All subjects had mildly symptomatic COVID-19 pneumonia, the majority were tachypneic (respiratory rate: 21.8±7.2 breaths per minute, range 9-38), 22 had dyspnoea, and most were febrile at the time of testing (body temperature: 38.0±1.0ºC, range 36.5-40ºC)). No patient required ICU admission. Exhaled CO2 was collected between 2 and 100 seconds (35±10 seconds) prior to the arterial blood gas sample. PaO2 ranged from 52.9 to 107.5 mmHg (72.0±12.7 mmHg), arterial oxygen saturation ranged from 89%-99% (94±2 %), PaCO2 ranged from 27.8-46.8 mmHg (36.3±4.6 mmHg) while ⩒Arel ranged from 1.1 to 1.7 (1.3±0.2)). Around 50% of patients had ⩒Arel that were in broad agreement with normal values. For all remaining patients, ⩒Arel was greater than expected from the normal data. Most importantly, in no patient was ⩒Arel lower than that seen in normal subjects at any PaO2.
More Evidence for Inflammatory Thrombosis in Chronic Thromboembolic Pulmonary Hypertension – Is the Embolic Hypothesis Losing Grounds?
American Journal of Respiratory and Critical Care Medicine, February 3, 2022
Chronic thromboembolic pulmonary hypertension (CTEPH) is a subset of pulmonary vascular disease that is characterized by obstruction of pulmonary arteries with fibrotic thrombus, with layers of fresh thrombus in about 40% of cases, that is amenable to cure by surgical pulmonary endarterectomy (PEA). In recent years, multimodality treatments including balloon pulmonary angioplasty and medical treatments have made CTEPH one of the best treatable forms of pulmonary vascular disease. CTEPH has been reported as a long-term complication of acute pulmonary embolism (PE), with estimated cumulative incidences between 0.1 and 9.1% within the first two years after symptomatic PE. Both recurrent venous thromboembolism and unprovoked PE are associated with a higher risk of CTEPH, with odds ratios of 3.2 and 4.1 respectively. These observations are confirmed by data from the European CTEPH registry, lending support to the concept of a thromboembolic origin of CTEPH. However, CTEPH pathogenesis is still not easily explained. Only recently, research has underpinned the concept of “inflammatory thrombosis” as a trigger for abnormal propagation of fresh thrombus on the endothelial surface, and the transition of fresh thrombus to fibrotic tissue. Here, Manz et al, performed meticulous studies using endothelial cells isolated from patients during PEAs and modeled flow of whole blood and platelets in vitro to study platelet-endothelial cell interactions. The authors show that von Willebrand Factor (vWF) is increased in plasma and in the pulmonary endothelium of CTEPH. CTEPH patient-derived pulmonary artery endothelial cells show increased platelet adhesion compared with control, which is abrogated by a monoclonal antibody directed against the A1 domain of vWF. Increased platelet adhesion is mediated by enhanced vWF gene expression and by an increase of endothelial nuclear Factor κB 2 (NFκB2). Increased histone acetylation of the vWF promotor in CTEPH endothelium, and reduced histone trimethylation (H3K27me3) facilitate binding of NFκB2 to the vWF promotor during vWF transcription. Genetic interference of NFκB2 normalized high vWF RNA expression levels and reversed the pro-thrombotic phenotype. This work provides powerful confirmation of an important role of ‘inflammatory thrombosis‘ in the pathogenesis of CTEPH.
Oral corticosteroid use, prior asthma hospitalization up risk for poor COVID-19 outcomes
Healio | Pulmonology, February 2, 2022
Risk for COVID-19 hospitalization, ICU admission or death was increased for adults in Scotland with asthma who had a prior hospitalization or required two or more courses of oral corticosteroids in the previous 2 years, researchers reported. The national incident cohort study, published in The Lancet Respiratory Medicine, included 4,421,663 adults in Scotland who participated in the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II).The researchers evaluated the risk for COVID-19 hospitalization and composite outcomes in COVID-19-related ICU admission or mortality in adults with asthma. Associations were stratified by markers of asthma exacerbation history, which were defined by oral corticosteroid prescription in the past 2 years or asthma hospitalization prior to March 2020. In total, 12.7% of participants had clinician-diagnosed and recorded asthma from March 2020 to July 2021. Seven percent had confirmed SARS-CoV-2 infection, with 12.3% of those admitted to the hospital for COVID-19. Those with asthma had an increased risk for COVID-19-related hospital admission compared with participants without asthma (adjusted HR = 1.27; 95% CI, 1.23-1.32). This association was also present among adults with asthma who received three or more prior courses of prescribed oral corticosteroids (aHR = 1.54; 95% CI, 1.46-1.61), two prescribed courses (aHR = 1.37; 95% CI, 1.26-1.48), one prescribed course (aHR = 1.3; 95% CI, 1.23-1.37) and no oral corticosteroids (aHR = 1.15; 95% CI, 1.11-1.21) in the previous 2 years.
Effective deep learning approaches for predicting COVID-19 outcomes from chest computed tomography volumes
Scientific Reports, February 2, 2022
The rapid evolution of the novel coronavirus disease (COVID-19) pandemic has resulted in an urgent need for effective clinical tools to reduce transmission and manage severe illness. Numerous teams are quickly developing artificial intelligence approaches to these problems, including using deep learning to predict COVID-19 diagnosis and prognosis from chest computed tomography (CT) imaging data. In this work, we assess the value of aggregated chest CT data for COVID-19 prognosis compared to clinical metadata alone. We develop a novel patient-level algorithm to aggregate the chest CT volume into a 2D representation that can be easily integrated with clinical metadata to distinguish COVID-19 pneumonia from chest CT volumes from healthy participants and participants with other viral pneumonia. Furthermore, we present a multitask model for joint segmentation of different classes of pulmonary lesions present in COVID-19 infected lungs that can outperform individual segmentation models for each task. We directly compare this multitask segmentation approach to combining feature-agnostic volumetric CT classification feature maps with clinical metadata for predicting mortality. We show that the combination of features derived from the chest CT volumes improve the AUC performance to 0.80 from the 0.52 obtained by using patients’ clinical data alone. These approaches enable the automated extraction of clinically relevant features from chest CT volumes for risk stratification of COVID-19 patients.
COVID-19 and Lung Cancer: What We Know and Don’t Know
Pulmonology Advisor, January 28, 2022
Research has provided data on morbidity and mortality in patients with lung cancer and COVID-19, shown how the pandemic has disrupted lung cancer screening and clinical trials, and provided some insight into the efficacy of COVID-19 vaccination in patients with lung cancer. However, the underlying biology of SARS-CoV-2 infection in lung cancer patients is not well understood, and more research is needed to better understand how lung cancer patients respond to COVID-19 vaccines. A recent review highlighted these knowledge gaps and summarized what is known to date about COVID-19 in the context of lung cancer. “[The review] is a call to action for our colleagues and information for the public and people with lung cancer,” explained senior author Fred Hirsch, MD, PhD, executive director of the Center for Thoracic Oncology at Mount Sinai Health System in New York, New York. “By answering the questions we raise in the review, we can hopefully find out how to prevent and manage COVID-19 in this patient population,” he added. The review cited research suggesting that, compared with the general population, patients with lung cancer have a 7.7-fold higher risk of developing COVID-19. A separate study showed a 3.6-fold higher risk of hospitalization and a 5.7-fold higher risk of death among lung cancer patients. The review authors also cited meta-analysis data showing a 32.4% COVID-19 mortality rate for patients with lung cancer and a 25.4% COVID-19 mortality rate for all cancer patients studied.
Around 7% of Lung Transplants Due to COVID-19 Respiratory Failure
Pulmonology Advisor, January 28, 2022
From August 2020 through September 2021, about 7 percent of lung transplantations were performed in patients with COVID-19-related respiratory failure, according to a letter to the editor published online Jan. 26 in the New England Journal of Medicine. Amy Roach, M.D., from Cedars-Sinai Medical Center in Los Angeles, and colleagues analyzed lung transplantations performed between Aug. 1, 2020, and Sept. 30, 2021, and reported in the United Network for Organ Sharing registry. The researchers found that 7.0 percent of the 3,039 lung transplantations were performed for COVID-19-related respiratory failure, including 4.6 and 2.4 percent for acute respiratory distress syndrome and pulmonary fibrosis, respectively. Per center, a median of 2.5 lung transplantations were performed for COVID-19-related respiratory failure. Overall, 197 (92.1 percent) and 17 (7.9 percent) of the 214 lung transplantations were bilateral- and single-lung transplantations, respectively. Of the 183 patients with validated data, the median patient age was 52 years, 20.8 percent were female, and 36.6 percent were Hispanic. About half (53.0 percent) received mechanical ventilation preoperatively; 64.5 percent received extracorporeal membrane oxygenation and 4.9 percent underwent dialysis. The median lung allocation score was 87.5. Patients were followed for a median of 1.9 months. There were nine postoperative deaths, with 30-day mortality of 2.2 percent and three-month survival of 95.6 percent. “Because the three-month survival among these patients approached that among patients who underwent lung transplantation for reasons other than COVID-19, we believe that lung transplantation may be an acceptable treatment for selected patients with irreversible respiratory failure due to COVID-19,” the authors write.
Eosinophilia linked to better COVID-19 outcomes when patients use inhaled corticosteroids
Healio | Allergy/Asthma, January 24, 2022
Patients with high eosinophil counts experienced improved COVID-19 outcomes when they received inhaled corticosteroids, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice. “This study, funded by NIH-NHLBI, was done to assess the effect of eosinophils in COVID-19,” Joe G. Zein, MD, PhD, MBA, staff physician at Cleveland Clinic Respiratory Institute, told Healio. The study involved 46,397 patients in the Cleveland Clinic COVID-19 Research Registry database who tested positive for SARS-CoV-2 between April 1, 2020, and March 31, 2021, and who had a complete blood count prior to their COVID-19 diagnosis. These patients included 6,739 who had been diagnosed with asthma and 3,066 with COPD/emphysema. Overall, 5,011 patients had been prescribed inhaled corticosteroids (iCS). Of the patients, 9,096 (19.6%) were hospitalized, 2,129 (4.6%) required ICU admission and 1,402 (3%) died during hospitalization. The database identified 19,506 patients with baseline eosinophilia (> 0.15 × 103 cells/µL; median age, 56.3 years; interquartile range [IQR], 42.1-69.3; 54.4% women). The remaining 26,891 patients had low eosinophil levels (< 0.15 × 103 cells/µL; median age, 50.6 years; IQR, 35.8-64.4; 61.8% women). Results of that adjusted analysis showed significantly lower odds for hospitalization (adjusted OR = 0.96; 95% CI, 0.93-0.99) and ICU admission (aOR = 0.92; 95% CI, 0.87-0.98) for patients with vs. without eosinophilia. Patients with COPD who were treated with iCS demonstrated an association between eosinophilia and lower odds for hospitalization (aOR = 0.8; 95% CI, 0.7-0.91), ICU admission (aOR = 0.78; 95% CI, 0.65-0.93) and mortality (aOR = 0.8, 95% CI = 0.7-0.91). Patients with asthma and eosinophilia experienced lower odds for hospitalization related to COVID-19 (aOR = 0.78; 95% CI, 0.69-0.87) and ICU admission (aOR = 0.72; 95% CI, 0.59-0.87). However, people with asthma treated with iCS did not demonstrate an association between eosinophilia and lower in-hospital mortality (aOR = 0.84; 95% CI, 0.66-1.09).
Clinical characteristics and outcomes of post-COVID-19 pulmonary fibrosis: A case-control study
Medicine, January 21, 2022
The development of pulmonary fibrosis is a rare complication of the novel coronavirus disease 2019 (COVID-19). Limited information is available in the literature about that, and the present study aimed to address this gap. This case-control study included 64 patients with post-COVID-19 pulmonary fibrosis who were hospitalized for COVID-19. The percentage of patients aged ≥65 years (44%) who demised was higher than those who survived (25%). Male patients (62%) had higher mortality than female patients (37%). The most frequently reported clinical symptoms were shortness of breath (98%), cough (91%), and fever (70%). Most COVID-19 patients with pulmonary fibrosis (81%) were admitted to an intensive care unit (ICU), and 63% required mechanical ventilation. Bilateral lung infiltrates (94%), “ground glass” opacity (91%), “honeycomb” lung (25%), and pulmonary consolidation (9%) were commonly identified in COVID-19 patients with pulmonary fibrosis who survived. The findings for computed tomography and dyspnea scale were significantly higher in severe cases admitted to the ICU who required mechanical ventilation. A higher computerized tomography score also correlated significantly with a longer duration of stay in hospital and a higher degree of dyspnea. Half of the COVID-19 patients with pulmonary fibrosis (50%) who survived required oxygen therapy, and those with “honeycomb” lung required long-term oxygen therapy to a far greater extent than others. Cox regression revealed that smoking and asthma were significantly associated with ICU admission and the risk of mortality. Post-COVID-19 pulmonary fibrosis is a severe complication that leads to permanent lung damage or death.
Asthma severity tied to more severe COVID-19 outcomes
Healio | Pulmonology, January 20, 2022
In a new study, all asthma phenotypes were associated with risk for more severe COVID-19 outcomes, except for type 2 inflammation, researchers reported in the American Journal of Respiratory and Critical Care Medicine. Researchers conducted a study to analyze the effect of asthma phenotype on COVID-19 outcomes and also to compare rates of COVID-19 hospitalization with influenza and pneumonia. The study included 434,348 adults with asthma (median age, 49.5 years; 58% women) and 748,327 matched individuals (median age, 48.5 years; 57.3% women) in the U.K. who were identified using electronic medical record data. The researchers linked patient-level data to Public Health England SARS-CoV-2 test, hospital and mortality data. Patients with asthma were phenotyped by medication, asthma exacerbation history and type 2 inflammation. All asthma phenotypes were associated with significantly increased risk for general practitioner-diagnosed COVID-19. The researchers reported significantly higher risks for ICU admission and mortality among patients with asthma and regular ICS plus add-on therapy (aHR = 1.7; 95% CI, 1.27-2.26) and those with frequent exacerbations (aHR = 1.66; 95% CI, 1.03-2.68). “Our findings suggest that COVID-19 outcomes are related to asthma severity, as defined by use of maintenance inhaler medication and exacerbation history,” Bloom and colleagues wrote.
One-year outcomes of invasively managed acute coronary syndrome patients with COVID-19
Heart & Lung, January 20, 2022
There is a limited data about the one-year outcomes of patients diagnosed with acute coronary syndrome (ACS) and coronavirus disease 2019 (COVID-19). The objective was to assess one-year mortality of invasively managed patients with ACS and COVID-19 compared to ACS patients without COVID-19. In our investigation, we defined the study time period as April 30 through September 1, 2020. The control groups consisted of ACS patients without COVID-19 at the same time period and ACS patients prior to the pandemic, within the same months as those of the study. COVID-19 infection was confirmed in all participants utilizing real-time polymerase chain reaction testing. This investigation examined 721 ACS participants in total. Among the participants, 119 patients were diagnosed with ACS and COVID-19, while 149 were diagnosed with ACS and without COVID-19. The other 453 ACS participants were diagnosed before the outbreak of the pandemic, within the same months as those of the study. One-year mortality rates were higher in the ACS participants with COVID-19 than in the ACS participants without COVID-19 and the pre-COVID-19 ACS participants (21.3% vs. 6.5% vs. 6.9%, respectively). An ACS along with COVID-19 was the only independent predictor of one-year mortality (HR=2.902, 95%CI=1.211–6.824, P = 0.018). According to the Kaplan-Meier survival curves, patients with ACS and COVID-19 had a lower chance of survival in the short-term and one-year periods. This is believed to be the first study to report that ACS patients with COVID-19 had higher one-year risk of mortality compared to ACS patients without COVID-19.
COVID-19: Does Omicron cause less damage to the lungs?
Medical News Today, January 14, 2022
Early reports following the emergence of the Omicron variant suggest that the variant is more likely to cause less severe illness than previous variants of SARS-CoV-2. Sequencing of the Omicron genome suggested that this variant carries a large number of mutations, including on the spike protein. The large number of mutations carried by Omicron could be a potential reason for this reduction in illness severity. However, the milder disease due to an Omicron infection could also be a result of a person’s enhanced immunity, acquired due to vaccination or past SARS-CoV-2 infections. Although an increase in immunity may influence the severity of illness, studies in animals and cells cultured in the laboratory suggest that the mutations carried by the Omicron variant have made it less efficient at infecting the lungs than the Delta variant. This could explain the less severe illness that the Omicron variant causes. The SARS-CoV-2 virus can affect both the upper and lower respiratory tracts. The upper respiratory tract consists of the nose, sinuses, and throat, whereas the lower respiratory tract includes the trachea and the lungs. Mild illness or early SARS-CoV-2 infections are likely to involve upper respiratory tract symptoms, such as a runny nose and sore throat. Severe illness due to the wild-type SARS-CoV-2 and the previous variants often Trusted Source involves the infection and inflammation of the lungs. Inflammation can cause fluid to accumulate in the air sacs, or alveoli, in the lungs, reducing the capacity of the lungs to transfer oxygen to the blood. Scientists have conducted experiments using animal models and laboratory cultures of lung cells to characterize the ability of Omicron to infect the respiratory tract and cause severe illness. Read more.
Risk of serious COVID-19 outcomes among adults with asthma in Scotland: a national incident cohort study
The Lancet | Respiratory Medicine, January 13, 2022
There is considerable uncertainty over whether adults with asthma should be offered booster vaccines against SARS-CoV-2. We were asked by the UK’s Joint Commission on Vaccination and Immunisation to undertake an urgent analysis to identify which adults with asthma were at an increased risk of serious COVID-19 outcomes to inform deliberations on booster COVID-19 vaccines. This national incident cohort study was done in all adults in Scotland aged 18 years and older who were included in the linked dataset of Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II). We used data from EAVE II to investigate the risk of COVID-19 hospitalisation and the composite outcome of intensive care unit (ICU) admission or death from COVID-19 among adults with asthma. Analyses were adjusted for age, sex, socioeconomic status, comorbidity, previous hospitalisation, and vaccine status. Between March 1, 2020, and July 27, 2021, 561 279 (12·7%) of 4 421 663 adults in Scotland had clinician-diagnosed-and-recorded-asthma. Among adults with asthma, 39 253 (7·0%) had confirmed SARS-CoV-2 infections, of whom 4828 (12·3%) were admitted to hospital for COVID-19 (among them, an estimated 600 [12·4%] might have been due to nosocomial infections). Adults with asthma were found to be at an increased risk of COVID-19 hospital admission (adjusted HR 1·27, 95% CI 1·23–1·32) compared with those without asthma. When using oral corticosteroid prescribing in the preceding 2 years as a marker for history of an asthma attack, the adjusted HR was 1·54 (95% CI 1·46–1·61) for those with three or more prescribed courses of oral corticosteroids, 1·37 (1·26–1·48) for those with two prescribed courses, 1·30 (1·23–1·37) for those with one prescribed course, and 1·15 (1·11–1·21) for those without any courses, compared with those aged 18 years or older without asthma. Adults with asthma were found to be at an increased risk of COVID-19 ICU admission or death compared with those without asthma (adjusted HR 1·13, 95 % CI 1·05–1·22). The adjusted HR was 1·44 (95% CI 1·31–1·58) for those with three or more prescribed courses of oral corticosteroids, 1·27 (1·09–1·48) for those with two prescribed courses, 1·04 (0·93–1·16) for those with one prescribed course, and 1·06 (0·97–1·17) for those without any course, compared with adults without asthma. Adults with asthma who have required two or more courses of oral corticosteroids in the previous 2 years or a hospital admission for asthma are at increased risk of both COVID-19 hospitalisation and ICU admission or death. Patients with a recent asthma attack should be considered a priority group for booster COVID-19 vaccines.
Are People With Asthma at a Greater Risk of Severe COVID-19?
Pulmonology Advisor, January 10, 2022
A large systematic review of the effects of asthma on the risk of poor COVID-19 outcomes in adults and children found that, overall, asthma was not associated with severe COVID-19 outcomes, although the evidence supporting this conclusion was deemed to be of very low certainty. This was among the findings of an article recently published in BMJ Evidence-Based Medicine. Early in the pandemic, it was expected that people with asthma would have a higher risk of adverse outcomes from COVID-19. The initial primary studies on this subject contradicted this expectation, reporting that people with asthma represented a lower proportion of patients with COVID-19 admitted to the hospital than that seen in the general population. Subsequent reviews and meta-analyses engendered conflicting conclusions, but analysis of the quality of these reviews showed important pitfalls. The current analysis, based studies spanning multiple continents, is one of the largest on the effects of asthma on the risk of poor COVID-19 outcomes, said the authors. Conducted in the UK at Oxford University, this systematic review and meta-analysis sought to determine whether individuals with asthma were predisposed to experiencing worse cases of COVID-19. The researchers’ review of electronic databases in October 2020 yielded 30 studies that met inclusion criteria for the analysis. The studies all included at least 1 of the following outcome measures, stratified by asthma status: risk of SARS-CoV-2 infection, or hospitalization, intensive care unit admission, or mortality from COVID-19. Participants in all studies (n = 112,420) included adults and children who tested positive for or were suspected to have COVID-19. Among the 30 studies analyzed, 12 were deemed to be high quality, 15 medium quality, and 3 low quality. Notably, few provided indications of asthma severity. Certainty of findings was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. Investigators found that in people with asthma, allergic asthma was associated with lower COVID-19 risk, and concurrent chronic obstructive pulmonary disease was linked with higher risk. In some studies, corticosteroids correlated with higher risk, but this finding could simply imply higher risk in people with more severe asthma. In people with asthma, the risks associated with COVID-19 seem to go up with age, as seen in the general population. Pooled results showed that, overall, asthma was not associated with severe COVID-19 outcomes, although the evidence was judged to be of very low certainty.
Proteomic profiling reveals a distinctive molecular signature for critically ill COVID-19 patients compared with asthma and COPD: A distinctive molecular signature for critically ill COVID-19 patients
International Journal of Infectious Diseases, January 10, 2022
The mortality rate for critically ill coronavirus disease 2019 (COVID-19) cases was more than 80%. Nonetheless, research about the effect of common respiratory diseases on critically ill COVID-19 expression and outcomes is scarce. We performed proteomic analyses on airway mucus obtained by bronchoscopy from severe COVID-19 patients, or induced sputum from patients with chronic obstructive pulmonary disease (COPD), asthma, and healthy controls. Out of the total identified and quantified proteins, 445 differentially expressed proteins (DEPs) were found in different comparison groups. In comparison to COPD, asthma, and controls, 11 proteins were uniquely present in COVID-19 patients. Apart from DEPs associated with COPD vs controls and asthma vs controls, there were a total of 59 DEPs specific to COVID-19 patients. Finally, the findings revealed that there were 8 overlapping proteins in COVID-19 patients, including C9, FGB, FGG, PRTN3, HBB, HBA1, IGLV3-19, and COTL1. Functional analyses revealed that the majority of them were associated with complement and coagulation cascades, platelet activation, or iron metabolism, and anemia-related pathways. This study provides fundamental data for identifying COVID-19-specific proteomic changes in comparison to COPD and asthma, which may suggest molecular targets for specialized therapy.
Can Practice Guidelines for COVID-19 Inpatient Drug Therapies Be Trusted?
Pulmonology Advisor, January 7, 2022
During the COVID-19 pandemic, clinicians need swift and urgent guidance to manage affected patients and forestall transmission. But few clinical practice guidelines (CPGs) developed for pharmacologic treatments in hospitalized patients with COVID-19 meet National Academy of Medicine standards for trustworthy guidelines, according to a systematic review recently published in JAMA Network Open. Researchers in Canada searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials and screened all titles and abstracts of citations for guidelines eligible for review. All 32 CPGs included in the review covered pharmacologic treatment in COVID-19 and were investigator-led and sponsored or produced by a national or international scientific organization or a government or nongovernment organization related to global health. The investigators found that most of the CPGs were of low quality. Few CPGs (1) reported funding sources or conflicts of interest; (2) included a methodologist; (3) described a search strategy or study selection process; or {4) synthesized evidence. Although 14 CPGs (43.8%) made recommendations or suggestions for or against treatments, only 6 (18.8%) rated confidence in the quality of the evidence; 6 (18.8%) described potential benefits and harms; and 5 (15.6%) included a methodologist and graded the strength of recommendations. Just 7 CPGs (21.9%) reported funding sources and 12 (37.5%) divulged conflicts of interest. According to investigators, the chaos and urgency surrounding COVID-19 surely contributed to the deficiencies found in the CPGs, but strong methodologic standards for CPGs are critical to avoid promotion of useless or potentially harmful treatments and the squandering of precious health care resources. Certain strategies could enhance the development of trustworthy CPGs, even in a pandemic, they asserted, suggesting that: (1) CPG panels should include a methodologist such as an epidemiologist, biostatistician, or health services researcher; (2) collaborations of multidisciplinary participants from at least 2 World Health Organization regions could pool their expertise to produce fewer but better-quality CPGs; and (3) journal editors and peer reviewers could require the use of CPG appraisal tools at the time of submission to assure the publication of high-quality guidelines.
Q&A: How will omicron affect long COVID?
Healio | Infectious Disease, January 6, 2022
The omicron variant of SARS-CoV-2 now accounts for 95% of COVID-19 cases in the United States, CDC Director Rochelle P. Walensky, MD, MPH, said during a White House briefing on Wednesday. If omicron causes less severe disease than the delta variant, could any lasting effects of COVID-19 also be less serious? We asked Ziyad Al-Aly, MD, FASN, a physician at the VA St. Louis Health Care System who studies long COVID, to answer this and other lingering questions about the variant.
Q&A: Does asthma mitigate the risk for COVID-19?
Healio | Allergy/Asthma, January 3, 2022
In a study conducted in collaboration with National Jewish Health, University of Colorado Denver, Cedars-Sinai Medical Center and University of California, Los Angeles, researchers are investigating how three separate viruses interact with the biological mechanisms that control inflammation in asthma. In an interview with Healio, Monica Kraft, MD, Robert and Irene Flinn endowed chair in medicine at University of Arizona College of Medicine, Tucson and deputy director of the Asthma and Airway Disease Research Center, discussed what is known about the link between asthma and other respiratory diseases and what researchers hope to discover about its link to COVID-19.
Asthma Phenotypes and COVID-19 Risk: A Population-based Observational Study
American Journal of Respiratory and Critical Care Medicine, January 1, 2022
Studies have suggested some patients with asthma are at risk of severe coronavirus disease (COVID-19), but they have had limited data on asthma phenotype and have not considered if risks are specific to COVID-19. Our objective was to determine the effect of asthma phenotype on three levels of COVID-19 outcomes. Compare hospitalization rates with influenza and pneumonia. Electronic medical records were used to identify patients with asthma and match them to the general population. Patient-level data were linked to Public Health England severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test data, hospital, and mortality data. Asthma was phenotyped by medication, exacerbation history, and type 2 inflammation. The risk of each outcome, adjusted for major risk factors, was measured using Cox regression. A total of 434,348 patients with asthma and 748,327 matched patients were included. All patients with asthma had a significantly increased risk of a General Practice diagnosis of COVID-19. Asthma with regular inhaled corticosteroid (ICS) use (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.01–1.61), intermittent ICS plus add-on asthma medication use (HR, 2.00; 95% CI, 1.43–2.79), regular ICS plus add-on use (HR, 1.63; 95% CI, 1.37–1.94), or with frequent exacerbations (HR, 1.82; 95% CI, 1.34–2.47) was significantly associated with hospitalization. These phenotypes were significantly associated with influenza and pneumonia hospitalizations. Only patients with regular ICS plus add-on asthma therapy (HR, 1.70; 95% CI, 1.27–2.26) or frequent exacerbations (HR, 1.66; 95% CI, 1.03–2.68) had a significantly higher risk of ICU admission or death. Atopy and blood eosinophil count were not associated with severe COVID-19 outcomes. More severe asthma was associated with more severe COVID-19 outcomes, but type 2 inflammation was not. The risk of COVID-19 hospitalization appeared to be similar to the risk with influenza or pneumonia.
Does Lenzilumab Improve Survival in Patients With COVID-19 Pneumonia?
Pulmonology Advisor, December 29, 2021
In hospitalized patients with COVID-19 pneumonia, treatment with the monoclonal antibody lenzilumab has been shown to significantly improve survival without the need for mechanical ventilation. The phase 3, randomized, double-blind, placebo-controlled LIVE-AIR trial. Results of the analysis were published in The Lancet Respiratory Medicine. The investigators sought to evaluate the efficacy and safety of lenzilumab for treating COVID-19 beyond the available treatments. The study enrolled patients hospitalized with COVID-19 pneumonia from 29 sites in the US and Brazil between May 2020 and January 2021, with 85% of the participants from US sites. Patients eligible for enrollment in LIVE-AIR needed to be at least 18 years of age, have virologically confirmed SARS-CoV-2 infection, and have pneumonia diagnosed by a chest x-ray or computed tomography scan. All of the participants were randomly assigned in a 1:1 ratio to receive lenzilumab or matched placebo, in addition to standard treatment, per the institutional guidelines at each of the sites. All patients were stratified at randomization by age (≤65 years and >65 years) and disease severity. After screening and baseline measurements, lenzilumab or matching placebo was administered by intravenous (IV) infusions beginning on day 0 within 12 hours of randomization, in addition to standard care. Overall, 3 doses of lenzilumab (600 mg each) or placebo were administered 8 hours apart via a 1-hour IV infusion per dose. Survival without the need for invasive mechanical ventilation to day 28 was attained in 84% (198 of 236) of patients in the lenzilumab group (95% CI, 79-89) and 78% (190 of 243) of those in the placebo group (95% CI, 72 -83). The likelihood of survival was greater with lenzilumab than with placebo (hazard ratio, 1.54; 95% CI, 1.02-2.32; P =.040). Overall, 27% (68 of 255) of patients in the lenzilumab arm and 33% (84 of 257) of those in the placebo arm experienced at least 1 adverse event (AE) that was grade 3 or higher in severity. The most commonly reported treatment-emergent AEs (TEAEs) of grade 3 or higher were associated with respiratory disorders (26%) and cardiac disorders (6%), with none of the TEAEs leading to death. The researchers concluded that “Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalized patients with COVID-19, with a safety profile similar to that of placebo.”
Outcomes of Positive Expiratory Pressure Flute Therapy in Adults With COVID-19
Pulmonology Advisor, December 28, 2021
Positive expiratory pressure (PEP) flute therapy led to a small yet statistically significant decrease in the severity of respiratory symptoms in adults with COVID-19 recovering at home, according to results of an open-label, randomized controlled trial published in BMJ. Between October 2020 and February 2021, investigators recruited community-dwelling adults with symptomatic SARS-CoV-2 infection, confirmed via reverse transcription polymerase chain reaction testing, who were able to perform self-care. Patients were randomly assigned in a 1:1 fashion to receive either standard care or standard care plus PEP flute self-care, administered 3 times daily for 30 days. Standard care included self-quarantine, adequate fluid intake, and over-the-counter medications to relieve symptoms. All patients completed a daily chronic obstructive pulmonary disease assessment test (CAT). The primary outcome was a change in symptom severity from baseline to day 30 based on self-reported CAT scores, with adjustments for baseline values and stratification by age and sex. Secondary outcomes were self-reported urgent care center visits for COVID-19, the number of COVID-19-related symptoms, and change in self-rated health. Among a total of 378 patients included in the study, 190 received standard care plus PEP flute self-care and 188 received standard care alone. Overall, most patients were women (72.5%) and younger than 60 years (85.7%; range, 19-80 years), and most (95.8%) self-rated their health as “good” or “excellent” prior to developing COVID-19. The median duration of COVID-19-related symptoms at enrollment was 4 days (IQR, 3-7 days), and cough was the predominant respiratory symptom. Patients in the PEP flute self-care group used the PEP flute for a median of 21 days (IQR, 13-25 days) for a median of 2.5 sessions daily (IQR, 1.5-2.9). The investigators found that the mean number of daily PEP sessions decreased as mean CAT scores decreased during the 30-day study period. Among patients in the PEP flute self-care group, investigators noted a significant decrease in CAT scores from baseline to day 30 (-1.2 points; 95% CI, -2.1 to -0.2; P =.017). There also was a small yet significant increase in self-rated health scores from baseline to day 30 among patients in the PEP flute group (0.2 points; 95% CI, 0.01-0.4; P =.041). In a sensitivity analysis of individual CAT items, there was a significant difference between groups for chest tightness (-0.24 points; 95% CI, -0.40 to -0.09; P =.002), dyspnea (-0.28 points; 95% CI, -0.46 to -0.09; P =.004), activities of daily living (-0.40 points; 95% CI, -0.60 to -0.21); P <.001), and vigor (-0.42 points; 95% CI, -0.62 to -0.22; P <.001).
Most patients with asthma follow mask guidelines, encourage others to do the same
Healio | Allergy/Asthma, December 20, 2021
Nearly all people with asthma said they wear masks to protect themselves and others against COVID-19, despite having some symptoms from doing so, according to survey results. The researchers administered the online Face Mask Use in Adults with Asthma survey between November 2020 and February 2021, garnering 501 complete responses. “We had previously surveyed adults with asthma to determine the impact of the pandemic on this vulnerable population,” study author Barbara J. Polivka, PhD, associate dean for research and professor at the University of Kansas School of Nursing, told Healio. “Once the mask mandates became the norm, we were curious about how adults with asthma were managing with masks. We were able to resurvey the over 500 participants who gave us permission to contact them again for additional studies,” Polivka said. The 45 items on the survey included questions about how frequently participants wore masks in public places, their comfort levels with other people wearing masks in those settings, how long they wore a mask each day, what type of mask they wore and if they carried an inhaler while wearing a mask. Primarily, the participants were female (83.3%), white (89.2%), college educated (89.5%), residents of the United States (96.6), residents of urban (22.6%) or suburban (37.3%) areas and homeowners (55.1%). They also had well-controlled asthma (mean ACT score = 20.1 ± 4.2). Age ranged from 20 to 88 years (mean, 46.1 ± 15.2), 56% had a BMI < 30 and 88.4% reported having no symptoms of COVID-19 or having had a negative COVID-19 test.
Health care provider recommendation key to COVID-19 vaccine uptake
Healio, December 16, 2021
Adults who said a health care provider recommended that they receive a COVID-19 vaccine were more likely to get one, data published in MMWR show. Kimberly H. Nguyen, DrPH, a member of CDC’s COVID-19 Vaccine Task Force, and colleagues analyzed data from 340,543 U.S. adults who completed a phone survey during one of four different time periods between April 22 and Sept. 25. About 51% of the survey respondents were women, most (24.5%) were aged 50 to 64 years and 62.1% were white. The researchers reported that proportion of adults who received a provider recommendation for COVID-19 vaccination increased from 34.6% to 40.5% during the survey period. Respondents who said a health care provider recommended COVID-19 vaccination were more likely to have received at least one dose of the vaccine than those who did not receive a recommendation (77.6% vs. 61.9%, adjusted prevalence ratio [aPR] = 1.12). A COVID-19 vaccination recommendation was also associated with a respondent’s concern about COVID-19 (aPR = 1.31), thinking COVID-19 vaccines were “important to protect oneself” (aPR = 1.15), thinking COVID-19 vaccination “was very or completely safe” (aPR = 1.17) and that “many or all of their family and friends had received COVID-19 vaccination” (aPR = 1.19). The researchers noted that the survey response rate was low, and it did not measure the number of health care provider visits. The study’s cross-sectional design was also a limitation, according to Nguyen and colleagues. However, they emphasized that “provider recommendation will continue to serve an important role in motivating individual patient vaccination acceptance and completion.” .
Lenzilumab improves survival without ventilation in patients hospitalized with COVID-19
Healio | Pulmonology, December 16, 2021
Lenzilumab significantly improved survival without the need for invasive mechanical ventilation among patients hospitalized with COVID-19, according to results of the LIVE-AIR trial published in The Lancet Respiratory Medicine. The safety profile of lenzilumab was similar to that of placebo, researchers reported. “Lenzilumab is a novel anti-human granulocyte-macrophage colony-stimulating factor monoclonal antibody that directly binds granulocyte-macrophage colony-stimulating factor, with high specificity and affinity, and a slow off-rate to prevent signaling through its receptor,” Zelalem Temesgen, MD, infectious disease specialist in the division of infectious diseases at Mayo Clinic, Rochester, Minnesota, and colleagues wrote. “It has shown efficacy in clinical studies of various disease settings with no serious adverse events attributed to its administration.” LIVE-AIR was a randomized, double-blind, placebo-controlled phase 3 trial that included 479 adults with COVID-19 pneumonia (mean age, 61 years; 65% men) who did not require invasive mechanical ventilation. Patients were enrolled from May 2020 to January 2021 at 29 sites in the U.S. and Brazil. Patients were randomly assigned to receive three doses of IV lenzilumab 600 mg (Humanigen; n = 236) or placebo (n = 243) administered 8 hours apart. In addition, all patients received standard supportive care including remdesivir (Veklury, Gilead Sciences) and corticosteroids; 94% of patients received steroids, 72% received remdesivir and 69% received both. The primary outcome was survival at 28 days without invasive mechanical ventilation. The primary outcome was achieved in 84% of patients who received lenzilumab compared with 78% who received placebo (HR = 1.54; 95% CI, 1.02-2.32; P = .04). .
Initial severity of COVID-19 correlates with adverse pulmonary outcome 1 year later
Healio | Pulmonology, December 15, 2021
Initial severity of COVID-19 respiratory failure was associated with the degree of pulmonary impairment and respiratory quality of life 1 year after infection, according to results published in Respiratory Medicine. The ongoing single-center, prospective, observational study included 180 patients with acute COVID-19 (median age, 57 years; 37.8% women) who were followed up as outpatients from May 2020 to June 2021. At 6 weeks, 3, 6 and 12 months after COVID-19 symptom onset, patients underwent chest CT scans to assess pulmonary function and completed the St. George’s Respiratory Questionnaire to assess symptoms. Researchers categorized patients based on severity of acute infection. Three-quarters of patients were initially hospitalized. The median age of patients increased with the level of respiratory support required: 44 years in those never hospitalized; median age, 56 years in those who required extracorporeal membrane oxygenation; 61 years in those who required mechanical ventilation. Older age (P < .0001), male sex (P = .001) and higher BMI (P = .004) were all associated with severity of acute COVID-19. In addition, pulmonary restriction (P < .0001) and reduced carbon monoxide diffusion capacity (P = .01) were also associated with COVID-19 severity. Pulmonary restriction occurred in 32% of patients, and reduced carbon monoxide diffusion capacity was observed in 61%. Over 12 months, among patients with pulmonary restriction and impaired carbon monoxide diffusion capacity, there was an improvement in FVC (P = .002), total lung capacity (P= .045), diffusing capacity of carbon monoxide (P = .0002) and diffusion coefficient (P = .0005). Researchers reported an association between the CT score of lung involvement in the acute COVID-19 phase and pulmonary restriction and reduction in diffusion capacity during follow-up. Fatigue, dyspnea, cough, cognitive impairment and joint pain were the most commonly reported symptoms within 1 year. At 1 year, more than 60% of patients reported fatigue, 43% shortness of breath and 23% persistent cognitive impairment. Respiratory symptoms improved during follow-up for patients with higher disease severity, but the same was not observed among patients with initially mild COVID-19. .
Asthma presents hospitalization risks for children with COVID-19, but not worse outcomes
Healio | Allergy/Asthma, December 14, 2021
Researchers identified asthma as a risk factor for hospitalization among children who had COVID-19, but not for worse COVID-19 outcomes, according to a nested case-control study published in Pediatric Allergy and Immunology. The researchers also found that SARS-CoV-2 did not seem to be a strong trigger for pediatric asthma exacerbations, nor did asthma severity correlate with higher risk for COVID-19. “As the pandemic started, spread and eventually reached Allegheny County, [Pennsylvania] in March 2020, there were many unanswered questions about how the virus affected children, and particularly those with underlying chronic conditions,” study author Erick Forno, MD, MPH, ATSF, associate professor of pediatrics at University of Pittsburgh School of Medicine, told Healio. A multidisciplinary group of physicians and nurse practitioners at University of Pittsburgh Medical Center (UPMC) Children’s Hospital of Pittsburgh and Children’s Community Pediatrics in Pittsburgh then launched the Pediatric COVID-19 Registry to guide conversations with patients and families so providers would not need to rely on anecdotal memory. Further, there has been conflicting evidence on whether COVID-19 affects people with asthma worse than other people, Forno said. Whereas most data have come from studies of adults, he continued, this new study was one of the first to focus on children. “We were surprised to find that children with asthma presenting with COVID-19 were much more likely to be admitted to the hospital,” Forno said. “However, we found no other indications of COVID-19 being more severe, so the explanations could be that the virus triggered significant asthma exacerbations that required hospitalization, or that physicians were admitting children with asthma as a precautionary measure.”
Convalescent plasma fails to reduce respiratory failure, death in COVID-19 pneumonia
Healio | Pulmonology, December 13, 2021
Convalescent plasma failed to reduce progression to severe respiratory failure or death within 30 days in patients with moderate to severe COVID-19 pneumonia, according to a new study published in JAMA Network Open. “Randomized clinical trials already published or available as preprint versions have not shown a clear benefit of [convalescent plasma] in reducing the risk of disease progression of death,” Francesco Menichetti, MD, head of the infectious diseases unit at Pisan University Hospital, University of Pisa, Italy, and colleagues wrote. “However, a relationship between neutralizing antibody titer and a more favorable clinical outcome have been suggested and [convalescent plasma] was associated with a decreased 28-day mortality rate when higher titer plasma was used or when [convalescent plasma] was administered early in the course of the disease.” The prospective, open-label, randomized clinical TSUNAMI trial included 487 adults who were hospitalized with COVID-19 pneumonia (median age, 64 years; 64.1% men) with a partial pressure of oxygen-to-fraction of inspired oxygen ratio between 350 mm Hg and 200 mm Hg. Patients were randomly assigned to receive convalescent plasma plus standard therapy (n = 241) or standard therapy alone (n = 246) from July to December 2020 at 27 sites in Italy. The convalescent plasma plus standard therapy group received IV high-titer convalescent plasma at 200 mL in one to three infusions. Standard therapy consisted of remdesivir, glucocorticoids and low-molecular weight heparin. The modified intention-to-treat population included 473 patients. The primary outcome was a composite of worsening acute respiratory failure or death within 30 days. The primary outcome occurred in 25.5% of patients who received convalescent plasma plus standard therapy compared with 28% of patients who received standard therapy alone (OR = 0.88; 95% CI, 0.59-1.33; P = .54), according to the results.
Chest Radiograph and CT Findings in Patients Hospitalized with Breakthrough COVID-19
Radiology: Cardiothoracic Imaging, December 9, 2021
The purpose of this study was to characterize chest radiograph and CT imaging appearance in patients with breakthrough COVID-19 (defined as an illness occurring in patients that previously received a COVID-19 vaccination) in a hospital setting. In this retrospective study, all patients admitted to the hospital between August 26 and September 8, 2021 with a positive SARS-CoV-2 reverse transcription polymerase chain reaction-confirmed infection who were fully vaccinated against COVID-19 were evaluated. Clinical, laboratory data, and outcomes were collected and assessed. All patients had chest imaging performed (either radiography, CT, or a combination of both). Chest radiographs and CTs were assessed and scored on admission and on follow up to determine the extent and type of pulmonary involvement. Descriptive statistics were used. Charts of 60 hospitalized patients that tested positive for SARS-CoV-2 were reviewed for a prior history of COVID-19 vaccination. Eight (13.3%) such patients were identified and included for analysis (mean age, 54 years; range 34–81 years; four women). Patients received either two doses of Pfizer-BioNTech (n = 6), two doses of Moderna (n = 1), or one dose of Johnson and Johnson (n = 1). Five (63%) patients were immunosuppressed at the time of presentation, and six (75%) reported respiratory symptoms. Most of the patients had normal radiographs (4 of 7; 57%). The most common chest CT findings were ground glass opacities (three of five), with mild to moderate severity scores (average, 51; range 8–88). Two patients required intensive care unit admission. However, no patients died and all were either discharged or were on room air without residual respiratory symptoms by the end of the study period. In hospitalized patients with COVID-19 breakthrough illness, normal to mild or moderately positive imaging findings were observed.
Pathologists find evidence of usual interstitial pneumonia in people with long COVID
Healio | Pulmonology, December 7, 2021
Usual interstitial pneumonia was a common finding in lung biopsies of people evaluated for post-COVID-19 interstitial lung disease, according to data published in EClinicalMedicine. “We were seeing a lot of usual interstitial pneumonia, which isn’t the pattern we tend to associate with acute lung injury,” Kristine E. Konopka, MD, associate professor of thoracic pathology in the department of pathology and program director of the Pulmonary Pathology Fellowship at the University of Michigan, Ann Arbor, said in a university press release. “So, we think these are patients who had lung disease prior to COVID and maybe they just weren’t being followed by primary care physicians. They then have COVID, are still sick and their usual interstitial pneumonia is finally being picked up.” Konopka and colleagues conducted a retrospective observational study to analyze surgical lung biopsies in the Michigan Medicine pathology database. The researchers evaluated surgical lung biopsies from 18 people with persistent ILD who were recovering from acute COVID-19 through April 2021. The median age was 56 years and 44% were women. Each case was independently reviewed by two thoracic pathologists who were masked to patient clinical data, radiographic findings, and original pathologic diagnoses and diagnoses made during consultation. Nine cases had evidence of usual interstitial pneumonia. Two of those patients had superimposed acute lung injury. In addition, five cases showed a spectrum of acute lung injury, which ranged from persistent diffuse alveolar damage to organizing pneumonia. Four cases showed desquamative interstitial pneumonia, acute and organizing bronchopneumonia or no diagnostic abnormality, according to the results. People with evidence of usual interstitial pneumonia on surgical lung biopsy were generally older (57 years vs. 53 years; P = .042) with preexisting lung disease prior to their COVID-19 infection (44% vs. 11%; P = .294) compared with those with no evidence of usual interstitial pneumonia.
Analysis finds noninvasive respiratory support for COVID-19 safe, may improve outcomes
Healio | Pulmonology, December 6, 2021
Among patients with COVID-19-related acute respiratory failure, noninvasive respiratory support appears to be safe, effective and may yield better outcomes, according to an analysis published in The Lancet Respiratory Medicine. In addition, authors of the personal view concluded that noninvasive respiratory support may reduce the need for intubation and improve resource utilization. Sampath Weerakkody, BMBS, from the Centre for Human Health and Performance at the Institute of Sport, Exercise and Health at the University College London, and colleagues conducted an analysis of two randomized controlled trials and 83 observational studies that assessed the effects of high-flow nasal oxygen, CPAP and bilevel positive airway pressure (BiPAP) in patients with COVID-19. Across the studies, the patient population included 13,931 patients with COVID-19-related acute respiratory failure. “Rising case numbers in China, Europe and the USA in the spring of 2020, allied with shortages of mechanical ventilators and ICU beds, led to noninvasive respiratory support being increasingly adopted outside ICUs, with guidelines altered accordingly,” the authors wrote. “Nonetheless, the role and benefits of CPAP and high-flow nasal oxygen in the management of COVID-19 remain contentious, with lively debates about the timing of intubation and the risk-benefit balance between patient self-inflicted lung injury and ventilator-induced lung injury.” Overall, 5,120 patients from 40 studies were candidates for full treatment escalation, and the authors evaluated data from 4,669 patients. Data showed that 1,880 (37%) received invasive mechanical ventilation and 78% survived until the end of the studies. Median survival was similar across the noninvasive respiratory support modalities, at 79% for CPAP only, 83% for high-flow nasal oxygen only, 76% for BiPAP only and 78% for those who received CPAP, BiPAP or high-flow nasal oxygen. There was a 29.8% survival rate among the 1,050 patients who received noninvasive respiratory support in 22 studies.
COVID-19 hospitalization risk elevated in children with poorly controlled asthma
Healio | Pulmonology, December 1, 2021
In a new study, school-aged children in Scotland with uncontrolled asthma had a 3 to 6 times higher risk for COVID-19 hospitalization compared with those without asthma, researchers reported in The Lancet Respiratory Medicine. “The findings from this linkage of multiple data sources have helped inform the prioritization of school-aged children with poorly controlled asthma for vaccines,” Ting Shi, PhD, chancellor’s fellow at the Usher Institute, University of Edinburgh, U.K., and colleagues wrote. The study included all children in Scotland aged 5 to 17 years in the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) linked dataset from March 2020 to July 2021. The researchers evaluated the risk for COVID-19 hospitalization among children with markers of uncontrolled asthma, which was defined as a previous asthma hospitalization or prescriptions for oral corticosteroids within the previous 2 years. Among 752,867 children, 8.4% had clinician-diagnosed and recorded asthma; of those, 6.8% had confirmed SARS-CoV-2 infection. Of those with a confirmed infection, 1.5% were hospitalized with COVID-19. When the researchers evaluated children without asthma (n = 689,404), 5.8% had confirmed SARS-CoV-2 infection and, of those, 0.9% were hospitalized with COVID-19. The researchers reported a higher rate of COVID-19 hospitalization among children with poorly controlled asthma than those with well controlled or no asthma. Compared with patients without asthma, the adjusted HR for COVID-19 hospitalization in those with a previous admission for asthma was 6.4 (95% CI, 3.27-12.53) for those with poorly controlled asthma and 1.36 (95% CI, 1.02-1.8) for those with well-controlled asthma, according to the results. Compared with patients without asthma, the adjusted HR for COVID-19 hospitalization in those with a history of oral corticosteroids, the adjusted HR was 3.38 (95% CI, 1.84-6.21) for those with three or more prescribed courses, 1.52 (95% CI, 0.9-2.57) for those with one course and 1.34 (95% CI, 0.98-1.82) for those not prescribed oral corticosteroids, according to the results.
Allergic diseases, especially paired with asthma, linked to lower COVID-19 infection risk
Healio | Allergy/Asthma, December 1, 2021
People with hay fever, rhinitis, atopic eczema and other allergic conditions had a lower risk for developing COVID-19, particularly if they also had asthma, according to a study published in Thorax. Older age, male sex and other underlying conditions did not indicate an increased risk for developing COVID-19, the study also showed. But Asian ethnicity, obesity, household overcrowding, indoor socialization with other households, and people-facing roles in fields other than health and social care all were independently associated with higher susceptibility, the researchers found. “There have been numerous studies investigating risk factors for severe COVID-19, such as risk factors for hospitalization, but there is a relative lack of population-based studies investigating risks for developing COVID-19 irrespective of severity,” Adrian R. Martineau, BMedSci, DTM&H, MRCP, PhD, FRSB, clinical professor of respiratory infection and immunity at Blizard Institute at Barts and The London School of Medicine and Dentistry, Queen Mary University of London, told Healio. “Studies investigating the effects of diet, lifestyle, behavior, etc., on risk for developing COVID-19 were lacking. We therefore launched COVIDENCE UK, which is an n = 20,000 population-based cohort study investigating these risks in the general U.K. population,” Martineau said. Some risk factors for developing COVID-19 may differ from those that predispose patients to severe disease and the need for intensive care, according to a growing body of evidence, the researchers noted. The researchers surveyed 14,348 adults (mean age, 59.4 years; 69.8% women; 94.9% white) in the United Kingdom about their age, household circumstances, job, lifestyle, weight, height, longstanding medical conditions, medication use, vaccination status, diet and supplement intake upon enrollment in the study and again in subsequent months. Almost 3% of participants (n = 446) had at least one episode of confirmed SARS-CoV-2 infection determined by swab during 2,613,921 person-days of follow-up, and 32 were admitted to a hospital.
CPAP, high-flow nasal oxygen to treat COVID-19 not linked to heightened infection risk
Healio | Pulmonology, November 24, 2021
In a new study, the use of CPAP and high-flow nasal oxygen to treat patients with moderate to severe COVID-19 did not produce higher levels of air or surface viral contamination in the immediate environment compared with supplemental oxygen. “Our findings show that the noninvasive breathing support methods do not pose a higher risk of transmitting infection, which has significant implications for the management of the patients,” Danny McAuley, MD, professor at Queen’s University Belfast, Northern Ireland, and consultant in intensive care medicine at the Royal Victoria Hospital, Montreal, said in a related press release. “If there isn’t a higher risk of infection transmission, current practice may be over cautious measures for certain settings, for example preventing relatives visiting the sickest patients, whilst underestimating the risk in other settings, such as coughing patients with early infection on general wards.” The observational, environmental-sampling study included 30 patients hospitalized with COVID-19 (mean age, 56 years; 13 women) at three centers in the U.K. from December 2020 to February 2021. All patients had a fraction of inspired oxygen of 0.4 or more to maintain oxygen saturation of 94% or more. Patients received supplemental oxygen (n = 10), CPAP (n = 10) or high-flow nasal oxygen (n = 10). Researchers collected a nasopharyngeal swab, three air samples and three surface samples from each participant and the clinical environment. Twenty-one patients (70%) tested positive for SARS-CoV-2 RNA by PCR nasopharyngeal swab at the time of assessment. Four (4%) air samples and six (7%) surface samples tested positive for viral RNA. An additional 10 samples were suspected to be positive in both air and surface samples. The use of CPAP or high-flow nasal oxygen or coughing in this patient population was not associated with significantly more environmental viral contamination compared with the use of supplemental oxygen, according to the researchers. Of 51 positive or suspected-positive samples, only one sample from the nasopharynx of a patient who received high-flow nasal oxygen was culture-positive, according to the results.
Multiplexed detection of respiratory pathogens with a portable analyzer in a “raw-sample-in and answer-out” manner
Nature, November 23, 2021
Coronavirus disease 2019 (COVID-19) has emerged, rapidly spread and caused significant morbidity and mortality worldwide. There is an urgent public health need for rapid, sensitive, specific, and on-site diagnostic tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, a fully integrated and portable analyzer was developed to detect SARS-CoV-2 from swab samples based on solid-phase nucleic acid extraction and reverse transcription loop-mediated isothermal amplification (RT-LAMP). The swab can be directly inserted into a cassette for multiplexed detection of respiratory pathogens without pre-preparation. The overall detection process, including swab rinsing, magnetic bead-based nucleic acid extraction, and 8-plex real-time RT-LAMP, can be automatically performed in the cassette within 80 min. The functionality of the cassette was validated by detecting the presence of a SARS-CoV-2 pseudovirus and three other respiratory pathogens, i.e., Klebsiella pneumoniae, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. The limit of detection (LoD) for the SARS-CoV-2 pseudovirus was 2.5 copies/μL with both primer sets (N gene and ORF1ab gene), and the three bacterial species were successfully detected with an LoD of 2.5 colony-forming units (CFU)/μL in 800 μL of swab rinse. Thus, the analyzer developed in this study has the potential to rapidly detect SARS-CoV-2 and other respiratory pathogens on site in a “raw-sample-in and answer-out” manner.
Usual Interstitial Pneumonia is the Most Common Finding in Surgical Lung Biopsies from Patients with Persistent Interstitial Lung Disease Following Infection with SARS-CoV-2
EClinicalMedicine, November 23, 2021
There is increasing interest in persistent interstitial lung disease (ILD) following resolution of acute COVID-19. No studies have yet reported findings in surgical lung biopsies (SLB) from this patient population. Our Michigan Medicine pathology database was queried for SLB reviewed between January 2020 and April 2021 from patients with persistent ILD following recovery from acute COVID-19. Slides for our retrospective observational study were independently reviewed by two thoracic pathologists, who were blinded to patient clinical data, radiographic findings, and previous pathologic diagnosis. Eighteen cases met inclusion criteria. Of these, nine had usual interstitial pneumonia (UIP). These included two patients with superimposed acute lung injury (ALI). Five cases showed a spectrum of ALI that ranged from persistent diffuse alveolar damage to organizing pneumonia. Four patients had desquamative interstitial pneumonia (1), acute and organizing bronchopneumonia (1), or no diagnostic abnormality (2). Compared to patients without UIP, those with UIP tended to be older and have pre-existing lung disease prior to COVID-19. In patients with UIP, pre-SLB chest computed tomography changes included groundglass with interstitial thickening or peripheral reticulations with bronchiectasis; no UIP patients had groundglass only. The most common radiographic finding in patients without UIP was groundglass opacities only. UIP was the most common pathologic finding in patients undergoing evaluation for post-COVID-19 ILD. Our preliminary data suggests that CT changes described as interstitial thickening, peripheral reticulations, and/or bronchiectasis may be helpful in identifying patients with underlying fibrotic chronic interstitial pneumonia for which UIP is the chief concern.
Steroid Dose and Days Alive Without Life Support in COVID + Severe Hypoxemia
Pulmonology Advisor, November 22, 2021
In patients with COVID-19 and severe hypoxemia, treatment with dexamethasone 12 mg/day compared with dexamethasone 6 mg/day is not associated with any statistically significant days alive without life support at 28 days. These were among the findings of COVIDSTEROID2, a multicenter, randomized clinical trial at 26 hospitals in Europe and India. Results of the analysis were published in JAMA. In COVIDSTEROID2, the investigators sought to evaluate the effects of 2 different doses of dexamethasone in patients with COVID-19 who also had severe hypoxemia. The primary study outcome was the number of days alive without life support (ie, invasive mechanical ventilation [MV], circulatory support, or kidney replacement therapy) at 28 days. Secondary outcomes included number of days alive without life support at 90 days, number of days alive when out of the hospital at 90 days, mortality at 28 days, mortality at 90 days, and 1 or more serious adverse reactions at 28 days. The study analysis included 982 patients with COVID-19 who required at least 10 L/minute of oxygen or MV. The median participant age was 65 years (range, 55 to 73 years); 31% of participants were women. Primary outcome data were available for 971 participants, 491 in the dexamethasone 12-mg group and 480 in the dexamethasone 6-mg group. Results of the study showed that the median number of days alive without the use of life support was 22.0 days (range, 6.0 to 28.0 days) in the 12-mg arm and 20.5 days (range, 4.0 to 28.0 days) in the 6-mg arm (adjusted mean difference, 1.3 days; 95% CI, 0-2.6 days; P =.07). At 28 days, mortality was 27.1% in the 12-mg group and 32.3% in the 6-mg group (adjusted relative risk, 0.86; 99% CI, 0.68-1.08). At 90 days, the mortality rate was 32.0% in the dexamethasone 12-mg/day arm vs 37.7% in the dexamethasone 6-mg/day arm (adjusted relative risk, 0.87; 99% CI, 0.70-1.07).
Early Treatment With Sotrovimab Decreases Risk for Progression to Severe COVID-19
Pulmonology Advisor, November 22, 2021
Treatment with sotrovimab, a pan-sarbecovirus monoclonal antibody, was found to decrease the risk for severe disease progression among high-risk patients with mild-to-moderate COVID-19, according to results of an ongoing, multicenter, double-blind, prospective phase 3 trial published in The New England Journal of Medicine. In this study, investigators enrolled adult patients with at least 1 risk factor for severe disease progression who developed symptomatic SARS-CoV-2 infection within the past 5 days. Risk factors for severe disease progression included patients older than55 years age, and those with either diabetes requiring medication, obesity, chronic kidney disease, congestive heart failure, chronic obstructive pulmonary disease, or moderate-to-severe asthma. Investigators randomly assigned patients in a 1:1 fashion to receive either a single infusion of sotrovimab 500 mg or placebo on day 1 of the trial, followed by treatment at their physician’s discretion. The primary outcome was hospitalization for more than 24 hours or death from any cause within 29 days after the infusion. Investigators also conducted a safety analysis analyzing adverse events and infusion-related reactions. Among a total of 583 patients included in the intention-to-treat population, 291 received sotrovimab and 292 received placebo. Of patients in both treatment groups, 22% were aged 65 years and older, 7% were Black, 63% were Hispanic or Latino, and 42% had 2 or more risk factors for severe disease progression. The investigators found that 3 patients (1%) in the sotrovimab group vs 21 (7%) in the placebo group were hospitalized or died due to severe disease progression (relative risk reduction, 85%; 97.24% CI, 44-96; P =.002). There were 868 patients included in the safety analysis, of whom 430 were in the sotrovimab group and 438 were in the placebo group. Adverse events were reported by 17% and 19% of patients in the sotrovimab and placebo groups, respectively, and the frequency of severe adverse events was decreased among those who received sotrovimab vs those who received placebo (2% vs 6%). Of note, the percentage of patients with infusion-related reactions was similar in both groups.
Alvesco no better than placebo for alleviating COVID-19 symptoms
Helio | Primary Care, November 22, 2021
Nonhospitalized patients with COVID-19 who received the inhaled glucocorticoid Alvesco had the same recovery time as those who received placebo, data from a phase 3 trial showed. Alvesco (ciclesonide, Covis Pharma) is approved by the FDA as prophylactic therapy for patients aged 12 years and older with asthma, according to the agency. Systemic corticosteroids are often used in patients with severe COVID-19, but the role of inhaled corticosteroids in patients with mild to moderate COVID-19 “is less clear,” researchers wrote in JAMA Internal Medicine. “In vitro, ciclesonide has been shown to have antiviral properties against COVID-19 and blocks COVID-19 viral replication,” Brian M. Clemency, DO, a professor in the department of emergency medicine at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, and colleagues wrote. “A case series described three elderly patients with hypoxia due to COVID-19 who recovered following treatment with ciclesonide. Clinical trials are needed to determine the effects of ciclesonide on COVID-19 in the clinical setting.” Clemency and colleagues randomly assigned 400 nonhospitalized patients with COVID-19 (mean age, 43.3 years; 55.3% women; 86.3% white) to a metered dose inhaler that administered 320 g ciclesonide (n = 197) or placebo (n = 203) twice daily. According to the researchers, the median time until COVID-19-related symptoms were alleviated — which was the trial’s primary efficacy endpoint — was 19 days (95% CI, 14-21) in the ciclesonide cohort and 19 days (95% CI, 16-23) in the placebo cohort. In addition, there was no significant difference in resolution of all COVID-19 symptoms by day 30 (OR = 1.28; 95% CI, 0.84-1.97).
Bacteraemic Pneumococcal Pneumonia and SARS-COV-2 Pneumonia: Differences And Similarities
International Journal of Infectious Diseases, November 18, 2021
Our objective was to analyse differences in clinical presentation and outcome between bacteraemic pneumococcal community-acquired pneumonia (B-PCAP), and SARS-CoV-2 pneumonia. This observational multicenter study was conducted on patients hospitalized for B-PCAP between 2000-2020 and SARS-CoV-2 pneumonia during 2020. We compared 30-day survival, predictors of mortality and intensive care unit (ICU) admission. We included 663 B-PCAP and 1561 SARS-CoV-2 pneumonia. B-PCAP patients had higher severity, ICU admission and more complications. SARS-CoV-2 pneumonia patients had higher in-hospital mortality (10.8%vs6.8%, p 0.004). Among ICU patients, need for invasive mechanical ventilation (69.7%vs36.2%, p<0.001) and mortality were higher in SARS-CoV-2 pneumonia. In B-PCAP, our predictive model related mortality to systemic complications (hyponatremia, septic shock, neurological complications), lower respiratory reserve or tachypnoea; whereas chest pain and purulent sputum were protective. In SARS-CoV-2, mortality was related to previous liver and cardiac disease, advanced age, altered mental status, tachypnoea, hypoxemia, bilateral involvement, pleural effusion, septic shock, neutrophilia, and high blood urea nitrogen; in contrast, ≥7 days of symptoms was a protective factor. In-hospital mortality occurred earlier in B-PCAP. Although B-PCAP was associated with higher severity and ICU rate, SARS-CoV-2 pneumonia-related mortality was higher and occurred later. New prognostic scales and more effective treatments are needed for SARS-CoV-2 pneumonia.
The Effect of the COVID-19 Pandemic on Pulmonary Diagnostic Procedures
American Journal of Respiratory and Critical Care Medicine, November 16, 2021
Pulmonary diagnostic procedures have been dramatically affected by the COVID-19 pandemic as many have been thought to have high infectious transmission risk. This potential risk made many pulmonary function laboratories either shut down or reduce testing to minimal in fear of causing viral spread in the early months of the pandemic. The purpose of this study is to provide brief overview of trends regarding total number of pulmonary diagnostic testing performed throughout 2020 and into 2021 as compared to 2019. This was a multi-center retrospective cohort study from 50 institutions utilizing data from the National COVID Cohort Collaboration (N3C). This database includes all patients with complete data (n=4,960,128) seen at 50 institutions across the US. Daily unique counts of different pulmonary diagnostic procedures, which included pulmonary function tests (complete pulmonary function tests and spirometries) (PFTs), bronchoscopies (flexible bronchoscopies, biopsies, and rigid bronchoscopies), cardiopulmonary exercise tests (CPETs), and ambulatory exercise testing (six-minute walk tests and oxygen titration tests) were obtained. Differences in totals at notable time points were then compared by calculating a percentage change. PFTs peaked at 13,305 tests in January 2020 and dropped to the lowest in April 2020 at 1,561 tests, an 88.2% decrease. PFTs rebounded to total 10806 in October 2020 then trended slightly downward to 9442 being performed in March 2021, similar to pre-pandemic amounts. Bronchoscopy totals steadily increased throughout 2019, peaking at 3,303 in January 2020. There was a decrease to 2,304 in April 2020, a 30.2% decrease. Bronchoscopic procedures rebounded to a total of 3,605 in July 2020 and have remained higher than 2019. Ambulatory exercise tests increased into 2020, peaking at 1,948 tests in January 2020 (pre-pandemic) and decreasing to 307 in April 2020, an 84.2% decrease. Exercise testing rebounded to a total of 1,815 in October 2020 and has remained elevated with 1,670 tests being performed in March 2021. CPETs peaked at 414 tests January 2020 and dropped to 81 in April 2020, an 80.4% decrease. CPETs rebounded to total 647 in October 2020 then remained higher than before the pandemic.
Common cardiac medications potently inhibit ACE2 binding to the SARS-CoV-2 Spike, and block virus penetration and infectivity in human lung cells
Scientific Reports, November 12, 2021
To initiate SARS-CoV-2 infection, the Receptor Binding Domain (RBD) on the viral spike protein must first bind to the host receptor ACE2 protein on pulmonary and other ACE2-expressing cells. We hypothesized that cardiac glycoside drugs might block the binding reaction between ACE2 and the Spike (S) protein, and thus block viral penetration into target cells. To test this hypothesis we developed a biochemical assay for ACE2:Spike binding, and tested cardiac glycosides as inhibitors of binding. Here we report that ouabain, digitoxin, and digoxin, as well as sugar-free derivatives digitoxigenin and digoxigenin, are high-affinity competitive inhibitors of ACE2 binding to the Original [D614] S1 and the α/β/γ [D614G] S1 proteins. These drugs also inhibit ACE2 binding to the Original RBD, as well as to RBD proteins containing the β [E484K], Mink [Y453F] and α/β/γ [N501Y] mutations. As hypothesized, we also found that ouabain, digitoxin and digoxin blocked penetration by SARS-CoV-2 Spike-pseudotyped virus into human lung cells, and infectivity by native SARS-CoV-2. These data indicate that cardiac glycosides may block viral penetration into the target cell by first inhibiting ACE2:RBD binding. Clinical concentrations of ouabain and digitoxin are relatively safe for short term use for subjects with normal hearts. It has therefore not escaped our attention that these common cardiac medications could be deployed worldwide as inexpensive repurposed drugs for anti-COVID-19 therapy.
Are Second COVID Vax Doses Too Risky After Allergic Reaction to the First?
MedPage Today, November 10, 2021
Everyone who received their second dose of the Moderna or Pfizer mRNA vaccine against COVID-19 at military facilities after experiencing allergic reactions to the first did just fine without any pretreatment, a physician reported here. These individuals were observed closely, of course, and some underwent allergy testing beforehand to ascertain whether they were genuinely reactive to the vaccines or its components, said Benjamin St. Clair, DO, of Walter Reed National Military Medical Center in Washington, D.C., in a talk at the American College of Allergy, Asthma and Immunology’s annual meeting. A few individuals ultimately were advised not to have the second vaccine dose. But for the majority, physicians determined that the risk was minimal, and none of those accepting the second dose had further problems, St. Clair said. That is likely to prove significant now that the Biden administration is requiring service members to be vaccinated against COVID-19, he noted—a total of more than 2.2 million people. Whereas his group found only 23 people experiencing reactions to the first dose through June 15 (the vaccine mandate was implemented in September but hasn’t been fully enforced yet), the number will surely increase by orders of magnitude. And even more so if the administration succeeds in its effort to require vaccination for all large civilian employers. For their study, St. Clair and colleagues searched records of all individuals receiving COVID vaccinations at Walter Reed or the Defense Health Agency’s vaccination division. (Not all were necessarily active-duty personnel, he said — some may have been family members.) The 23 included for analysis were those experiencing reactions classified as either probable or possible anaphylaxis, or having potential “late” allergic reactions occurring more than 24 hours post-jab. Overall, St. Clair said, 15 of the 23 “tolerated the second dose with minimal to no adverse effects.” Another five refused the second dose “despite being offered”; and “two patients were advised against” second doses. In summary, he said the study dovetailed with others showing that second mRNA vaccine doses could be tolerated in individuals having anaphylactic reactions to the first dose. “This highlights that first-dose anaphylaxis does not always mean they are allergic,” nor that one should expect the same reaction with later challenge.
Asthma exacerbations after COVID-19 last longer in Latino patients
Helio | Primary Care, November 7, 2021
After a SARS-CoV-2 infection, Latino patients were more likely than non-Latino Black and white patients to develop asthma exacerbations and experience these exacerbations for a longer duration, according to a recent study. The findings were presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting. Katharine Foster, MD, of the department of internal medicine at Rush University Medical Center in Chicago, and colleagues examined data on 174 adults with a history of asthma (23 Latino, 44 Black) who tested positive for SARS-CoV-2 between February and April 2020 at their medical center, “which primarily serves Cook County and an overall ethnically diverse population,” Foster said. The patients were enrolled at the time of infection and followed for a mean of 6.8 months. The researchers found that Latino patients were 4.6 times more likely to develop asthma exacerbations than non-Latino Black patients and 2.9 times more likely to develop exacerbations than non-Latino white patients. In addition, Latino patients experienced asthma exacerbations for 3.2 weeks compared with 1.4 weeks among non-Latino Black patients and 1.59 weeks among non-Latino white patients. “This stayed true when statistically adjusted for gender, BMI, age, inhaled corticosteroid use and allergic/atopic status,” Foster told Healio Primary Care. “We included these adjusters since these factors have proven significant for predicting a person’s, in particular an asthmatic patient’s, susceptibility to severe COVID-19 infection.” Despite the differences in symptoms, there was no significant difference “in the likelihood of starting steroids for symptom relief, nor for starting asthma step-up therapy between Latino, non-Latino white and non-Latino Black populations,” study co-author and ACAAI member Mahboobeh Mahdavinia, MD, PhD, said in a press release. The researchers also found a similar number of asthma-related provider visits, including clinic, ED and telehealth visits, across the groups, with a mean of 1.9 total visits for exacerbation-related concerns per patient. “We want to recommend that providers consider initiating increased scheduled follow-up visits with Latino patients with asthma who become infected with COVID-19 and consider step-up therapy early in the exacerbation,” Foster said.
The Bronchial Circulation in COVID-19 Pneumonia
American Journal of Respiratory and Critical Care Medicine, November 3, 2021
The primary life-limiting pulmonary morbidity of severe COVID-19 is characterized by pulmonary endothelialitis, microangiopathy and aberrant angiogenesis. Although numerous studies have highlighted the pronounced microangiopathy in pulmonary circulation, the impact of the bronchial vascular system has not been fully elucidated. Therefore, we comprehensively analyzed complete lung lobes from three male patients (age 63.7±14.2 yrs; hospitalization time 22±1 days, mechanically ventilated) who succumbed to severe COVID-19 using conventional CT, histology, microvascular corrosion casting, and hierarchial phase-contrast tomography (HiP-CT). We used three control lungs from body donors (age 78.3±13.6 yrs; nonventilated, 2 female and 1 male died from cerebral stroke or uterine carcinoma). In pulmonary CT angiography, we found the previously reported pulmonary sequelae of COVID-19 lung injury in the form of bilateral, peripheral ground-glass opacities, peribronchial consolidations and peripheral macrovascular congestion. Peribronchial and perivascular micro-vessels (vasa vasorum) were distinctly dilated. This intrapulmonary shunting by the bronchial circulation accounts for the continued perfusion in a variety of airway conditions, such as inflammation, ARDS, and chronic thromboembolism. In severe COVID-19 pneumonia, the microvascular architecture of the peribronchial vessels showed a microvascular architecture with densely packed aberrant bundles of blood vessels. The expansion of the peribronchial plexus is mainly driven by intussusceptive angiogenesis (IA) as evidenced by the appearance of transluminal endothelial tissue pillars. Spatial analysis of peribronchial vessels in COVID-19 pneumonia by HiPCT demonstrated the expansion of peribronchial and perivascular arterio-venous anastomoses and a recruitment of “Sperrarterien” (blockade arteries) across individual secondary pulmonary lobules in the third dimension for the first time. This intralobular shunting is accompanied by different spots of glomerouid-like vascular expansion.
The associations of previous influenza/upper respiratory infection with COVID-19 susceptibility/morbidity/mortality: a nationwide cohort study in South Korea
Scientific Reports, November 3, 2021
We aimed to investigate the associations of previous influenza/URI with the susceptibility of COVID-19 patients compared to that of non-COVID-19 participants. A nationwide COVID-19 cohort database was collected by the Korea National Health Insurance Corporation. A total of 8,070 COVID-19 patients (1 January 2020 through 4 June 2020) were matched with 32,280 control participants. Severe COVID-19 morbidity was defined based on the treatment histories of the intensive care unit, invasive ventilation, and extracorporeal membrane oxygenation and death. The susceptibility/morbidity/mortality associated with prior histories of 1–14, 1–30, 1–90, 15–45, 15–90, and 31–90 days before COVID-19 onset were analyzed using conditional/unconditional logistic regression. Prior influenza infection was related to increased susceptibility to COVID-19 (adjusted odds ratio [95% confidence interval] = 3.07 [1.61–5.85] for 1–14 days and 1.91 [1.54–2.37] for 1–90 days). Prior URI was also associated with increased susceptibility to COVID-19 (6.95 [6.38–7.58] for 1–14 days, 4.99 [4.64–5.37] for 1–30 days, and 2.70 [2.55–2.86] for 1–90 days). COVID-19 morbidity was positively associated with influenza (3.64 [1.55–9.21] and 3.59 [1.42–9.05]) and URI (1.40 [1.11–1.78] and 1.28 [1.02–1.61]) at 1–14 days and 1–30 days, respectively. Overall, previous influenza/URI did not show an association with COVID-19 mortality. Previous influenza/URI histories were associated with increased COVID-19 susceptibility and morbidity. Our findings indicate why controlling influenza/URI is important during the COVID-19 pandemic.
Impact of Allergic Rhinitis and Asthma on COVID-19 Infection, Hospitalization and Mortality
https://www.sciencedirect.com/science/article/pii/S2213219821012022
The Journal of Allergy and Clinical Immunology: In Practice, October 30, 2021
It remains unclear if patients with AR and/or asthma are susceptible to COVID-19 infection, severity and mortality. To investigate the role of AR and/or asthma in COVID-19 infection, severity, and mortality, and assess whether long-term AR and/or asthma medications affected the outcomes of COVID-19.Demographic and clinical data of 70,557 adult participants completed SARS-Cov-2 testing between March 16 and December 31, 2020 in the UK Biobank were analyzed. The rates of COVID-19 infection, hospitalization and mortality in relation to preexisting AR and/or asthma were assessed based on adjusted generalized linear models. We further analyzed the impact of long-term AR and/or asthma medications on the risk of COVID-19 hospitalization and mortality. AR patients of all ages had lower positive rates of SARS-Cov-2 tests (RR:0.75, 95% CI: 0.69-0.81, p<0.001), with lower susceptibility in males (RR: 0.74, 95%CI: 0.65-0.85, p<0.001) than females (RR: 0.8, 95% CI: 0.72-0.9, p<0.001). However, similar effects of asthma against COVID-19 hospitalization were only major in participants aged <65 (RR:0.93, 95% CI: 0.86-1, p=0.044) instead of elderlies. In contrast, asthma patients tested positively had higher risk of hospitalization (RR:1.42, 95% CI: 1.32-1.54, p<0.001). Neither AR nor asthma had impact on COVID-19 mortality. None of conventional medications for AR or asthma, e.g., antihistamines, corticosteroids or β2 adrenoceptor agonists showed association with COVID-19 infection or severity. AR (all ages) and asthma (aged<65) act as protective factors against COVID-19 infection, while asthma increase risk for COVID-19 hospitalization. None of the long-term medications had significant association with infection, severity and mortality of COVID-19 among patients with AR and/or asthma.
High-flow nasal cannula oxygen therapy in hypoxic patients with COVID-19 pneumonia: a retrospective cohort study confirming the utility of respiratory rate index
Respiratory Investigation, October 30, 2021
Although high-flow nasal cannula (HFNC) oxygen treatment has been frequently used in coronavirus disease 2019 (COVID-19) patients with acute respiratory failure after the 3rd wave of the pandemic in Japan, the usefulness of the indicators of ventilator avoidance, including respiratory rate-oxygenation (ROX) index and other parameters, namely oxygen saturation/fraction of inspired oxygen ratio and respiratory rate (RR), remain unclear. Between January and May 2021, our institution treated 189 COVID-19 patients with respiratory failure requiring oxygen, among which 39 patients requiring HFNC treatment were retrospectively analyzed. The group that switched from HFNC treatment to conventional oxygen therapy (COT) was defined as the HFNC success group, and the group that switched from HFNC treatment to a ventilator was defined as the HFNC failure group. We followed the patients’ oxygenation parameters for a maximum of 30 days. HFNC treatment success occurred in 24 of 39 patients (62%) treated with HFNC therapy. Compared with the HFNC failure group, the HFNC success group had a significantly higher degree of RR improvement in the univariate analysis. Logistic regression analysis of HFNC treatment success adjusting for age, respiratory improvement, and a ROX index ≥5.55 demonstrated that an improved RR was associated with HFNC treatment success. The total COT duration was significantly shorter in the HFNC success group than in the HFNC failure group. HFNC treatment can be useful for ventilator avoidance and allow the quick withdrawal of oxygen administration. RR improvement may be a convenient, useful, and simple indicator of HFNC treatment success.
COVID-19 infection localization and severity grading from chest X-ray images
Computers in Biology and Medicine, October 30, 2021
The immense spread of coronavirus disease 2019 (COVID-19) has left healthcare systems incapable to diagnose and test patients at the required rate. Given the effects of COVID-19 on pulmonary tissues, chest radiographic imaging has become a necessity for screening and monitoring the disease. Numerous studies have proposed Deep Learning approaches for the automatic diagnosis of COVID-19. Although these methods achieved outstanding performance in detection, they have used limited chest X-ray (CXR) repositories for evaluation, usually with a few hundred COVID-19 CXR images only. Thus, such data scarcity prevents reliable evaluation of Deep Learning models with the potential of overfitting. In addition, most studies showed no or limited capability in infection localization and severity grading of COVID-19 pneumonia. In this study, we address this urgent need by proposing a systematic and unified approach for lung segmentation and COVID-19 localization with infection quantification from CXR images. To accomplish this, we have constructed the largest benchmark dataset with 33,920 CXR images, including 11,956 COVID-19 samples, where the annotation of ground-truth lung segmentation masks is performed on CXRs by an elegant human-machine collaborative approach. An extensive set of experiments was performed using the state-of-the-art segmentation networks, U-Net, U-Net++, and Feature Pyramid Networks (FPN). The developed network, after an iterative process, reached a superior performance for lung region segmentation with Intersection over Union (IoU) of 96.11% and Dice Similarity Coefficient (DSC) of 97.99%. Furthermore, COVID-19 infections of various shapes and types were reliably localized with 83.05% IoU and 88.21% DSC. Finally, the proposed approach has achieved an outstanding COVID-19 detection performance with both sensitivity and specificity values above 99%.
Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial
The Lancet | Respiratory Medicine, October 29, 2021
Infections with SARS-CoV-2 continue to cause significant morbidity and mortality. Interleukin (IL)-1 and IL-6 blockade have been proposed as therapeutic strategies in COVID-19, but study outcomes have been conflicting. We sought to study whether blockade of the IL-6 or IL-1 pathway shortened the time to clinical improvement in patients with COVID-19, hypoxic respiratory failure, and signs of systemic cytokine release syndrome. We did a prospective, multicentre, open-label, randomised, controlled trial, in hospitalised patients with COVID-19, hypoxia, and signs of a cytokine release syndrome across 16 hospitals in Belgium. The COV-AID trial has a 2 × 2 factorial design to evaluate IL-1 blockade versus no IL-1 blockade and IL-6 blockade versus no IL-6 blockade. Patients were randomly assigned by means of permuted block randomisation with varying block size and stratification by centre. In a first randomisation, patients were assigned to receive subcutaneous anakinra once daily (100 mg) for 28 days or until discharge, or to receive no IL-1 blockade (1:2). In a second randomisation step, patients were allocated to receive a single dose of siltuximab (11 mg/kg) intravenously, or a single dose of tocilizumab (8 mg/kg) intravenously, or to receive no IL-6 blockade (1:1:1). The primary outcome was the time to clinical improvement, defined as time from randomisation to an increase of at least two points on a 6-category ordinal scale or to discharge from hospital alive. The primary and supportive efficacy endpoints were assessed in the intention-to-treat population. Safety was assessed in the safety population. 342 patients were randomly assigned to IL-1 blockade (n=112) or no IL-1 blockade (n=230) and simultaneously randomly assigned to IL-6 blockade (n=227; 114 for tocilizumab and 113 for siltuximab) or no IL-6 blockade (n=115). The estimated median time to clinical improvement was 12 days (95% CI 10–16) in the IL-1 blockade group versus 12 days (10–15) in the no IL-1 blockade group (hazard ratio [HR] 0·94 [95% CI 0·73–1·21]). For the IL-6 blockade group, the estimated median time to clinical improvement was 11 days (95% CI 10–16) versus 12 days (11–16) in the no IL-6 blockade group (HR 1·00 [0·78–1·29]).
Germinal center-induced immunity is correlated with protection against SARS-CoV-2 reinfection but not lung damage
Journal of Infectious Diseases, October 28, 2021
Germinal centers (GCs) elicit protective humoral immunity through a combination of antibody-secreting cells and memory B cells, following pathogen invasion or vaccination. However, the possibility of a GC response inducing protective immunity against reinfection following SARS-CoV-2 infection remains unknown. Here, we found that GC activity was consistent with the seroconversion observed in recovered macaques and humans. Rechallenge with a different clade of virus resulted in a significant reduction in replicating virus titers in respiratory tracts in macaques with a high GC activity. However, diffuse alveolar damage and increased fibrotic tissue were observed in the lungs of reinfected macaques. Our study highlights the importance of GCs developed during natural SARS-CoV-2 infection in managing viral loads in the subsequent infections. However, their ability to alleviate lung damage remains to be determined. These results may improve our understanding of SARS-CoV-2-induced immune responses, resulting in better COVID-19 diagnosis, treatment, and vaccine development.
Factors Linked to Mortality in Invasively Ventilated Patients With COVID-19
Renal & Urology News, October 27, 2021
Hypertension and obesity were the main comorbidities of patients with COVID-19 requiring invasive ventilation in Argentina, according to findings of the SATICOVID19 study, recently published in Lancet Respiratory Medicine. This multicenter, prospective study examined the associations between clinical characteristics and outcomes in 1909 adults requiring invasive ventilation for COVID-19 in 63 intensive care units (ICUs) in Argentina. The primary outcome was all-cause in-hospital mortality. Secondary outcomes included ICU mortality, duration of invasive mechanical ventilation, patterns of change in physiological respiratory, and other independent predictors of mortality and mechanical ventilation variables. Among the 1909 invasively ventilated patients with COVID-19 in the cohort, the median age was 62 years and 67.8% of the population were male. When comorbidities were examined, hypertension and obesity were the main comorbidities. Acute respiratory distress syndrome developed in 87.6% of patients, and 61.6% received prone positioning. Overall, in-hospital mortality was 57.7% and ICU mortality was 57.0%. Age, endotracheal intubation outside of the ICU, vasopressor use on day 1, D-dimer concentration, arterial pH on day 1, driving pressure on day 1, acute kidney injury, and month of admission were identified as independent predictors of mortality. The study authors wrote, “[S]igns of early organ dysfunction (ie, alterations in oxygenation, presence of hypotension, acidosis, acute kidney injury, and activation of coagulation) appear to be a prognostic factor in severe COVID-19.” They added, “We also found a paradoxical increase in mortality throughout the first wave of the pandemic, possibly reflecting increasing strain on the health-care system. Long duration of mechanical ventilation and prolonged ICU stay contributed to the pressure on ICU capacity.”
Improvement of clinical outcome, laboratory findings and inflammatory cytokines levels using plasmapheresis therapy in severe COVID-19 cases
Respiratory Medicine, October 26, 2021
Cytokine storm is one of the consequences of the severe forms of COVID-19 due to excessive immune response. In this study, we investigated the therapeutic effect of plasmapheresis and its role on the inflammatory cytokines levels in patients suffering from severe COVID-19. In plasmapheresis group, 22 severe cases of COVID-19 receiving three cycles of plasmapheresis with time interval of 24–36 h and 22 COVID-19 patients as the control group were enrolled. Clinical history and laboratory parameters as well as IL-1, IL-6, IFN-γ and IL-17 cytokines serum levels in the time points of before and after plasmapheresis were studied. In severe COVID-19 patients, plasmapheresis significantly improved clinical and laboratory parameters such as cough, weakness, fever, blood oxygen saturation and CRP levels. Serum levels of IL-1, IL-6, IFN-γ and IL-17 in the group of patients receiving plasmapheresis, had a significant decrease following plasmapheresis courses. Although only IL-6 level in the control group had a significant decrease between the days 1–14 of disease. Also, at both time points of before and after plasmapheresis, serum levels of IL-1, IL-6, IFN-γ and IL-17 were inversely correlated to blood oxygen saturation. Based on the obtained results, plasmapheresis therapy in severe forms of COVID-19 can effectively improve the clinical symptoms of the disease and reduce inflammatory markers. Therefore, it is suggested that plasmapheresis can be evaluated in standard treatment protocols for severe forms of COVID-19.
Intubated COVID-19 predictive (ICOP) score for early mortality after intubation in patients with COVID-19
Scientific Reports, October 26, 2021
Patients with coronavirus disease 2019 (COVID-19) can have increased risk of mortality shortly after intubation. The aim of this study is to develop a model using predictors of early mortality after intubation from COVID-19. A retrospective study of 1945 intubated patients with COVID-19 admitted to 12 Northwell hospitals in the greater New York City area was performed. Logistic regression model using backward selection was applied. This study evaluated predictors of 14-day mortality after intubation for COVID-19 patients. The predictors of mortality within 14 days after intubation included older age, history of chronic kidney disease, lower mean arterial pressure or increased dose of required vasopressors, higher urea nitrogen level, higher ferritin, higher oxygen index, and abnormal pH levels. We developed and externally validated an intubated COVID-19 predictive score (ICOP). The area under the receiver operating characteristic curve was 0.75 (95% CI 0.73–0.78) in the derivation cohort and 0.71 (95% CI 0.67–0.75) in the validation cohort; both were significantly greater than corresponding values for sequential organ failure assessment (SOFA) or CURB-65 scores. The externally validated predictive score may help clinicians estimate early mortality risk after intubation and provide guidance for deciding the most effective patient therapies.
Symptom Persistence Despite Improvement in Cardiopulmonary Health – Insights from longitudinal CMR, CPET and lung function testing post-COVID-19
EClinicalMedicine, October 20, 2021
The longitudinal trajectories of cardiopulmonary abnormalities and symptoms following infection with coronavirus disease (COVID-19) are unclear. We sought to describe their natural history in previously hospitalised patients, compare this with controls, and assess the relationship between symptoms and cardiopulmonary impairment at 6 months post-COVID-19. Fifty-eight patients and thirty matched controls (single visit), underwent symptom-questionnaires, cardiac and lung magnetic resonance imaging (CMR), cardiopulmonary exercise test (CPET), and spirometry at 3 months following COVID-19. Of them, forty-six patients returned for follow-up assessments at 6 months. At 2-3 months, 83% of patients had at least one cardiopulmonary symptom versus 33% of controls. Patients and controls had comparable biventricular volumes and function. Native cardiac T1 (marker of fibroinflammation) and late gadolinium enhancement (LGE, marker of focal fibrosis) were increased in patients at 2-3 months. Sixty percent of patients had lung parenchymal abnormalities on CMR and 55% had reduced peak oxygen consumption (pV̇O2) on CPET. By 6 months, 52% of patients remained symptomatic. On CMR, indexed right ventricular (RV) end-diastolic volume (-4·3 mls/m2, P=0·005) decreased and RV ejection fraction (+3·2%, P=0·0003) increased. Native T1 and LGE improved and was comparable to controls. Lung parenchymal abnormalities and peak V̇O2, although better, were abnormal in patients versus controls. 31% had reduced pV̇O2 secondary to symptomatic limitation and muscular impairment. Cardiopulmonary symptoms in patients did not associate with CMR, lung function, or CPET measures. In patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health.
Lung response to a higher positive end-expiratory pressure in mechanically ventilated patients with COVID-19
CHEST, October 16, 2021
International guidelines suggest using a higher (>10 cmH2O) positive end-expiratory pressure (PEEP) in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) due to the novel coronavirus disease (COVID-19). However, even if oxygenation generally improves with a higher PEEP, compliance and arterial carbon dioxide tension (PaCO2) frequently do not, as if recruitment was small.
So our research question was, “Is the potential for lung recruitment small in patients with early ARDS due to COVID-19?” Forty patients with ARDS due to COVID-19 were studied in the supine position within three days of endotracheal intubation. They all underwent a PEEP trial, where oxygenation, compliance, and PaCO2 were measured with 5, 10, and 15 cmH2O of PEEP and all other ventilatory settings unchanged. Twenty underwent a whole-lung static computed tomography at 5 and 45 cmH2O, and the other twenty at 5 and 15 cmH2O of airway pressure. Recruitment and hyperinflation were defined as a decrease in the volume of the non-aerated (density above -100 HU) and an increase in the volume of the over-aerated (density below -900 HU) lung compartments, respectively. From 5 to 15 cmH2O, oxygenation improved in thirty-six (90%) patients but compliance only in eleven (28%) and PaCO2 only in fourteen (35%). From 5 to 45 cmH2O, recruitment was 351 (161-462) ml and hyperinflation 465 (220-681) ml. From 5 to 15 cmH2O, recruitment was 168 (110-202) ml and hyperinflation 121 (63-270) ml. Hyperinflation variably developed in all patients and exceeded recruitment in more than half of them. Patients with early ARDS due to COVID-19, ventilated in the supine position, present with a large potential for lung recruitment. Even so, their compliance and PaCO2 do not generally improve with a higher PEEP, possibly due to hyperinflation.
Inhaled budesonide in early symptomatic COVID-19 reduced need for urgent care
Helio | Critical Care, September 22, 2021
Inhaled budesonide twice daily administered early in the course of COVID-19 reduced the need for urgent medical care, according to results of the STOIC trial presented at the virtual European Respiratory Society International Congress. “Treatments to prevent deterioration from COVID-19 are urgently needed, especially with the vaccination programs in Western countries,” Sanjay Ramakrishnan, MD, pulmonologist and clinical research fellow in the Nuffield department of clinical medicine at the University of Oxford, U.K., said during a presentation. The randomized, open-label STOIC trial included 146 adults with chronic respiratory disease and symptoms suggesting COVID-19 infection within the previous 7 days. Participants were randomly assigned to inhaled budesonide 800 µg twice daily in addition to usual care of antibiotic therapy with paracetamol and ibuprofen (n = 70; mean age, 44 years; 44% women) or usual care alone (n = 69; mean age, 46 years; 41% women). This study was completed at home by the participants. Participants were instructed to continue budesonide use until COVID-19 symptom resolution or hospitalization. Each participant filled out questionnaires and recorded daily temperatures and blood oxygen saturations. The primary outcome was COVID-19-related urgent care visit, ED visit or hospitalization within 20 days. Secondary outcomes included time to self-reported recovery, viral symptoms, patient physiology and quantitative polymerase chain reaction (PCR) test as a surrogate for nasal pharyngeal SARS-CoV-2 viral load.
Outpatient Lung Ultrasound Findings in COVID May Not Help With Risk Stratification
Pulmonology Advisor, September 21, 2021
A new study suggests that although there is a high prevalence of lung ultrasound (LUS) findings in outpatients positive for SARS-CoV-2 infection, most of these patients show an improvement or resolution of these findings after 1 to 2 weeks, suggesting LUS may not be an appropriate risk stratification tool in outpatients with COVID-19. Findings from this study were published in BMJ Open Respiratory Research. In the prospective cohort study, researchers from Stanford assessed LUS findings from 102 outpatients positive for SARS-CoV-2 (mean age, 43.6 years; 52% female) to identify interstitial pneumonia. A total of 14 healthy controls (mean age, 43.8 years; 71% female) were also enrolled and underwent LUS examinations at baseline. Videos of LUS were randomized and scored by 2 independent sonographers. The severity of B-lines, pleural irregularity, and consolidations were determined for each of the 6 lung zones for each patient. Out of 158 LUS examinations performed, 102 were performed at baseline and 42 were performed over follow-up. The median duration between testing positive for COVID-19 and baseline LUS was 6.8 days. At baseline, the LUS severity scores ranged from 0 to 14. Among patients with COVID-19, approximately 41% (n=42) were LUS-positive, while 59% (n=60) were LUS-negative. All 14 healthy controls were LUS-negative. At 8 weeks, only 1 patient who responded to the follow-up survey was hospitalized for fever and shortness of breath. These events occurred 2 days following the baseline examination in the patient who had a severity score of 6. None of the patients in the study died or required mechanical ventilation over the 8-week follow-up period.
COVID Deaths Surpass 1918 Flu Deaths
MedPage Today, September 21, 2021
U.S. COVID-19 deaths have now surpassed the 675,000 estimated deaths that occurred during the H1N1 influenza pandemic of 1918, but SARS-CoV-2 hasn’t exacted as heavy a toll as that pandemic. With a national population of around 103 million people at that time — about a third of the current total of 330 million Americans — the 1918 pandemic killed roughly 1 in 150 people in the U.S.; COVID has killed 1 in 500 Americans. Globally, the 1918 flu wrought more havoc than COVID, too, infecting about 500 million people, or a third of the world’s population at that time. It killed about 50 million people globally, according to CDC estimates. SARS-CoV-2 has infected nearly 230 million people around the world and killed some 4.7 million of them. There are many reasons for the differences in infection and mortality. The 1918 pandemic hit while the world was enmeshed in World War I and international travel was frequent; hospitals didn’t have the same medicines and technology at their disposal to treat patients; the cause of the illness was unidentifiable and therefore a test, targeted treatment, or vaccine was impossible. During the COVID-19 pandemic, global travel came to a halt and public health measures such as social distancing and masking were implemented relatively rapidly, vaccines were produced in record time, and treatments were investigated in real-time with a few proving helpful (with more still in development). Still, misinformation and disinformation campaigns stymied the effectiveness of some of those approaches in the U.S., and the virus threw humanity a curveball with the far more transmissible Delta variant.
A Deep Learning Based Approach for Patient Pulmonary CT Image Screening to Predict Coronavirus (SARS-CoV-2) Infection
Diagnostics, September 21, 2021
The novel coronavirus (nCoV-2019) is responsible for the acute respiratory disease in humans known as COVID-19. This infection was found in the Wuhan and Hubei provinces of China in the month of December 2019, after which it spread all over the world. By March, 2020, this epidemic had spread to about 117 countries and its different variants continue to disturb human life all over the world, causing great damage to the economy. Through this paper, we have attempted to identify and predict the novel coronavirus from influenza-A viral cases and healthy patients without infection through applying deep learning technology over patient pulmonary computed tomography (CT) images, as well as by the model that has been evaluated. The CT image data used under this method has been collected from various radiopedia data from online sources with a total of 548 CT images, of which 232 are from 12 patients infected with COVID-19, 186 from 17 patients with influenza A virus, and 130 are from 15 healthy candidates without infection. From the results of examination of the reference data determined from the point of view of CT imaging cases in general, the accuracy of the proposed model is 79.39%. Thus, this deep learning model will help in establishing early screening of COVID-19 patients and thus prove to be an analytically robust method for clinical experts.
CPAP reduced intubation, death in patients with COVID-19-related acute respiratory failure
Helio | Pulmonology, September 20, 2021
CPAP reduced tracheal intubation and death within 30 days, compared with conventional oxygen therapy, in adults hospitalized with acute respiratory failure due to COVID-19, according to a new study.
“Early on in the pandemic, there was global concern about whether intensive care units would meet the surge capacity and would have the capacity to meet the surge demand in patients requiring invasive mechanical ventilation. That drove an urgent need to determine the clinical effectiveness of noninvasive respiratory support strategies,” Bronwen Connolly, PhD, senior lecturer in critical care, Queen’s University Belfast, Northern Ireland, said during a presentation at the virtual European Respiratory Society International Congress. The Recovery Respiratory Support trial was an adaptive three-arm, open-label, randomized controlled trial that included 1,272 adults with suspected or confirmed COVID-19 infection and acute respiratory failure. The researchers aimed to evaluate whether CPAP and high-flow nasal oxygen were clinically effective in this patient population compared with conventional oxygen therapy. Patients at 75 hospitals in the United Kingdom were randomly assigned to CPAP (n = 380), high-flow nasal oxygen (n = 417) or conventional oxygen therapy (n = 475). The primary outcome was a composite of tracheal intubation or death within 30 days. Tracheal intubation or death within 30 days occurred in fewer patients assigned CPAP compared with conventional oxygen therapy (OR = 0.72; 95% CI, 0.53-0.96; P = .03). However, there was no difference in the primary outcome between those assigned high-flow nasal oxygen compared with conventional oxygen therapy (OR = 0.97; 95% CI, 0.73-1.29; P = .85), Connolly said.
Per-COVID-19: A Benchmark Dataset for COVID-19 Percentage Estimation from CT-Scans
Journal of Imaging, September 18, 2021
COVID-19 infection recognition is a very important step in the fight against the COVID-19 pandemic. In fact, many methods have been used to recognize COVID-19 infection including Reverse Transcription Polymerase Chain Reaction (RT-PCR), X-ray scan, and Computed Tomography scan (CT- scan). In addition to the recognition of the COVID-19 infection, CT scans can provide more important information about the evolution of this disease and its severity. With the extensive number of COVID-19 infections, estimating the COVID-19 percentage can help the intensive care to free up the resuscitation beds for the critical cases and follow other protocol for less severity cases. In this paper, we introduce COVID-19 percentage estimation dataset from CT-scans, where the labeling process was accomplished by two expert radiologists. Moreover, we evaluate the performance of three Convolutional Neural Network (CNN) architectures: ResneXt-50, Densenet-161, and Inception-v3. For the three CNN architectures, we use two loss functions: MSE and Dynamic Huber. In addition, two pretrained scenarios are investigated (ImageNet pretrained models and pretrained models using X-ray data). The evaluated approaches achieved promising results on the estimation of COVID-19 infection. Inception-v3 using Dynamic Huber loss function and pretrained models using X-ray data achieved the best performance for slice-level results: 0.9365, 5.10, and 9.25 for Pearson Correlation coefficient (PC), Mean Absolute Error (MAE), and Root Mean Square Error (RMSE), respectively. On the other hand, the same approach achieved 0.9603, 4.01, and 6.79 for PCsubj, MAEsubj, and RMSEsubj, respectively, for subject-level results. These results prove that using CNN architectures can provide accurate and fast solution to estimate the COVID-19 infection percentage for monitoring the evolution of the patient state.
Early versus late awake prone positioning in non-intubated patients with COVID-19
Critical Care, September 17, 2021
Awake prone positioning (APP) is widely used in the management of patients with coronavirus disease (COVID-19). The primary objective of this study was to compare the outcome of COVID-19 patients who received early versus late APP. Post hoc analysis of data collected for a randomized controlled trial (ClinicalTrials.gov NCT04325906). Adult patients with acute hypoxemic respiratory failure secondary to COVID-19 who received APP for at least one hour were included. Early prone positioning was defined as APP initiated within 24 h of high-flow nasal cannula (HFNC) start. Primary outcomes were 28-day mortality and intubation rate. We included 125 patients (79 male) with a mean age of 62 years. Of them, 92 (73.6%) received early APP and 33 (26.4%) received late APP. Median time from HFNC initiation to APP was 2.25 (0.8–12.82) vs 36.35 (30.2–75.23) hours in the early and late APP group (p < 0.0001), respectively. Average APP duration was 5.07 (2.0–9.05) and 3.0 (1.09–5.64) hours per day in early and late APP group (p < 0.0001), respectively. The early APP group had lower mortality compared to the late APP group (26% vs 45%, p = 0.039), but no difference was found in intubation rate. Advanced age (OR 1.12 [95% CI 1.0–1.95], p = 0.001), intubation (OR 10.65 [95% CI 2.77–40.91], p = 0.001), longer time to initiate APP (OR 1.02 [95% CI 1.0–1.04], p = 0.047) and hydrocortisone use (OR 6.2 [95% CI 1.23–31.1], p = 0.027) were associated with increased mortality. Early initiation (< 24 h of HFNC use) of APP in acute hypoxemic respiratory failure secondary to COVID-19 improves 28-day survival.
Lung disease network reveals impact of comorbidity on SARS-CoV-2 infection and opportunities of drug repurposing
BMC Medical Genomics, September 17, 2021
Higher mortality of COVID-19 patients with lung disease is a formidable challenge for the health care system. Genetic association between COVID-19 and various lung disorders must be understood to comprehend the molecular basis of comorbidity and accelerate drug development. Lungs tissue-specific neighborhood network of human targets of SARS-CoV-2 was constructed. This network was integrated with lung diseases to build a disease–gene and disease-disease association network. Network-based toolset was used to identify the overlapping disease modules and drug targets. The functional protein modules were identified using community detection algorithms and biological processes, and pathway enrichment analysis. In total, 141 lung diseases were linked to a neighborhood network of SARS-CoV-2 targets, and 59 lung diseases were found to be topologically overlapped with the COVID-19 module. Topological overlap with various lung disorders allows repurposing of drugs used for these disorders to hit the closely associated COVID-19 module. Further analysis showed that functional protein–protein interaction modules in the lungs, substantially hijacked by SARS-CoV-2, are connected to several lung disorders. FDA-approved targets in the hijacked protein modules were identified and that can be hit by exiting drugs to rescue these modules from virus possession. Read the conclusion.
Dynamics of the Upper Respiratory Tract Microbiota and its Association with Mortality in COVID-19
American Journal of Respiratory and Clinical Care Medicine, September 17, 2021
Alteration of human respiratory microbiota had been observed in COVID-19. How the microbiota is associated with the prognosis in COVID-19 is unclear. The objective was to characterize the feature and dynamics of the respiratory microbiota and its associations with clinical features in COVID-19 patients. We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 COVID-19 patients (including 39 deceased patients), and 95 healthy controls from the same geographic area. Meanwhile, the concentration of 27 cytokines and chemokines in plasma was measured for COVID-19 patients. The upper respiratory tract (URT) microbiota in COVID-19 patients differed from that in healthy controls, while deceased patients possessed a more distinct microbiota, both on admission and before discharge/death. The alteration of URT microbiota showed a significant correlation with the concentration of proinflammatory cytokines and mortality. Specifically, Streptococcus-dominated microbiota was enriched in recovered patients, and show high temporal stability and resistance against pathogens. In contrast, the microbiota in deceased patients was more susceptible to secondary infections, and became more deviated from the normality after admission. Moreover, the abundance of S. parasanguinis on admission was significantly correlated with prognosis in non-severe patients (lower vs. higher abundance, odds ratio=7.80, [95% CI 1.70-42.05]). URT microbiota dysbiosis is a remarkable manifestation of COVID-19; its association with mortality suggests it may reflect the interplay between pathogens, symbionts, and the host immune status. Whether URT microbiota could be used as a biomarker for the diagnosis and prognosis of respiratory diseases merits further investigation.
Asthma and COVID-19 pandemic: focused on the eosinophil count and ACE2 expression
European Annals of Allergy and Clinical Immunology, September 11, 2021
Currently, the world is engaged with a coronavirus disease 2019 (COVID-19) caused by acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection. The Center for Disease Control and Prevention (CDC) has proposed moderate to severe asthma as a risk factor for COVID-19 susceptibility and severity. However, current evidences have not identified asthma in the top 10 comorbidities associated with COVID-19 fatalities. It raises the question that why patients with different type of asthma are not more vulnerable to SARS-CoV-2 infection like other respiratory infection. Increased number of eosinophils and elevated angiotensin-converting enzyme 2 (ACE2) expressions in asthma are supposed as two mechanisms which associated with decreased COVID-19 susceptibility in asthmatics. Some studies have been performed to evaluate two mentioned factors in asthmatic patients compared with healthy individuals. Herein, we address these mechanisms and investigate whether ACE2 and eosinophil could protect asthmatic patients against SARS-CoV-2 infection.
Coronavirus disease-19 and the gut-lung axis
International Journal of Infectious Diseases, September 10, 2021
Gastrointestinal and respiratory tract diseases often occur together. There are many overlapping pathologies, leading to the concept of the “gut-lung axis,” in which stimulation on one side triggers a response on the other side. This axis appears to be implicated in infections involving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has triggered the global pandemic of coronavirus disease 2019 (COVID-19), in which respiratory symptoms of fever, cough, and dyspnea often occur together with gastrointestinal symptoms such as nausea, vomiting, abdominal pain, and diarrhea. Besides the gut-lung axis, it should be noted that the gut participates in numerous axes, which may affect lung function and consequently COVID-19 severity through several pathways. However, in this article, we mainly pay attention to the latest evidence and the mechanisms that drive the operation of the gut-lung axis, as well as discuss the interaction between the gut-lung axis and its possible involvement in COVID-19 from the perspective of microbiota, microbiota metabolites, microbial dysbiosis, common mucosal immunity and angiotensin-converting enzyme II (ACE2). Raising hypotheses and providing methods to guide future research on this new disease and its treatments.
Diagnostic classification of coronavirus disease 2019 (COVID-19) and other pneumonias using radiomics features in CT chest images
Scientific Reports, September 9, 2021
We propose a classification method using the radiomics features of CT chest images to identify patients with coronavirus disease 2019 (COVID-19) and other pneumonias. The chest CT images of two groups of participants (90 COVID-19 patients who were confirmed as positive by nucleic acid test of RT-PCR and 90 other pneumonias patients) were collected, and the two groups of data were manually drawn to outline the region of interest (ROI) of pneumonias. The radiomics method was used to extract textural features and histogram features of the ROI and obtain a radiomics features vector from each sample. Then, we divided the data into two independent radiomic cohorts for training (70 COVID-19 patients and 70 other pneumonias patients), and validation (20 COVID-19 patients and 20 other pneumonias patients) by using support vector machine (SVM). This model used 20 rounds of tenfold cross-validation for training. Finally, single-shot testing of the final model was performed on the independent validation cohort. In the COVID-19 patients, correlation analysis (multiple comparison correction—Bonferroni correction, P < 0.05/7) was also conducted to determine whether the textural and histogram features were correlated with the laboratory test index of blood, i.e., blood oxygen, white blood cell, lymphocytes, neutrophils, C-reactive protein, hypersensitive C-reactive protein, and erythrocyte sedimentation rate. The final model showed good discrimination on the independent validation cohort, with an accuracy of 89.83%, sensitivity of 94.22%, specificity of 85.44%, and AUC of 0.940. This proved that the radiomics features were highly distinguishable, and this SVM model can effectively identify and diagnose patients with COVID-19 and other pneumonias. The correlation analysis results showed that some textural features were positively correlated with WBC, and NE, and also negatively related to SPO2H and NE. Our results showed that radiomic features can classify COVID-19 patients and other pneumonias patients. The SVM model can achieve an excellent diagnosis of COVID-19.
Blood fibrocytes are associated with severity and prognosis in COVID-19 pneumonia
American Journal of Physiology Lung Cellular and Molecular Physiology, September 8, 2021
Increased blood fibrocytes are associated with a poor prognosis in fibrotic lung diseases. We aimed to determine whether the percentage of circulating fibrocytes could be predictive of severity and prognosis during Coronavirus disease 2019 (COVID-19) pneumonia. Blood fibrocytes were quantified by flow cytometry as CD45+/CD15-/CD34+/Collagen-1+cells in patients hospitalized for COVID-19 pneumonia. In a subgroup of patients admitted in ICU, fibrocytes were quantified in blood and broncho-alveolar lavage (BAL). Serum amyloid P (SAP), TGF-b1,CXCL12, CCL2, and FGF2 serum concentration were measured in serum. We included 57 patients in the Hospitalized group (median age 59 years [23-87]) and 16 Healthy controls. The median percentage of circulating fibrocytes was higher in patients compared to controls (3.6% [0.2-9.2] vs. 2.1% [0.9-5.1], p=0.04). Blood fibrocyte count was lower in the 6 patients who died compared to survivors (1.6% [0.2-4.4] vs. 3.7% [0.6-9.2], p=0.02). Initial fibrocyte count was higher in patients showing a complete lung CT resolution at 3 months. Circulating fibrocyte count was decreased in the ICU group (0.8% [0.1-2.0]) whereas BAL fibrocyte count was 6.7% [2.2-15.4]. Serum SAP and TGF-b1 concentrations were increased in Hospitalized patients. SAP was also increased in ICU patients. CXCL12 and CCL2 were increased in ICU patients, and negatively correlated with circulating fibrocyte count. We conclude that circulating fibrocytes were increased in patients hospitalized for COVID-19 pneumonia and a lower fibrocyte count was associated with an increased risk of death and a slower resolution of lung CT opacities.
Conventional oxygen therapy versus CPAP as a ceiling of care in ward-based patients with COVID-19: a multi-centre cohort evaluation
EClinicalMedicine, September 8, 2021
Continuous positive airway pressure (CPAP) therapy is commonly used for respiratory failure due to severe COVID-19 pneumonitis, including in patients deemed not likely to benefit from invasive mechanical ventilation (nIMV). Little evidence exists demonstrating superiority over conventional oxygen therapy, whilst ward-level delivery of CPAP presents practical challenges. We sought to compare clinical outcomes of oxygen therapy versus CPAP therapy in patients with COVID-19 who were nIMV. This retrospective multi-centre cohort evaluation included patients diagnosed with COVID-19 who were nIMV, had a treatment escalation plan of ward-level care and clinical frailty scale ≤ 6. Recruitment occurred during the first two waves of the UK COVID-19 pandemic in 2020; from 1st March to May 31st, and from 1st September to 31st December. Patients given CPAP were compared to patients receiving oxygen therapy that required FiO2 ≥0.4 for more than 12 hours at hospitals not providing ward-level CPAP. Logistic regression modelling was performed to compare 30-day mortality between treatment groups, accounting for important confounders and within-hospital clustering. Seven hospitals provided data for 479 patients during the UK COVID-19 pandemic in 2020. Overall 30-day mortality was 75.6% in the oxygen group (186/246 patients) and 77.7% in the CPAP group (181/233 patients). A lack of evidence for a treatment effect persisted in the adjusted model (adjusted odds ratio 0.84 95% CI 0.57-1.23, p=0.37). 49.8% of patients receiving CPAP-therapy (118/237) chose to discontinue it. No survival difference was found between using oxygen alone or CPAP to treat patients with severe COVID-19 who were nIMV. A high patient-initiated discontinuation rate for CPAP suggests a significant treatment burden. Further reflection is warranted on the current treatment guidance and widespread application of CPAP in this setting.
Good News (Mostly) for Asthma Patients During Pandemic
MedPage Today, September 7, 2021
Two studies presented at the European Respiratory Society (ERS) virtual meeting should reassure asthma patients and their physicians about their risks from COVID-19. On the one hand, “no evidence of excess deaths was directly attributed to asthma” in a study of Scottish data on hospital admissions and death certificates during the first COVID-19 wave in early 2020, said Steven Smith, MRCP, of Gartnavel General Hospital in Glasgow. And on the other, analysis of asthma patients receiving biologic drugs in Greek clinics showed no overall increase in COVID infection rates relative to the general population through April of this year, reported Andriana Papaioannou, MD, PhD, of Attikon University Hospital in Athens. These encouraging results come against a backdrop of worry about how patients with preexisting respiratory disease, who may also be taking immune-modulating drugs, would fare during the pandemic. There were two concerning blips in the Greek data, however. Papaioannou’s group found that, among the 26 biologic-treated patients who did come down with COVID-19, nine needed hospitalization — a considerably higher proportion than among COVID patients in the general Greek population, she said. More startling perhaps was that all nine of these patients needing inpatient care were taking mepolizumab (Nucala; of 16 COVID-infected patients on the therapy) while none of the nine patients on omalizumab (Xolair) with COVID infection required hospital admission (P=0.014). The sole COVID death in the cohort was in a mepolizumab patient. Mepolizumab was the drug of choice for 61% of the entire 591-patient cohort.
Pathological disease in the lung periphery after acute COVID-19
The Lancet Respiratory Medicine, September 7, 2021
As we progress through the pandemic phase of COVID-19, the burden of so-called long COVID, a chronic illness with ongoing multidimensional symptomatology and disability after SARS-CoV-2 infection, has become evident. Current prevalence estimates for long COVID suggest that 1–2 million people in the UK are affected. Data acquired from people with long COVID indicate that respiratory symptoms are among the most prevalent. For example, the UK Office for National Statistics has highlighted that breathlessness is the second most common symptom after tiredness in people at least 12 weeks after infection. A systematic review and meta-analysis of persistent or long-term symptoms following acute COVID-19 showed that breathlessness was present in 24% of patients and cough was present in 19%. The REACT study has reported two long COVID symptom clusters, one of which was dominated by respiratory symptoms. The burden of both respiratory and non-respiratory symptoms appears to be even greater in patients who were hospitalised with acute COVID-19 than in those who were not, with failure to fully recover being reported in 30–50% of people who were hospitalised. These observations point to a high burden of respiratory symptomatology in patients with long COVID. Studies that have evaluated lung function after COVID-19 are limited to patients who were hospitalised. However, follow-up data are available in approximately 1000 individuals for 2–7 months after infection, and in 83 individuals with 12 months’ follow-up. The group mean data from these studies have consistently shown a normal ratio of FEV1 to forced vital capacity (FVC), with a normal forced expiratory flow at 25–75% where reported. The largest of these studies found that 10% of the participants had evidence of airflow obstruction, but this finding was in line with the proportion that had pre-existing obstructive lung disease. By contrast, most but not all of these studies reported abnormal lung diffusion in approximately one-third of patients.
Physical and Mental Health Impacts of the COVID-19 Pandemic among US Adults with Chronic Respiratory Conditions
Journal of Clinical Medicine, September 2, 2021
Adults living with chronic respiratory diseases are at higher risk of death due to COVID-19. Our objective was to evaluate the physical and mental health symptoms among US adults living with chronic respiratory conditions. We used data of 10,760 US adults from the nationally representative COVID-19 Impact Survey. Chronic respiratory conditions were self-reported and included asthma (14.7%), chronic obstructive pulmonary disease or COPD (4.7%), and bronchitis/emphysema (11.6%). We used multivariable Poisson regression to evaluate physical health symptoms. We estimated associations of mental health symptoms using multinomial logistic regression. In multivariable models, adults with asthma were more likely to report physical symptoms including runny or stuffy nose, chest congestion, fever, and chills. In addition, adults with COPD were more likely to report several physical symptoms including fever (adjusted prevalence ratio [aPR]: 1.37, 95% confidence interval [CI]: 1.09–1.72), chills (aPR: 2.10, 95% CI: 1.67–2.64), runny or stuffy nose (aPR: 1.78, 95% CI: 1.39–2.27), chest congestion (aPR: 2.14, 95% CI: 1.74–2.61), sneezing (aPR: 1.59, 95% CI: 1.23–2.05), and muscle or body aches (aPR: 1.38, 95% CI: 1.06–1.81). Adults with chronic respiratory conditions are more likely to report physical and mental health symptoms during the COVID-19 pandemic compared to others. Providers should prioritize discussing mental health symptom management as the pandemic continues to be a public health concern in the US.
CT Findings of COVID-19–associated Pulmonary Mucormycosis: A Case Series and Literature Review
Radiology, August 31, 2021
There has been an unprecedented spike in COVID-19-associated mucormycosis (CAM), with most patients showing rhino-orbital involvement, while limited data is available on COVID-19-associated pulmonary mucormycosis (CAPM). Pulmonary mucormycosis (PM) is rare and has a high mortality. COVID-19 pneumonia makes it further challenging to identify PM on radiology. Herein, we describe the imaging findings of three confirmed CAPM cases and supplement it with a systematic review of the literature. In this retrospective study (approved by the Institute Ethics Committee), we describe the imaging and clinical features of three microbiologically confirmed cases of CAPM. We performed a systematic review of the PubMed and Embase databases, using the search terms (“COVID” OR “SARS-CoV” OR “coronavirus”) AND (mucor* OR “zygomycosis”) until 14th June 2021 to identify published cases of CAPM (diagnosed as per current recommendations), and included them for analysis if individual patient and imaging data was provided. At our center, we diagnosed three cases of CAPM. Two of the three cases had no risk factor other than COVID-19. One case was of a diabetic male with both rhino-orbital and PM. Two patients survived. We identified 180 cases of CAM in the literature during the review period and included only those 88 cases (14 CAPM and 74 non-pulmonary CAM) for which individual patient details were available. Of the 14 CAPM cases reported (from USA [n=3], UK [n=2], Netherlands [n=3], India [n=2], and one each from Italy, Austria, Chile, and France), Computed Tomography (CT) details were not available in one. After exclusions, we report the CT features of these 13 cases along with the three index cases reported by us (n=16).
Effect of COVID-19-Related Lockdown οn Hospital Admissions for Asthma and COPD Exacerbations: Associations with Air Pollution and Patient Characteristics
Journal of Personalized Medicine, August 30, 2021
We conducted a retrospective observational study to assess the hospitalization rates for acute exacerbations of asthma and COPD (chronic obstructive pulmonary disease) during the first imposed lockdown in Athens, Greece. Patient characteristics and the concentration of eight air pollutants [namely, NO (nitrogen monoxide), NO2 (nitrogen dioxide), CO (carbon monoxide), PM2.5 (particulate matter 2.5), PM10 (particulate matter 10), O3 (ozone), SO2 (sulfur dioxide) and benzene] were considered. A total of 153 consecutive hospital admissions were studied. Reduced admissions occurred in the Lockdown period compared to the Pre-lockdown 2020 (p < 0.001) or the Control 2019 (p = 0.007) period. Furthermore, the concentration of 6/8 air pollutants positively correlated with weekly hospital admissions in 2020 and significantly decreased during the lockdown. Finally, admitted patients for asthma exacerbation during the lockdown were younger (p = 0.046) and less frequently presented respiratory failure (p = 0.038), whereas patients with COPD presented higher blood eosinophil percentage (p = 0.017) and count (p = 0.012). Overall, admissions for asthma and COPD exacerbations decreased during the lockdown. This might be partially explained by reduction of air pollution during this period while medical care avoidance behavior, especially among elderly patients cannot be excluded. Our findings aid in understanding the untold impact of the pandemic on diseases beyond COVID-19, focusing on patients with obstructive diseases.
Effectiveness of a Three-Week Inpatient Pulmonary Rehabilitation Program for Patients after COVID-19: A Prospective Observational Study
International Journal of Environmental Research and Public Health, August 26, 2021
For COVID-19 patients who remain symptomatic after the acute phase, pulmonary rehabilitation (PR) is recommended. However, only a few studies have investigated the effectiveness of PR, especially considering the duration between the acute phase of COVID-19 and the onset of rehabilitation, as well as the initial severity. This prospective observational study evaluated the efficacy of PR in patients after COVID-19. A total of 120 still-symptomatic patients referred for PR after overcoming acute COVID-19 were asked to participate, of whom 108 (mean age 55.6 ± 10.1 years, 45.4% female) consented. The patients were assigned to three groups according to the time of referral and initial disease severity (severe acute; severe after interval; mild after interval). The primary outcome was dyspnea. Secondary outcomes included other respiratory disease symptoms, physical capacity, lung function, fatigue, quality of life (QoL), depression, and anxiety. Furthermore, patients rated the overall effectiveness of PR and their subjective change in health status. At the end of PR, we detected improvements with large effect sizes in exertional dyspnea, physical capacity, QoL, fatigue, and depression in the overall group. Other parameters changed with small to medium effect sizes. PR was effective after acute COVID-19 in all three groups analyzed.
Nerve Growth Factor: A Potential Therapeutic Target for Lung Diseases
International Journal of Molecular Sciences, August 24, 2021
The lungs play a very important role in the human respiratory system. However, many factors can destroy the structure of the lung, causing several lung diseases and, often, serious damage to people’s health. Nerve growth factor (NGF) is a polypeptide, which is widely expressed in lung tissues. Under different microenvironments, NGF participates in the occurrence and development of lung diseases by changing protein expression levels and mediating cell function. In this review, we summarize the functions of NGF as well as some potential underlying mechanisms in pulmonary fibrosis (PF), coronavirus disease 2019 (COVID-19), pulmonary hypertension (PH), asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Furthermore, we highlight that anti-NGF may be used in future therapeutic strategies.
On the Use of Deep Learning for Imaging-Based COVID-19 Detection Using Chest X-rays
Sensors, August 24, 2021
The global COVID-19 pandemic that started in 2019 and created major disruptions around the world demonstrated the imperative need for quick, inexpensive, accessible and reliable diagnostic methods that would allow the detection of infected individuals with minimal resources. Radiography, and more specifically, chest radiography, is a relatively inexpensive medical imaging modality that can potentially offer a solution for the diagnosis of COVID-19 cases. In this work, we examined eleven deep convolutional neural network architectures for the task of classifying chest X-ray images as belonging to healthy individuals, individuals with COVID-19 or individuals with viral pneumonia. All the examined networks are established architectures that have been proven to be efficient in image classification tasks, and we evaluated three different adjustments to modify the architectures for the task at hand by expanding them with additional layers. The proposed approaches were evaluated for all the examined architectures on a dataset with real chest X-ray images, reaching the highest classification accuracy of 98.04% and the highest F1-score of 98.22% for the best-performing setting.
Pollen antigens and atmospheric circulation driven seasonal respiratory viral outbreak and its implication to the Covid-19 pandemic
Scientific Reports, August 20, 2021
The patterns of respiratory virus illness are expressed differently between temperate and tropical climates. Tropical outbreaks often peak in wet seasons. Temperate outbreaks typically peak during the winter. The prevailing causal hypotheses focus on sunlight, temperature and humidity variations. Yet no consistent factors have been identified to sufficiently explain seasonal virus emergence and decline at any latitude. Here we demonstrate close connections among global-scale atmospheric circulations, IgE antibody enhancement through seasonal pollen inhalation, and respiratory virus patterns at any populated latitude, with a focus on the US. Pollens emerge each Spring, and the renewed IgE titers in the population are argued to terminate each winter peak of respiratory illness. Globally circulated airborne viruses are postulated to subsequently deposit across the Southern US during lower zonal geostrophic winds each late Summer. This seasonally refreshed viral load is postulated to trigger a new influenza outbreak, once the existing IgE antibodies diminish to a critical value each Fall. Our study offers a new and consistent explanation for the seasonal diminishment of respiratory viral illnesses in temperate climates, the subdued seasonal signature in the tropics, the annually circulated virus phenotypes, and the northerly migration of influenza across the US every year. Our integrated geospatial and IgE hypothesis provides a new perspective for prediction, mitigation and prevention of the outbreak and spread of seasonal respiratory viruses including Covid-19 pandemic.
Risk factors for pulmonary embolism in patients with COVID-19: a systemic review and meta-analysis
International Journal of Infectious Diseases, August 18, 2021
The purpose of the research was to detect the risk factors for pulmonary embolism (PE) in patients with COVID-19. We searched for studies in PubMed, Cochrane Library, Web of Science, and EMBASE. Two authors independently screened articles and extracted data. The data were pooled by meta-analysis, and three subgroup analyses were performed. Of the 2210 articles identified, 27 studies were included. Pooled analysis suggested that males (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.26−1.75, P = 0.000), obesity (OR 1.37, 95% CI 1.03−1.82, P = 0.033), mechanical ventilation (MV) (OR 3.34, 95% CI 1.90−5.86, P = 0.000), severe parenchymal abnormalities (OR 1.92, 95% CI 1.43−2.58, P = 0.000), ICU admission (OR 2.44, 95% CI 1.48−4.03, P = 0.000), and elevated D-dimer and white blood cell (WBC) values (at two points in time: hospital admission or closet to computer tomography pulmonary angiography (CTPA)) (P = 0.000) were correlated with a risk for PE occurrence in COVID-19 patients. However, the age and common comorbidities had no association with PE occurrence. The CTPA, unclear-ratio/low-ratio, and hospitalization subgroups had consistent risk factors with the whole studies. However, other subgroups got fewer PE risk factors. PE risk factors in COVID-19 are different from the classic PE risk factors. And they were likely to differ in diverse study populations.
A Child Infected with COVID-19 in China—A Case Report
Journal of Tropical Pediatrics, August 18, 2021
A 16-month-old boy was admitted with cough for 2 days and fever for 1 day. Chest computed tomography (CT) scan of the child revealed large areas of ground-glass opacities in both lungs. Nucleic acid amplification tests (NAATs) were performed repeatedly to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the results were all negative. On day 13 of hospitalization, no clinical symptoms except diarrhea were present in the patient, and re-examination by chest CT revealed lesion shrinkage, but the NAAT on throat swabs was positive. On day 22 of hospitalization, the NAAT on throat swabs was negative and the fecal samples were positive. Positive fecal samples nucleic acid lasted for 62 days. Suggesting that pediatric patients may be important sources of infection during the recovery phase of clinical symptoms and whether SARS-CoV-2 has fecal–oral transmission needs further study. COVID-19 is still a serious global problem. All populations are generally susceptible to COVID-19. The clinical characteristics of COVID-19 in children are different from those in adults.
Bacterial Superinfection Pneumonia in Patients Mechanically Ventilated for COVID-19 Pneumonia
American Journal of Respiratory and Critical Care Medicine, August 17, 20221
Current guidelines recommend patients with SARS-CoV-2 pneumonia receive empirical antibiotics for suspected bacterial superinfection based on weak evidence. Rates of ventilator-associated pneumonia (VAP) in clinical trials of patients with SARS-CoV-2 pneumonia are unexpectedly low. We conducted an observational single center study to determine the prevalence and etiology of bacterial superinfection at the time of initial intubation and the incidence and etiology of subsequent bacterial VAP in patients with severe SARS-CoV-2 pneumonia. Bronchoscopic bronchoalveolar lavage (BAL) fluid samples from all patients with SARS-CoV-2 pneumonia requiring mechanical ventilation were analyzed using quantitative cultures and a multiplex polymerase chain reaction panel. Actual antibiotic use was compared with guideline-recommended therapy. We analyzed 386 BAL samples from 179 patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. Bacterial superinfection within 48 hours of intubation was detected in 21% of patients. 72 patients (44.4%) developed at least one VAP episode (VAP incidence rate 45.2/1000 ventilator days); 15 (20.8%) of initial VAPs were caused by difficult-to-treat pathogens. Clinical criteria did not distinguish between patients with or without bacterial superinfection. BAL-based management was associated with significantly reduced antibiotic use compared with guideline recommendations. In patients with SARS-CoV-2 pneumonia requiring mechanical ventilation, bacterial superinfection at the time of intubation occurs in less than 25% of patients. Guideline-based empirical antibiotic management at the time of intubation results in antibiotic overuse. Bacterial VAP developed in 44% of patients and could not be accurately identified in the absence of microbiologic analysis of BAL fluid.
Lung Function Levels Influence the Association Between Obesity and Risk of COVID-19
American Journal of Respiratory and Critical Care Medicine, August 16, 20221
Obesity is associated with immune suppression and may be associated with increased risk of COVID-19. This association may be modified by factors such as lung function. We explored here the association between obesity and COVID-19 in relation to the underlying lung function strata. To our knowledge, this possible interaction has not been investigated to date. We investigated the association between obesity and risk of a positive SARS-CoV-2 test, and how lung function levels influenced this association in 36,896 participants in the UK Biobank tested for SARS-CoV-2. The UK Biobank study recruited 502,543 participants aged 40 – 69 years living close to one of 22 assessment centres across England, Scotland, and Wales; however, data on SARSCoV-2 test results derives from the English subgroup alone. Body mass index (BMI) at recruitment (baseline) was used to define normal (BMI<25), overweight (25≤BMI<30) and obesity (BMI≥30) groups. Forced Expiratory Volume in the first second (FEV1), Forced Vital Capacity (FVC) and their ratio at baseline were categorized using the median and quartiles (of their z score values). Multivariable logistic regression models were generated to investigate the association of obesity with SARS-CoV-2 positivity adjusting for age, sex, smoking, socio-economic status (Townsend index), diabetes, cardiovascular disease (CVD), physical activity and ethnicity. Stratified analyses for lung function levels and formal interaction tests to investigate potential effect modification were conducted. Of the 36,896 participants tested (mean age 69·3±8·3 years), 5,757 were positive for SARS-CoV-2. The prevalence of overweight and obesity were 42.3% and 29.0 % respectively. Compared to normal weight, both overweight (OR:1.20 [95%CI: 1.12, 1.30]) and obesity (OR:1.31 [1.21, 1.42]) were associated with increased risk of testing positive for SARS-CoV-2, with the risk being greater in those who were obese when compared to those who were overweight (p=0.017).
Mortality from COVID-19 in Patients with COPD: A US Study in the N3C Data Enclave
International Journal of Chronic Obstructive Pulmonary Disease, August 13, 2021
COVID-19 has resulted in over 2.6 million deaths worldwide and over 500,000 deaths in the United States as of February 2021. Observational research suggests that the risk of mortality increases with the presence of comorbidities: obesity, hypertension (HTN), diabetes mellitus type 2 (DM), and chronic lung disease. Over the last 40 years in the United States, chronic obstructive pulmonary disease (COPD) has become the fourth leading cause of death. Pneumonia is associated with an increased risk of hospitalization, intubation, and mortality in people with COPD. Patients with COPD may be susceptible to worse outcomes from COVID-19 pneumonia than patients without COPD. Given the increased vulnerability of this population, it is important to understand the risk of COVID-19 related mortality in people with COPD. The National Center for Advancing Translational Sciences (NCATS) established the National COVID Cohort Collaboration (N3C), a partnership among 81 academic hubs to share COVID-19 clinical data from electronic health records as part of a platform for answering critical research questions. We used this novel tool to assess the risk of mortality following COVID-19 diagnosis in patients with COPD compared with patients without COPD. Statistical analysis was done using the secure NCATS Data Enclave, which utilizes the Palantir platform and resides in Amazon Web Services GovCloud. 387,008 patients tested positive for COVID-19 by PCR and 7549 had a diagnosis of COPD. The majority of patients with COPD were white (71%) followed by African American (19%). Patients with COPD had higher rates of HTN (74% vs 39%), DM (38% vs 22%), obesity (34% vs 24%), and CKD (31% vs 10%). Patients with COPD had higher rates of hospital admissions (62% vs 28%). The mortality rate of patients with COPD was 15% compared to 4% in patients without COPD. Our unadjusted odds ratio of mortality of patients with COPD and COVID-19 diagnosis was 6.19 (95% CI 5.79–6.62, p-value <0.001). In a multivariable logistic regression analysis the adjusted odds ratio for mortality [95% CI] in patients with versus without COPD was 2.1 [1.96, 2.26, p-value <0.001]
FDA Authorizes COVID Booster Shots for Certain Populations
MedPage Today, August 13, 12021
After weeks of speculation, the FDA amended the emergency use authorizations (EUAs) for Pfizer and Moderna’s COVID-19 vaccines to include an additional booster dose for certain immunocompromised people, the agency said late Thursday. These populations include solid-organ transplant recipients or others diagnosed with conditions “considered to have a similar level of immunocompromise” who previously received one of the two mRNA vaccines. After weeks of speculation, the FDA amended the emergency use authorizations (EUAs) for Pfizer and Moderna’s COVID-19 vaccines to include an additional booster dose for certain immunocompromised people, the agency said late Thursday. These populations include solid-organ transplant recipients or others diagnosed with conditions “considered to have a similar level of immunocompromise” who previously received one of the two mRNA vaccines. The FDA kept the language purposely vague, as clinical considerations are set to be defined Friday during CDC’s Advisory Committee on Immunization Practices (ACIP) meeting. FDA merely added that individuals immunocompromised “in a manner similar” to those who underwent solid-organ transplantation have a reduced ability to fight disease and are vulnerable to infections, such as COVID-19.
COVID-19 and the effects on pulmonary function following infection: A retrospective analysis
EClinical Medicine, August 12, 2021
The coronavirus disease 2019 (COVID-19) has been identified in over 110 million people with no studies comparing pre-infection pulmonary function to post-infection. This study’s aim was to compare preinfection and post-infection pulmonary function tests (PFT) in COVID-19 infected patients to better delineate between preexisting abnormalities and effects of the virus. Methods: This was a retrospective multi-center cohort study. Patients were identified based on having COVID-19 and a pre- and post-infection PFT within one year of infection during the time period of March 1, 2020 to November 10, 2020. There was a total of 80 patients, with an even split in gender; the majority were white (n = 70, 87·5%) and never smokers (n = 42, 52·5%). The majority had mild to moderate COVID-19 disease (n = 60, 75·1%) with 25 (31·2%) requiring hospitalization. There was no difference between the pre- and post-PFT data, specifically with the forced vital capacity (FVC) (p = 0·52), forced expiratory volume in 1 s (FEV1)(p = 0·96), FEV1/FVC(p = 0·66), total lung capacity (TLC) (p = 0·21), and diffusion capacity (DLCO)(p = 0·88). There was no difference in the PFT when analyzed by hospitalization and disease severity. After adjusting for potential confounders, interstitial lung disease (ILD) was independently associated with a decreased FEV1 (-2·6 [95% CI, -6·7 to – 1·6] vs. -10·3 [95% CI, -17·7 to -2·9]; p = 0·03) and an increasing age (p = 0·01) and cystic fibrosis (-1·1 [95% CI, -4·5 to- 2·4] vs. -36·5 [95% CI, -52·1 to -21·0]; p < 0·01) were associated with decreasing FVC when comparing pre and post infection PFT. Only increasing age was independently associated with a reduction in TLC (p = 0·01) and DLCO (p = 0·02) before and after infection. This study showed that there is no difference in pulmonary function as measured by PFT before and after COVID-19 infection in non-critically ill classified patients. There could be a relationship with certain underlying lung diseases (interstitial lung disease and cystic fibrosis) and decreased lung function following infection. This information should aid clinicians in their interpretation of pulmonary function tests obtained following COVID-19 infection.
CT of Postacute Lung Complications of COVID-19
Radiology, August 10, 2021
The acute course of coronavirus disease 2019 (COVID-19) is variable and ranges from asymptomatic infection to fulminant respiratory failure. Patients recovering from COVID-19 can have persistent symptoms and computed tomography (CT) abnormalities of variable severity. At 3 months after acute infection, a subset of patients will have CT abnormalities that include ground glass abnormalities (GGO) and subpleural bands with concomitant pulmonary function abnormalities. At 6 months after acute infection, some patients have persistent CT changes to include the resolution of GGOs seen in the early recovery phase and the persistence or development of changes suggestive of fibrosis such as reticulation with or without parenchymal distortion. Predictors of post-COVID lung disease include need for intensive care unit (ICU) admission, mechanical ventilation, higher inflammatory markers, longer hospital stay and a diagnosis of acute respiratory distress syndrome (ARDS). Treatments of post-COVID lung disease are being investigated with anti-fibrotic agents being investigated for the prevention of post-COVID lung fibrosis. The etiology of post-COVID lung disease may be a sequela of prolonged mechanical ventilation, COVID-induced ARDS or direct injury from the virus. Future research is needed to determine the long-term persistence of post-COVID lung disease, its impact on patients and ways to prevent or treat it.
Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial
The Lancet, August 10, 2021
Our aim was to establish whether inhaled budesonide reduces time to recovery and COVID-19-related hospital admissions or deaths among people at high risk of complications in the community. PRINCIPLE is a multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial done remotely from a central trial site and at primary care centres in the UK. Eligible participants were aged 65 years or older or 50 years or older with comorbidities, and unwell for up to 14 days with suspected COVID-19 but not admitted to hospital. Participants were randomly assigned to usual care, usual care plus inhaled budesonide (800 μg twice daily for 14 days), or usual care plus other interventions, and followed up for 28 days. Participants were aware of group assignment. The coprimary endpoints are time to first self-reported recovery and hospital admission or death related to COVID-19, within 28 days, analysed using Bayesian models. The primary analysis population included all eligible SARS-CoV-2-positive participants randomly assigned to budesonide, usual care, and other interventions, from the start of the platform trial until the budesonide group was closed. 4700 participants were randomly assigned to budesonide (n=1073), usual care alone (n=1988), or other treatments (n=1639). The primary analysis model includes 2530 SARS-CoV-2-positive participants, with 787 in the budesonide group, 1069 in the usual care group, and 974 receiving other treatments. There was a benefit in time to first self-reported recovery of an estimated 2·94 days (95% Bayesian credible interval [BCI] 1·19 to 5·12) in the budesonide group versus the usual care group (11·8 days [95% BCI 10·0 to 14·1] vs 14·7 days [12·3 to 18·0]; hazard ratio 1·21 [95% BCI 1·08 to 1·36]), with a probability of superiority greater than 0·999, meeting the prespecified superiority threshold of 0·99. For the hospital admission or death outcome, the estimated rate was 6·8% (95% BCI 4·1 to 10·2) in the budesonide group versus 8·8% (5·5 to 12·7) in the usual care group (estimated absolute difference 2·0% [95% BCI –0·2 to 4·5]; odds ratio 0·75 [95% BCI 0·55 to 1·03]), with a probability of superiority 0·963, below the prespecified superiority threshold of 0·975. Two participants in the budesonide group and four in the usual care group had serious adverse events (hospital admissions unrelated to COVID-19). Inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although our results did not meet the superiority threshold), in people with COVID-19 in the community who are at higher risk of complications.
Impact of early corticosteroids on 60-day mortality in critically ill patients with COVID-19: A multicenter cohort study of the OUTCOMEREA network
PLOS ONE, August 4, 2021
In severe COVID-19 pneumonia, the appropriate timing and dosing of corticosteroids (CS) is not known. Patient subgroups for which CS could be more beneficial also need appraisal. The aim of this study was to assess the effect of early CS in COVID-19 pneumonia patients admitted to the ICU on the occurrence of 60-day mortality, ICU-acquired-bloodstream infections (ICU-BSI), and hospital-acquired pneumonia and ventilator-associated pneumonia(HAP-VAP). We included patients with COVID-19 pneumonia admitted to 11 ICUs belonging to the French OutcomeRea™ network from January to May 2020. We used survival models with ponderation with inverse probability of treatment weighting (IPTW). The study population comprised 303 patients having a median age of 61.6 (53–70) years of whom 78.8% were male and 58.6% had at least one comorbidity. The median SAPS II was 33 (25–44). Invasive mechanical ventilation was required in 34.8% of the patients. Sixty-six (21.8%) patients were in the Early-C subgroup. Overall, 60-day mortality was 29.4%. The risks of 60-day mortality (IPTWHR = 0.86;95% CI 0.54 to 1.35, p = 0.51), ICU-BSI and HAP-VAP were similar in the two groups. Importantly, early CS treatment was associated with a lower mortality rate in patients aged 60 years or more (IPTWHR, 0.53;95% CI, 0.3–0.93; p = 0.03). In contrast, CS was associated with an increased risk of death in patients younger than 60 years without inflammation on admission (IPTWHR = 5.01;95% CI, 1.05, 23.88; p = 0.04). For patients with COVID-19 pneumonia, early CS treatment was not associated with patient survival. Interestingly, inflammation and age can significantly influence the effect of CS.
Reduction in hospitalised COPD exacerbations during COVID-19: A systematic review and meta-analysis
PLOS ONE, August 3, 2021
Reports have suggested a reduction in exacerbations of chronic obstructive pulmonary disease (COPD) during the coronavirus disease 2019 (COVID-19) pandemic, particularly hospital admissions for severe exacerbations. However, the magnitude of this reduction varies between studies. Electronic databases were searched from January 2020 to May 2021. Two independent reviewers screened titles and abstracts and, when necessary, full text to determine if studies met inclusion criteria. A modified version of the Newcastle-Ottawa Scale was used to assess study quality. A narrative summary of eligible studies was synthesised, and meta-analysis was conducted using a random effect model to pool the rate ratio and 95% confidence intervals (95% CI) for hospital admissions. Exacerbation reduction was compared against the COVID-19 Containment and Health Index. A total of 13 of 745 studies met the inclusion criteria and were included in this review, with data from nine countries. Nine studies could be included in the meta-analysis. The pooled rate ratio of hospital admissions for COPD exacerbations during the pandemic period was 0.50 (95% CI 0.44–0.57). Findings on the rate of community-treated exacerbations were inconclusive. Three studies reported a significant decrease in the incidence of respiratory viral infections compared with the pre-pandemic period. There was not a significant relationship between exacerbation reduction and the COVID-19 Containment and Health Index (rho = 0.20, p = 0.53). There was a 50% reduction in admissions for COPD exacerbations during the COVID-19 pandemic period compared to pre-pandemic times, likely associated with a reduction in respiratory viral infections that trigger exacerbations.
Deceleration capacity is associated with acute respiratory distress syndrome in COVID-19
Heart & Lung, August 2, 2021
Acute respiratory distress syndrome (ARDS) is considered the main cause of COVID-19 associated morbidity and mortality. Early and reliable risk stratification is of crucial clinical importance in order to identify persons at risk for developing a severe course of disease. Deceleration capacity (DC) of heart rate as a marker of cardiac autonomic function predicts outcome in persons with myocardial infarction and heart failure. We hypothesized that reduced modulation of heart rate may be helpful in identifying persons with COVID-19 at risk for developing ARDS. We prospectively enrolled 60 consecutive COVID-19 positive persons presenting at the University Hospital of Tuebingen. Arterial blood gas analysis and 24h-Holter ECG recordings were performed and analyzed at admission. The primary end point was defined as development of ARDS with regards to the Berlin classification. 61.7% (37 of 60 persons) developed an ARDS. In persons with ARDS DC was significantly reduced when compared to persons with milder course of infection (3.2 ms vs. 6.6 ms, p < 0.001). DC achieved a good discrimination performance (AUC = 0.76) for ARDS in COVID-19 persons. In a multivariate analysis, decreased DC was associated with the development of ARDS. Our data suggest a promising role of DC to risk stratification in COVID-19.
COVID-19 and pulmonary tuberculosis – a diagnostic dilemma
Radiology Case Reports, August 2, 2021
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Meanwhile, pulmonary tuberculosis (TB) is one of the most common infective lung diseases in developing nations. The concurrence of pulmonary TB and COVID-19 can lead to poor prognosis, owing to the pre-existing lung damage caused by TB. Case presentation: We describe the imaging findings in 3 cases of COVID-19 pneumonia with co-existing pulmonary TB on HRCT thorax. The concurrence of COVID-19 and pulmonary TB can be a diagnostic dilemma. Correct diagnosis and prompt management is imperative to reduce mortality and morbidity. Hence, it is pertinent for imaging departments to identify and report these distinct entities when presenting in conjunction. We present the imaging findings in COVID-19 with concurrent pulmonary TB in 3 patients without any prior history of mycobacterial pulmonary infection. HRCT Thorax was done using 32-slice Multidetector CT machine using thin sections (1 mm slice thickness). Final diagnosis of pulmonary TB was made by demonstrating acid-fast bacilli (AFB) on sputum microscopy, as per the current guidelines. Confirmation of COVID-19 was made based on Reverse transcriptase-polymerase chain reaction (RT-PCR) from nasopharyngeal swab.
SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation
Nature Communications, August 2, 2021
Excessive inflammatory responses induced upon SARS-CoV-2 infection are associated with severe symptoms of COVID-19. Inflammasomes activated in response to SARS-CoV-2 infection are also associated with COVID-19 severity. Here, we show a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. N protein facilitates maturation of proinflammatory cytokines and induces proinflammatory responses in cultured cells and mice. Mechanistically, N protein interacts directly with NLRP3 protein, promotes the binding of NLRP3 with ASC, and facilitates NLRP3 inflammasome assembly. More importantly, N protein aggravates lung injury, accelerates death in sepsis and acute inflammation mouse models, and promotes IL-1β and IL-6 activation in mice. Notably, N-induced lung injury and cytokine production are blocked by MCC950 (a specific inhibitor of NLRP3) and Ac-YVAD-cmk (an inhibitor of caspase-1). Therefore, this study reveals a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation and induces excessive inflammatory responses.
Importance of Lung Epithelial Injury in COVID-19–associated Acute Respiratory Distress Syndrome: Value of Plasma Soluble Receptor for Advanced Glycation End-Products
American Journal of Respiratory and Critical Care Medicine, August 1, 2021
[Letter to the Editor] The respiratory form of coronavirus disease (COVID-19) has led to an unprecedented number of hospitalizations for acute respiratory distress syndrome (ARDS). To date, the pathophysiology of COVID-19–associated ARDS (CARDS) remains poorly understood. This has led to discussion about a different presentation from non–COVID-19 ARDS, regarding lung mechanics abnormalities and hypoxemia mechanisms. However, little attention has been paid to the value of biomarkers of lung injury. The soluble form of the receptor for advanced glycation end-products (sRAGE) is a well-characterized marker of lung alveolar epithelial injury and has been associated with both prognostic and pathogenic values in patients with ARDS. This study aims to investigate the value of baseline plasma sRAGE in CARDS and how it could differ between COVID-19 and non–COVID-19 ARDS. We prospectively enrolled all consecutive adult patients admitted to the medical ICU of the Saint-Louis hospital, Paris, France. Management of patients included protective volume-controlled ventilation, neuromuscular blockers, and prone position if needed. All measurements were performed within 24 hours after intubation. Ventilator settings and respiratory mechanics measures were collected, together with dead space fraction, ventilatory ratio, and shunt fraction. When available, measurements of the recruitment-to-inflation ratio were collected. A value ⩽0.5 was considered as a potential for lung recruitment. The severity of lung edema was assessed using the Radiographic Assessment of Lung Edema (RALE) score, evaluated by two independent physicians on the chest radiography of the day of mechanical ventilation (MV) initiation. Levels of plasma sRAGE were measured in duplicate from thawed samples collected within 24 hours after MV initiation. A commercially available sandwich enzyme immunoassay kit (Human sRAGE Quantikine ELISA Kit; R&D Systems) was used following recommendations from the manufacturer. Patients with CARDS were then compared with a historical multicentric prospective cohort of patients with ARDS in whom plasma sRAGE had been measured and with control patients (e.g., mechanically ventilated patients without COVID-19 infection or ARDS, n = 15).
The effect of the outbreak of COVID-19 on respiratory physicians and healthcare in Japan: Serial nationwide surveys by the Japanese Respiratory Society
Respiratory Investigation, July 31, 2021
The impact of the outbreak of COVID-19 on the work of respiratory physicians in Japan has not yet been evaluated. The study investigates the impact of the outbreak on respiratory physicians’ work over time and identifies problems to be addressed in the future. We conducted a web-based survey of respiratory physicians in 848 institutions. The survey comprised 32 questions and four sections: Survey 1 (April 20, 2020), Survey 2 (May 27, 2020), Survey 3 (August 31, 2020), and Survey 4 (December 4, 2020). The mean survey response rate was 24.9%, and 502 facilities (59.2%) participated in at least one survey. The proportion of facilities that could perform PCR tests for diagnosis and more than 20 tests per day gradually increased. The percentage capable of managing extracorporeal membrane oxygenation (ECMO) or more than five ventilators did not increase over time. The proportion that reported work overload of 150% or more, stress associated with lack of personal protective equipment (PPE), and harassment or stigma in the surrounding community did not sufficiently improve. While there was an improvement in expanding the examination system and medical cooperation in the community, there was no indication of enhancement of the critical care management system. The overwork of respiratory physicians, lack of PPE, and harassment and stigma related to COVID-19 did not sufficiently improve and need to be addressed urgently.
Pulmonary parenchymal changes in COVID-19 survivors
Annals of Thoracic Surgery, July 31, 2021
As the COVID-19 pandemic moves into the survivorship phase, questions regarding long-term lung damage remain unanswered. Previous histopathological studies are limited to autopsy reports. We studied lung specimens from COVID-19 survivors who underwent elective lung resections to determine whether post-acute histopathological changes are present. In this multicenter observational study, we included adult COVID-19 survivors (n=11) who had recovered but subsequently underwent unrelated elective lung resection for indeterminate lung nodules or lung cancer. We compared these to an age- and procedure-matched control group who never contracted COVID-19 (n=5), and an end-stage COVID-19 group (n=3). A blinded pulmonary pathologist examined the lung parenchyma focusing on four compartments: airways, alveoli, interstitium, and vasculature. Eleven COVID-19 survivors with asymptomatic (n=4), moderate (n=4), and severe (n=3) COVID-19 infections underwent elective lung resection at a median 68.5 days (range 24-142) after COVID-19 diagnosis. The most common operation was lobectomy (75%). On histopathological examination, no differences were identified between the lung parenchyma of COVID-19 survivors and controls across all compartments examined. Conversely, patients in the end-stage COVID-19 group showed fibrotic diffuse alveolar damage with intra-alveolar macrophages, organizing pneumonia, and focal interstitial emphysema. In this first study to examine the lung parenchyma of COVID-19 survivors, we did not find distinct post-acute histopathological changes to suggest permanent pulmonary damage. These results are reassuring for COVID-19 survivors who recover and become asymptomatic.
Aerosol delivery systems for treating obstructive airway diseases during the SARS-CoV-2 pandemic
Internal and Emergency Medicine, July 30, 2021
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes CoronaVirus Disease 2019 (COVID-19), has resulted in a worldwide pandemic and currently represents a major public health crisis. It has caused outbreaks of illness through person-to-person transmission of the virus mainly via close contacts, and droplets produced by an infected person’s cough or sneeze. Aerosolised inhaled therapy is the mainstay for treating obstructive airway diseases at home and in healthcare settings, but there is heightened particular concern about the potential risk for transmission of SARS-CoV-2 in the form of aerosolised respiratory droplets during the nebulised treatment of patients with COVID-19. As a consequence of this concern, the use of hand-held inhalers, especially pressurised metered dose inhalers, has risen considerably as an alternative to nebulisers, and this switch has led to inadequate supplies of inhalers in some countries. However, there is no evidence supporting an increased risk of viral transmission during nebulisation in COVID-19 patients. Furthermore, some patients may be unable to adequately use their new device and may not benefit fully from the switch to treatment via hand-held inhalers. Thus, there is no compelling reason to alter aerosol delivery devices for patients with established nebuliser-based regimens. The purpose of this paper is to discuss the current evidence and understanding of the use of aerosolised inhaled therapies during the SARS-CoV-2 pandemic and to provide some guidance on the measures to be taken to minimise the risk of transmitting infection, if any, during aerosol therapies.
Noninvasive respiratory support outside the intensive care unit for acute respiratory failure related to coronavirus-19 disease: a systematic review and meta-analysis
Critical Care, July 30, 2021
Noninvasive respiratory support (NIRS) has been diffusely employed outside the intensive care unit (ICU) to face the high request of ventilatory support due to the massive influx of patients with acute respiratory failure (ARF) caused by coronavirus-19 disease (COVID-19). We sought to summarize the evidence on clinically relevant outcomes in COVID-19 patients supported by NIV outside the ICU. We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials register, along with medRxiv and bioRxiv repositories for pre-prints, for observational studies and randomized controlled trials, from inception to the end of February 2021. Two authors independently selected the investigations according to the following criteria: (1) observational study or randomized clinical trials enrolling ≥ 50 hospitalized patients undergoing NIRS outside the ICU, (2) laboratory-confirmed COVID-19, and (3) at least the intra-hospital mortality reported. Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed. Data extraction was independently performed by two authors to assess: investigation features, demographics and clinical characteristics, treatments employed, NIRS regulations, and clinical outcomes. Methodological index for nonrandomized studies tool was applied to determine the quality of the enrolled studies. The primary outcome was to assess the overall intra-hospital mortality of patients under NIRS outside the ICU. The secondary outcomes included the proportions intra-hospital mortalities of patients who underwent invasive mechanical ventilation following NIRS failure and of those with ‘do-not-intubate’ (DNI) orders. Seventeen investigations (14 peer-reviewed and 3 pre-prints) were included with a low risk of bias and a high heterogeneity, for a total of 3377 patients. The overall intra-hospital mortality of patients receiving NIRS outside the ICU was 36% [30–41%]. 26% [21–30%] of the patients failed NIRS and required intubation, with an intra-hospital mortality rising to 45% [36–54%]. 23% [15–32%] of the patients received DNI orders with an intra-hospital mortality of 72% [65–78%]. Oxygenation on admission was the main source of between-study heterogeneity.
Postacute Sequelae of COVID-19 Pneumonia: 6-month Chest CT Follow-up
Radiology, July 27, 2021
The long-term post acute pulmonary sequelae of COVID-19 remain unknown. The objective was to evaluate lung injury in patients affected by COVID-19 pneumonia at six-month follow-up compared to baseline chest CT. From March 19th,2020 to May 24th,2020, patients with moderate to severe COVID-19 pneumonia and baseline Chest CT were prospectively enrolled at six-months follow-up. CT qualitative findings, semi-quantitative Lungs Severity Score (LSS) and well-aerated lung quantitative Chest CT (QCCT) were analyzed. Baseline LSS and QCCT performances in predicting fibrotic-like changes (reticular pattern and/or honeycombing) at six-month follow-up Chest CT were tested with receiver operating characteristic curves. Univariable and multivariable logistic regression analysis were used to test clinical and radiological features predictive of fibrotic-like changes. The multivariable analysis was performed with clinical parameters alone (clinical model), radiological parameters alone (radiological model) and the combination of clinical and radiological parameters (combined model). One-hundred-eighteen patients, with both baseline and six-month follow-up Chest CT, were included in the study (62 female, mean age 65±12 years). At follow-up Chest CT, 85/118 (72%) patients showed fibrotic-like changes and 49/118 (42%) showed GGOs. Baseline LSS (>14), QCCT (≤3.75L and ≤80%) showed an excellent performance in predicting fibrotic-like changes at Chest CT follow-up. In the multivariable analysis, AUC was .89 (95%CI .77-.96) for the clinical model, .81 (95%CI .68-.9) for the radiological model and .92 (95%CI .81-.98) for the combined model. At six-month follow-up Chest CT, 72% of patients showed late sequelae, in particular fibrotic-like changes. Baseline LSS and QCCT of well-aerated lung showed an excellent performance in predicting fibrotic-like changes at six-month Chest CT (AUC>.88). Male sex, cough, lymphocytosis and QCCT well-aerated lung were significant predictors of fibrotic-like changes at six-month with an inverse correlation (AUC .92).
Fibrotic Interstitial Lung Abnormalities at 1-year Follow-up CT after Severe COVID-19
Radiology, July 27, 2021
Fibrotic interstitial lung abnormalities in severe COVID-19 survivors depicted on 6-month CT scans were persistent on 1-year CT scans and were negatively correlated with the lung diffusion capacity. Given the large scale of COVID-19 pandemic worldwide, lung sequelae post-COVID-19 is a major concern to all populations. Our previous study showed that about one third of severe COVID-19 survivors had lung “fibrotic-like” changes [fibrotic interstitial lung abnormalities (ILAs) according to Fleischner Society Glossary] on 6 months follow up. However, whether these fibrotic ILAs changes are permanent, progressive or reversible remained unclear and little is known about the one-year sequela of COVID-19. The purpose of this study was to assess the chest CT changes of fibrotic ILAs at one-year follow-up in COVID-19 survivors. All participants remained anonymous, and written informed content was acquired by June 1, 2020. A total of 71 participants (41 men, 30 women; mean age, 57±10 years) who harbored lung sequelae (40 cases with fibrotic ILAs [previously described as fibrotic-like changes], 31 cases without fibrotic ILAs, including ground-glass opacification (GGO), consolidation or reticular abnormalities) at six-month follow up in our previous study were invited to this one-year follow-up study. Nine cases were excluded due to refusal to participate in the study. Finally, 62 participants (34 men, 28 women; mean age, 57±10 years; 35 cases with fibrotic ILAs, 27 cases without fibrotic ILAs) were prospectively enrolled in this study. The final study group consisted of 62 participants (34 men, 28 women; mean age, 57±10 years; range, 34-84 years), of which 35/62 (56%) participants (group 1) showed fibrotic ILAs and the remaining 27/62 (44%) participants (group 2) showed no fibrotic ILAs on 6-month follow-up CT scans. Six-month and one-year follow-up CT scans were obtained on 182 [169, 196] days and 363 [355, 372] days after symptoms onset, respectively.
Importance of Lung Ultrasound Follow-Up in Patients Who Had Recovered from Coronavirus Disease 2019: Results from a Prospective Study
Journal of Clinical Medicine, July 20, 2021
There is growing evidence regarding the imaging findings of coronavirus disease 2019 (COVID‐19) in lung ultrasounds, however, their role in predicting the prognosis has yet to be explored. Our objective was to assess the usefulness of lung ultrasound in the short‐term follow‐up (1 and 3 months) of patients with SARS‐CoV‐2 pneumonia, and to describe the progression of the most relevant lung ultrasound findings. We conducted a prospective, longitudinal and observational study performed in patients with confirmed COVID‐19 who underwent a lung ultrasound examination during hospitalization and repeated it 1 and 3 months after hospital discharge. A total of 96 patients were enrolled. In the initial ultrasound, bilateral involvement was present in 100% of the patients with mild, moderate or severe ARDS. The most affected lung area was the posteroinferior (93.8%) followed by the lateral (88.7%). Subpleural consolidations were present in 68% of the patients and consolidations larger than 1 cm in 24%. One month after the initial study, only 20.8% had complete resolution on lung ultrasound. This percentage rose to 68.7% at 3 months. Residual lesions were observed in a significant percentage of patients who recovered from moderate or severe ARDS (32.4% and 61.5%, respectively). In conclusion, lung injury associated with COVID‐19 might take time to resolve. The findings in this report support the use of lung ultrasound in the short‐term follow‐up of patients recovered from COVID‐19, as a radiation‐sparing, easy to use, novel care path worth exploring.
High In-Hospital Mortality in COVID Patients Receiving ECMO in Germany – A Critical Analysis
American Journal of Respiratory and Critical Care Medicine, July 20, 2021
Extracorporeal membrane-oxygenation (ECMO) is an established treatment option for severe acute respiratory failure. In the context of the SARS-CoV-2 pandemic with the occurrence of many severe ARDS cases, ECMO is increasingly being used worldwide depending on the available resources. Data from high-volume centers show that ECMO therapy may reduce inhospital mortality rate of ventilated patients that would otherwise reach more than 50-80%. Analyzing 10,021 hospitalized patients being treated in 920 different Germany hospitals during the first wave of the pandemic, ECMO was reportedly used in 119 patients (1.2%) with a mortality rate of 71%. In contrast, a recent worldwide meta-analysis revealed a lower inhospital mortality of 37% in 1896 patients. The recent data of the EURO-ELSO point into the same direction. The aim of the current research letter was to determine the in-hospital mortality during the first and second COVID-19 wave in Germany, a country having always quantitively sufficient health care resources during the pandemic without major restrictions.
Surges in Hospital Caseload Tied to Higher COVID-19 Mortality
Pulmonology Advisor, July 16, 2021
Hospitalized COVID-19 patients cared for in hospitals with the greatest surges in caseload have twofold greater mortality risk than patients in hospitals not experiencing surges, according to a study published online July 6 in the Annals of Internal Medicine. Sameer S. Kadri, M.D., from the National Institutes of Health Clinical Center in Bethesda, Maryland, and colleagues evaluated the association between hospitals’ severity-weighted COVID-19 caseload and COVID-19 mortality risk. The analysis included adult COVID-19-coded inpatients admitted from March to August 2020 with discharge dispositions by October 2020. The researchers found that of the 144,116 inpatients with COVID-19 at 558 U.S. hospitals, 54.2 percent were admitted to hospitals in the top surge index decile and, overall, 17.6 percent of patients died. Crude COVID-19 mortality decreased over time across all surge index strata, but the risk for death increased in the 50 to 75, 75 to 90, 90 to 95, 95 to 99, and >99 percentiles (odds ratios, 1.11, 1.24, 1.42, 1.59, and 2.00, respectively) compared with nonsurging (< 50th surge index percentile) hospital-months. The association between surge index and mortality was visible across ward, intensive care unit, and intubated patients. Despite greater corticosteroid use and more judicious intubation during later and higher-surging months, the surge-mortality relationship was stronger in June to August than in March to May. It is estimated that nearly one in four COVID-19 deaths (23.2 percent) were potentially attributable to hospitals strained by surging caseload.
Proteomics and metabonomics analyses of Covid-19 complications in patients with pulmonary fibrosis
Scientific Reports, July 16, 2021
Pulmonary fibrosis is a devastating disease, and the pathogenesis of this disease is not completely clear. Here, the medical records of 85 Covid-19 cases were collected, among which fibrosis and progression of fibrosis were analyzed in detail. Next, data independent acquisition (DIA) quantification proteomics and untargeted metabolomics were used to screen disease-related signaling pathways through clustering and enrichment analysis of the differential expression of proteins and metabolites. The main imaging features were lesions located in the bilateral lower lobes and involvement in five lobes. The closed association pathways were FcγR-mediated phagocytosis, PPAR signaling, TRP-inflammatory pathways, and the urea cycle. Our results provide evidence for the detection of serum biomarkers and targeted therapy in patients with Covid-19.
The Impact of the COVID-19 Pandemic on Exacerbations and Symptoms in Bronchiectasis: A Prospective Study
American Journal of Respiratory and Critical Care Medicine, July 14, 2021
The underlying mechanisms leading to bronchiectasis symptoms and exacerbations are poorly understood. The COVID-19 pandemic resulted in the introduction of social distancing and mitigation measures that have reduced person to person interactions worldwide. This has reduced the circulation of respiratory viruses such as influenza and rhinovirus, which are commonly identified in exacerbations of bronchiectasis. The COVID-19 pandemic therefore represents a “natural experiment” to test the hypothesis that many bronchiectasis exacerbations are related to external exposures while daily chronic symptoms such as cough and sputum are more “intrinsic”. In this study we therefore hypothesised that social distancing during 2020 would be associated with reduced reported exacerbations but no change in chronic symptoms typically experienced during stable state. We performed a prospective observational study embedded within the EMBARC registry of patients with CT confirmed bronchiectasis. Patients were enrolled as part of a study to validate a novel patient reported outcome measure (the Bronchiectasis Impact Measure – BIM) which has recently been reported. We included 173 patients in the original study. 19 patients were lost to follow-up and 7 patients had died, resulting in 147 patients included in the present analysis. The median age (interquartile range) was 70 years (64-75), 84 (57.1%) patients were female. The mean baseline FEV1 was 84.0% predicted (standard deviation 28.4). The median bronchiectasis severity index score was 6 (4-9). 64 (43.5%) had Haemophilus influenzae chronic infection and 25 (17.0%) had Pseudomonas aeruginosa chronic infection. 82.1% of the patients reported to be “shielding” during the pandemic. ‘Shielding’ was used to describe recommended additional protective measures encouraged in the UK for people who were at high-risk and extremely vulnerable, this included leaving their homes as little as possible and minimising all person to person contact. Only 2 patients in the cohort had PCR confirmed SARS-CoV2 infection. There was a statistically significant reduction in the frequency of reported exacerbations during the lockdown period.
Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity
Nature Communications, July 14, 2021
Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response. Additionally, we identify basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.
Pulmonary Embolism in Hospitalized Patients with COVID-19: A Multicenter Study
Radiology, July 13, 2021
Pulmonary embolism (PE) commonly complicates SARS-CoV-2 infection but there is heterogeneity in incidence and mortality in the single center reports and risk factors. Our objective was to determine the incidence of PE in COVID-19 and its associations with clinical and laboratory parameters. Electronic medical records were searched retrospectively for demographic, clinical and laboratory data and outcomes in patients admitted with COVID-19 at 4 hospitals March-June 2020. PE on CT pulmonary angiography (CTPA) and perfusion scintigraphy was correlated with clinical and laboratory parameters. D-dimer was used to predict PE and the obtained threshold underwent an external validation on 85 hospitalized patients with COVID-19 at a 5th hospital. We also assessed the association between right heart strain and embolic burden in patients with PE undergoing echocardiography. Four-hundred-thirteen patients with COVID-19 (230 men, aged 20-98 years, mean + SD = 60+16 years) were evaluated. PE was diagnosed in 25% (102/413, 95%CI: 21%-29%) of hospitalized patients with COVID-19, undergoing CTPA or perfusion scintigraphy. PE was observed in 29% (21/73, 95% CI:19% -41%) of ICU vs. 24% (81/340, 95% CI:20% -29%) of non-ICU patients (p=0.37). PE was associated with male sex (Odds Ratio=OR [95% CI]: 1.7[1.1–2.8], p=0.02), smoking (OR [95% CI]:1.8[1.01–3.4], p=0.04) and increased d-dimer (p < 0.001), lactate dehydrogenase (p < 0.001), ferritin (p=0.001) and IL-6 (p=0.02). Mortality in hospitalized patients was similar between those with PE and without PE (14% [13/102, 95% CI: 8% – 22%] vs 13% [40/311, 95% CI: 9% – 17%], p=0.98), suggesting that diagnosis and treatment of PE was not associated with excess mortality. D-dimer>1600 ng/mL predicts PE with 100% sensitivity and 62% specificity in an external validation cohort. Embolic burden was higher in patients with right heart strain among the patients with PE undergoing echocardiogram (p=0.03).
Genetic Risk and COPD Independently Predict the Risk of Incident Severe COVID-19
Annals of the American Thoracic Society, July 9, 2021
Both genetic variants and chronic obstructive pulmonary disease (COPD) contribute to the risk of incident severe coronavirus disease 2019 (COVID-19). Whether genetic risk of incident severe COVID-19 is the same regardless of pre-existing COPD is unknown. In this study, we aimed to investigate the potential interaction between genetic risk and COPD in relation to severe COVID-19. We constructed a polygenic risk score (PRS) for severe COVID-19 by using 112 single-nucleotide polymorphisms in 430,582 participants from the UK Biobank study. We examined the associations of genetic risk and COPD with severe COVID-19 by using logistic regression models. Of 430,582 participants, 712 participants developed severe COVID-19 as of February 22, 2021, of whom 19.8% had pre-existing COPD. Compared with participants at low genetic risk, those at intermediate genetic risk (OR, 1.34; 95% CI, 1.09–1.66) and high genetic risk (OR, 1.50; 95% CI, 1.18–1.92) had higher risk of severe COVID-19 (P for trend = 0.001), and the association was independent of COPD (P for interaction = 0.76). COPD was associated with a higher risk of incident severe COVID-19 (OR, 1.37; 95% CI, 1.12–1.67; P = 0.002). Participants at high genetic risk and with COPD had a higher risk of severe COVID-19 (OR, 2.05; 95% CI, 1.35–3.04; P < 0.001) than those at low genetic risk and without COPD. The PRS, which combines multiple risk alleles can be effectively used in screening for high-risk populations of severe COVID-19. High genetic risk correlates with a higher risk of severe COVID-19, regardless of pre-existing COPD.
Discovery of potential imaging and therapeutic targets for severe inflammation in COVID-19 patients
Scientific Reports, July 8, 2021
The Coronavirus disease 2019 (COVID-19) has been spreading worldwide with rapidly increased number of deaths. Hyperinflammation mediated by dysregulated monocyte/macrophage function is considered to be the key factor that triggers severe illness in COVID-19. However, no specific targeting molecule has been identified for detecting or treating hyperinflammation related to dysregulated macrophages in severe COVID-19. In this study, previously published single-cell RNA-sequencing data of bronchoalveolar lavage fluid cells from thirteen COVID-19 patients were analyzed with publicly available databases for surface and imageable targets. Immune cell composition according to the severity was estimated with the clustering of gene expression data. Expression levels of imaging target molecules for inflammation were evaluated in macrophage clusters from single-cell RNA-sequencing data. In addition, candidate targetable molecules enriched in severe COVID-19 associated with hyperinflammation were filtered. We found that expression of SLC2A3, which can be imaged by [18F]fluorodeoxyglucose, was higher in macrophages from severe COVID-19 patients. Furthermore, by integrating the surface target and drug-target binding databases with RNA-sequencing data of severe COVID-19, we identified candidate surface and druggable targets including CCR1 and FPR1 for drug delivery as well as molecular imaging. Our results provide a resource in the development of specific imaging and therapy for COVID-19-related hyperinflammation.
Inspiratory Effort and Lung Mechanics in Spontaneously Breathing Patients with Acute Respiratory Failure Due to COVID-19: A Matched Control Study
American Journal of Respiratory and Critical Care Medicine, July 1, 2021
A great debate started as to whether acute respiratory failure (ARF) induced by CoronaVirus (SARS-CoV-2) infection (COVID-19) should be classified as a classic form of acute respiratory distress syndrome (ARDS), or constitute a subtype of lung injury with different pathophysiological characteristics and mechanisms for progression. The magnitude of inspiratory effort correlated with the need to switch to invasive ventilation in non-COVID-19 patients, suggesting that self-inflicted lung injury (SILI) could play a role. We aimed at describing and comparing the inspiratory effort (primary outcome) and the breathing pattern of spontaneously breathing patients with ARF due to COVID-19 and historically matched non-COVID-19 patients, either candidate to NIV. COVID-19 patients were 1:1 propensity-matched (by PaO2/FiO2 ratio, age, body mass index [BMI] and sequential organ failure assessment score [SOFA]) with non-COVID-19 extracted from our dataset (period 2016 to 2021). The logit of the score was taken with a caliper of 0.2 in order to maximize the number of patients without comprising the match. All patients were in a similar phase from onset of ARF, unable to maintain SaO2> 92% despite optimized high flow oxygen (HFO), thus candidate to receive NIV according to local protocol. On admission, demographics, clinical characteristics and severity, respiratory function, and peripheral blood lactate and D-dimer levels were recorded.
Symptom-based early-stage differentiation between SARS-CoV-2 versus other respiratory tract infections—Upper Silesia pilot study
Scientific Reports, June 30, 2021
In the DECODE project, data were collected from 3,114 surveys filled by symptomatic patients RT-qPCR tested for SARS-CoV-2 in a single university centre in March-September 2020. The population demonstrated balanced sex and age with 759 SARS-CoV-2(+) patients. The most discriminative symptoms in SARS-CoV-2(+) patients at early infection stage were loss of taste/smell (OR = 3.33, p < 0.0001), body temperature above 38º C. (OR = 1.67, p < 0.0001), muscle aches (OR = 1.30, p = 0.0242), headache (OR = 1.27, p = 0.0405), cough (OR = 1.26, p = 0.0477). Dyspnea was more often reported among SARS-CoV-2(-) (OR = 0.55, p < 0.0001). Cough and dyspnea were 3.5 times more frequent among SARS-CoV-2(-) (OR = 0.28, p < 0.0001). Co-occurrence of cough, muscle aches, headache, loss of taste/smell (OR = 4.72, p = 0.0015) appeared significant, although co-occurrence of two symptoms only, cough and loss of smell or taste, means OR = 2.49 (p < 0.0001). Temperature > 38º C with cough was most frequent in men (20%), while loss of taste/smell with cough in women (17%). For younger people, taste/smell impairment is sufficient to characterise infection, whereas in older patients co-occurrence of fever and cough is necessary. The presented study objectifies the single symptoms and interactions significance in COVID-19 diagnoses and demonstrates diverse symptomatology in patient groups.
Early extubation with immediate non-invasive ventilation versus standard weaning in intubated patients for coronavirus disease 2019: a retrospective multicenter study
Scientific Reports, June 28, 2021
In patients intubated for hypoxemic acute respiratory failure (ARF) related to novel coronavirus disease (COVID-19), we retrospectively compared two weaning strategies, early extubation with immediate non-invasive ventilation (NIV) versus standard weaning encompassing spontaneous breathing trial (SBT), with respect to IMV duration (primary endpoint), extubation failures and reintubations, rate of tracheostomy, intensive care unit (ICU) length of stay and mortality (additional endpoints). All COVID-19 adult patients, intubated for hypoxemic ARF and subsequently extubated, were enrolled. Patients were included in two groups, early extubation followed by immediate NIV application, and conventionally weaning after passing SBT. 121 patients were enrolled and analyzed, 66 early extubated and 55 conventionally weaned after passing an SBT. IMV duration was 9 [6–11] days in early extubated patients versus 11 [6–15] days in standard weaning group (p = 0.034). Extubation failures [12 (18.2%) vs. 25 (45.5%), p = 0.002] and reintubations [12 (18.2%) vs. 22 (40.0%) p = 0.009] were fewer in early extubation compared to the standard weaning groups, respectively. Rate of tracheostomy, ICU mortality, and ICU length of stay were no different between groups. Compared to standard weaning, early extubation followed by immediate NIV shortened IMV duration and reduced the rate of extubation failure and reintubation.
Lung Recruiting Effect of Prone Positioning in Spontaneously Breathing COVID-19 Patients Assessed by Electrical Impedance Tomography
American Journal of Respiratory and Critical Care Medicine, June 25, 2021
A 72-year-old male known for obesity (body mass index of 38 kg.m-2) and smoking was admitted to intensive care unit (ICU) for acute respiratory failure. Chest CT-scan revealed interstitial lung infiltrates with sub pleural and posterior lung condensation. Coronavirus disease-19 (COVID-19) pneumonia was confirmed by a positive result of real-time reverse transcriptase-polymerase chain reaction from nasal and pharyngeal swab. The patient presented rapid decrease in the ROX index (respiratory rate: 28 breaths/min, pulse oximetry: 91%; oxygen flow rate: 5 L/min) and was invited to initiate prone positioning combined with conventional oxygen therapy as the first-line ventilation strategy according to the routine practice in our center. Prone positioning was maintained according to patient tolerance for a total duration of 290 min. Global and regional ventilation patterns were checked using electrical impedance tomography (Draeger Pulmovista® 500). Since the start of prone positioning, electrical impedance tomography revealed a constant improvement in global and regional delta end expiratory lung impedance that predominated in the posterior area of the lungs. At the same time, the respiratory rate decreased from 28 to 20 breaths/min, and the pulse oximetry increased from 91% to 97% while the oxygen flow rate was reduced from 5 L/min to 3 L/min. Finally, intubation was avoided, and the patient was discharged from ICU. Prone positioning combined with conventional oxygen therapy could be proposed in severe COVID-19 patients to avoid intubation by promoting alveolar recruitment in lung area lacking hypoxic vasoconstriction.
Pulmonary adverse drug event data in hypertension with implications on COVID-19 morbidity
Scientific Reports, June 25, 2021
Hypertension is a recognized comorbidity for COVID-19. The association of antihypertensive medications with outcomes in patients with hypertension is not fully described. However, angiotensin-converting enzyme 2 (ACE2), responsible for host entry of the novel coronavirus (SARS-CoV-2) leading to COVID-19, is postulated to be upregulated in patients taking angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). Here, we evaluated the occurrence of pulmonary adverse drug events (ADEs) in patients with hypertension receiving ACEIs/ARBs to determine if disparities exist between individual drugs within the respective classes using data from the FDA Spontaneous Reporting Systems. For this purpose, we proposed the proportional reporting ratio to provide a statistical summary for the commonality of an ADE for a specific drug as compared to the entire database for drugs in the same or other classes. In addition, a statistical procedure, multiple logistic regression analysis, was employed to correct hidden confounders when causative covariates are underreported or untrusted to correct analyses of drug-ADE combinations. To date, analyses have been focused on drug classes rather than individual drugs, which may have different ADE profiles depending on the underlying diseases present. A retrospective analysis of thirteen pulmonary ADEs showed significant differences associated with quinapril and trandolapril, compared to other ACEIs and ARBs. Specifically, quinapril and trandolapril were found to have a statistically significantly higher incidence of pulmonary ADEs compared with other ACEIs as well as ARBs (P < 0.0001) for group comparison (i.e., ACEIs vs. ARBs vs. quinapril vs. trandolapril) and (P ≤ 0.0007) for pairwise comparison (i.e., ACEIs vs. quinapril, ACEIs vs. trandolapril, ARBs vs. quinapril, or ARBs vs. trandolapril). This study suggests that specific members of the ACEI antihypertensive class (quinapril and trandolapril) have a significantly higher cluster of pulmonary ADEs.
FDA issues EUA for tocilizumab to treat patients hospitalized with COVID-19
Healio | Rheumatology, June 25, 2021
The FDA has issued an emergency use authorization for tocilizumab to treat hospitalized patients receiving corticosteroids who require supplemental oxygen, mechanical ventilation or extracorporeal membrane oxygenation, according to a press release. The emergency use authorization for tocilizumab (Actemra, Genentech) — now the fourth monoclonal antibody authorized for COVID-19 — is specifically for hospitalized adults and children aged 2 years and older; it is not intended for outpatients or as a treatment for COVID-19, the FDA noted. “Today’s action demonstrates the FDA’s commitment to making new therapies available through every stage of the global COVID-19 pandemic,” Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a press release. “Although vaccines have been successful in decreasing the number of patients with COVID-19 who require hospitalization, providing additional therapies for those who do become hospitalized is an important step in combating this pandemic.” The FDA based its emergency use authorization on results from four randomized, controlled trials — RECOVERY, EMPACTA, COVACTA and REMDACTA — that evaluated the safety and efficacy of tocilizumab in more than 5,500 hospitalized patients with COVID-19. In particular, the RECOVERY and EMPACTA trials provided the “most important scientific evidence on the potential benefit of Actemra for its authorized use,” the FDA noted. In the RECOVERY trial, hospitalized patients with severe COVID-19 pneumonia (n=4,116) were randomized to receive either tocilizumab plus standard care (n=2,022) or standard care alone (n=2,094). The primary endpoint was death through 28 days of follow-up.
Respiratory risk, not death, increased for adults with obesity in ICU with COVID-19
Endocrine Today, June 25, 2021
Obesity is not associated with an increased risk for death for adults admitted to the ICU with COVID-19, but BMI is linked to acute respiratory distress syndrome in these patients, according to a study published in Obesity. In the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID), researchers analyzed the records of adults admitted to the ICU with COVID-19 at 68 U.S. hospitals. Although having a higher BMI was associated with a higher risk for acute respiratory distress syndrome and acute kidney injury requiring renal replacement therapy, there was no increased risk for mortality observed. “The absence of an association between BMI and circulating biomarkers of inflammation and thrombosis challenges their hypothesized links with obesity and adverse outcomes in COVID-19,” Allon N. Friedman, MD, assistant professor of medicine in the division of nephrology at the Indiana University School of Medicine, and colleagues wrote. Researchers analyzed data from 4,925 consecutive adults (mean age, 60.9 years; 62.8% men; 2,552 with obesity) who tested positive for COVID-19 and were admitted to the ICUs of 68 U.S. hospitals. Patients were followed until hospital discharge, death or the end of the analysis on Aug. 1, 2020. Demographics, comorbidities, laboratory values, physiologic parameters, medications, treatments, organ support and clinical outcomes were obtained through a detailed chart review. The primary outcome was in-hospital mortality, and secondary outcomes included acute respiratory distress syndrome, acute kidney injury requiring renal replacement therapy and thrombotic events during the first 14 days of ICU admission. Acute respiratory distress syndrome was observed in 72.2% of the study cohort. In an unadjusted model, an increased risk for acute respiratory distress syndrome was observed in people with a BMI of 25 kg/m2 to 29.9 kg/m2 (HR = 1.21; 95% CI, 1.11-1.33), 30 kg/m2 to 34.9 kg/m2 (HR = 1.4; 95% CI, 1.24-1.58), 35 kg/m2 to 39.9 kg/m2 (HR = 1.36; 95% CI, 1.24-1.48) and 40 kg/m2 or more (HR = 1.34; 95% CI, 1.15-1.56). Similar associations were observed in multivariable analysis.
Incidence, Characteristics, and Outcomes of Ventilator-Associated Events during the COVID-19 Pandemic
Annals of the American Thoracic Society, June 24, 2021
Ventilator-associated event (VAE) surveillance provides an objective means to measure and compare complications that develop during mechanical ventilation by identifying patients with sustained increases in ventilator settings after a period of stable or decreasing ventilator settings. The impact of the Covid-19 pandemic on VAE rates and characteristics is unknown. Our objective was to compare the incidence, causes, and outcomes of VAE during the Covid-19 pandemic year vs pre-pandemic years and amongst ventilated patients with and without Covid-19. In this retrospective cohort study of mechanically ventilated adults at four academic and community hospitals in Massachusetts, we compared VAE incidence rates between March 1-August 31 for each of 2017-2020 (corresponding to the timeframe of the pandemic first wave in 2020) and among Covid-19 positive and negative patients in 2020. The medical records of 200 randomly selected patients with VAEs in 2020 (100 with Covid-19, 100 without) were analyzed to compare conditions precipitating VAEs in patients with vs without Covid-19. VAEs per 100 episodes of mechanical ventilation were more common in 2020 vs prior years (11.2 vs 6.7, p<.01) but the rate of VAEs per 1000 ventilator-days was similar (14.2 vs 12.7, p=.08). VAEs were more frequent in Covid-19 positive vs negative patients within 2020 (29.0 vs. 7.1 per 100 ventilator episodes, p<.01 and 17.2 vs 12.2 per 1000 ventilator days, p<.01). Compared to non-Covid-19 patients with VAEs, Covid-19 patients with VAEs had similar rates of infection-related ventilator-associated complications, longer median duration of mechanical ventilation (22 vs 14 days, p<.01), and similar in-hospital mortality (30% vs 38%, p=.15). Progressive ARDS accounted for 53% of VAEs in Covid-19 patients versus 14% amongst non-Covid-19 patients. VAE rates per 100 episodes of mechanical ventilation and per 1000 ventilator days were higher amongst Covid-19 positive versus negative patients. Over 50% of VAEs in Covid-19 patients were caused by progressive ARDS versus less than 15% in patients without Covid-19. These findings provide insight into the natural history of Covid-19 in ventilated patients and may inform targeted strategies to mitigate complications in this population.
FDA to Add Warning on Rare Myocarditis Risk After COVID Vaccination
MedPage Today, June 23, 2021
Given the reported cases of myocarditis in young people who received mRNA COVID-19 vaccines, FDA will include a warning statement about the risks and characteristics of this rare condition, an agency representative said at CDC’s Advisory Committee on Immunization Practices (ACIP) meeting on Wednesday. Data presented by CDC staff estimated a rate of 12.6 cases per million within 3 weeks of a second dose of either Pfizer’s or Moderna’s mRNA vaccine for individuals ages 12 to 39. Rates were highest among boys and younger men. The side effect was rare, but when it occurred, it was typically within a week of vaccination. FDA liaison representative, Doran Fink, MD, PhD, noted the agency will add a warning about the risk of myocarditis or pericarditis following vaccination that states “these events have occurred in some recipients following dose 2, onset of symptoms was several days to a week” and based on limited follow-up, “most cases had a resolution of symptoms.” The warning would also advise anyone experiencing these symptoms to “seek medical attention” and state that information on long-term sequelae with the condition is limited. CDC staff said they would update their vaccine fact sheets with more comprehensive information in the coming days. While there was no vote scheduled during the ACIP meeting, the committee seemed to agree with CDC staff that the benefits of COVID-19 vaccination continue to outweigh the risks of vaccination in people ages 12 and older.
Early tracheostomy for managing ICU capacity during the COVID-19 outbreak: a propensity-matched cohort study
CHEST, June 17, 2021
During the first wave of the COVID-19 pandemic, shortages of ventilators and intensive care unit (ICU) beds overwhelmed healthcare systems. Whether early tracheostomy reduces the duration of mechanical ventilation and ICU stay is controversial. Can “failure-free days” outcomes focused on ICU resources could help decide the optimal timing of tracheostomy in overburdened healthcare systems during viral epidemics? This retrospective cohort study included consecutive patients with COVID-19 pneumonia tracheostomized in 15 Spanish ICUs during the surge, when ICU occupancy modified clinicians criteria to perform tracheostomy in COVID-19 patients. We compared ventilator-free days at 28 and 60 days and ICU- and hospital bed-free days at 28 and 60-days in propensity-score-matched cohorts tracheostomized at different timings (≤7 days, 8–10 days, 11–14 days after intubation). Of 1939 patients admitted with COVID-19 pneumonia, 682 (35.2%) were tracheostomized, 382 (56%) within 14 days. Earlier tracheostomy was associated with more ventilator-free days at 28 days [≤7 vs. >7d (116 patients included in the analysis): median 9 days (IQR 0–15) vs. 3 (0–7), difference between groups 4.5 days, 95%CI (2.3 to 6.7); 8–10 vs. >10d (222 patients analysed): 6 (0–10) vs. 0 (0–6), difference 3.1 days, 95%CI (1.7 to 4.5); 11–14 vs. >14d (318 patients analysed): 4 (0–9) vs. 0 (0-2), difference 3 days, 95%CI (2.1 to 3.9)]. Except hospital bed-free days at 28 days, all other endpoints were better in early tracheostomy. Optimal timing of tracheostomy may improve patient outcomes and alleviate ICU capacity strain during the COVID-19 pandemic without increasing mortality. Tracheostomy within the first work on ventilator may particularly improve ICU availability.
Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia
New England Journal of Medicine, June 16, 2021
The efficacy and safety of tofacitinib, a Janus kinase inhibitor, in patients who are hospitalized with coronavirus disease 2019 (Covid-19) pneumonia are unclear. We randomly assigned, in a 1:1 ratio, hospitalized adults with Covid-19 pneumonia to receive either tofacitinib at a dose of 10 mg or placebo twice daily for up to 14 days or until hospital discharge. The primary outcome was the occurrence of death or respiratory failure through day 28 as assessed with the use of an eight-level ordinal scale (with scores ranging from 1 to 8 and higher scores indicating a worse condition). All-cause mortality and safety were also assessed. A total of 289 patients underwent randomization at 15 sites in Brazil. Overall, 89.3% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death or respiratory failure through day 28 was 18.1% in the tofacitinib group and 29.0% in the placebo group (risk ratio, 0.63; 95% confidence interval [CI], 0.41 to 0.97; P=0.04). Death from any cause through day 28 occurred in 2.8% of the patients in the tofacitinib group and in 5.5% of those in the placebo group (hazard ratio, 0.49; 95% CI, 0.15 to 1.63). The proportional odds of having a worse score on the eight-level ordinal scale with tofacitinib, as compared with placebo, was 0.60 (95% CI, 0.36 to 1.00) at day 14 and 0.54 (95% CI, 0.27 to 1.06) at day 28. Serious adverse events occurred in 20 patients (14.1%) in the tofacitinib group and in 17 (12.0%) in the placebo group. Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo.
Practice, Outcomes and Complications of Emergent Endotracheal Intubation By Critical Care Practitioners During the COVID-19 Pandemic
CHEST, June 14, 2021
For patients with novel coronavirus 2019 (COVID-19) who undergo emergency endotracheal intubation, there is limited data regarding the practice, outcomes and complications of this procedure. For COVID-19 patients requiring emergency endotracheal intubation, how do the procedural techniques, the incidence of first pass success and the complications associated with the procedure compare with intubations on critically ill patients prior to the COVID-19 pandemic? We conducted a retrospective study of adult COVID-19 patients at Montefiore Medical Center who underwent first-time endotracheal intubation by critical care physicians between July 19, 2019 and May 1, 2020. The first COVID-19 patient was admitted to our institution on March 11, 2020, before which patients were designated as the pre-pandemic cohort. Descriptive statistics was used to compare groups. A Fischer’s exact test was used to compare categorical variables. A two-tailed Student’s t-test for parametric variables or a Wilcoxon rank sum test for nonparametric variables were utilized for continuous variables. 1,260 intubations met inclusion criteria (782 pre-pandemic, 478 pandemic). Patients during the pandemic were more likely to be intubated for hypoxemic respiratory failure (72.6% vs 28.1%; P<0.01). During the pandemic, operators were more likely to use video laryngoscopy (89.4% vs 53.3%, P<0.01) and neuromuscular blocking agents (86.0% vs 46.2%; P<0.01). First pass success was higher during the pandemic period (94.6% vs 82.9%; P<0.01). The rate of associated complications was higher during the pandemic (29.5% vs 15.2%; P<0.01), a finding driven by a higher rate of associated hypoxemia during or immediately after the procedure (25.7% vs 8.2%; P<0.01). We have shown that video laryngoscopy and neuromuscular blockade were increasingly utilized during the COVID-19 pandemic. Despite a higher rate of first pass success during the pandemic, the incidence of complications associated with the procedure was higher.
Increased pulmonary embolism in patients with COVID-19: a case series and literature review
Tropical Diseases, Travel Medicine and Vaccines, June 12, 2021
There is some recent evidence that the coronavirus disease 2019 (COVID-19) increases the risk of venous thromboembolism by creating a prothrombotic state. COVID-19 and pulmonary embolism (PE) are both associated with tachypnoea, hypoxemia, dyspnoea, and increased D-dimer. Diagnosis of pulmonary embolism in a patient with COVID-19 compared to an individual without it, using the conventional clinical and biochemical evidence is challenging and somehow impossible. In this study, we reported four male cases affected by COVID-19 and admitted to hospitals in Sanandaj, Iran. The patients were all older adults (ranging between 56 and 95 years of age). Fever, chills, muscle pain, and cough were evident in all the cases. Red blood cell levels were low, and pulmonary embolism was clearly detected on spiral computed tomographic (CT) angiography of the pulmonary circulation of all patients. These cases demonstrated that COVID-19 may lead to pulmonary embolism by causing blood coagulation problems. As COVID-19 continues to cause considerable mortality, more information is emerging which reveals its complicated pathogenicity. In the meantime, venous thromboembolism remains an uncommon finding in patients with COVID-19. It is essential that health care providers perform the necessary diagnostic evaluations and provide appropriate treatment for patients.
AMA survey: 96% of physicians fully vaccinated against COVID-19
Healio | Primary Care, June 11, 2021
Most practicing physicians in the United States who were surveyed reported being fully vaccinated against COVID-19, with no significant differences in vaccination by gender, age or geographic location, according to the AMA. The organization administered the survey from June 3 to 8. About 300 physicians responded to the survey; half of them were primary care physicians. Of the 11 non-vaccinated physicians who participated in the survey, five said that they plan on receiving the COVID-19 vaccine. The AMA said that the most common reason for not being vaccinated was that the COVID-19 vaccine is “too new and has unknown long-term effects.” With more than 96% of physicians reporting to be fully vaccinated, the data yield a 20% increase in vaccinated physicians compared with a poll conducted by Medscape last month, according to an AMA press release. “Practicing physicians across the country are leading by example, with an amazing uptake of the COVID-19 vaccines,” AMA President Susan R. Bailey, MD, said in the release. “Physicians and clinicians are uniquely positioned to listen to and validate patient concerns, and one of the most powerful anecdotes a physician can offer is that they themselves have been vaccinated.”
FDA Approves Third COVID-19 Antibody Treatment for Emergency Use
Pulmonology Advisor, June 11, 2021
A third antibody treatment designed to keep high-risk COVID-19 patients from being hospitalized was approved for emergency use by the U.S. Food and Drug Administration on Wednesday. Importantly, in lab tests, the newly authorized drug, dubbed sotrovimab, neutralized the highly infectious virus variant that is crippling India, as well as variants first spotted in Britain, South Africa, Brazil, California, and New York. “With the authorization of this monoclonal antibody treatment, we are providing another option to help keep high-risk patients with COVID-19 out of the hospital,” Patrizia Cavazzoni, M.D., director of the FDA Center for Drug Evaluation and Research, said in an agency news release. “It is important to expand the arsenal of monoclonal antibody therapies that are expected to retain activity against the circulating variants of COVID-19 in the United States.” Developed by GlaxoSmithKline, in concert with the American company Vir Biotechnology, the drug should become available to Americans “in the coming weeks,” company officials said in a statement. “Sotrovimab is a critical new treatment option in the fight against the current pandemic and potentially for future coronavirus outbreaks as well,” said George Scangos, Ph.D., Vir’s chief executive officer. GSK and Vir’s treatment is a single drug, designed to mimic the antibodies generated when the immune system fights off the coronavirus. Its emergency use authorization was based on a study of 583 volunteers who had started experiencing symptoms within the previous five days. The study showed that those who received the GSK-Vir treatment had an 85 percent reduction in their risk for hospitalization or death compared with those who received placebo.
Prebronchoscopy COVID-19 Testing Does Not Decrease Infection Rates Among HCW
Pulmonology Advisor, June 7, 2021
Mandatory preprocedurual COVID-19 testing for asymptomatic patients does not necessarily decrease rates of infection among health care workers (HCWs), according to study results published in CHEST. Bronchoscopy is an aerosol-generating procedure; therefore, several medical societies have recommended methods to reduce the transmission of SARS-CoV-2 among HCWs and patients. These recommendations included mandating universal COVID-19 testing, which may have contributed to the delay of necessary medical procedures and have added burdens to the health care system and the patients themselves. Since the beginning of the pandemic, the University of Florida has had a flexible policy regarding preprocedural COVID-19 testing, wherein all patients and visitors are symptomatically screened and asked about recent travel history and exposure to COVID-19-positive patients. A temperature check is also performed at the hospital entrance and preprocedural COVID-19 polymerase chain reaction (PCR) testing is up to the individual provider and procedural team discretion. Out of 664 patients who underwent outpatient bronchoscopies between March 2020 and February 2021, researchers at the university found that 172 (25.9%) patients were tested for COVID-19 in the 30 days before the procedure at the provider’s discretion and none of these tests came back positive. A total of 114 (17.2%) patients were tested in the 30 days following the procedure and of those, only 1 patient (0.8%) tested positive 27 days after the procedure. During the study period, there were zero COVID-19 infections among the bronchoscopy suite staff workers.
Asthma Flares Decreased Among Black, Hispanic Patients During COVID-19 Pandemic
Pulmonology Advisor, June 7, 2021
There was a substantial decrease in asthma exacerbations among Black and Hispanic patients during the COVID-19 pandemic, according to a study recently published in the Journal of Allergy and Clinical Immunology: In Practice. Justin D. Salciccioli, M.B.B.S., from Brigham and Women’s Hospital in Boston, and colleagues used data from the PREPARE study of reliever-triggered inhaled corticosteroid strategy in African American/Black and Hispanic/Latinx adults (aged 18 to 75 years) with moderate-to-severe asthma. Changes in asthma control during the COVID-19 pandemic were assessed (first and second quarters of 2019 versus 2020) for 1,178 participants. The researchers observed a significant decrease from Q1 to Q2 of 2020 versus the same time period in 2019, with a difference-in-differences of −0.47 exacerbations per year (representing a relative reduction of 41 percent). Asthma exacerbation decreased 50 percent in Hispanic/Latinx and 27 percent in African American/Black patients. Decreases were larger among participants who worked outside of the home at study entry (−65 percent) versus those who worked at home (−23 percent). For individuals without a type-2 helper T-cell phenotype, decreases in exacerbations were greater, with exacerbations falling by 51 percent for individuals with a blood eosinophil count below the median (192 cells/μL) versus 34 percent for those above the median. “This is the first study to assess asthma exacerbation before and after the COVID-19 pandemic using data that are unlikely to be affected by patients avoiding the health care system,” Salciccioli said in a statement. “Because this was part of a prospective trial that started before the pandemic and was planned to be remote, it gave us a unique window into how changes during the pandemic may have led to a dramatic decrease in asthma exacerbation.”
Association between risk of VTE and mortality in patients with COVID-19
International Journal of Infectious Diseases, June 6, 2021
The objective was to investigate the association between risk of VTE with 30-day mortality in COVID-19 patients. 1030 COVID-19 patients were retrospective collected, with baseline data on demographics, Sequential Organ Failure Assessment (SOFA) score, and VTE risk assessment models (RAMs) including Padua Prediction Score (PPS), International Medical Prevention Registry (IMPROVE) and Caprini RAM. Thirty-day mortality increased progressively from 2% in patients at low risk of VTE to 63% in those at high risk defined by PPS. Similar findings were also observed by IMPROVE and Caprini score. Progressive increases in VTE risk also were associated with higher SOFA score. The presence of high risk of VTE was independently associated with mortality regardless of adjusted gender, smoking status and some comorbidities with hazard ratios of 29.19, 37.37, 20.60 for PPS, IMPROVE and Caprini RAM, respectively (P < 0.001 for all comparisons). Predictive accuracy of PPS (Area Under Curve, AUC, 0.900), IMPROVE (AUC, 0.917) or Caprini RAM (AUC, 0.861) as the risk of mortality was markedly well. We firstly investigate that the presence of high risk of VTE identifies a group of COVID-19 patients at higher risk for mortality. Furthermore, there is higher accuracy of VTE RAMs to predict mortality in these patients.
Improved Outcomes With Methylprednisolone in Hospitalized Hypoxic Patients With COVID-19
Cardiology Advisor, June 4, 2021
Treatment with methylprednisolone led to significantly greater improvements in clinical status and shortened hospital length of stay than treatment with dexamethasone in hospitalized COVID-19 patients with hypoxia, according to the results of a study published in BMC Infectious Diseases. This prospective trial included 86 hospitalized patients with COVID-19 in Iran. Participants were randomly assigned to either methylprednisolone 2 mg/kg/d (n=44) or dexamethasone 6 mg/kg/d (n=42). Treatment was administered in conjunction with standard of care for 10 days. The primary endpoint was 28-day mortality rate and clinical status at 5 and 10 days. The data were examined using a 9-point World Health Organization (WHO) ordinal scale ranging from uninfected (point 0) to death (point 8). Secondary endpoints included intensive care unit admission and the need for invasive mechanical ventilation. No significant differences were observed between the treatment groups in terms of demographic variables, comorbid diseases, or disease severity at time of admission. At day 5, however, patients treated with methylprednisolone reached a significantly better clinical status compared with patients who received dexamethasone (4.02 vs 5.21, respectively; P =.002). Patients in the methylprednisolone group also had better clinical status at day 10 (2.90 vs 4.71; P =.001). Patients in the methylprednisolone group had a significantly better overall mean 9-point WHO score (3.909 vs 4.873; P =.004). The use of methylprednisolone was also associated with a significantly shorter mean length of hospital stay (7.43±3.64 vs 10.52±5.47 days; P =.015). A lower proportion of patients in the methylprednisolone group required a ventilator during hospitalization (18.2% vs 38.1%; P =.040).
Correlation between clinical course and radiographic development on CT scan in patients with COVID
Journal of Intensive Medicine, May 26, 2021
Our objective was to analyze the correlation between clinical course and radiographic development on computed tomography (CT) in patients with confirmed coronavirus disease 2019 (COVID-19) and to provide more evidence for treatment. This retrospective, observational, cohort study enrolled 49 patients with Reverse transcription-polymerase chain reaction (RT-PCR)-confirmed COVID-19, which included 30 patients admitted to the intensive care unit (ICU) of Wuhan Third Hospital and 19 patients either admitted to or receiving telemedicine consultation from Shanghai General Hospital, Shanghai Xuhui Dahua Hospital, and hospitals in other provinces. CT scans were performed in all enrolled patients and the radiographic features including simple ground-glass opacities (GGOs), GGO with interlobular septal thickening, consolidations with GGO, and consolidations only were monitored by repeating the CT. The progression of these radiographic features was analyzed in combination with their clinical staging and the time interval between onset of symptoms to CT. Based on illness severity, the 49 patients were classified into four stages: mild (n = 6), moderate (n = 12), severe (n = 16), and critically ill (n = 15). The CT findings were classified into three phases: early (n = 5), progression (n = 39), and recovery (n = 5). Among the 49 patients, 9 had bilateral diffuse GGO or diffuse consolidations (white lungs) and were counted as 18 lesions. Three patients had no abnormal findings on initial CT, but their repeat CT showed new lesions. In all, we identified 892 lesions including simple GGO, GGO with interlobular septal thickening, consolidations with GGO, and consolidations only.
Tailored modulation of the inflammatory balance in COVID-19 patients admitted to the ICU?—a viewpoint
Critical Care, May 25, 2021
A growing consensus seems to be emerging that dexamethasone is a crucial component in the treatment of COVID-19-associated oxygen-dependent respiratory failure. Although dexamethasone has an undeniably beneficial effect on the inflammatory response in a subgroup of patients, the potential negative effects of corticosteroids must also be considered. In view of these negative effects, we argue that a one-size-fits-all dexamethasone approach may be potentially harmful in specific subsets of patients with COVID-19-associated ARDS. We propose a different individually tailored treatment strategy based on the patient’s inflammatory response.
Importance of Lung Epithelial Injury in COVID-19 Associated Acute Respiratory Distress Syndrome: Value of Plasma sRAGE
American Journal of Respiratory and Critical Care Medicine, May 24, 2021
[Letter to the Editor] The respiratory form of the coronavirus disease (COVID-19) has led to an unprecedented number of hospitalizations for acute respiratory distress syndrome (ARDS). To date, pathophysiology of COVID-19 associated ARDS (CARDS) remains poorly understood. This has led to discuss a different presentation from non-COVID-19 ARDS, regarding lung mechanics abnormalities and hypoxemia mechanisms. However little attention has been paid to the value of biomarkers of lung injury. The soluble form of the receptor for advanced glycation end-products (sRAGE) is a well-characterized marker of lung alveolar epithelial injury and has been associated with both prognostic and pathogenic values in patients with ARDS. This study aims to investigate the value of baseline plasma sRAGE in CARDS and how it could differ between COVID-19 and non-COVID-19 ARDS. Patients and methods We prospectively enrolled all consecutive adult patients admitted to the medical intensive care unit of the Saint-Louis hospital, Paris, France between March 1st and June 1st, 2020 for CARDS according to the Berlin definition. Management of patients included protective volume-controlled ventilation, neuromuscular blockers and prone position if needed. All measurements were performed within 24 hours post intubation. Ventilator’s settings and respiratory mechanics measures were collected, together with dead space fraction, ventilatory ratio and, shunt fraction. When available, measurements of the Recruitment-to-Inflation (R/I) ratio measurement were collected. A Value up or equal to 0.5 was considered as a potential for lung recruitment. The severity of lung edema was assessed using the RALE score, evaluated by two independent physicians on the chest radiography of the day of MV initiation.
Trial supports tocilizumab in moderate-to-severe COVID-19-associated pneumonia
Helio | Primary Care, May 24, 2021
A follow-up analysis of the CORIMUNO-TOCI-1 randomized clinical trial showed that tocilizumab may be considered for treating patients with moderate-to-severe COVID-19-associated pneumonia and high C-reactive protein levels. Xavier Mariette, MD, PhD, the head of the rheumatology department at Hôpital Bicêtre in France, and colleagues noted that eight randomized clinical trials of tocilizumab for the treatment of COVID-19 reported heterogeneous results. Improved 28-day survival was demonstrated in only two of those trials — RECOVERY and REMAP-CAP — both of which included a significant number of patients who took dexamethasone. The studies also differed in terms of population, design and length of follow-up, the researchers said. In CORIMUNO-TOCI-1, Mariette and colleagues compared survival rates in patients with COVID-19 who required supplemental oxygen but not high-flow or mechanical ventilation. About half the cohort received tocilizumab and the other half received usual care. The study met its primary endpoint — the proportion of patients who required noninvasive ventilation or intubation or who died at day 14 — but they found no survival difference at day 28 between patients who received tocilizumab and those who did not. The researchers extended the follow-up period to 3 months and found that 11% of the 63 patients in the tocilizumab group and 18% of the 67 patients in the usual care group had died (adjusted HR = 0.64; 95% CI, 0.25-1.65). Those who received tocilizumab and had CRP levels higher than 15 mg/dL had an 18% chance of needing ventilation at day 14 or of dying compared with 57% in the usual care group (HR = 0.18; 95% CI, 0.06-0.59). In addition, mortality in patients with high CRP levels at day 90 was 9% in the tocilizumab group and 35% in the usual care group (HR = 0.18; 95% CI, 0.04-0.89).
COVID-19 vaccine benefits still outweigh risks, despite possible rare heart complications
American Heart Association, May 23, 2021
Late last week, the U.S. Centers for Disease Control and Prevention (CDC) alerted health care professionals that they are monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of young adults developing the rare heart-related complication myocarditis, after receiving a COVID-19 vaccine manufactured by Pfizer-BioNTech or Moderna. The COVID-19 Vaccine Safety Technical Work Group (VaST) of the CDC’s Advisory Committee on Immunization Practices (ACIP) is reviewing several dozen cases of myocarditis that have been reported in adolescents and young adults: more often in males rather than females; more frequently after the second dose rather than the first dose of either the Pfizer-BioNTech or Moderna vaccine; and typically appearing within 4 days of vaccination. The benefits of COVID-19 vaccination enormously outweigh the rare, possible risk of heart-related complications, including inflammation of the heart muscle, or myocarditis. The American Heart Association/American Stroke Association, a global force for longer, healthier lives, urges all adults and children ages 12 and older in the U.S. to receive a COVID vaccine as soon as they can.
Greater Burden of COVID-19 on Families of Color, Families of Children With Asthma
Pulmonology Advisor, May 21, 2021
Families of color and families of children with asthma have suffered greater COVID-19 pandemic-related consequences compared with non-Hispanic White (NHW) families, according to results of a study recently published in Journal of Pediatric Psychology. While the adverse effects of COVID-19 are pervasive, it appears that the burden has been greater for parents of children with chronic medical conditions and for Black, Indigenous, or other People of Color (BIPOC) families. Previous studies have suggested that social determinants of health (SDOH) such as discrimination, poverty, access to health care and housing have highlighted ethnic/racial disparities and are linked to negative outcomes in both COVID-19 patients and in patients with asthma. However, there have been limited studies specifically investigating the psychosocial burden on BIPOC families and on families of children with asthma. The goal of this study was to quantify group differences in SDOH and psychosocial impacts of COVID-19 in 4 groups: NWH parents of children with asthma, NWH parents of healthy children (referent), BIPOC parents of children with asthma, and BIPOC parents of healthy children. A total of 321 participants were recruited using the crowdsourcing participant panel Prolific. Parents completed the COVID-19 Adolescent Symptoms and Psychological Experience Questionnaire-Parent (CASPE-P) and the Mental Health Impacts module and the Coronavirus Impacts and Pandemic Stress module from the Johns Hopkins University COVID-19 Community Response Survey. In terms of differences across the 4 groups in SDOH, food insecurity was more likely among BIPOC parents of children with asthma vs NHW parents of healthy children. Discrimination was experienced more in both BIPOC groups compared with NHW parents of healthy children. BIPOC parents of children with asthma (P =.08) and BIPOC parents of healthy children (P =.01) were more likely to feel they would have received better health care if they were of a different race or ethnicity vs NHW parents of healthy children.
Risk factors for persistent abnormality on chest radiographs at 12-weeks post hospitalisation with PCR confirmed COVID-19
Respiratory Research, May 21, 2021
The long-term consequences of COVID-19 remain unclear. There is concern a proportion of patients will progress to develop pulmonary fibrosis. We aimed to assess the temporal change in CXR infiltrates in a cohort of patients following hospitalisation for COVID-19. We conducted a single-centre prospective cohort study of patients admitted to University Hospital Southampton with confirmed SARS-CoV2 infection between 20th March and 3rd June 2020. Patients were approached for standard-of-care follow-up 12-weeks after hospitalisation. Inpatient and follow-up CXRs were scored by the assessing clinician for extent of pulmonary infiltrates; 0–4 per lung (Nil = 0, < 25% = 1, 25–50% = 2, 51–75% = 3, > 75% = 4). 101 patients with paired CXRs were included. Demographics: 53% male with a median (IQR) age 53.0 (45–63) years and length of stay 9 (5–17.5) days. The median CXR follow-up interval was 82 (77–86) days with median baseline and follow-up CXR scores of 4.0 (3–5) and 0.0 (0–1) respectively. 32% of patients had persistent CXR abnormality at 12-weeks. In multivariate analysis length of stay (LOS), smoking-status and obesity were identified as independent risk factors for persistent CXR abnormality. Serum LDH was significantly higher at baseline and at follow-up in patients with CXR abnormalities compared to those with resolution. A 5-point composite risk score (1-point each; LOS ≥ 15 days, Level 2/3 admission, LDH > 750 U/L, obesity and smoking-status) strongly predicted risk of persistent radiograph abnormality (0.81).
Monoclonal antibody cocktail cut COVID-19 hospitalization, death by 70% in outpatient setting
Healio | Pulmonology, May 17, 2021
A cocktail of two monoclonal antibodies — casirivimab and imdevimab — significantly reduced the risk for hospitalization or death in nonhospitalized patients with COVID-19, according to results of a phase 3 pivotal trial. Casirivimab with imdevimab (REGEN-COV, Regenerson) also shortened symptom duration and reduced viral load, researchers reported during a breaking news session at the American Thoracic Society International Conference. “In this phase 3 study [of] patients with confirmed COVID-19, a single IV dose of casirivimab with imdevimab compared with placebo significantly reduced hospitalizations or death by 70%, significantly shortened duration of symptoms by 4 days and the results were consistent across subgroups, including those with high baseline viral load who have been shown to have a poor prognosis with higher incidence of hospitalizations and longer symptom duration,” Julie Philley, MD, pulmonary critical care physician and chair of internal medicine at the University of Texas Health Sciences Center, Houston, said during the presentation. The trial evaluated two REGEN-COV doses: 2,400 mg and 1,200 mg. The 2,400 mg dose is currently authorized for emergency use by the FDA and the lower dose is under evaluation, according to a company press release. Patients were randomly assigned to receive casirivimab plus imdevimab at 2,400 mg or 1,200 mg or placebo within 7 days of symptom onset and within 72 hours of a positive SARS-CoV-2 test. Follow-up was 28 days. During follow-up, patients underwent nasal swabs and daily electronic clinical outcomes assessment and were monitored for safety with medically attended visits.
Pathophysiological Association of Endothelial Dysfunction with Fatal Outcome in COVID-19
International Journal of Molecular Sciences, May 12, 2021
The outbreak of coronavirus disease 2019 (COVID-19) caused by the betacoronavirus SARS-CoV-2 is now a worldwide challenge for healthcare systems. Although the leading cause of mortality in patients with COVID-19 is hypoxic respiratory failure due to viral pneumonia and acute respiratory distress syndrome, accumulating evidence has shown that the risk of thromboembolism is substantially high in patients with severe COVID-19 and that a thromboembolic event is another major complication contributing to the high morbidity and mortality in patients with COVID-19. Endothelial dysfunction is emerging as one of the main contributors to the pathogenesis of thromboembolic events in COVID-19. Endothelial dysfunction is usually referred to as reduced nitric oxide bioavailability. However, failures of the endothelium to control coagulation, inflammation, or permeability are also instances of endothelial dysfunction. Recent studies have indicated the possibility that SARS-CoV-2 can directly infect endothelial cells via the angiotensin-converting enzyme 2 pathway and that endothelial dysfunction caused by direct virus infection of endothelial cells may contribute to thrombotic complications and severe disease outcomes in patients with COVID-19. In this review, we summarize the current understanding of relationships between SARS-CoV-2 infection, endothelial dysfunction, and pulmonary and extrapulmonary complications in patients with COVID-19.
Pulmonary arterial hypertension post COVID-19: A sequala of SARS-CoV-2 infection?
Respiratory Medicine Case Reports, May 12, 2021
[Case Report] It has been suggested that pulmonary arterial hypertension (PAH) could be a potential sequela of coronavirus disease 2019 (COVID-19) in particular in those with hypertension; however, development of PAH after the course of COVID-19 in normotensive individuals are rarely reported. Here, we report a patient who developed PAH two months post-COVID-19. The patient was a 55-year-old female and normotensive, tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developed mild respiratory distress syndrome and necessitated continuous positive airway pressure during the treatment in the hospital. After two months discharged from the hospital with RT-PCR negative for SARS-CoV-2, the patient presented with exertional dyspnea, dry cough, fatigue and episodes of syncope during exertion. Based on clinical presentation, electrocardiography, computed tomography, and transthoracic echocardiography assessment, PAH diagnosis was made. To our knowledge, this is a rare PAH case and this highlights the possible of PAH as sequala that might present in post COVID-19 patients.
COVID-19 pandemic and coronary angiography for ST-elevation myocardial infarction, use of mechanical support and mechanical complications in Canada; a Canadian Association of Interventional Cardiology national survey
CJC Open, May 12, 2021
As a result of the COVID-19 pandemic first wave, reductions in STEMI invasive care ranging from 23% to 76% have been reported from various countries. Whether it had any impact on coronary angiography (CA) volume or on mechanical support device use for ST-elevation myocardial infarction (STEMI) and post-STEMI mechanical complications in Canada is unknown. We administered a Canada-wide survey to all Cardiac Catheterization Laboratory Directors seeking the volume of CA for STEMI performed during 01/03/2020-31/05/2020 (pandemic period) and from two control periods (01/03/2019-31/05/2019 and 01/03/2018-31/05/2018). The number of left ventricular support devices used, as well as the number of ventricular septal defects or papillary muscle rupture cases diagnosed, were also recorded. We also assessed if the number of COVID-19 cases recorded in each province was associated with STEMI CA volume. Forty-one out of 42 Canadian catheterization laboratories (98%) provided data. There was a modest but statistically significant 16% reduction (Incidence Rate Ratio or IRR 0.84; 95%CI 0.80-0.87) in CA for STEMI during the first wave of the pandemic compared to control periods. IRR was not associated with provincial COVID-19 caseload. We observed a 26% reduction (IRR 0.74; 95%CI 0.61-0.89) in the use of intra-aortic balloon pump in STEMI. Use of Impella® and mechanical complications from STEMI were exceedingly rare. We observed a modest 16% decrease in CA for STEMI during the pandemic first wave in Canada, lower than reported in other countries.
COVID-19 after lung resection in Northern Italy
Seminars in Thoracic and Cardiovascular Surgery, May 11, 2021
We reviewed surgical cases from 4 Thoracic Surgery departments in the Lombardia region of Italy, the area mostly affected by Coronavirus pandemic in Europe, with the aim to describe the impact of COVID-19 on the treatment of thoracic surgical patients. Clinical, radiological and laboratory data from patients who underwent lung resection from December 2019 to March 2020 were retrospectively collected until June 2020. Univariable Cox regression models were estimated to evaluate potential prognostic factors for developing COVID-19 and to investigate postoperative mortality among patients who developed symptomatic COVID-19 infection. We examined data from 107 patients. (74 lobectomies, 32 wedge/segmentectomies and 1 pneumonectomy). Twelve patients developed COVID-19 (Group 1), whereas 95 patients were not infected (Group 2). In Group 1, six patients (50%) died from complications related to infection; in Group 2, one patient (1%) died because of non-COVID-19-related causes. Median days from surgery to first symptoms, CT confirmation, clinical confirmation and PCR positivity was 48.1, 54.3, 55.1 and 55.2 respectively. At univariable analysis, DLCO/VA% (p=0.008), duration of the surgery (p=0.009), smoking history (pack/year) (p<0.001), BMI (p<0.001) and number of segments resected (p=0.010) were associated with COVID-19 onset. Moreover, CCI (p<0.001), DLCO/VA% (p=0.002), cigarette pack/year (p<0.001), BMI (p<0.001) and COVID-19 (p<0.001) were associated with death. Patients who undergo lung resection and then develop symptomatic COVID-19 infection are at higher risk of developing severe respiratory complications and postoperative death. Insidious symptoms’ onset may lead to a delay in diagnosis. We suggest two mitigating strategies: 1) Improve symptoms surveillance and isolation during recovery period, 2) Be aware of a potential greater risk of developing symptomatic COVID-19 and death correlated with elevated CCI, BMI, smoking history, DLCO/VA%, number of resected segments and duration of surgery.
COVID-19-Associated ARDS Can Be Treated With Extracorporeal Membrane Oxygenation
Pulmonology Advisor, May 7, 2021
COVID-19-associated acute respiratory distress syndrome (ARDS) can be efficiently treated with extracorporeal membrane oxygenation (ECMO), according to the findings of a multicenter cohort study published in The Lancet Respiratory Medicine. In France, ECMO for severe ARDS was considered early on during the COVID-19 pandemic even though early reports from China indicated unfavorable outcomes and some argued that ECMO could even be deleterious. Therefore, researchers conducted a study to analyze 302 adult patients with laboratory-confirmed SARS-CoV-2 infection and severe ARDS requiring ECMO who were admitted to 17 intensive care units (ICU) within the Greater Paris area between March 8, 2020, and June 3, 2020. The researchers reported on the characteristics and 90-day clinical outcomes of patients who received ECMO for SARS-CoV-2 infection. Before ECMO, 285 (94%) patients were placed in the prone position, median driving pressure was 18 cm H2O, and median ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen was 61 mm Hg. During ECMO, 43% (115/270) patients had a major bleeding event, 43% (130/301) patients received renal replacement therapy, and 18% (53/294) had a pulmonary embolism. A total of 46% (138/302) of patients were alive 90 days after ECMO.
Intravenous Immunoglobulin Efficacious in Treating Moderate COVID-19 Pneumonia
Pulmonology Advisor, May 6, 2021
Patients with moderate pneumonia due to COVID-19 showed significant clinical improvement with intravenous immunoglobulin (IVIG) in addition to standard of care treatment compared with standard of care treatment alone, according to a small study published in the Journal of Infectious Diseases. In this randomized, open-label, phase 2 study, patients across 4 centers in India were randomly assigned in a 1:1 ratio to receive either IVIG plus standard of care treatment (experimental group, n=50) or standard of care treatment alone (control group, n=50) to determine the safety and efficacy of IVIG therapy for treating moderate COVID-19 pneumonia. The primary outcome was the number of days of hospitalization. Secondary outcomes included number of days on mechanical ventilation, days until cessation of cough, duration of stay at an intensive care unit, and the number of days it took to achieve normal body temperature, oxygen level, and respiratory rate. Of the 100 patients included in the study, 67% were men and the mean age was 48.7 years. The 2 groups were similar in age, sex, BMI, and comorbidity distribution. In addition, there was no difference in hematological and biochemical parameters both at baseline and end of study, which was 28 days from initiation of treatment.
The Reign of the Ventilator: Acute Respiratory Distress Syndrome, COVID-19, and Technological Imperatives in Intensive Care
Annals of Internal Medicine, May 4, 2021
In the early phase of the COVID-19 pandemic, a dispute arose as to whether the disease caused a typical or atypical version of acute respiratory distress syndrome (ARDS). This essay recounts the emergence of ARDS and places it in the context of the technological transformation of modern hospital care—particularly the emergence of intensive care after the 1952 Copenhagen polio epidemic. The polio epidemic seemed to show the value of manual positive-pressure ventilation, leading to the proliferation of mechanical ventilators and the expansion of intensive care units in the 1960s. This created the conditions of possibility for ARDS to be described and institutionalized within modern intensive care. Yet the centrality of the ventilator to descriptions and definitions of ARDS quickly made it difficult to conceive of the disorder outside the framework of mechanical ventilation and blood gas levels, or to acknowledge the degree to which the ventilator was a source of iatrogenic injury and complications. Moreover, the imperative to understand and treat ARDS with mechanical ventilation set the stage for the early confusion about whether patients with COVID-19 should receive mechanical ventilation. This history offers many crucial lessons about how new technologies can lead to new and valuable therapies but can also subtly shape and constrain medical thinking. Moreover, ventilators not only changed how respiratory disorders were conceived; they also brought new forms of respiratory illness into existence.
SARS-CoV-2 reinfection milder than primary infection in US study
Helio | Infectious Disease News, May 4, 2021
SARS-CoV-2 reinfection was uncommon and milder than primary infection but was associated with two deaths, according to findings from a U.S. study published in Clinical Infectious Diseases. “Reinfection remains a possibility in survivors of initial SARS-CoV-2 infection and should be considered if [the] clinical picture is consistent with SARS-CoV-2 infection,” Adnan I. Qureshi MD, professor of clinical neurology at the University of Missouri, told Healio. “Therefore, policies regarding face masks, social distancing and vaccination apply to survivors of initial SARS-CoV-2 infection as well,” Qureshi said. “The results also indirectly suggest that vaccination may not provide complete immunity over a long period of time and periodic boosters may be necessary.” According to the results, reinfection occurred in 0.7% (95% CI, 0.15%-0.9%) of patients, with an average gap between positive tests of 116 ± 21 days. They found that asthma (OR = 1.9; 95% CI, 1.1-3.2) and nicotine dependence or tobacco use (OR = 2.7; 95% CI, 1.6-4.5) were associated with reinfection. Qureshi said that the reinfection rate observed in this study is similar to rates observed in studies from the United Kingdom, Denmark and Qatar, but regional differences including immunization, COVID-19 protocols, the prevalence of variants and population density mean it is “very important to get data from each region.”
Critically Ill COVID-19 Patients Are at High Risk for Hospital-Acquired Infections
Pulmonology Advisor, May 4, 2021
Critically ill patients with COVID-19 are at high risk for hospital-acquired infections (HAIs), particularly ventilator-associated pneumonias (VAPs) and bloodstream infections (BSIs), and therefore clinicians should make every effort to implement protocols for surveillance and prevention of infectious complications, according to study results published in CHEST. Few small studies have described HAIs during COVID-19; therefore, researchers sought to determine the characteristics associated with HAIs and how HAIs relate to outcomes in critically ill patients with COVID-19. The researchers conducted a retrospective analysis of prospectively collected data in adult patients with severe COVID-19 admitted to the intensive care units (ICU) of 8 Italian hospitals. Among 774 patients, 359 (46%) patients developed 759 HAIs (44.7 infections/1000 ICU patient-days), 35% of which were caused by multidrug resistant (MDR) bacteria. Ventilator-associated pneumonias (n=389; 51%), BSIs (n=257; 34%), and catheter-related bloodstream infections (CRBSIs; n=74; 10%) were the most frequent HAIs, with 26.0 VAPs per 1000 patient intubation-days, 11.7 BSIs per 1000 ICU patient-days, and 4.7 CRBSIs per 1000 patient-days. “Critically ill COVID-19 patients are at high risk for HAIs, especially VAP and BSIs, frequently caused by [MDR] bacteria,” the study authors wrote. “Patients with HAIs complicated by shock had almost doubled mortality, and infected patients had prolonged [invasive mechanical ventilation] and hospitalization.”
Study identifies two distinct phenotypes of COVID-19-associated ARDS
Helio | Pulmonology, April 30, 2021
Researchers identified distinct phenotypes of COVID-19-associated acute respiratory distress syndrome were that have substantial differences in their response to disease and risk for mortality. “The motivation for our work is that if we can identify subsets of patients with different biochemical characteristics, and then those patients respond differently to treatment or have different clinical outcomes, we would be one step closer to a more mechanism-based understanding of ARDS,” Sylvia Ranjeva, MD, PhD, investigator in the department of anesthesia, critical care and pain medicine at Massachusetts General Hospital, said in a press release. Researchers collected clinical and biochemical data from 263 patients (mean age, 58.8 years; 66.5% men) admitted to the ICU at Massachusetts General Hospital with COVID-19-associated ARDS from March to August 2020. To identify distinct phenotypes, researchers used latent class modeling via a multivariate mixture model in the cohort. There were substantial differences in the biochemical profiles of the two distinct phenotypes of COVID-19-associated ARDS that were identified. Seventy patients (26.6%) had the minority class 2 phenotype, with increased biomarker levels in the bloodstream that indicated blood-clotting disorders (D-dimer: 2,335 ng/L vs. 1,326 ng/L; P < .001), higher inflammation (prothrombin time: 17.2 seconds vs. 14.2 seconds; P < .001) and organ dysfunction (pH: 7.34 vs. 7.36; P = .046) compared with 193 patients (72.2%) who had the class 1 phenotype. Among the class 2 phenotype, odds for 28-day mortality were more than double that of the class 1 phenotype (40% vs. 23.3%; OR = 2.2; 95% CI, 1.2-3.9).
Extracorporeal Membrane Oxygenation Instead of Invasive Mechanical Ventilation in a Patient with Severe COVID-19-associated Acute Respiratory Distress Syndrome
American Journal of Respiratory and Critical Care Medicine, April 26, 2021
Venovenous-extracorporeal membrane oxygenation (VV-ECMO) has been used as a rescue therapy for patients with refractory coronavirus disease 2019 (COVID-19)-associated severe acute respiratory distress syndrome (ARDS) with survival rates similar to those reported for ECMO support of ARDS of other causes. However, the need for prolonged ventilation, sedation, and immobility may limit long-term benefits of ECMO in these patients. Specifically, they are exposed to a high risk of ventilator-associated pneumonia. According to a recent case-series, single-access, dual-stage VV-ECMO with extubation on ECMO (median time to extubation: 13 days) appeared to be safe and associated with a favourable prognosis for patients with severe COVID-19–associated ARDS. VV-ECMO has anecdotally been applied as an alternative to invasive mechanical ventilation (MV) in awake, spontaneously-breathing patients with ARDS caused by Pneumocystis pneumonia (5) or immunocompromised status (6). We report herein a COVID-19 patient, with severe ARDS not responding to high-flow nasal oxygen and noninvasive ventilation (NIV), who was successfully treated with prolonged “awake ECMO”, thereby avoiding endotracheal intubation and MV.
Bamlanivimab Monotherapy No Longer Authorized for COVID-19 Treatment
Pulmonary Advisor, April 26, 2021
The Food and Drug Administration (FDA) has revoked the Emergency Use Authorization (EUA) for bamlanivimab, an investigational monoclonal antibody therapy, for use as monotherapy in the treatment of mild to moderate COVID-19, based on emerging data suggesting an increased frequency of resistant SARS-CoV-2 variants. In November 2020, the FDA issued an EUA for bamlanivimab monotherapy for the treatment of mild to moderate COVID-19 in adults and pediatric patients with positive results of direct SARS-CoV-2 viral testing who are 12 years of age and older weighing at least 40kg, and who are at high risk for progressing to severe COVID-19 and/or hospitalization. However, the Agency has determined that the known and potential benefits of bamlanivimab monotherapy no longer outweigh the known and potential risks for its authorized use. According to recent data from the Centers for Disease Control and Prevention’s (CDC) national surveillance program, there has been an increase in the frequency of SARS-CoV-2 variants that are expected to be resistant to bamlanivimab. As of mid-March 2021, the CDC reported that roughly 20% of the viruses sequenced in the US were observed to be resistant to bamlanivimab monotherapy, an increase from approximately 5% seen in mid-January 2021. At this time, there are no testing technologies available to healthcare providers to aid in the detection of these variants prior to initiating monoclonal antibody therapy.
Comprehensive evaluation of bronchoalveolar lavage from patients with severe COVID-19 and correlation with clinical outcomes
Human Pathology, April 24, 2021
Information on bronchoalveolar lavage (BAL) in patients with COVID-19 is limited, and clinical correlation has not been reported. This study investigated the key features of BAL fluids from COVID-19 patients and assessed their clinical significances. A total of 320 BAL samples from 83 COVID-19 patients and 70 non-COVID-19 patients (27 patients with other respiratory viral infections) were evaluated, including cell count/differential, morphology, flow cytometric immunophenotyping and immunohistochemistry. The findings were correlated with clinical outcomes. Compared to non-COVID-19 patients, BAL from COVID-19 patients was characterized by significant lymphocytosis (p<0.001), in contrast to peripheral blood lymphopenia commonly observed in COVID-19 patients, and the presence of atypical lymphocytes with plasmacytoid/plasmablastic features (p<0.001). Flow cytometry and immunohistochemistry demonstrated that BAL lymphocytes, including plasmacytoid and plasmablastic cells, were composed predominantly of T cells with a mixture of CD4+ and CD8+ cells. Both populations had increased expression of T-cell activation markers, suggesting important roles of helper and cytotoxic T-cells in immune response to SARS-CoV-2 infection in the lung. More importantly, BAL lymphocytosis was significantly associated with longer hospital stay (p<0.05) and longer requirement for mechanical ventilation (p<0.05), whereas the median atypical (activated) lymphocyte count was associated with shorter hospital stay (p<0.05), shorter time on mechanical ventilation (p<0.05) and improved survival. Our results indicate that BAL cellular analysis and morphologic findings provide additional important information for diagnostic and prognostic work-up, and potential new therapeutic strategies for patients with severe COVID-19.
SARS-CoV-2 serology increases diagnostic accuracy in CT-suspected, PCR-negative COVID-19 patients during pandemic
Respiratory Research, April 23, 2021
In the absence of PCR detection of SARS-CoV-2 RNA, accurate diagnosis of COVID-19 is challenging. Low-dose computed tomography (CT) detects pulmonary infiltrates with high sensitivity, but findings may be non-specific. This study assesses the diagnostic value of SARS-CoV-2 serology for patients with distinct CT features but negative PCR. IgM/IgG chemiluminescent immunoassay was performed for 107 patients with confirmed (group A: PCR + ; CT ±) and 46 patients with suspected (group B: repetitive PCR-; CT +) COVID-19, admitted to a German university hospital during the pandemic’s first wave. A standardized, in-house CT classification of radiological signs of a viral pneumonia was used to assess the probability of COVID-19. Seroconversion rates (SR) determined on day 5, 10, 15, 20 and 25 after symptom onset (SO) were 8%, 25%, 65%, 76% and 91% for group A, and 0%, 10%, 19%, 37% and 46% for group B, respectively; (p < 0.01). Compared to hospitalized patients with a non-complicated course (non-ICU patients), seroconversion tended to occur at lower frequency and delayed in patients on intensive care units. SR of patients with CT findings classified as high certainty for COVID-19 were 8%, 22%, 68%, 79% and 93% in group A, compared with 0%, 15%, 28%, 50% and 50% in group B (p < 0.01). SARS-CoV-2 serology established a definite diagnosis in 12/46 group B patients. In 88% (8/9) of patients with negative serology > 14 days after symptom onset (group B), clinico-radiological consensus reassessment revealed probable diagnoses other than COVID-19. Sensitivity of SARS-CoV-2 serology was superior to PCR > 17d after symptom onset. Implementation of SARS-CoV-2 serology testing alongside current CT/PCR-based diagnostic algorithms improves discrimination between COVID-19-related and non-related pulmonary infiltrates in PCR negative patients.
Human nasal and lung tissues infected ex vivo with SARS-CoV-2 provide insights into differential tissue-specific and virus-specific innate immune responses in the upper and lower respiratory tract
Journal of Virology, April 23, 2021
The nasal-mucosa constitutes the primary entry site for respiratory viruses including SARS-CoV-2. While the imbalanced innate immune response of end-stage COVID-19 has been extensively studied, the earliest stages of SARS-CoV-2 infection at the mucosal entry site have remained unexplored. Here we employed SARS-CoV-2 and influenza virus infection in native multi-cell-type human nasal turbinate and lung tissues ex vivo, coupled with genome-wide transcriptional analysis, to investigate viral susceptibility and early patterns of local-mucosal innate immune response in the authentic milieu of the human respiratory tract. SARS-CoV-2 productively infected the nasal turbinate tissues, predominantly targeting respiratory epithelial cells, with rapid increase in tissue-associated viral sub-genomic mRNA, and secretion of infectious viral progeny. Importantly, SARS-CoV-2 infection triggered robust antiviral and inflammatory innate immune responses in the nasal mucosa. The upregulation of interferon stimulated genes, cytokines and chemokines, related to interferon signaling and immune-cell activation pathways, was broader than that triggered by influenza virus infection. Conversely, lung tissues exhibited a restricted innate immune response to SARS-CoV-2, with a conspicuous lack of type I and III interferon upregulation, contrasting with their vigorous innate immune response to influenza virus. Our findings reveal differential tissue-specific innate immune responses in the upper and lower respiratory tract, that are distinct to SARS-CoV-2. The studies shed light on the role of the nasal-mucosa in active viral transmission and immune defense, implying a window of opportunity for early interventions, whereas the restricted innate immune response in early-SARS-CoV-2-infected lung tissues could underlie the unique uncontrolled late-phase lung damage of advanced COVID-19.
Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19
New England Journal of Medicine, April 22, 2021
The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support–free days, on an ordinal scale combining in-hospital death (assigned a value of −1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support–free days, or both. Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support–free days was 10 (interquartile range, −1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, −1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists.
Incidence and Risk Factors for Secondary Pulmonary Infections in Patients Hospitalized with Coronavirus Disease 2019 Pneumonia
American Journal of the Medical Sciences, April 20, 2021
Secondary pulmonary infections (SPI) have not been well described in COVID-19 patients. Our study aims to examine the incidence and risk factors of SPI in hospitalized COVID-19 patients with pneumonia. This was a retrospective, single-center study of adult COVID-19 patients with radiographic evidence of pneumonia admitted to a regional tertiary care hospital. SPI was defined as microorganisms identified on the respiratory tract with or without concurrent positive blood culture results for the same microorganism obtained at least 48 hours after admission. Thirteen out of 244 (5%) had developed SPI during hospitalization. The median of the nadir lymphocyte count during hospitalization was significantly lower in patients with SPI as compared to those without SPI [0.4 K/uL (IQR 0.3-0.5) versus 0.6 K/uL (IQR 0.3-0.9)]. Patients with lower nadir lymphocyte had an increased risk of developing SPI with odds ratio (OR) of 1.21 (95% CI: 1.00 to 1.47, p=0.04) per 0.1 K/uL decrement in nadir lymphocyte. The baseline median inflammatory markers of CRP [166.4 mg/L vs. 100.0 mg/L, p=0.01] and D-dimer (18.5 mg/L vs. 1.4 mg/L, p<0.01), and peak procalcitonin (1.4 ng/mL vs. 0.3 ng/mL, p<0.01) and CRP (273.5 mg/L vs. 153.7 mg/L, p<0.01) during hospitalization were significantly higher in SPI group. The incidence of SPI in hospitalized COVID-19 patients was 5%. Lower nadir median lymphocyte count during hospitalization was associated with an increased OR of developing SPI. The CRP and D-dimer levels on admission, and peak procalcitonin and CRP levels during hospitalization were higher in patients with SPI.
Appraising the Real-Life Need for ECMO During the COVID-19 Pandemic
American Journal of Respiratory and Critical Care Medicine, April 19, 2021
The coronavirus disease 2019 (COVID-19) has become the leading cause of acute respiratory distress syndrome (ARDS) worldwide since January 2020. In a recent meta-analysis of 69 studies including 57,420 adult patients requiring invasive mechanical ventilation (MV) for COVID-19, the overall case fatality rate was estimated as 45% (95%CI 39-52%), and was higher than in the LUNGSAFE cohort (40%, 95%CI, 38-42%). Since the publication of the EOLIA trial, and its post-hoc Bayesian analysis, veno-venous extracorporeal membrane oxygenation (ECMO) has increasingly been used for patients with severe ARDS. As the COVID-19 pandemic drastically increased the demand for ECMO, data on the outcomes of this very specific population were eagerly awaited. In the largest series published to date, including 1035 COVID-19 patients from the Extracorporeal Life Support Organization (ELSO) registry, originating from 213 hospitals in 36 countries, the estimated 90-day probability of mortality was 37% (95% CI 34–40). It was 36% (95% CI 27-48), in a cohort of 83 ECMO-treated patients at the Paris-Sorbonne University hospitals in France. More recently, the 60-day mortality of 190 ECMO-treated COVID-19 ARDS in 55 centers in the USA was 33%. The authors performed an emulated target trial in this cohort, comparing patients initiated on ECMO in the first 7 days of ICU admission with those who did not receive ECMO, with lower mortality in the ECMO group (HR 0.55; 95% CI 0.41-0.74). This is the first cohort study evaluating the need for ECMO in COVID-19-related ARDS at a national level, in a country which has developed a coordinated national ECMO program, using data from comprehensive national databases of mechanically ventilated and ECMO-treated patients. During the study period, 13 ECMO centers were commissioned by the Chilean National Advisory Commission to provide ECMO in adult COVID-19 patients.
FDA rescinds EUA for bamlanivimab monotherapy as COVID-19 treatment
Infectious Disease News, April 16, 2021
The FDA has rescinded the emergency use authorization for bamlanivimab monotherapy for the treatment of mild-to-moderate COVID-19 in adults and certain children. The emergency use authorization (EAU) has been revoked because of the sustained increase in COVID-19 viral variants that are resistant to bamlanivimab (Eli Lilly) alone, resulting in treatment failure, according to an FDA-issued press release. Last year, the FDA issued an EUA to Eli Lilly for the emergency use of bamlanivimab, a monoclonal antibody, alone. Eli Lilly has now requested the FDA to revoke the EUA because they want to focus on the combination of bamlanivimab and etesevimab. Alternative monoclonal antibody therapies remain available under EUA for this same indication. These include the combination of casirivimab (REGN10933, Regeneron Pharmaceuticals) and imdevimab (REGN10987, Regeneron Pharmaceuticals), or REGEN-COV, and bamlanivimab combined with etesevimab, according to the FDA.
Lung Recruitability Evaluated by Recruitment-to-Inflation Ratio and Lung Ultrasound in COVID-19 Acute Respiratory Distress Syndrome
American Journal of Respiratory and Critical Care Medicine, April 15, 2021
A substantial proportion of patients with COVID-19 admitted to the ICU require invasive mechanical ventilation for acute respiratory distress syndrome (ARDS), which is still associated with a high mortality rate. Applying the optimal positive end-expiratory pressure (PEEP) to ensure lung recruitment while limiting lung hyperinflation remains challenging in ARDS. Yet, there are a few simple tools that might help personalize the level of PEEP in those patients at the bedside. Among them, the lung ultrasound (LUS) aeration score and the recruitment-to-inflation (R/I) ratio have the potential to identify patients who are more likely to benefit from PEEP. Previous studies suggested that LUS could assess spatial distribution of PEEP-induced lung recruitment but does not reliably detect hyperinflation. The R/I ratio is a tool that has recently been developed to evaluate both the potential for lung recruitment and the risk for hyperinflation, but it does not provide regional information about lung recruitment. Therefore, these two tools, readily available at the bedside in most ICUs, could provide additive and complementary information on lung recruitment. In the present study, we aimed to assess lung recruitability simultaneously by the R/I ratio and the LUS in patients with COVID-19–related ARDS. We conducted a prospective observational study in a 26-bed university-affiliated ICU in Lyon, France, which was approved by our institutional ethics committee. Consecutive adult patients with COVID-19–associated ARDS in whom PEEP-induced lung recruitment was assessed simultaneously with both the LUS and the R/I ratio within the first 48 hours after intubation were included. COVID-19 was biologically confirmed and ARDS diagnosis was based on the Berlin criteria. Ventilator settings and respiratory mechanics were recorded in sedated and curarized patients, ventilated in volume control with an Evita XL respirator. All measurements were performed in patients in the semirecumbent position. The presence of complete airway closure was assessed by measuring the airway opening pressure (AOP), as previously described.
Impact of COVID-19 on Interventional Pulmonology Training
ATS Scholar, April 13, 2021
The impact of the coronavirus disease (COVID-19) pandemic extends beyond the realms of patient care and healthcare resource use to include medical education; however, the repercussions of COVID-19 on the quality of training and trainee perceptions have yet to be explored. The purpose of this study was to determine the degree of interventional pulmonology (IP) fellows’ involvement in the care of COVID-19 and its impact on fellows’ clinical education, procedure skills, and postgraduation employment search. An internet-based survey was validated and distributed among IP fellows in North American fellowship training programs. Of 40 eligible fellows, 38 (95%) completed the survey. A majority of fellows (76%) reported involvement in the care of patients with COVID-19. Fellows training in the Northeast United States reported involvement in the care of a higher number of patients with COVID-19 than in other regions (median, 30 [interquartile range, 20–50] vs. 10 [5–13], respectively; P < 0.01). Fifty-two percent of fellows reported redeployment outside IP during COVID-19, mostly into intensive care units. IP procedure volume decreased by 21% during COVID-19 compared with pre–COVID-19 volume. This decrease was mainly accounted for by a reduction in bronchoscopies. A majority of fellows (82%) reported retainment of outpatient clinics during COVID-19 with the transition from face-to-face to telehealth-predominant format. Continuation of academic and research activities during COVID-19 was reported by 86% and 82% of fellows, respectively. After graduation, all fellows reported having secured employment positions. Although IP fellows were extensively involved in the care of patients with COVID-19, most IP programs retained educational activities through the COVID-19 outbreak. The impact of the decrease in procedure volume on trainee competency would be best addressed individually within each training program. These data may assist in focusing efforts regarding the education of medical trainees during the current and future healthcare crises.
Bioinformatics and system biology approach to identify the influences of SARS-CoV-2 infections to idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease patients
Briefings in Bioinformatics, April 13, 2021
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), better known as COVID-19, has become a current threat to humanity. The second wave of the SARS-CoV-2 virus has hit many countries, and the confirmed COVID-19 cases are quickly spreading. Therefore, the epidemic is still passing the terrible stage. Having idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are the risk factors of the COVID-19, but the molecular mechanisms that underlie IPF, COPD, and CVOID-19 are not well understood. Therefore, we implemented transcriptomic analysis to detect common pathways and molecular biomarkers in IPF, COPD, and COVID-19 that help understand the linkage of SARS-CoV-2 to the IPF and COPD patients. Here, three RNA-seq datasets (GSE147507, GSE52463, and GSE57148) from Gene Expression Omnibus (GEO) is employed to detect mutual differentially expressed genes (DEGs) for IPF, and COPD patients with the COVID-19 infection for finding shared pathways and candidate drugs. A total of 65 common DEGs among these three datasets were identified. Various combinatorial statistical methods and bioinformatics tools were used to build the protein–protein interaction (PPI) and then identified Hub genes and essential modules from this PPI network. Moreover, we performed functional analysis under ontologies terms and pathway analysis and found that IPF and COPD have some shared links to the progression of COVID-19 infection. Transcription factors–genes interaction, protein–drug interactions, and DEGs-miRNAs coregulatory network with common DEGs also identified on the datasets. We think that the candidate drugs obtained by this study might be helpful for effective therapeutic in COVID-19.
The Utility of Chest CT imaging in suspected or diagnosed COVID-19 Patients – a review of literature
CHEST, April 13, 2021
The COVID-19 pandemic has had devastating medical and economic consequences globally. The severity of COVID-19 is related, in a large measure, to the extent of pulmonary involvement. The role of chest CT in the management of patients with COVID-19 has evolved since the onset of the pandemic. Specifically, the description of CT findings, use of CT chest in various acute and subacute settings and its usefulness in predicting chronic disease have been better defined. We performed a review of published data on CT scans in COVID-19 patients. A summary of the range of imaging findings, from typical to less common abnormalities is provided. Familiarity with these findings may facilitate in the diagnosis and management of this disease. A comparison of sensitivity and specificity of CT chest with RT-PCR testing highlights the potential role of CT imaging in difficult to diagnose cases of Covid-19. The utility of CT imaging to assess prognosis, guide management, and identify acute pulmonary complications associated with SARS-COV-2 is highlighted. Beyond the acute stage, it is important for clinicians to recognize pulmonary parenchymal abnormalities, progressive fibrotic lung disease and vascular changes that may be responsible for persistent respiratory symptoms. A large collection of multi institutional images has been included to elucidate the CT findings described.
Cytosorb treatment in severe COVID-19 cardiac and pulmonary disease
European Heart Journal-Case Reports, April 12, 2021
A 75-year-old man was admitted for COVID-19-related respiratory failure (p/F ratio 205 on Day 1). He was treated with intravenous dexamethasone (6 mg per day), enoxaparin (4000 international units once daily), and non-invasive ventilation. Levels of cardiac damage and inflammatory biomarkers, including high-sensitivity troponin T (25 pg/mL, normal values 0–14 pg/mL), N-terminal pro-brain natriuretic peptide (2546 ng/L, normal values 0–125 ng/L), D-dimer (633 ng/mL, normal values 0–500 ng/mL), and interleukin-6 (6768 ng/L, normal values 0–7 ng/L), were significantly elevated. On Days 2 and 3 from admission, the patient received two cycles of tocilizumab therapy (two intravenous bolus of 400 mg over 2 days) but during the following 72 h his clinical conditions deteriorated due to severe respiratory failure with severe hypoxaemia (p/F ratio 95), hypotension, and hypoperfusion. He was intubated and transferred to COVID-19 intensive care. Contrast-enhanced chest computed tomography (CT) showed bilateral ground-glass lesions, subpleural consolidations, pleural effusions, and subsegmental pulmonary embolism. Echocardiography showed normal left ventricular function but signs of acute cor pulmonale with reduced tricuspid annular systolic excursion plane, fractional area change, and right ventricular (RV) longitudinal strain with increased systolic pulmonary artery pressure. Despite treatment with high-dose vasoactive drugs, unfractionated heparins and antibiotics, he developed refractory shock with anuria. Due to the presence of persisting anuria with hyperkaliaemia (6.0 mmol/L), we started continuous renal replacement therapy (CRRT) and immunoadsorption with Cytosorb™ (Cytosorbents Corporation, NJ, USA) system. After 72 h, we observed a significant haemodynamic improvement together with an important decline of inflammatory and cardiac damage markers levels and, due to the presence of spontaneous diuresis with negative fluid balance, we stopped CRRT and immunoadsorption therapy. Control chest CT showed significant reduction of consolidations, pleural effusions and ground-glass lesions, while echocardiography documented significant improvement of RV function. The patient was extubated 3 days later and on Day 14 (p/F ratio 390) transferred to a respiratory rehabilitation centre with stable haemodynamics and no need for CRRT. After 6 months, the patient has completely recovered, with normal RV function.
Broad SARS-CoV-2 cell tropism and immunopathology in lung tissues from fatal COVID-19
Journal of Infectious Diseases, April 10, 2021
COVID-19 patients manifest with pulmonary symptoms reflected by diffuse alveolar damage (DAD), excessive inflammation, and thromboembolism. The mechanisms mediating these processes remain unclear. We performed multicolor staining for SARS-CoV-2 proteins and lineage markers to define viral tropism and lung pathobiology in 5 autopsy cases. Lung parenchyma showed severe DAD with thromboemboli. Viral infection was found in an extensive range of cells including pneumocyte type II, ciliated, goblet, club-like and endothelial cells. Over 90% infiltrating immune cells were positive for viral proteins including macrophages, monocytes, neutrophils, and natural killer (NK), B and T cells. Most but not all infected cells were ACE2-positive. The numbers of infected and ACE2-positive cells are associated with extensive tissue damage. Infected tissues exhibited high inflammatory cells including macrophages, monocytes, neutrophils and NK cells, and low B- but abundant T-cells consisting of mainly T helper cells, few cytotoxic T cells, and no T regulatory cell. Robust interleukin-6 expression was present in most cells, with or without infection. In fatal COVID-19 lungs, there are broad SARS-CoV-2 cell tropisms, extensive infiltrated innate immune cells, and activation and depletion of adaptive immune cells, contributing to severe tissue damage, thromboemboli, excess inflammation and compromised immune responses.
Home oxygen for patients with COVID-19 pneumonia conferred low mortality, readmission
Helio News, April 7, 2021
Patients with COVID-19 pneumonia who were discharged from the hospital on home oxygen had low rates of mortality and readmission within 30 days, according to new data published in JAMA Network Open. “In preparation for the COVID-19 surges this past year, we sought to develop a formal home oxygen program that would enhance patient safety and improve flow through the hospital, to prevent the hospital from being overwhelmed by COVID patients,” Brad Spellberg, MD, chief medical officer at the Los Angeles County-University of Southern California Medical Center, told Healio. “Being in the hospital when one does not need to be is unsafe; hospitals are dangerous places. If we can provide the care the patient needs at home, that is always preferred.” The retrospective cohort study enrolled 621 adults (median age, 51 years; 34.9% women) with COVID-19 pneumonia who received emergency or inpatient care for COVID-19 infection and were discharged on home oxygen from two hospitals in Los Angeles from March to August 2020. Stable patients receiving at least 3 L per minute of oxygen without other indications for inpatient care were discharged with home oxygen equipment, educational resources and nursing follow-up by telephone within 12 to 18 hours of discharge and continued, if indicated. The main outcomes were all-cause mortality and all-cause 30-day readmissions. Twenty-four percent of patients were discharged from the ED and 76% were discharged from inpatient encounters. During a median follow-up of 26 days, the rate of all-cause mortality was 1.3% (95% CI, 0.6-2.5) and the rate of all-cause 30-day readmissions was 8.5% (95% CI, 6.2-10.7) among patients discharged receiving home oxygen.
Hypoxic and pharmacological activation of HIFs inhibits SARS-CoV-2 infection of lung epithelial cells
Cell Reports, April 5, 2021
COVID-19, caused by the novel coronavirus SARS-CoV-2, is a global health issue with more than 2 million fatalities to date. Viral replication is shaped by the cellular microenvironment and one important factor to consider is oxygen tension, where hypoxia inducible factor (HIF) regulates transcriptional responses to hypoxia. SARS-CoV-2 primarily infects cells of the respiratory tract, entering via its Spike glycoprotein binding to angiotensin-converting enzyme (ACE2). We demonstrate that hypoxia and the HIF prolyl hydroxylase inhibitor Roxadustat reduce ACE2 expression and inhibit SARS-CoV-2 entry and replication in lung epithelial cells via a HIF-1α dependent pathway. Hypoxia and Roxadustat inhibit SARS-CoV-2 RNA replication showing that post-entry steps in the viral life cycle are oxygen-sensitive. This study highlights the importance of HIF signaling in regulating multiple aspects of SARS-CoV-2 infection and raises the potential use of HIF prolyl hydroxylase inhibitors in the prevention or treatment of COVID-19.
Current Testing Strategies for SARS-CoV-2 in the United States
Clinical Chemistry, April 5, 2021
Since the discovery and recognition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the official declaration of the coronavirus disease-2019 (COVID-19) pandemic at the beginning of 2020, various different test methodologies have been developed at record speeds and made available for the diagnosis, screening, surveillance, and management of SARS-CoV-2 infection and COVID-19 illness. The rapid scientific developments in the quest to learn and define the mechanisms of SARS-CoV-2 transmission, illness, and recovery, in combination with the public health challenges of a rapidly spreading virus, have forced the healthcare community to adapt continuously to the unfolding pandemic. To help answer some of the questions about how testing is being used and how the in vitro diagnostic industry can help meet diagnostic testing needs, a panel of experts was convened with the objective of gaining critical insights regarding different testing strategies for SARS-CoV-2 in a variety of healthcare, community, congregate, and public health settings. We have invited back a select group of experts who participated in the Scientific Advisory Board to share their perspectives and to provide an update on the current state of testing strategies for SARS-CoV-2 from their respective points of view.
Association between pre-existing respiratory disease and its treatment, and severe COVID-19: a population cohort study
The Lancet | Respiratory Medicine, April 1, 2021
Previous studies suggested that the prevalence of chronic respiratory disease in patients hospitalised with COVID-19 was lower than its prevalence in the general population. The aim of this study was to assess whether chronic lung disease or use of inhaled corticosteroids (ICS) affects the risk of contracting severe COVID-19. In this population cohort study, records from 1205 general practices in England that contribute to the QResearch database were linked to Public Health England’s database of SARS-CoV-2 testing and English hospital admissions, intensive care unit (ICU) admissions, and deaths for COVID-19. All patients aged 20 years and older who were registered with one of the 1205 general practices on Jan 24, 2020, were included in this study. With Cox regression, we examined the risks of COVID-19-related hospitalisation, admission to ICU, and death in relation to respiratory disease and use of ICS, adjusting for demographic and socioeconomic status and comorbidities associated with severe COVID-19. Between Jan 24 and April 30, 2020, 8 256 161 people were included in the cohort and observed, of whom 14 479 (0·2%) were admitted to hospital with COVID-19, 1542 (<0·1%) were admitted to ICU, and 5956 (0·1%) died. People with some respiratory diseases were at an increased risk of hospitalisation (chronic obstructive pulmonary disease [COPD] hazard ratio [HR] 1·54 [95% CI 1·45–1·63], asthma 1·18 [1·13–1·24], severe asthma 1·29 [1·22–1·37; people on three or more current asthma medications], bronchiectasis 1·34 [1·20–1·50], sarcoidosis 1·36 [1·10–1·68], extrinsic allergic alveolitis 1·35 [0·82–2·21], idiopathic pulmonary fibrosis 1·59 [1·30–1·95], other interstitial lung disease 1·66 [1·30–2·12], and lung cancer 2·24 [1·89–2·65]) and death (COPD 1·54 [1·42–1·67], asthma 0·99 [0·91–1·07], severe asthma 1·08 [0·98–1·19], bronchiectasis 1·12 [0·94–1·33], sarcoidosis 1·41 [0·99–1·99), extrinsic allergic alveolitis 1·56 [0·78–3·13], idiopathic pulmonary fibrosis 1·47 [1·12–1·92], other interstitial lung disease 2·05 [1·49–2·81], and lung cancer 1·77 [1·37–2·29]) due to COVID-19 compared with those without these diseases. In another post-hoc analysis, people with two or more prescriptions for ICS in the 150 days before study start were at a slightly higher risk of severe COVID-19 compared with all other individuals (ie, no or one ICS prescription): HR 1·13 (1·03–1·23) for hospitalisation, 1·63 (1·18–2·24) for ICU admission, and 1·15 (1·01–1·31) for death.
Chest radiography predictor of COVID-19 adverse outcomes. A lesson learnt from the first wave
Clinical Radiology, March 31, 2021
The aim of this study was to assess the role of a severity score based on chest radiography (CXR) in predicting the risk of adverse outcomes in coronavirus disease 2019 (COVID-19). Of the patients who presented to Hospital between 21 February and 31 March 2020, patients with a laboratory confirmation of COVID-19 who also underwent a CXR were included in the study. To quantify the extent of lung involvement, each CXR image was given a score ([Blinded] score), ranging from 0 to 24, depending on the presence of reticular pattern and/or ground-glass opacities and/or extensive consolidations in each of the 12 areas in which the lungs were divided. The score was calculated by an expert radiologist, blinded to laboratory tests. The ability of the [Blinded] score to predict hospital admission and mortality, after adjusting for some variables (age; gender; comorbidities; time between symptoms onset and admission), using univariate and multivariate statistical analysis was investigated retrospectively. Among the 554 patients, 115 of which (21%) had a negative CXR, the in-hospital mortality was 16% (90/554). At univariate analysis, age, gender, and comorbidities were significant predictors of mortality and hospital admission. At multivariate analysis, adjusting for age and gender, the [Blinded] score was an independent predictor of mortality and hospitalisation. In particular, patients with a [Blinded] score ≥ 9 had a mortality risk five-times higher than those with a lower score. Other independent predictors of mortality were gender and age.
A Fully Automated Deep Learning-based Network For Detecting COVID-19 from a New And Large Lung CT Scan Dataset
Biomedical Signal Processing and Control, March 31 2021
This paper aims to propose a high-speed and accurate fully-automated method to detect COVID-19 from the patient’s chest CT scan images. We introduce a new dataset that contains 48260 CT scan images from 282 normal persons and 15589 images from 95 patients with COVID-19 infections. At the first stage, this system runs our proposed image processing algorithm that analyzes the view of the lung to discard those CT images that inside the lung is not properly visible in them. This action helps to reduce the processing time and false detections. At the next stage, we introduce a novel architecture for improving the classification accuracy of convolutional networks on images containing small important objects. Our architecture applies a new feature pyramid network designed for classification problems to the ResNet50V2 model so the model becomes able to investigate different resolutions of the image and do not lose the data of small objects. As the infections of COVID-19 exist in various scales, especially many of them are tiny, using our method helps to increase the classification performance remarkably. After running these two phases, the system determines the condition of the patient using a selected threshold. We are the first to evaluate our system in two different ways on Xception, ResNet50V2, and our model. In the single image classification stage, our model achieved 98.49% accuracy on more than 7996 test images. At the patient condition identification phase, the system correctly identified almost 234 of 245 patients with high speed.
Risk of acute pulmonary embolism in COVID-19 pneumonia compared to community-acquired pneumonia: a retrospective case–control study
Clinical Radiology, March 31, 2021
Our aim was to compare the incidence of pulmonary embolism (PE) in COVID-19 pneumonia and non-COVID-19-related community-acquired pneumonia (CAP) in hospitalised patients. A retrospective case–control study was conducted. This included patients hospitalised with pneumonia and investigated for suspected PE with computed tomography pulmonary angiogram (CTPA). Cases were defined as patients with COVID-19 pneumonia from 1 March 2020 to 17 May 2020; controls were patients with CAP from 5 July 2019 to 31 January 2020. The primary outcome was to determine the risk of developing PE in both groups. Multivariable logistic regression was used to calculate the adjusted odds ratio for PE. One hundred and forty-four patients were included; 72 cases (47% male; mean age 59 (±15) years), and 72 controls (56% male; mean age 58 (±20) years). PE was diagnosed in 23.6% of the cases versus 6.9% of the controls. The adjusted odds ratio for PE in hospitalised patients with COVID-19 pneumonia compared with those with CAP was 3.23 (95% confidence interval [CI] 1.04–10.04, p=0.04).
Lung Ultrasonography for long-term follow-up of COVID-19 survivors compared to chest CT scan
Respiratory Medicine, March 31, 2021
While lung ultrasonography (LUS) has utility for the evaluation of the acute phase of COVID-19 related lung disease, its role in long-term follow-up of this condition has not been well described. The objective of this study is to compare LUS and chest computed tomography (CT) results in COVID-19 survivors with the intent of defining the utility of LUS for long-term follow-up of COVID-19 respiratory disease. Prospective observational study that enrolled consecutive survivors of COVID-19 with acute hypoxemic respiratory failure (HARF) admitted to the Respiratory Intensive Care Unit. Three months following hospital discharge, patients underwent LUS, chest CT, body plethysmography and laboratory testing, the comparison of which forms the basis of this report. Thirty-eight patients were enrolled, with a total of 190 lobes analysed: men 27/38 (71.1%), mean age 60.6 y (SD 10.4). LUS findings and pulmonary function tests outcomes were compared between patients with and without ILD, showing a statistically significant difference in terms of LUS score (p: 0.0002), FEV1 (p: 0.0039) and FVC (p: 0.012). ROC curve both in lobe by lobe and in patient’s overall analysis revealed an outstanding ILD discrimination ability of LUS (AUC: 0.94 and 0.95 respectively) with a substantial Cohen’s coefficient (K: 0.74 and 0.69).
How Information About Race-based Health Disparities Affects Policy Preferences: Evidence from a Survey Experiment About the COVID-19 Pandemic in the United States
Social Science & Medicine, March 29, 2021
In this article, we report on the results of an experimental study to estimate the effects of delivering information about racial disparities in COVID-19-related death rates. On the one hand, we find that such information led to increased perception of risk among those Black respondents who lacked prior knowledge; and to increased support for a more concerted public health response among those White respondents who expressed favorable views towards Blacks at baseline. On the other hand, for Whites with colder views towards Blacks, the informational treatment had the opposite effect: it led to decreased risk perception and to lower levels of support for an aggressive response. Our findings highlight that well-intentioned public health campaigns spotlighting disparities might have adverse side effects and those ought to be considered as part of a broader strategy. The study contributes to a larger scholarly literature on the challenges of making and implementing social policy in racially-divided societies.
Interstitial lung abnormalities and pulmonary fibrosis in COVID-19 patients: a short-term follow-up case series
Clinical Imaging, March 29, 2021
Fibrotic lung changes are well-known complications of SARS, MERS, and ARDS from other causes and are anticipated in recovered COVID patients. However, there is limited data so far showing a temporal relationship between lung changes on imaging in the acute phase and follow-up imaging after recovery from the infection. We present 12 patients who demonstrate the development of interstitial lung changes and pulmonary fibrosis in the same distribution and pattern as the acute phase findings, up to 6 months after the acute infection, demonstrating a direct relationship between these changes and COVID-19 pneumonia.
Reduced mortality in COVID-19 patients treated with colchicine: Results from a retrospective, observational study
PLOS ONE, March 24, 2021
Effective treatments for coronavirus disease 2019 (COVID-19) are urgently needed. We hypothesized that colchicine, by counteracting proinflammatory pathways implicated in the uncontrolled inflammatory response of COVID-19 patients, reduces pulmonary complications, and improves survival. This retrospective study included 71 consecutive COVID-19 patients (hospitalized with pneumonia on CT scan or outpatients) who received colchicine and compared with 70 control patients who did not receive colchicine in two serial time periods at the same institution. We used inverse probability of treatment propensity-score weighting to examine differences in mortality, clinical improvement (using a 7-point ordinary scale), and inflammatory markers between the two groups. In this retrospective cohort study, colchicine was associated with reduced mortality and accelerated recovery in COVID-19 patients. This support the rationale for current larger randomized controlled trials testing the safety/efficacy profile of colchicine in COVID-19 patients.
Subacute cerebellar ataxia following respiratory symptoms of COVID-19: a case report
BMC Infectious Diseases, March 24, 2021
Severe acute respiratory syndrome virus 2 (SARS-CoV-2) is spreading globally and causes most frequently fever and respiratory symptoms, i.e. Coronavirus disease 2019 (COVID-19), however, distinct neurological syndromes associated with SARS-CoV-2 infection have been described. Among SARS-CoV-2-infections-associated neurological symptoms fatigue, headache, dizziness, impaired consciousness and anosmia/ageusia are most frequent, but less frequent neurological deficits such as seizures, Guillain-Barré syndrome or ataxia may also occur. This case presentation is of a 62-year-old man who developed a subacute cerebellar syndrome with limb-, truncal- and gait ataxia and scanning speech 1 day after clinical resolution of symptomatic SARS-CoV-2 infection of the upper airways. Apart from ataxia, there were no signs indicative of opsoclonus myoclonus ataxia syndrome or Miller Fisher syndrome. Cerebral magnetic resonance imaging showed mild cerebellar atrophy. SARS-CoV-2 infection of the cerebellum was excluded by normal cerebrospinal fluid cell counts and, most importantly, absence of SARS-CoV-2 RNA or intrathecal SARS-CoV-2-specific antibody production. Other causes of ataxia such as other viral infections, other autoimmune and/or paraneoplastic diseases or intoxication were ruled out. The neurological deficits improved rapidly after high-dose methylprednisolone therapy. The laboratory and clinical findings as well as the marked improvement after high-dose methylprednisolone therapy suggest a post-infectious, immune-mediated cause of ataxia. This report should make clinicians aware to consider SARS-CoV-2 infection as a potential cause of post-infectious neurological deficits with an atypical clinical presentation and to consider high-dose corticosteroid treatment in case that a post-infectious immune-mediated mechanism is assumed.
Time spent in prior hospital stay and outcomes for ventilator patients in long-term acute care hospitals
BMC Pulmonary Medicine, March 24, 2021
Long-term acute care hospitals (LTACHs) treat mechanical ventilator patients who are difficult to wean and expected to be on mechanical ventilator for a prolonged period. However, there are varying views on who should be transferred to LTACHs and when they should be transferred. The purpose of this study is to assess the relationship between length of stay in a short-term acute care hospital (STACH) after endotracheal intubation (time to LTACH) and weaning success and mortality for ventilated patients discharged to an LTACH. Using 2014–2015 Medicare claims and assessment data, we identified patients who had an endotracheal intubation in STACH and transferred to an LTACH with prolonged mechanical ventilation (defined as 96 or more consecutive hours on a ventilator). We controlled for age, gender, STACH stay procedures and diagnoses, Elixhauser comorbid conditions, and LTACH quality characteristics. We used instrumental variable estimation to account for unobserved patient and provider characteristics. The study cohort included 13,622 LTACH cases with median time to LTACH of 18 days. The unadjusted ventilator weaning rate at LTACH was 51.7%, and unadjusted 90-day mortality rate was 43.7%. An additional day spent in STACH after intubation is associated with 11.6% reduction in the odds of weaning, representing a 2.5 percentage point reduction in weaning rate at 18 days post endotracheal intubation. We found no statistically significant relationship between time to LTACH and the odds of 90-day mortality.
Computing infection distributions and longitudinal evolution patterns in lung CT images
BMC Medical Imaging, March 23, 2021
Spatial and temporal lung infection distributions of coronavirus disease 2019 (COVID-19) and their changes could reveal important patterns to better understand the disease and its time course. This paper presents a pipeline to analyze statistically these patterns by automatically segmenting the infection regions and registering them onto a common template. A VB-Net is designed to automatically segment infection regions in CT images. After training and validating the model, we segmented all the CT images in the study. The segmentation results are then warped onto a pre-defined template CT image using deformable registration based on lung fields. Then, the spatial distributions of infection regions and those during the course of the disease are calculated at the voxel level. Visualization and quantitative comparison can be performed between different groups. We compared the distribution maps between COVID-19 and community acquired pneumonia (CAP), between severe and critical COVID-19, and across the time course of the disease. For the performance of infection segmentation, comparing the segmentation results with manually annotated ground-truth, the average Dice is 91.6% ± 10.0%, which is close to the inter-rater difference between two radiologists (the Dice is 96.1% ± 3.5%). The distribution map of infection regions shows that high probability regions are in the peripheral subpleural (up to 35.1% in probability). COVID-19 GGO lesions are more widely spread than consolidations, and the latter are located more peripherally. Onset images of severe COVID-19 (inpatients) show similar lesion distributions but with smaller areas of significant difference in the right lower lobe compared to critical COVID-19 (intensive care unit patients).
Afro-Communitarianism and the Role of Traditional African Healers in the COVID-19 Pandemic
Public Health Ethics, March 20, 2021
The COVID-19 pandemic has brought significant challenges to healthcare systems worldwide, and in Africa, given the lack of resources, they are likely to be even more acute. The usefulness of Traditional African Healers in helping to mitigate the effects of pandemic has been neglected. We argue from an ethical perspective that these healers can and should have an important role in informing and guiding local communities in Africa on how to prevent the spread of COVID-19. Particularly, we argue not only that much of the philosophy underlying Traditional African Medicine is adequate and compatible with preventive measures for COVID-19, but also that Traditional African Healers have some unique cultural capital for influencing and enforcing such preventive measures. The paper therefore suggests that not only given the cultural context of Africa where Traditional African Healers have a special role, but also because of the normative strength of the Afro-communitarian philosophy that informs it, there are good ethical reasons to endorse policies that involve Traditional Healers in the fight against COVID-19. We also maintain that concerns about Traditional African Healers objectionably violating patient confidentiality or being paternalistic are much weaker in the face of COVID-19.
Early effects of ventilatory rescue therapies on systemic and cerebral oxygenation in mechanically ventilated COVID-19 patients with acute respiratory distress syndrome: a prospective observational study
Critical Care, March 19, 2021
In COVID-19 patients with acute respiratory distress syndrome (ARDS), the effectiveness of ventilatory rescue strategies remains uncertain, with controversial efficacy on systemic oxygenation and no data available regarding cerebral oxygenation and hemodynamics. This is a prospective observational study conducted at San Martino Policlinico Hospital, Genoa, Italy. We included adult COVID-19 patients who underwent at least one of the following rescue therapies: recruitment maneuvers (RMs), prone positioning (PP), inhaled nitric oxide (iNO), and extracorporeal carbon dioxide (CO2) removal (ECCO2R). Arterial blood gas values (oxygen saturation [SpO2], partial pressure of oxygen [PaO2] and of carbon dioxide [PaCO2]) and cerebral oxygenation (rSO2) were analyzed before (T0) and after (T1) the use of any of the aforementioned rescue therapies. The primary aim was to assess the early effects of different ventilatory rescue therapies on systemic and cerebral oxygenation. The secondary aim was to evaluate the correlation between systemic and cerebral oxygenation in COVID-19 patients. Forty-five rescue therapies were performed in 22 patients. The median [interquartile range] age of the population was 62 [57–69] years, and 18/22 [82%] were male. After RMs, no significant changes were observed in systemic PaO2 and PaCO2 values, but cerebral oxygenation decreased significantly (52 [51–54]% vs. 49 [47–50]%, p < 0.001). After PP, a significant increase was observed in PaO2 (from 62 [56–71] to 82 [76–87] mmHg, p = 0.005) and rSO2 (from 53 [52–54]% to 60 [59–64]%, p = 0.005). The use of iNO increased PaO2 (from 65 [67–73] to 72 [67–73] mmHg, p = 0.015) and rSO2 (from 53 [51–56]% to 57 [55–59]%, p = 0.007). The use of ECCO2R decreased PaO2 (from 75 [75–79] to 64 [60–70] mmHg, p = 0.009), with reduction of rSO2 values (59 [56–65]% vs. 56 [53–62]%, p = 0.002). In the whole population, a significant relationship was found between SpO2 and rSO2 (R = 0.62, p < 0.001) and between PaO2 and rSO2 (R0 0.54, p < 0.001).
Lung Epithelial Cell Transcriptional Regulation as a Factor in COVID-19 Associated Coagulopathies
American Journal of Respiratory Cell and Molecular Biology, March 18, 2021
SARS-CoV-2 has rapidly become a global pandemic. In addition to the acute pulmonary symptoms of COVID-19 (the disease associated with SARS-CoV-2 infection), pulmonary and distal coagulopathies have caused morbidity and mortality in many patients. Currently, the molecular pathogenesis underlying COVID-19 associated coagulopathies are unknown. Identifying the molecular basis of how SARS-CoV-2 drives coagulation is essential to mitigating short- and long-term thrombotic risks of sick and recovered COVID-19 patients. We aimed to perform coagulation focused transcriptome analysis of in vitro infected primary respiratory epithelial cells, patient derived bronchial alveolar lavage (BALF) cells, and circulating immune cells during SARS-CoV-2 infection. Our objective was to identify transcription mediated signaling networks driving coagulopathies associated with COVID-19. We analyzed recently published experimentally and clinically derived bulk or single cell RNA sequencing datasets of SARS-CoV-2 infection to identify changes in transcriptional regulation of blood coagulation. We also confirmed that the transcriptional expression of a key coagulation regulator was recapitulated at the protein level. We specifically focused our analysis on lung tissue expressed genes regulating the extrinsic coagulation cascade and the plasminogen activation system. Analyzing transcriptomic data of in vitro infected normal human bronchial epithelial (NHBE) cells and patient derived BALF samples revealed that SARS-CoV-2 infection induces the extrinsic blood coagulation cascade and suppresses the plasminogen activation system.
Invasive pulmonary aspergillosis in critically ill patients with severe COVID-19 pneumonia: Results from the prospective AspCOVID-19 study
PLOS ONE, March 17, 2021
Superinfections, including invasive pulmonary aspergillosis (IPA), are well-known complications of critically ill patients with severe viral pneumonia. Aim of this study was to evaluate the incidence, risk factors and outcome of IPA in critically ill patients with severe COVID-19 pneumonia. We prospectively screened 32 critically ill patients with severe COVID-19 pneumonia for a time period of 28 days using a standardized study protocol for observation of development of COVID-19 associated invasive pulmonary aspergillosis (CAPA). We collected laboratory, microbiological, virological and clinical parameters at defined timepoints in combination with galactomannan-antigen-detection from nondirected bronchial lavage (NBL). We used logistic regression analyses to assess if COVID-19 was independently associated with IPA and compared it with matched controls. CAPA is highly prevalent and associated with a high mortality rate. COVID-19 is independently associated with invasive pulmonary aspergillosis. A standardized screening and diagnostic approach as presented in our study can help to identify affected patients at an early stage.
COVID-19 vaccine testing & administration guidance for allergists/immunologists from the Canadian Society of Allergy and Clinical Immunology (CSACI)
Allergy, Asthma & Clinical Immunology, March 15, 2021
Safe and effective vaccines provide the first hope for mitigating the devastating health and economic impacts resulting from coronavirus disease 2019 (COVID-19) and related public health orders. Recent case reports of reactions to COVID-19 vaccines have raised questions about their safety for use in individuals with allergies and those who are immunocompromised. In this document, we aim to address these concerns and provide guidance for allergists/immunologists. Scoping review of the literature regarding COVID-19 vaccination, adverse or allergic reactions, and immunocompromise from PubMed over the term of December 2020 to present date. We filtered our search with the terms “human” and “English” and limited the search to the relevant subject age range with the term “adult.” Reports resulting from these searches and relevant references cited in those reports were reviewed and cited on the basis of their relevance. Assessment by an allergist is warranted in any individual with a suspected allergy to a COVID-19 vaccine or any of its components. Assessment by an allergist is NOT required for individuals with a history of unrelated allergies, including to allergies to foods, drugs, insect venom or environmental allergens. COVID-19 vaccines should be offered to immunocompromised patients if the benefit is deemed to outweigh any potential risks of vaccination.
Upregulation of ACE2 and TMPRSS2 by particulate matter and idiopathic pulmonary fibrosis: a potential role in severe COVID-19
Particle and Fibre Toxicology, March 11, 2021
Air pollution exposure and idiopathic pulmonary fibrosis (IPF) cause a poor prognosis after SARS-CoV-2 infection, but the underlying mechanisms are not well explored. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the keys to the entry of SARS-CoV-2. We therefore hypothesized that air pollution exposure and IPF may increase the expression of ACE2 and TMPRSS2 in the lung alveolar region. We measured their expression levels in lung tissues of control non-IPF and IPF patients, and used murine animal models to study the deterioration of IPF caused by particulate matter (PM) and the molecular pathways involved in the expression of ACE2 and TMPRSS2. In non-IPF patients, cells expressing ACE2 and TMPRSS2 were limited to human alveolar cells. ACE2 and TMPRSS2 were largely upregulated in IPF patients, and were co-expressed by fibroblast specific protein 1 (FSP-1) + lung fibroblasts in human pulmonary fibrotic tissue. In animal models, PM exposure increased the severity of bleomycin-induced pulmonary fibrosis. ACE2 and TMPRSS2 were also expressed in FSP-1+ lung fibroblasts in bleomycin-induced pulmonary fibrosis, and when combined with PM exposure, they were further upregulated. The severity of pulmonary fibrosis and the expression of ACE2 and TMPRSS2 caused by PM exposure were blocked by deletion of KC, a murine homologue of IL-8, or treatment with reparixin, an inhibitor of IL-8 receptors CXCR1/2.
Proximal deep vein thrombosis and pulmonary embolism in COVID-19 patients: a systematic review and meta-analysis
Thrombosis Journal, March 9, 2021
COVID-19 appears to be associated with a high risk of venous thromboembolism (VTE). We aimed to systematically review and meta-analyze the risk of clinically relevant VTE in patients hospitalized for COVID-19. This meta-analysis included original articles in English published from January 1st, 2020 to June 15th, 2020 in Pubmed/MEDLINE, Embase, Web of science, and Cochrane. Outcomes were major VTE, defined as any objectively diagnosed pulmonary embolism (PE) and/or proximal deep vein thrombosis (DVT). Primary analysis estimated the risk of VTE, stratified by acutely and critically ill inpatients. Secondary analyses explored the separate risk of proximal DVT and of PE; the risk of major VTE stratified by screening and by type of anticoagulation. In 33 studies (n = 4009 inpatients) with heterogeneous thrombotic risk factors, VTE incidence was 9% (95%CI 5–13%, I2 = 92.5) overall, and 21% (95%CI 14–28%, I2 = 87.6%) for patients hospitalized in the ICU. Proximal lower limb DVT incidence was 3% (95%CI 1–5%, I2 = 87.0%) and 8% (95%CI 3–14%, I2 = 87.6%), respectively. PE incidence was 8% (95%CI 4–13%, I2 = 92.1%) and 17% (95%CI 11–25%, I2 = 89.3%), respectively. Screening and absence of anticoagulation were associated with a higher VTE incidence. When restricting to medically ill inpatients, the VTE incidence was 2% (95%CI 0–6%).
Predictors of failure with high-flow nasal oxygen therapy in COVID-19 patients with acute respiratory failure: a multicenter observational study
Journal of Intensive Care, March 5, 2021
We aimed to describe the use of high-flow nasal oxygen (HFNO) in patients with COVID-19 acute respiratory failure and factors associated with a shift to invasive mechanical ventilation. This is a multicenter, observational study from a prospectively collected database of consecutive COVID-19 patients admitted to 36 Spanish and Andorran intensive care units (ICUs) who received HFNO on ICU admission during a 22-week period (March 12-August 13, 2020). Outcomes of interest were factors on the day of ICU admission associated with the need for endotracheal intubation. We used multivariable logistic regression and mixed effects models. A predictive model for endotracheal intubation in patients treated with HFNO was derived and internally validated. From a total of 259 patients initially treated with HFNO, 140 patients (54%) required invasive mechanical ventilation. Baseline non-respiratory Sequential Organ Failure Assessment (SOFA) score [odds ratio (OR) 1.78; 95% confidence interval (CI) 1.41-2.35], and the ROX index calculated as the ratio of partial pressure of arterial oxygen to inspired oxygen fraction divided by respiratory rate (OR 0.53; 95% CI: 0.37-0.72), and pH (OR 0.47; 95% CI: 0.24-0.86) were associated with intubation. Hospital site explained 1% of the variability in the likelihood of intubation after initial treatment with HFNO. A predictive model including non-respiratory SOFA score and the ROX index showed excellent performance (AUC 0.88, 95% CI 0.80-0.96).
Quantitative and semi-quantitative CT assessments of lung lesion burden in COVID-19 pneumonia
Scientific Reports, March 4, 2021
This study aimed to clarify and provide clinical evidence for which computed tomography (CT) assessment method can more appropriately reflect lung lesion burden of the COVID-19 pneumonia. A total of 244 COVID-19 patients were recruited from three local hospitals. All the patients were assigned to mild, common and severe types. Semi-quantitative assessment methods, e.g., lobar-, segmental-based CT scores and opacity-weighted score, and quantitative assessment method, i.e., lesion volume quantification, were applied to quantify the lung lesions. All four assessment methods had high inter-rater agreements. At the group level, the lesion load in severe type patients was consistently observed to be significantly higher than that in common type in the applications of four assessment methods (all the p < 0.001). In discriminating severe from common patients at the individual level, results for lobe-based, segment-based and opacity-weighted assessments had high true positives while the quantitative lesion volume had high true negatives. In conclusion, both semi-quantitative and quantitative methods have excellent repeatability in measuring inflammatory lesions, and can well distinguish between common type and severe type patients. Lobe-based CT score is fast, readily clinically available, and has a high sensitivity in identifying severe type patients. It is suggested to be a prioritized method for assessing the burden of lung lesions in COVID-19 patients.
Time series analysis of the demand for COVID-19 related chest imaging during the first wave of the SARS-CoV-2 pandemic: An explorative study
PLOS ONE, March 3, 2021
The aim of this study was to investigate possible patterns of demand for chest imaging during the first wave of the SARS-CoV-2 pandemic and derive a decision aid for the allocation of resources in future pandemic challenges. Time data of requests for patients with suspected or confirmed coronavirus disease 2019 (COVID-19) lung disease were analyzed between February 27th and May 27th 2020. A multinomial logistic regression model was used to evaluate differences in the number of requests between 3 time intervals (I1: 6am – 2pm, I2: 2pm – 10pm, I3: 10pm – 6am). A cosinor model was applied to investigate the demand per hour. Requests per day were compared to the number of regional COVID-19 cases. 551 COVID-19 related chest imagings (32.8% outpatients, 67.2% in-patients) of 243 patients were conducted (33.3% female, 66.7% male, mean age 60 ± 17 years). Most exams for outpatients were required during I2 (I1 vs. I2: odds ratio (OR) = 0.73, 95% confidence interval (CI) 0.62–0.86, p = 0.01; I2 vs. I3: OR = 1.24, 95% CI 1.04–1.48, p = 0.03) with an acrophase at 7:29 pm. Requests for in-patients decreased from I1 to I3 (I1 vs. I2: OR = 1.24, 95% CI 1.09–1.41, p = 0.01; I2 vs. I3: OR = 1.16, 95% CI 1.05–1.28, p = 0.01) with an acrophase at 12:51 pm. The number of requests per day for outpatients developed similarly to regional cases while demand for in-patients increased later and persisted longer. The demand for COVID-19 related chest imaging displayed distinct distribution patterns depending on the sector of patient care and point of time during the SARS-CoV-2 pandemic. These patterns should be considered in the allocation of resources in future pandemic challenges with similar disease characteristics.
Pulmonary Function and Radiological Features in Survivors of Critical Covid-19: A 3-Month Prospective Cohort
CHEST, March 3, 2021
More than 20% of hospitalized patients with coronavirus disease 2019 (COVID-19) develop acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) admission. The long-term respiratory sequelae in ICU survivors remain unclear. Our objective was to determine the major long-term pulmonary sequelae in critical COVID-19 survivors. Patients with COVID-19 requiring ICU admission were recruited and evaluated 3 months after hospitalization discharge. The follow-up comprised symptom and quality of life, anxiety and depression questionnaires, pulmonary function tests, exercise test (6-minute walking test (6MWT)) and chest computed tomography (CT). 125 ICU patients with ARDS secondary to COVID-19 were recruited between March and June 2020. At the 3-month follow-up, 62 patients were available for pulmonary evaluation. The most frequent symptoms were dyspnea (46.7%) and cough (34.4%). Eighty-two percent of patients showed a lung diffusing capacity of less than 80%. The median (IQR) distance in the 6MWT was 400 (362;440) meters. CT scans were abnormal in 70.2% of patients, showing reticular lesions in 49.1% and fibrotic patterns in 21.1%. Patients with more severe alterations on chest CT had worse pulmonary function and presented more degrees of desaturation in the 6MWT. Factors associated with the severity of lung damage on chest CT were age and length of invasive mechanical ventilation during the ICU stay. Interpretation Pulmonary structural abnormalities and functional impairment are highly prevalent in surviving ICU patients with ARDS secondary to COVID-19 3 months after hospital discharge. Pulmonary evaluation should be considered for all critical COVID-19 survivors 3 months post discharge.
Lung expression of genes putatively involved in SARS-CoV-2 infection is modulated in cis by germline variants
European Journal of Human Genetics, March 1, 2021
Germline variants in genes involved in SARS-CoV-2 cell entry and in host innate immune responses to viruses may influence the susceptibility to infection. This study used whole-genome analyses of lung tissue to identify polymorphisms acting as expression quantitative trait loci (eQTLs) for 60 genes of relevance to SARS-CoV-2 infection susceptibility. The expression of genes with confirmed or possible roles in viral entry–replication and in host antiviral responses was studied in the non-diseased lung tissue of 408 lung adenocarcinoma patients. No gene was differently expressed by sex, but APOBEC3H levels were higher and PARP12 levels lower in older individuals. A total of 125 cis-eQTLs (false discovery rate < 0.05) was found to modulate mRNA expression of 15 genes (ABO, ANPEP, AP2A2, APOBEC3D, APOBEC3G, BSG, CLEC4G, DDX58, DPP4, FURIN, FYCO1, RAB14, SERINC3, TRIM5, ZCRB1). eQTLs regulating ABO and FYCO1 were found in COVID-19 susceptibility loci. No trans-eQTLs were identified. Genetic control of the expression of these 15 genes, which encode putative virus receptors, proteins required for vesicle trafficking, enzymes that interfere with viral replication, and other restriction factors, may underlie interindividual differences in risk or severity of infection with SARS-CoV-2 or other viruses.
Survival after extracorporeal membrane oxygenation in severe COVID-19 ARDS: results from an international multicenter registry
Critical Care, March 1, 2021
Survival of coronavirus disease 2019 (COVID-19) patients with severe respiratory failure treated with veno-venous extracorporeal membrane oxygenation (V-V ECMO) ranges around 60%, according to recent studies. Initial recommendations for the use of V-V ECMO in COVID-19-related acute respiratory distress syndrome (ARDS) were largely based on studies from the pre-COVID-19 era. V-V ECMO was initiated in younger patients (i.e., < 71 years) and in those with rather short duration of mechanical ventilation (MV) prior to ECMO (i.e., < 7 or < 11 days, respectively). While it is reasonable to focus on selected ECMO cohorts in controlled trials, survival of COVID-19 patients treated with ECMO beyond these limitations remains unclear, so far. Here, we report survival data of COVID-19 ARDS patients treated with V-V ECMO from a large, international multicenter registry. Data were collected retrospectively from medical records at 3 ECMO centers in the USA, 9 in Germany, and 1 in Switzerland, Belgium, and Italy. At the participating centers, all patients with reverse transcriptase polymerase chain reaction (rtPCR) positive testing for SARS-CoV-2, who received V-V ECMO from March 12 to June 5, 2020 (i.e., during the first wave of the pandemic), were included. A total of 127 patients were analyzed: 53/127 (41.7%) of them survived at day 90 after ECMO implantation. Higher survival was observed in patients younger than 71 years when compared to others (110/127, 45.5% vs. 17/127, 17.6%, p = 0.004). However, patients being on MV before ECMO for less than 7 days had slightly higher survival rate than those with longer MV course though not reaching statistical significance (77/127, 46.8% vs. 50/127, 34.0%; p = 0.167). Similar results were observed when the duration of MV was dichotomized in < 11 and ≥ 11 days (101/127, 45.5% vs. 26/127, 26.9%; p = 0.044).
Recommended approaches to minimize aerosol dispersion of SARS-CoV2 during noninvasive ventilatory support can deteriorate ventilator performances: a benchmark comparative study
CHEST, March 1, 2021
SARS-CoV-2 aerosolization during noninvasive positive pressure ventilation may endanger healthcare professionals. Various circuit setups have been described in order to reduce virus aerosolization. However, these setups may alter ventilator performances. Our objective was to determine the consequences of the different suggested circuit setups on ventilator’s efficacy during continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV). Eight circuit setups were evaluated on a bench made of a 3-D printed head and an artificial lung. Setups were a dual-limb circuit with an oro-nasal mask, a dual-limb circuit with a helmet interface, a single-limb circuit with a passive exhalation valve, three single-limb circuits with custom-made additional leaks and two single-limb circuits with active exhalation valves. All setups were evaluated during NIV and CPAP. The following variables were recorded: the inspiratory flow preceding trigger of the ventilator, the inspiratory effort required to trigger the ventilator, the triggering delay, the maximal inspiratory pressure delivered by the ventilator, the tidal volume (Vt) generated to the artificial lung, the total work of breathing (WOB) and the pressure time product to trigger the ventilator (PTPt). With NIV, the type of circuit setup had a significant impact on inspiratory flow preceding the trigger of the ventilator (p<0.0001), the inspiratory effort required to trigger the ventilator (p<0.0001), the triggering delay (p<0.0001); the maximal inspiratory pressure (p<0.0001), the Vt (p:0.0008), the WOB (p<0.0001), the PTPt (p<0.0001). Similar differences and consequences were seen with CPAP as well as with the addition of bacterial filters. Best performance was achieved using a dual limb circuit with an oro-nasal mask. Worst performance was achieved using a dual-limb circuit with a helmet interface.
IL-1 inhibitors linked to ‘significant reduction’ in COVID-19 mortality
Healio | Rheumatology, February 23, 2021
Interleukin-1 inhibitors are associated with a “significant reduction” in mortality among patients hospitalized with COVID-19, respiratory insufficiency and hyperinflammation, according to data published in The Lancet Rheumatology. However, this association was not found with IL-6 inhibition, which was only effective in patients with “markedly high” C-reactive protein concentrations, the researchers noted. “A subset of patients with severe COVID-19 develop a life-threatening hyperinflammatory response to the virus, which resembles the cytokine storm that develops after chimeric antigen receptor T-cell treatment or in macrophage activation syndrome, with release of interleukin (IL)-1, IL-6, IL-18, and interferon-,” Giulio Cavalli, MD, of Vita-Salute San Raffaele University, in Milan, Italy, and colleagues wrote. “IL-1 inhibition, but not IL-6 inhibition, was associated with a significant reduction of mortality in a large cohort of patients admitted to hospital with COVID-19 and hyperinflammation,” Cavalli and colleagues wrote. “IL-6 inhibition was only effective in a subgroup of patients with markedly high C-reactive protein concentrations, whereas both IL-1 inhibition and IL-6 inhibition were more effective in patients with low lactate dehydrogenase concentrations. Validation of these study findings, particularly concerning the efficacy of IL-1 inhibition in COVID-19, requires controlled investigations.”
Does Non-COVID19 Lung Lesion Help? Investigating Transferability in COVID-19 CT Image Segmentation
Computer Methods and Programs in Biomedicine, February 23, 2021
Deep learning has been adopted as an effective technique to aid COVID-19 detection and segmentation from computed tomography (CT) images. The major challenge lies in the inadequate public COVID-19 datasets. Recently, transfer learning has become a widely used technique that leverages the knowledge gained while solving one problem and applying it to a different but related problem. However, it remains unclear whether various non-COVID19 lung lesions could contribute to segmenting COVID-19 infection areas and how to better conduct this transfer procedure. This paper provides a way to understand the transferability of non-COVID19 lung lesions and a better strategy to train a robust deep learning model for COVID-19 infection segmentation. Based on a publicly available COVID-19 CT dataset and three public non-COVID19 datasets, we evaluate four transfer learning methods using 3D U-Net as a standard encoder-decoder method. i) We introduce the multi-task learning method to get a multi-lesion pre-trained model for COVID-19 infection. ii) We propose and compare four transfer learning strategies with various performance gains and training time costs. Our proposed Hybrid-encoder Learning strategy introduces a Dedicated-encoder and an Adapted-encoder to extract COVID-19 infection features and general lung lesion features, respectively. An attention-based Selective Fusion unit is designed for dynamic feature selection and aggregation. Experiments show that trained with limited data, proposed Hybrid-encoder strategy based on multi-lesion pre-trained model achieves a mean DSC, NSD, Sensitivity, F1-score, Accuracy and MCC of 0.704, 0.735, 0.682, 0.707, 0.994 and 0.716, respectively, with better genetalization and lower over-fitting risks for segmenting COVID-19 infection. The results reveal the benefits of transferring knowledge from non-COVID19 lung lesions, and learning from multiple lung lesion datasets can extract more general features, leading to accurate and robust pre-trained models.
IDSA updates guidance to support use of tocilizumab for COVID-19
Helio | Infectious Disease News, February 23, 2021
The Infectious Diseases Society of America has backed the use of tocilizumab for COVID-19. In a change to its clinical guidelines, the IDSA now “suggests” the use of tocilizumab — a common rheumatoid arthritis medication — in addition to standard of care treatment such as steroids among patients hospitalized with progressive severe or critical COVID-19, rather than standard of care treatment alone. Initial guidance by IDSA recommended against the routine use of tocilizumab in patients hospitalized with COVID-19. The change followed the release of new results from the RECOVERY trial, which demonstrated that tocilizumab reduced deaths by an absolute difference of 4% among patients with COVID-19 who required oxygen and had evidence of inflammation. To date, RECOVERY has assessed numerous potential treatments for COVID-19, including dexamethasone. Tocilizumab was added to the trial last April and assessed in more than 4,000 patients who were randomly assigned to receive either an IV infusion of tocilizumab or usual care. The newly release data also suggested that, among patients with hypoxia and significant inflammation, tocilizumab in combination with a systemic corticosteroid like dexamethasone reduced mortality “by about one-third for patients requiring simple oxygen and nearly one-half for those requiring invasive mechanical ventilation,” according to a news release from the investigators.
Bacterial lung superinfections uncommon among people who died with COVID-19
Healio | Infectious Disease News, February 22, 2021
Up to 32% of people who died with COVID-19 had a bacterial lung superinfection, according to findings from a review of postmortem studies. Researchers said the review, which uncovered an “uneven” quality of data among such studies, showed that bacterial lung superinfections “complicated a minority of COVID-19 cases globally over the first months of the pandemic, and they were uncommonly the cause of death.” “There is still a lot of uncertainty about the extent to which bacterial superinfections complicate COVID-19, and the occurrence of antimicrobial-resistant infections,” Cornelius (Neil) J. Clancy, MD, associate professor of medicine and director of the extensively drug-resistant pathogen lab and mycology program at the University of Pittsburgh, told Healio. According to the study, the types of infections were pneumonia (95%) 75% of which were localized to a specific area as opposed to being more broadly found in the lungs abscesses or empyema (3.5%) and septic emboli (1.5%). Superinfections were proven by direct visualization or recovery of bacteria in 25.5% of potential cases and 8% of all patients in postmortem studies, Clancy and colleagues reported. According to the study, pathogens included Acinetobacter baumannii, Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumoniae. Overall, lung superinfections caused the death in 16% of patients with potential bacterial infections “in whom a cause of death was assigned,” and only 3% of all patients with COVID-19, Clancy and colleagues reported.
Prolonged SARS-CoV-2 cell culture replication in respiratory samples from patients with severe COVID-19
Clinical Microbiology and Infection, February 22, 2021
This study compares the infectivity of SARS-CoV-2 in respiratory samples from patients with mild COVID-19 with those from hospitalised patients with severe bilateral pneumonia. In severe COVID-19, we also analysed the presence of neutralising activity in paired sera. We performed cell cultures on 193 real-time reverse transcription polymerase chain reaction respiratory samples, positive for SARS-CoV-2, obtained from 189 patients at various times, from clinical diagnosis to follow-up. Eleven samples were obtained from asymptomatic individuals, 91 samples from 91 outpatients with mild forms of COVID-19, and 91 samples from 87 inpatients with severe pneumonia. In these patients, neutralising activity was analysed in 30 paired sera collected after symptom onset >10 days. We detected a cytopathic effect (CPE) in 91 (91/193, 47%) samples. Viral viability was maintained for up to 10 days in the patients with mild COVID-19. In the patients with severe COVID-19, the virus remained viable for up to 32 days after the onset of symptoms. Patients with severe COVID-19 presented infectious virus at a significantly higher rate in the samples with moderate to low viral load (cycle threshold value >26): 32/75 (43%) versus 14/63 (22%) for mild cases (P < 0.01). We observed a positive CPE despite the presence of clear neutralising activity (NT50 >1:1024 in 10% (3/30) of samples.
Efficacy and safety of systematic corticosteroids among severe COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials
Signal Transduction and Targeted Therapy, February 21, 2021
The benefits and harms of corticosteroids for patients with severe coronavirus disease 2019 (COVID-19) remain unclear. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from December 31, 2019 to October 1, 2020 to identify randomized controlled trials (RCTs) that evaluated corticosteroids in severe COVID-19 patients. The primary outcome was all-cause mortality at the longest follow-up. Secondary outcomes included a composite disease progression (progression to intubation, ventilation, extracorporeal membrane oxygenation, ICU transfer, or death among those not ventilated at enrollment) and incidence of serious adverse events. A random-effects model was applied to calculate risk ratio (RR) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation approach to evaluate the certainty of the evidence. Seven RCTs involving 6250 patients were included, of which the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial comprised nearly 78% of all included subjects. Results showed that corticosteroids were associated with a decreased all-cause mortality (27.3 vs. 31.1%; RR: 0.85; 95% CI: 0.73–0.99; P = 0.04; low-certainty evidence). Trial sequential analysis suggested that more trials were still required to confirm the results. However, such survival benefit was absent if RECOVERY trial was excluded (RR: 0.83; 95% CI: 0.65–1.06; P = 0.13). Furthermore, corticosteroids decreased the occurrence of composite disease progression (30.6 vs. 33.3%; RR: 0.77; 95% CI: 0.64–0.92; P = 0.005), but not increased the incidence of serious adverse events (3.5 vs. 3.4%; RR: 1.16; 95% CI: 0.39–3.43; P = 0.79).
Filtering efficiency measurement of respirators by laser-based particle counting method
Measurement, February 20, 2021
Respirators are one of the most useful personal protective equipment which can effectively limit the spreading of coronavirus (COVID-19). There are a worldwide shortage of respirators, melt-blown non-woven fabrics, and respirator testing possibilities. An easy and fast filtering efficiency measurement method was developed for testing the filtering materials of respirators. It works with a laser-based particle counting method, and it can determine two types of filtering efficiencies: Particle Filtering Efficiency (PFE) at given particle sizes and Concentration Filtering Efficiency (CFE) in the case of different aerosols. The measurement method was validated with different aerosol concentrations and with etalon respirators. Considerable advantages of our measurement method are simplicity, availability, and the relatively low price compared to the flame-photometer based methods. The ability of the measurement method was tested on ten different types of Chinese KN95 respirators. The quality of these respirators differs much, only two from ten reached 95% filtering efficiency.
High anxiety during COVID-19 pandemic may be risk factor for clinical worsening of asthma
Healio | Pulmonology, February 18, 2021
High anxiety during the COVID-19 pandemic is a potential risk factor for clinical worsening of severe asthma and decline in quality of life, researchers reported. “Mental health can have a significant role in managing chronic diseases, particularly during the global pandemic,” Piotr Lacwik, MD, professor in the School of Medicine at the Collegium Medicum of Jan Kochanowski University in Kielce, Poland, and colleagues wrote in The Journal of Allergy and Clinical Immunology: In Practice. Researchers surveyed 87 patients with severe asthma (mean age, 56.1 years; 39.1% men) who were receiving biological treatment with omalizumab (Xolair, Genentech), mepolizumab (Nucala, GlaxoSmithKline) and benralizumab (Fasenra, AstraZeneca) in the National Severe Asthma Treatment Program during March and June 2020 visits. At each visit, patients completed the State-Trait Anxiety Inventory (STAI) questionnaire and a COVID-19 survey to assess concerns regarding the impact of COVID-19 on patients’ anxiety, asthma and quality of life. Complete medical data were available for all patients, including changes in the Asthma Control Questionnaire (ACQ) and Mini Asthma Quality of Life Questionnaire (mAQLQ) to compare with their last visit before COVID-19. Forty-six percent of patients had an increase in their ACQscore, 17% reported no change and 37% had a reduction in their score. The researchers observed a larger impact on asthma-related quality of life: 62% of patients had a reduced mAQLQ score, 18% reported no change and 20% had an increased score. Mean change in ACQ score was 0.214 and mean change in mAQLQ was 0.248, according to the results.
The critical importance of mask seals on respirator performance: An analytical and simulation approach
PLOS ONE, February 17, 2021
Filtering facepiece respirators (FFRs) and medical masks are widely used to reduce the inhalation exposure of airborne particulates and biohazardous aerosols. Their protective capacity largely depends on the fraction of these that are filtered from the incoming air volume. While the performance and physics of different filter materials have been the topic of intensive study, less well understood are the effects of mask sealing. To address this, we introduce an approach to calculate the influence of face-seal leakage on filtration ratio and fit factor based on an analytical model and a finite element method (FEM) model, both of which take into account time-dependent human respiration velocities. Using these, we calculate the filtration ratio and fit factor for a range of ventilation resistance values relevant to filter materials, 500–2500 Pa∙s∙m−1, where the filtration ratio and fit factor are calculated as a function of the mask gap dimensions, with good agreement between analytical and numerical models. The results show that the filtration ratio and fit factor are decrease markedly with even small increases in gap area. We also calculate particle filtration rates for N95 FFRs with various ventilation resistances and two commercial FFRs exemplars. Taken together, this work underscores the critical importance of forming a tight seal around the face as a factor in mask performance, where our straightforward analytical model can be readily applied to obtain estimates of mask performance.
Novel Coronavirus Disease 2019 (COVID-19) and Cytokine Storms for More Effective Treatments from an Inflammatory Pathophysiology
Journal of Clinical Medicine, February 17, 2021
In cases of COVID-19, excessive inflammatory responses occur, and exaggerated proinflammatory cytokines and chemokines are detected in the serum, resulting in cytokine release syndrome or cytokine storm. This causes coagulation abnormalities, excessive oxidation developments, mitochondrial permeability transition, vital organ damage, immune system failure and eventually progresses to disseminated intravascular coagulation and multiple organ failure. Additionally, the excessive inflammatory responses also cause mitochondrial dysfunction due to progressive and persistent stress. This damages cells and mitochondria, leaving products containing mitochondrial DNA and cell debris involved in the excessive chronic inflammation as damage-associated molecular patterns. Thus, the respiratory infection progressively leads to disseminated intravascular coagulation from acute respiratory distress syndrome, including vascular endothelial cell damage and coagulation-fibrinolysis system disorders. This condition causes central nervous system disorders, renal failure, liver failure and, finally, multiple organ failure. Regarding treatment for COVID-19, the following are progressive and multiple steps for mitigating the excessive inflammatory response and subsequent cytokine storm in patients. First, administering of favipiravir to suppress SARS-CoV-2 and nafamostat to inhibit ACE2 function should be considered. Second, anti-rheumatic drugs (monoclonal antibodies), which act on the leading cytokines (IL-1β, IL-6) and/or cytokine receptors such as tocilizumab, should be administered as well. Finally, melatonin may also have supportive effects for cytokine release syndrome, resulting in mitochondrial function improvement. This paper will further explore these subjects with reports mostly from China and Europe.
YKL-40 as a new promising prognostic marker of severity in COVID infection
Critical Care, February 16, 2021
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a disease named COVID-19, which may be associated with common symptoms or lead patients to intensive care unit (ICU) or death. The severity of the disease is mainly driven by diffuse interstitial lung diseases (ILD). YKL-40 has a promitogenic action on pulmonary fibroblasts, increases the activity of macrophages and is associated with inflammatory disorders, arteriosclerosis and endothelial dysfunction. In ILD, YKL-40 has been described to be associated with the severity of lung diseases and with the risk of death. Yet, in COVID-19 infection, YKL-40 serum levels could therefore be of interest for diagnosis and prognosis since it is at the cross-link between vascular and epithelial lung damage, which are typical characteristics of COVID-19 infection. By closing the gap between those two pathological characteristics, we thought that YKL-40 could be of interest a specific biomarker of severe COVID-19 infection. We thus retrospectively compared serum levels of YKL-40 in a cohort of 103 patients infected by SARS-CoV-2 hospitalized between March 1 and April 29, 2020, with a group of 58 appariated healthy subjects (HS), 26 patients suffering from chronic obstructive pulmonary disease (COPD) and 53 from non-COVID ILD. Measurement of YKL-40 was taken with the MicroVue™ YKL-40 enzyme immunoassay kit during the 3 first days of admission and retrospectively analyzed and correlated the results with clinical data [ICU admission, acute renal failure (ARF) or multiple organ failure (MOF)].
The role of ibrutinib in COVID-19 hyperinflammation: a case report
International Journal of Infectious Diseases, February 16, 2021
Immune modulation in COVID-19 is emerging as an important therapeutic strategy as increasing evidence suggests that inflammatory pathways are implicated in lung damage (Mehta et al. 2020; Ye et al. 2020). Bruton tyrosine kinase inhibitors (BTKi), such as ibrutinib, are commonly used to treat indolent B-cell neoplasms and chronic graft-versus-host disease (GvHD). Given their potential to suppress pulmonary inflammatory cytokines and lessen acute lung injury (Florence et al. 2018), this could be applicable in the context of hospitalised COVID-19 patients (Thibaud et al. 2020; Treon et al. 2020; Woyach, 2020). Patients already on treatment with BTKis may be at high risk of infection with poor outcomes given advanced age, comorbidities and immune dysfunction. However, a recent multicenter analysis did not show any negative impact on survival of patients with chronic lymphocytic leukaemia hospitalised due to COVID-19 infection whilst receiving a BTKi (Mato et al. 2020). We report the outcome of an ibrutinib treated patient with COVID-19 who suffered respiratory deterioration after ibrutinib cessation, and promptly improved after ibrutinib re-introduction.
Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation
PLOS ONE, February 16, 2021
Mortality due to Covid-19 is highly associated with advanced age, owing in large part to severe lower respiratory tract infection. SARS-CoV-2 utilizes the host ACE2 receptor for infection. Whether ACE2 abundance in the lung contributes to age-associated vulnerability is currently unknown. We set out to characterize the RNA and protein expression profiles of ACE2 in aging human lung in the context of phenotypic parameters likely to affect lung physiology. Examining publicly available RNA sequencing data, we discovered that mechanical ventilation is a critical variable affecting lung ACE2 levels. Therefore, we investigated ACE2 protein abundance in patients either requiring mechanical ventilation or spontaneously breathing. ACE2 distribution and expression were determined in archival lung samples by immunohistochemistry (IHC). Tissues were selected from the specimen inventory at a large teaching hospital collected between 2010–2020. Twelve samples were chosen from patients receiving mechanical ventilation for acute hypoxic respiratory failure (AHRF). Twenty samples were selected from patients not requiring ventilation. We compared samples across age, ranging from 40–83 years old in the ventilated cohort and 14–80 years old in the non-ventilated cohort. Within the alveolated parenchyma, ACE2 expression is predominantly observed in type II pneumocytes (or alveolar type II / AT2 cells) and alveolar macrophages. All 12 samples from our ventilated cohort showed histologic features of diffuse alveolar damage including reactive, proliferating AT2 cells. In these cases, ACE2 was strongly upregulated with age when normalized to lung area (p = 0.004) or cellularity (p = 0.003), associated with prominent expression in AT2 cells. In non-ventilated individuals, AT2 cell reactive changes were not observed and ACE2 expression did not change with age when normalized to lung area (p = 0.231) or cellularity (p = 0.349). In summary, ACE2 expression increases with age in the setting of alveolar damage observed in patients on mechanical ventilation, providing a potential mechanism for higher Covid-19 mortality in the elderly.
Remdesivir for COVID-19 Treatment: APA Practice Points
American College of Cardiology, February 16, 2021
This second version of a guidelines document by the Scientific Medical Policy Committee of the American College of Physicians (ACP) based on an updated systematic review provides evidence-based recommendations surrounding the use of remdesivir in the treatment of coronavirus disease 2019 (COVID-19). Read 10 key points to remember summarizing the data and guidelines.
Clinical characteristics of COVID-19 complicated with pleural effusion
BMC Infectious Diseases, February 15, 2021
Epidemiological and clinical features of patients with corona virus disease 2019 (COVID-19) were well delineated. However, no researches described the patients complicated with pleural effusion (PE). In the present study, we aimed to clinically characterize the COVID-19 patients complicated with PE and to create a predictive model on the basis of PE and other clinical features to identify COVID-19 patients who may progress to critical condition. This retrospective study examined 476 COVID-19 inpatients, involving 153 patients with PE and 323 without PE. The data on patients’ past history, clinical features, physical checkup findings, laboratory results and chest computed tomography (CT) findings were collected and analyzed. LASSO regression analysis was employed to identify risk factors associated with the severity of COVID-19. Laboratory findings showed that patients with PE had higher levels of white blood cells, neutrophils, lactic dehydrogenase, C-reactive protein and D-dimer, and lower levels of lymphocytes, platelets, hemoglobin, partial pressure of oxygen and oxygen saturation. Meanwhile, patients with PE had higher incidence of severe or critical illness and mortality rate, and longer hospital stay time compared to their counterparts without pleural effusion. Moreover, LASSO regression analysis exhibited that pleural effusion, lactic dehydrogenase (LDH), D-dimer and total bilirubin (TBIL) might be risk factors for critical COVID-19.
Should COVID-19 Patients > 75 Years be Ventilated? An Outcome Study
QJM: An International Journal of Medicine, February 12, 2021
Elderly patients with COVID-19 disease are at increased risk for adverse outcomes. Current data regarding disease characteristics and outcomes in this population is limited. Our objective was to delineate the adverse factors associated with outcomes of COVID- 19 patients ≥75 years of age. In this retrospective cohort study, patients were classified into mild/moderate, severe/very severe, and critical disease (intubated) based on oxygen requirements. The primary outcome was in-hospital mortality. Three hundred fifty-five patients aged ≥75 years hospitalized with COVID-19 between March 19th and April 25th, 2020 were included. Mean age was 84.3 years. One-third of the patients developed critical disease. Mean length of stay was 7.10 days. Vasopressors were required in 27%, with the highest frequency in the critical disease group (74.1%). Overall mortality was 57.2%, with a significant difference between severity groups (mild/moderate disease: 17.4%, severe/very severe disease: 71.3%, critical disease: 94.9%, p < 0.001). Increased age, dementia, and severe/very severe and critical disease groups were each significantly associated with increased odds for mortality while diarrhea was associated with decreased odds for mortality (OR : 0.12, 95% CI : 0.02-0.60, p < 0.05)]. None of the cardiovascular comorbidities were significantly associated with mortality. Age and dementia are associated with increased odds for mortality in patients ≥75 years of age hospitalized with COVID-19.
Comparing Clinical Features and Outcomes in Mechanically Ventilated Patients with COVID-19 and the Acute Respiratory Distress Syndrome
Annals of the American Thoracic Society, February 12, 2021
Patients with severe coronavirus disease 2019 (COVID-19) meet clinical criteria for the acute respiratory distress syndrome (ARDS), yet early reports suggested they differ physiologically and clinically from patients with non-COVID-19 ARDS, prompting treatment recommendations that deviate from standard evidence-based practices for ARDS. The objective was to compare respiratory physiology, clinical outcomes, and extrapulmonary clinical features of severe COVID-19 with non-COVID ARDS. We performed a retrospective cohort study, comparing 130 consecutive mechanically ventilated patients with severe COVID-19 with 382 consecutive mechanically ventilated patients with non-COVID-19 ARDS. Initial respiratory physiology and 28-day outcomes were compared. Extrapulmonary manifestations (inflammation, extrapulmonary organ injury, and coagulation) were compared in an exploratory analysis. A comparison of patients with COVID-19 and non-COVID-19 ARDS suggested small differences in respiratory compliance, ventilatory efficiency, and oxygenation. 28-day mortality was 30% in COVID-19 patients and 38% in non-COVID ARDS. In adjusted analysis, point estimates of differences in time-to-breathing-unassisted at 28 days (adjusted SHR 0.98 [95% CI 0.77-1.26]) and 28-day mortality (risk ratio = 1.01 [95% CI 0.72-1.42]) were small for COVID-19 vs. non-COVID ARDS, although the confidence intervals for these estimates include moderate differences. Patients with COVID-19 had lower neutrophil counts but did not differ in lymphocyte count or other measures of systemic inflammation. In this single center cohort, we found no evidence for large differences between COVID-19 and non-COVID ARDS. Many key clinical features of severe COVID-19 were similar to those of non-COVID-19 ARDS, including respiratory physiology and clinical outcomes, although our sample size precludes definitive conclusions.
RECOVERY trial: Tocilizumab reduces death among seriously ill COVID-19 patients
Helio | Infectious Disease News, February 11, 2021
Compared with usual care, tocilizumab reduced deaths by an absolute difference of 4% among patients with COVID-19 who required oxygen and had evidence of inflammation, investigators from the RECOVERY trial reported Thursday. Data suggested that, among patients with hypoxia and significant inflammation, tocilizumab in combination with a systemic corticosteroid like dexamethasone reduced mortality “by about one-third for patients requiring simple oxygen and nearly one-half for those requiring invasive mechanical ventilation,” according to a news release from the investigators. “Previous trials of tocilizumab had shown mixed results, and it was unclear which patients might benefit from the treatment,” Peter Horby, MD, PhD, professor of emerging infectious diseases at the University of Oxford and joint chief investigator for the RECOVERY trial, said in a statement. “We now know that the benefits of tocilizumab extend to all COVID patients with low oxygen levels and significant inflammation. The double impact of dexamethasone plus tocilizumab is impressive and very welcome.”
Clinical characteristics and outcomes of critically ill COVID-19 patients in Tokyo: a single-center observational study from the first wave
BMC Infectious Diseases, February 9, 2021
Many studies have been published about critically ill COVID-19 during the early phases of the pandemic but the characteristic or survival of critically ill Japanese patients have not yet been investigated. We sought to investigate the characteristics, inflammatory laboratory finding trends, and outcomes among critically ill Japanese patients who were admitted to the ICU with the first wave of COVID-19. A retrospective observational study was performed in a single institution in the center of Tokyo. Laboratory-confirmed COVID-19 patients admitted to the ICU from March 19 to April 30, 2020 were included. Trends for significant inflammatory laboratory findings were analyzed. In-hospital death, days of mechanical ventilation or oxygen supplementation, days of ICU or hospital stay were followed until May 26, 2020. Twenty-four patients were included. Median age was 57.5 years, and 79% were male. The neutrophil-to-lymphocyte ratio was elevated to a median of 10.1 on admission and peaked on Day 10 of illness. Seventeen patients were intubated on Day 11 of illness and received mechanical ventilation. One patient underwent extracorporeal membrane oxygenation. The majority (88%) received systemic steroids, including 16 patients who received high dose methylprednisolone (500–1000 mg). Favipiravir was used in 38% of patients. Two patients, including one who refused intensive care, died. Eighteen patients were discharged. Median length of ICU and hospital stay for all patients was 6 and 22 days, respectively. Median length of ventilator dependency was 7 days. Four patients underwent a tracheostomy and received prolonged ventilation for more than 21 days. One patient receiving mechanical ventilation died. All survivors discontinued ventilator use. Mortality was remarkably low in our single institutional study. Three survivors received mechanical ventilation for more than 3 weeks.
COVID-19 lung CT image segmentation using deep learning methods: U-Net versus SegNet
BMC Medical Imaging, February 9, 2021
Currently, there is an urgent need for efficient tools to assess the diagnosis of COVID-19 patients. In this paper, we present feasible solutions for detecting and labeling infected tissues on CT lung images of such patients. Two structurally-different deep learning techniques, SegNet and U-NET, are investigated for semantically segmenting infected tissue regions in CT lung images. We propose to use two known deep learning networks, SegNet and U-NET, for image tissue classification. SegNet is characterized as a scene segmentation network and U-NET as a medical segmentation tool. Both networks were exploited as binary segmentors to discriminate between infected and healthy lung tissue, also as multi-class segmentors to learn the infection type on the lung. Each network is trained using seventy-two data images, validated on ten images, and tested against the left eighteen images. Several statistical scores are calculated for the results and tabulated accordingly. The results show the superior ability of SegNet in classifying infected/non-infected tissues compared to the other methods (with 0.95 mean accuracy), while the U-NET shows better results as a multi-class segmentor (with 0.91 mean accuracy). Semantically segmenting CT scan images of COVID-19 patients is a crucial goal because it would not only assist in disease diagnosis, also help in quantifying the severity of the illness, and hence, prioritize the population treatment accordingly. We propose computer-based techniques that prove to be reliable as detectors for infected tissue in lung CT scans.
Respiratory, Psychophysical Sequelae Identified 4 Months After Hospitalization
Pulmonology Advisor, February 8, 2021
For patients hospitalized with COVID-19, respiratory, physical, and psychological sequelae are common at four months after discharge, according to a study published online Jan. 27 in JAMA Network Open. Mattia Bellan, M.D., Ph.D., from the Università del Piemonte Orientale in Novara, Italy, and colleagues examined the prevalence of lung function anomalies, exercise function impairment, and psychological sequelae at four months after discharge among patients aged 18 years and older with confirmed severe acute respiratory syndrome coronavirus 2 infection serious enough to require hospital admission. Data were included for 238 patients. The researchers found that diffusing lung capacity for carbon monoxide was reduced to less than 80 percent and less than 60 percent of the estimated value in 51.6 and 15.5 percent of patients, respectively. In 53 patients (22.3 percent), the Short Physical Performance Battery (SPPB) score suggested limited mobility (score <11). Patients with SPPB scores within reference range underwent a two-minute walk test; 75 patients (40.5 percent) had a score outside reference ranges for expected performance. Based on these findings, 128 patients (53.8 percent) had functional impairment. Forty-one patients (17.2 percent) had posttraumatic stress symptoms.
Microvascular flow alterations in critically ill COVID-19 patients: A prospective study
PLOS ONE, February 8, 2021
Data on microcirculatory pattern of COVID-19 critically ill patients are scarce. The objective was to compare sublingual microcirculation parameters of critically ill patients according to the severity of the disease. The study is a single-center prospective study with critically ill COVID-19 patients admitted in ICU. Sublingual microcirculation was assessed by IDF microscopy within 48 hours of ICU admission. Microcirculatory flow index (MFI), proportion of perfused vessel (PPV), total vessel density (TVD), De Backer score (DBS), perfused vessel density (PVD) and heterogeneity index (HI) were assessed. Patients were divided in 2 groups (severe and critical) according to the World health organization definition. From 19th of March to 7th of April 2020, 43 patients were included. Fourteen patients (33%) were in the severe group and twenty-nine patients (67%) in the critical group. Patients in the critical group were all mechanically ventilated. The critical group had significantly higher values of MFI, DBS and PVD in comparison to severe group (respectively, PaCO2: 49 [44–45] vs 36 [33–37] mmHg; p <0,0001, MFI: 2.8 ± 0.2 vs 2.5 ± 0.3; p = 0.001, DBS: 12.7 ± 2.6 vs 10.8 ± 2.0 vessels mm-2; p = 0.033, PVD: 12.5 ± 3.0 vs 10.1 ± 2.4 mm.mm-2; p = 0.020). PPV, HI and TVD were similar between groups Correlation was found between microcirculatory parameters and PaCO2 levels. In conclusion, critical COVID-19 patients under mechanical ventilation seem to have higher red blood cell velocity than severe non-ventilated patients.
The association between clinical laboratory data and chest CT findings explains disease severity in a large Italian cohort of COVID-19 patients
BMC Infectious Diseases, February 8, 2021
Laboratory data and computed tomography (CT) have been used during the COVID-19 pandemic, mainly to determine patient prognosis and guide clinical management. The aim of this study was to evaluate the association between CT findings and laboratory data in a cohort of COVID-19 patients. This was an observational cross-sectional study including consecutive patients presenting to the Reggio Emilia (Italy) province emergency rooms for suspected COVID-19 for one month during the outbreak peak, who underwent chest CT scan and laboratory testing at presentation and resulted positive for SARS-CoV-2. Included were 866 patients. Total leukocytes, neutrophils, C-reactive protein (CRP), creatinine, AST, ALT and LDH increase with worsening parenchymal involvement; an increase in platelets was appreciable with the highest burden of lung involvement. A decrease in lymphocyte counts paralleled worsening parenchymal extension, along with reduced arterial oxygen partial pressure and saturation. After correcting for parenchymal extension, ground-glass opacities were associated with reduced platelets and increased procalcitonin, consolidation with increased CRP and reduced oxygen saturation. Pulmonary lesions induced by SARS-CoV-2 infection were associated with raised inflammatory response, impaired gas exchange and end-organ damage. These data suggest that lung lesions probably exert a central role in COVID-19 pathogenesis and clinical presentation
Static compliance of the respiratory system in COVID-19 related ARDS: an international multicenter study
Critical Care, February 8, 2021
Controversies exist on the nature of COVID-19 related acute respiratory distress syndrome (ARDS) in particular on the static compliance of the respiratory system (Crs). We aimed to analyze the association of Crs with outcome in COVID-19-associated ARDS, to ascertain its determinants and to describe its evolution at day-14. In this observational multicenter cohort of patients with moderate to severe Covid-19 ARDS, Crs was measured at day-1 and day-14. Association between Crs or Crs/ideal body weight (IBW) and breathing without assistance at day-28 was analyzed with multivariable logistic regression. Determinants were ascertained by multivariable linear regression. Day-14 Crs was compared to day-1 Crs with paired t-test in patients still under controlled mechanical ventilation. The mean Crs in 372 patients was 37.6 ± 13 mL/cmH2O, similar to as in ARDS of other causes. Multivariate linear regression identified chronic hypertension, low PaO2/FiO2 ratio, low PEEP, and low tidal volume as associated with lower Crs/IBW. After adjustment on confounders, nor Crs [OR 1.0 (CI 95% 0.98–1.02)] neither Crs/IBW [OR 0.63 (CI 95% 0.13–3.1)] were associated with the chance of breathing without assistance at day-28 whereas plateau pressure was [OR 0.93 (CI 95% 0.88–0.99)]. In a subset of 108 patients, day-14 Crs decreased compared to day-1 Crs (31.2 ± 14.4 mL/cmH2O vs 37.8 ± 11.4 mL/cmH2O, p < 0.001). The decrease in Crs was not associated with day-28 outcome. In a large multicenter cohort of moderate to severe COVID-19 ARDS, mean Crs was decreased below 40 mL/cmH2O and was not associated with day-28 outcome. Crs decreased between day-1 and day-14 but the decrease was not associated with day-28 outcome.
COVID-19 cognitive deficits after respiratory assistance in the subacute phase: A COVID-rehabilitation unit experience
PLOS ONE, February 8, 2021
COVID-19 complications can include neurological, psychiatric, psychological, and psychosocial impairments. Little is known on the consequences of SARS-COV-2 on cognitive functions of patients in the sub-acute phase of the disease. We aimed to investigate the impact of COVID-19 on cognitive functions of patients admitted to the COVID-19 Rehabilitation Unit of the San Raffaele Hospital (Milan, Italy). 87 patients admitted to the COVID-19 Rehabilitation Unit from March 27th to June 20th 2020 were included. Patients underwent Mini Mental State Evaluation (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton Rating Scale for Depression, and Functional Independence Measure (FIM). Data were divided in 4 groups according to the respiratory assistance in the acute phase: Group1 (orotracheal intubation), Group2 (non-invasive ventilation using Biphasic Positive Airway Pressure), Group3 (Venturi Masks), Group4 (no oxygen therapy). Follow-ups were performed at one month after home-discharge. Out of the 87 patients (62 Male, mean age 67.23 ± 12.89 years), 80% had neuropsychological deficits (MoCA and MMSE) and 40% showed mild-to-moderate depression. Group1 had higher scores than Group3 for visuospatial/executive functions (p = 0.016), naming (p = 0.024), short- and long-term memory (p = 0.010, p = 0.005), abstraction (p = 0.024), and orientation (p = 0.034). Group1 was younger than Groups2 and 3. Cognitive impairments correlated with patients’ age. Only 18 patients presented with anosmia. Their data did not differ from the other patients. FIM (<100) did not differ between groups. Patients partly recovered at one-month follow-up and 43% showed signs of post-traumatic stress disorder. In conclusion, patients with severe functional impairments had important cognitive and emotional deficits, which might have been influenced by the choice of ventilatory therapy, but mostly appeared to be related to aging, independently of FIM scores. These findings should be integrated for correct neuropsychiatric assistance of COVID-19 patients in the subacute phase of the disease, and show the need for long-term psychological support and treatment of post-COVID-19 patients.
S100A9 blockade prevents lipopolysaccharide-induced lung injury via suppressing the NLRP3 pathway
Respiratory Research, February 6, 2021
S100 calcium binding protein A9 (S100A9) is a pro-inflammatory alarmin associated with several inflammation-related diseases. However, the role of S100A9 in lung injury in sepsis has not been fully investigated. Therefore, the present study aimed to determine the role of S100A9 in a lipopolysaccharide (LPS)-induced lung injury murine model and its underlying molecular mechanisms. LPS was utilized to induce sepsis and lung injury in C57BL/6 or NOD-like receptor family pyrin domain containing 3 (NLRP3)−/− mice. To investigate the effects of S100A9 blockade, mice were treated with a specific inhibitor of S100A9. Subsequently, lung injury and inflammation were evaluated by histology and enzyme linked immunosorbent assay (ELISA), respectively. Furthermore, western blot analysis and RT-qPCR were carried out to investigate the molecular mechanisms underlying the effects of S100A9. S100A9 was upregulated in the lung tissues of LPS-treated mice. However, inhibition of S100A9 alleviated LPS-induced lung injury. Additionally, S100A9 blockade also attenuated the inflammatory responses and apoptosis in the lungs of LPS-challenged mice. Furthermore, the increased expression of NLRP3 was also suppressed by S100A9 blockade, while S100A9 blockade had no effect on NLRP3−/− mice. In vitro, S100A9 downregulation mitigated LPS-induced inflammation. Interestingly, these effects were blunted by NLRP3 overexpression. The results of the current study suggested that inhibition of S100A9 could protect against LPS-induced lung injury via inhibiting the NLRP3 pathway. Therefore, S100A9 blockade could be considered as a novel therapeutic strategy for lung injury in sepsis.
Oxygen administration for patients with ARDS
Journal of Intensive Care, February 6, 2021
Acute respiratory distress syndrome (ARDS) is a fatal condition with insufficiently clarified etiology. Supportive care for severe hypoxemia remains the mainstay of essential interventions for ARDS. In recent years, adequate ventilation to prevent ventilator-induced lung injury (VILI) and patient self-inflicted lung injury (P-SILI) as well as lung-protective mechanical ventilation has an increasing attention in ARDS. Ventilation-perfusion mismatch may augment severe hypoxemia and inspiratory drive and consequently induce P-SILI. Respiratory drive and effort must also be carefully monitored to prevent P-SILI. Airway occlusion pressure (P0.1) and airway pressure deflection during an end-expiratory airway occlusion (Pocc) could be easy indicators to evaluate the respiratory drive and effort. Patient-ventilator dyssynchrony is a time mismatching between patient’s effort and ventilator drive. Although it is frequently unrecognized, dyssynchrony can be associated with poor clinical outcomes. Dyssynchrony includes trigger asynchrony, cycling asynchrony, and flow delivery mismatch. Ventilator-induced diaphragm dysfunction (VIDD) is a form of iatrogenic injury from inadequate use of mechanical ventilation. Excessive spontaneous breathing can lead to P-SILI, while excessive rest can lead to VIDD. Optimal balance between these two manifestations is probably associated with the etiology and severity of the underlying pulmonary disease. High-flow nasal cannula (HFNC) and non-invasive positive pressure ventilation (NPPV) are non-invasive techniques for supporting hypoxemia. While they are beneficial as respiratory supports in mild ARDS, there can be a risk of delaying needed intubation. Mechanical ventilation and ECMO are applied for more severe ARDS. However, as with HFNC/NPPV, inappropriate assessment of breathing workload potentially has a risk of delaying the timing of shifting from ventilator to ECMO. Various methods of oxygen administration in ARDS are important. However, it is also important to evaluate whether they adequately reduce the breathing workload and help to improve ARDS.
Preexisting respiratory diseases and clinical outcomes in COVID-19: a multihospital cohort study on predominantly African American population
Respiratory Research, February 5, 2021
Comorbidities play a key role in severe disease outcomes in COVID-19 patients. However, the literature on preexisting respiratory diseases and COVID-19, accounting for other possible confounders, is limited. The primary objective of this study was to determine the association between preexisting respiratory diseases and severe disease outcomes among COVID-19 patients. Secondary aim was to investigate any correlation between smoking and clinical outcomes in COVID-19 patients. This is a multihospital retrospective cohort study on 1871 adult patients between March 10, 2020, and June 30, 2020, with laboratory confirmed COVID-19 diagnosis. The main outcomes of the study were severe disease outcomes, i.e. mortality, need for mechanical ventilation, and intensive care unit (ICU) admission. During statistical analysis, possible confounders such as age, sex, race, BMI, and comorbidities including, hypertension, coronary artery disease, congestive heart failure, diabetes, any history of cancer and prior liver disease, chronic kidney disease, end-stage renal disease on dialysis, hyperlipidemia and history of prior stroke, were accounted for. A total of 1871 patients (mean (SD) age, 64.11 (16) years; 965(51.6%) males; 1494 (79.9%) African Americans; 809 (43.2%) with ≥ 3 comorbidities) were included in the study. During their stay at the hospital, 613 patients (32.8%) died, 489 (26.1%) needed mechanical ventilation, and 592 (31.6%) required ICU admission. In fully adjusted models, patients with preexisting respiratory diseases had significantly higher mortality (adjusted Odds ratio (aOR), 1.36; 95% CI, 1.08–1.72; p = 0.01), higher rate of ICU admission (aOR, 1.34; 95% CI, 1.07–1.68; p = 0.009) and increased need for mechanical ventilation (aOR, 1.36; 95% CI, 1.07–1.72; p = 0.01). Additionally, patients with a history of smoking had significantly higher need for ICU admission (aOR, 1.25; 95% CI, 1.01–1.55; p = 0.03) in fully adjusted models. Preexisting respiratory diseases are an important predictor for mortality and severe disease outcomes, in COVID-19 patients. These results can help facilitate efficient resource allocation for critical care services.
Lung function fluctuation patterns unveil asthma and COPD phenotypes unrelated to type 2 inflammation
Journal of Allergy and Clinical Immunology, February 3, 2021
In all chronic airway diseases, the dynamics of airway function are influenced by underlying airway inflammation and bronchial hyperresponsiveness along with limitations in reversibility, due to airway and lung remodeling as well as mucous plugging. The relative contribution of each component translates into specific clinical patterns of symptoms, quality of life, exacerbation risk, and treatment success. We aimed to evaluate whether subgrouping of patients with obstructive airway diseases according to patterns of lung function fluctuation allows identification of specific phenotypes with distinct clinical characteristics. We applied the novel method of fluctuation-based clustering (FBC) to the twice-daily FEV1 measurements recorded over a one-year period in a mixed group of 134 adults with mild-to-moderate asthma, severe asthma, or COPD from the European BIOAIR cohort. Independent of clinical diagnosis, FBC divided patients into 4 fluctuation-based clusters with progressively increasing lung functional alterations that corresponded with patterns of increasing clinical severity, risk of exacerbation and lower quality of life. Clusters of patients with airway disease were identified with significantly elevated biomarkers relating to remodeling (osteonectin) and cellular senescence (plasminogen activator inhibitor-1), accompanied by a loss of airway reversibility, pulmonary hyperinflation and loss of diffusion capacity. The 4 clusters generated were stable over time and revealed no differences in markers of type 2 inflammation (blood eosinophils and periostin).
SARS-CoV-2 spike protein S1 subunit induces pro-inflammatory responses via Toll-like receptor 4 signaling in murine and human macrophages
Heliyon, February 2, 2021
Coronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has now spread globally. Some patients develop severe complications including multiple organ failure. It has been suggested that excessive inflammation associated with the disease plays major role in the severity and mortality of COVID-19. To elucidate the inflammatory mechanisms involved in COVID-19, we examined the effects of SARS-CoV-2 spike protein S1 subunit (hereafter S1) on the pro-inflammatory responses in murine and human macrophages. Murine peritoneal exudate macrophages produced pro-inflammatory mediators in response to S1 exposure. Exposure to S1 also activated nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) signaling pathways. Pro-inflammatory cytokine induction by S1 was suppressed by selective inhibitors of NF-κB and JNK pathways. Treatment of murine peritoneal exudate macrophages and human THP-1 cell-derived macrophages with a toll-like receptor 4 (TLR4) antagonist attenuated pro-inflammatory cytokine induction and the activation of intracellular signaling by S1 and lipopolysaccharide. Similar results were obtained in experiments using TLR4 siRNA-transfected murine RAW264.7 macrophages. In contrast, TLR2 neutralizing antibodies could not abrogate the S1-induced pro-inflammatory cytokine induction in either RAW264.7 or THP-1 cell-derived macrophages. These results suggest that SARS-CoV-2 spike protein S1 subunit activates TLR4 signaling to induce pro-inflammatory responses in murine and human macrophages. Therefore, TLR4 signaling in macrophages may be a potential target for regulating excessive inflammation in COVID-19 patients.
Mediastinal lymphadenopathy may predict 30-day mortality in patients with COVID-19
Clinical Imaging, February 2, 2021
There is scarce data on the impact of the presence of mediastinal lymphadenopathy on the prognosis of coronavirus-disease 2019 (COVID-19). We aimed to investigate whether its presence is associated with increased risk for 30-day mortality in a large group of patients with COVID-19. In this retrospective cross-sectional study, 650 adult laboratory-confirmed hospitalized COVID-19 patients were included. Patients with comorbidities that may cause enlarged mediastinal lymphadenopathy were excluded. Demographics, clinical characteristics, vital and laboratory findings, and outcome were obtained from electronic medical records. Computed tomography scans were evaluated by two blinded radiologists. Univariate and multivariate logistic regression analyses were performed to determine independent predictive factors of 30-day mortality. Patients with enlarged mediastinal lymphadenopathy (n = 60, 9.2%) were older and more likely to have at least one comorbidity than patients without enlarged mediastinal lymphadenopathy (p = 0.03, p = 0.003). There were more deaths in patients with enlarged mediastinal lymphadenopathy than in those without (11/60 vs 45/590, p = 0.01). Older age (OR:3.74, 95% CI: 2.06–6.79; p < 0.001), presence of consolidation pattern (OR:1.93, 95% CI: 1.09–3.40; p = 0.02) and enlarged mediastinal lymphadenopathy (OR:2.38, 95% CI:1.13–4.98; p = 0.02) were independently associated with 30-day mortality.
Helmet CPAP use in COVID-19 – A practical review
Pulmonology, February 1, 2021
Helmet CPAP (H-CPAP) has been recommended in many guidelines as a noninvasive respiratory support during COVID-19 pandemic in many countries around the world. It has the least amount of particle dispersion and air contamination among all noninvasive devices and may mitigate the ICU bed shortage during a COVID surge as well as a decreased need for intubation/mechanical ventilation. It can be attached to many oxygen delivery sources. The MaxVenturi setup is preferred as it allows for natural humidification, low noise burden, and easy transition to HFNC during breaks and it is the recommended transport set-up. The patients can safely be proned with the helmet. It can also be used to wean the patients from invasive mechanical ventilation. Our article reviews in depth the pathophysiology of COVID-19 ARDS, provides rationale of using H-CPAP, suggests a respiratory failure algorithm, guides through its setup and discusses the issues and concerns around using it.
Colchicine and SARS-CoV-2: Management of the Hyperinflammatory State
Respiratory Medicine, February 1, 2021
The global COVID-19 pandemic is currently underway. In December 2020, the European Agency of Medicine (EMA) licensed the first Sars-CoV-2 vaccine. Therapeutic management of the COVID-19 positive patient should primarily aim to avoid the severe complications and organ injury caused by generalized inflammation caused by a cytokine storm and occurring in the most severe stages of viral infection. Current knowledge of the pathophysiological mechanisms of SARS- CoV-2 suggests a central role for exaggerated activation of the innate immune system as an important contributor to the adverse outcomes of COVID-19. Several studies have shown that blocking the cytokine storm or acting early with prevention of it can be effective; studies are underway to evaluate agents that may be able to reduce this hyperinflammatory state. The search for effective management strategies for COVID-19 continues to evolve. The actions of colchicine, one of the oldest anti-inflammatory therapies, target multiple targets associated with excessive COVID-19 inflammation. Colchicine is easily administered, generally well tolerated, and inexpensive. This article reports the scientific and molecular rationale for the use of colchicine as monotherapy or in combination in the various stages of SARS-CoV-2 infection to modulate and control the inflammatory state. Low-dose colchicine may be considered safe and effective for the treatment and prevention of cytokine storm in patients with SARS-CoV-2 infection, particularly as an adjunctive remedy to other therapeutic agents. Well-organized clinical studies are needed in this direction.
COVIDetection-Net: A Tailored COVID-19 Detection from Chest Radiography Images Using Deep Learning
Optik, February 1, 2021
In this study, a medical system based on Deep Learning (DL) which we called “COVIDetection-Net” is proposed for automatic detection of new corona virus disease 2019 (COVID-19) infection from chest radiography images (CRIs). The proposed system is based on ShuffleNet and SqueezeNet architecture to extract deep learned features and Multiclass Support Vector Machines (MSVM) for detection and classification. Our dataset contains 1200 CRIs that collected from two different publicly available databases. Extensive experiments were carried out using the proposed model. The highest detection accuracy of 100% for COVID/NonCOVID, 99.72% for COVID/Normal/pneumonia and 94.44% for COVID/Normal/Bacterial pneumonia/Viral pneumonia have been obtained. The proposed system superior all published methods in recall, specificity, precision, F1-Score and accuracy. Confusion Matrix (CM) and Receiver Operation Characteristics (ROC) analysis are also used to depict the performance of the proposed model. Hence the proposed COVIDetection-Net can serve as an efficient system in the current state of COVID-19 pandemic and can be used in everywhere that are facing shortage of test kits.
Allergy and Coronavirus Disease (Covid-19) International Survey: Real-Life Data From the Allergy Community During the Pandemic
World Allergy Organization Journal, January 31, 2021
The COVID-19 outbreak brought an unprecedented challenge to the world. Knowledge in the field has been increasing exponentially and the main allergy societies have produced guidance documents for better management of allergic patients during this period. However, few publications so far have provided real-life data from the allergy community concerning the allergy practice during the COVID-19 outbreak. Therefore, we proposed an international survey on the management of allergic patients during the current pandemic. We performed an online survey undertaken to reach out the worldwide allergy community by e-mail and social media. The web-questionnaire contained 24 questions covering demographic data from the participants, clinical practice during this period, and questions related to the new international classification and coding tools addressed for COVID-19. It was circulated for 8 weeks and had anonymous and volunteer context. Data are presented for 635 participants from 78 countries of all continents. Allergists with long-term professional experience were the main audience. As expected, we received many responses as “I have no data” or “I don’t know” to the questions of the survey. However, most with more experience on managing allergic patients during the pandemic agreed that patients suffering from allergic or hypersensitivity conditions have no increased risk of contracting COVID-19 or developing SARS CoV-2. Also, participants mentioned that none of the allergy treatments (inhaled corticosteroids, allergen immunotherapy, biological agents) increased the risk of contracting COVID-19 infection including severe presentations. The information here presented intends to be helpful to the community but represents a course of action in a highly specific situation due to the state of emergency, and should be helpful to the health systems.
Bronchoscopy precautions and recommendations in the COVID-19 pandemic
Paediatric Respiratory Reviews, January 29, 2021
As the airways of SARS-CoV-2 infected patients contain a high viral load, bronchoscopy is associated with increased risk of patient to health care worker transmission due to aerosolised viral particles and contamination of surfaces during bronchoscopy. Bronchoscopy is not appropriate for diagnosing SARS-CoV-2 infection and, as an aerosol generating procedure involving a significant risk of transmission, has a very limited role in the management of SARS-CoV-2 infected patients including children. During the SARS-CoV-2 pandemic rigid bronchoscopy should be avoided due to the increased risk of droplet spread. Flexible bronchoscopy should be performed first in SARS-CoV-2 positive individuals or in unknown cases, to determine if rigid bronchoscopy is indicated. When available single-use flexible bronchoscopes may be considered for use; devices are available with a range of diameters, and improved image quality and degrees of angulation. When rigid bronchoscopy is necessary, jet ventilation must be avoided and conventional ventilation be used to reduce the risk of aerosolisation. Adequate personal protection equipment is key, as is training of health care workers in correct donning and doffing. Modified full face masks are a practical and safe alternative to filtering facepieces for use in bronchoscopy. When anaesthetic and infection prevention control protocols are strictly adhered to, bronchoscopy can be performed in SARS-CoV-2 positive children.
Spontaneous Pneumothorax: An Emerging Complication of COVID-19 Pneumonia
Heart & Lung, January 29, 2021
Spontaneous Pneumothorax in the setting of coronavirus disease 19 (COVID-19) has been rarely described and is a potentially lethal complication. We report our institutional experience from February 21, 2020 to May 21, 2020. Patients with confirmed COVID-19 who were admitted at 5 hospitals within the Inova Health System between February 21, 2020 and May 21, 2020 were included in the study. We identified 1619 patients, 22 patients (1.4%) developed spontaneous pneumothorax during their hospitalization without evidence of traumatic injury. The median age of the patients was 60 years and 82% were male. The majority of the cohort was Hispanic at 95%. The median BMI was 25.4, 52% of patients had a history of hypertension, 32% had a history of diabetes mellitus and 14% were smokers. Spontaneous pneumothorax was diagnosed between the 1st and 15th day of hospitalization (median 9th day) and 100% of patients were diagnosed by chest X-ray. There were 16 patients (73% of the overall population) who had a chest tube placed and the remaining 6 patients were monitored closely. Eight patients died (36% of the overall population) with fourteen patients either remaining in hospital or discharged to home. Of the 8 that remain hospitalized, 2 patients are on extracorporeal membrane oxygenation (ECMO), 2 patients remain on the vent. The median length of hospitalization was 18.5 days as of May 20, 2020.
Audio Interview: A Covid-19 Conversation with Anthony Fauci
New England Journal of Medicine, January 28, 2021
[Editorial, 43:42] The continuing spread of SARS-CoV-2 remains a Public Health Emergency of International Concern. What physicians need to know about transmission, diagnosis, and treatment of Covid-19 is the subject of ongoing updates from infectious disease experts at the Journal. In this audio interview conducted on January 27, 2021, the editors are joined by Dr. Anthony Fauci, U.S. Chief Medical Advisor, to discuss Covid-19 testing, therapeutics, and vaccines.
Six-Month Follow-up Chest CT findings after Severe COVID-19 Pneumonia
Radiology, January 26, 2021
Little is known about the long-term lung radiographic changes in convalescent COVID-19 patients, especially the severe cases. Our purpose was to prospectively assess pulmonary sequelae and explore the risk factors for lung fibrotic-like changes on six-month follow-up chest CT of survivors of severe COVID-19 pneumonia. 114 patients (80[70%] men; mean age, 54±12 years) were studied prospectively. Initial and follow-up CT scans were obtained on 17±11 days and 175±20 days respectively after symptom onset. Lung changes (opacification, consolidation, reticulation, and fibrotic-like changes) and CT extent scores (score per lobe, 0-5; maximum score, 25) were recorded. Patients were divided into two groups: group#1 presence and group#2 absence of CT evidence of fibrotic-like changes (traction bronchiectasis, parenchymal bands, and/or honeycombing) based on their six-month follow-up CT. Multiple logistic regression analyses were performed to identify the independent predictive factors of fibrotic-like changes. On follow-up CT, evidence of fibrotic-like changes was observed in 40/114 (35%) of patients (group#1), while the remaining 74/114 (65%) patients (group#2) showed either complete radiological resolution (43/114, 38%) or residual ground-glass opacification or interstitial thickening (31/114, 27%). Multivariable analysis identified age >50 years (odds ratio [OR]:8.5, 95%CI:1.9-38, p=.01), heart rate >100bpm at admission (OR:5.6, 95%CI:1.1-29, p=.04), duration of in-hospital stay ≥17 days (OR:5.5, 95%CI:1.5-21, p=.01), and acute respiratory distress syndrome (OR:13, 95%CI:3.3-55, p<.001), non-invasive mechanical ventilation (OR:6.3, 95%CI:1.3-30, p=.02) and total CT score ≥18 (OR:4.2, 95%CI:1.2-14, p=.02) on initial CT as independent predictors for lung fibrotic-like changes at 6 months.
Clinical course of COVID-19 patients needing supplemental oxygen outside the intensive care unit
Scientific Reports, January 26, 2021
Patients suffering from CVOID-19 mostly experience a benign course of the disease. Approximately 14% of SARS-CoV2 infected patients are admitted to a hospital. Cohorts exhibiting severe lung failure in the form of acute respiratory distress syndrome (ARDS) have been well characterized. Patients without ARDS but in need of supplementary oxygen have received much less attention. This study describes the diagnosis, symptoms, treatment and outcomes of hospitalized patients with COVID-19 needing oxygen support during their stay on regular ward. All 133 patients admitted to the RWTH Aachen university hospital with the diagnosis of COVID-19 were included in an observational registry. Clinical data sets were extracted from the hospital information system. This analysis includes all 57 patients requiring supplemental oxygen not admitted to the ICU. Fifty-seven patients needing supplemental oxygen and being treated outside the ICU were analyzed. Patients exhibited the typical set of symptoms for COVID-19. Of note, hypoxic patients mostly did not suffer from clinically relevant dyspnea despite oxygen saturations below 92%. Patients had fever for 7 [2–11] days and needed supplemental oxygen for 8 [5–13] days resulting in an overall hospitalization time of 12 [7–20] days. In addition, patients had persisting systemic inflammation with CRP levels remaining elevated until discharge or death. This description of COVID-19 patients requiring oxygen therapy should be taken into account when planning treatment capacity. Patients on oxygen need long-term inpatient care.
Lung ultrasound can predict response to the prone position in awake non-intubated patients with COVID 19 associated acute respiratory distress syndrome
Critical Care, January 25, 2021
[Letter to the Editor] Prone positioning (PP) is a well-known therapeutic strategy used in acute respiratory distress syndrome (ARDS). Several studies demonstrated positive effects of PP on oxygenation parameters in awake non-intubated patients with COVID-19-associated ARDS. However, PP is not effective in every case. The pilot study by Elharrar, et al. demonstrated a significant improvement of oxygenation parameters during PP in only 25% of the patients. The results of previous studies highlighted heterogeneity of COVID-19-associated ARDS, which demands further studies of the predictors of PP effectiveness and indications for its use in COVID-19 patients. The main objective of our study was to evaluate whether the changes of lung aeration assessed by lung ultrasound (LUS) can predict the oxygenation response during PP. This prospective cohort study was conducted in COVID-19 care units of two university-affiliated hospitals (Sechenov University) between April 8 and May 10, 2020. The study included spontaneously breathing patients with confirmed or suspected diagnosis of COVID-19, and bilateral changes detected by high-resolution computed tomography and PaO2/FiO2 < 300 mmHg. The study included 22 COVID-19 patients. Median age was 48.5 (39.8–62.8) years, 16 were male, and the median body mass index was 28.7 (27.3–31.6)kg/m2. The main co-morbidities were arterial hypertension (31.8%) and diabetes mellitus (18.2%). Sixteen patients (72.7%) received CPAP and 6 patients (27.3%) received oxygen therapy. Sixteen of 22 patients (72.7%) responded to PP treatment with significant increase in PaO2/FiO2. At the same time, fewer patients had clinically significant improvement in dyspnea score—3 patients (13.6%) at 15 min in PP and 12 patients (54.5%) at 3 h in PP. RR also significantly improved in responders.
The evaluation of maximum condyle-tragus distance can predict difficult airway management without exposing upper respiratory tract; a prospective observational study
BMC Anesthesiology, January 25, 2021
Routine preoperative methods to assess airway such as the interincisor distance (IID), Mallampati classification, and upper lip bite test (ULBT) have a certain risk of upper respiratory tract exposure and virus spread. Condyle-tragus maximal distance(C-TMD) can be used to assess the airway, and does not require the patient to expose the upper respiratory tract, but its value in predicting difficult laryngoscopy compared to other indicators (Mallampati classification, IID, and ULBT) remains unknown. The purpose of this study was to observe the value of C-TMD to predict difficult laryngoscopy and the influence on intubation time and intubation attempts, and provide a new idea for preoperative airway assessment during epidemic. Adult patients undergoing general anesthesia and tracheal intubation were enrolled. IID, Mallampati classification, ULBT, and C-TMD of each patient were evaluated before the initiation of anesthesia. The primary outcome was intubation time. Three hundred four patients were successfully enrolled and completed the study, 39 patients were identified as difficult laryngoscopy. The intubation time was shorter with the C-TMD>1 finger group 46.8 ± 7.3 s, compared with the C-TMD<1 finger group 50.8 ± 8.6 s (p<0.01). First attempt success rate was higher in the C-TMD>1 finger group 98.9% than in the C-TMD<1 finger group 87.1% (P<0.01). The correlation between the C-TMD and Cormack-Lehane Level was 0.317 (Spearman correlation coefficient, P<0.001), and the area under the ROC curve was 0.699 (P<0.01). The C-TMD < 1 finger width was the most consistent with difficult laryngoscopy (κ = 0.485;95%CI:0.286–0.612) and its OR value was 10.09 (95%CI: 4.19–24.28), sensitivity was 0.469 (95%CI: 0.325–0.617), specificity was 0.929 (95%CI: 0.877–0.964), positive predictive value was 0.676 (95%CI: 0.484–0.745), negative predictive value was 0.847 (95%CI: 0.825–0.865).
Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial
The Lancet, January 22, 2021
Mechanical ventilation in intensive care for 48 h or longer is associated with the acute respiratory distress syndrome (ARDS), which might be present at the time ventilatory support is instituted or develop afterwards, predominantly during the first 5 days. Survivors of prolonged mechanical ventilation and ARDS are at risk of considerably impaired physical function that can persist for years. An early pathogenic mechanism of lung injury in mechanically ventilated, critically ill patients is inflammation-induced pulmonary fibrin deposition, leading to thrombosis of the microvasculature and hyaline membrane formation in the air sacs. The main aim of this study was to determine if nebulised heparin, which targets fibrin deposition, would limit lung injury and thereby accelerate recovery of physical function in patients with or at risk of ARDS. The Can Heparin Administration Reduce Lung Injury (CHARLI) study was an investigator-initiated, multicentre, double-blind, randomised phase 3 trial across nine hospitals in Australia. Adult intensive care patients on invasive ventilation, with impaired oxygenation defined by a PaO2/FiO2 ratio of less than 300, and with the expectation of invasive ventilation beyond the next calendar day were recruited. Key exclusion criteria were heparin allergy, pulmonary bleeding, and platelet count less than 50X10⁹/L. Patients were randomly assigned 1:1, with stratification by site and using blocks of variable size and random seed, via a web-based system, to either unfractionated heparin sodium 25 000 IU in 5 mL or identical placebo (sodium chloride 0·9% 5 mL), administered using a vibrating mesh membrane nebuliser every 6 h to day 10 while invasively ventilated. Patients, clinicians, and investigators were masked to treatment allocation. The primary outcome was the Short Form 36 Health Survey Physical Function Score (out of 100) of survivors at day 60.
Surfactant for Treatment of ARDS in COVID-19 Patient
CHEST, January 22, 2021
Patients with coronavirus disease 2019 (COVID-19) suffer from severe respiratory symptoms consistent with acute respiratory distress syndrome (ARDS). The clinical presentation of ARDS in COVID-19 is often atypical, as COVID-19 patients exhibit a disproportionate hypoxemia as compared to a relatively preserved lung mechanics. This pattern is more similar to neonatal respiratory distress syndrome (RDS) secondary to surfactant deficiency, which has been shown to benefit from exogenous surfactant. We present our experience with exogenous surfactant treatment in a COVID-19 patient suffering from COVID-19 related ARDS. The patient responded with improved oxygenation, and we believe surfactant was the catalyst for the successful extubation and clinical improvement of the patient.
The use of electrical impedance tomography for individualized ventilation strategy in COVID-19: a case report
BMC Pulmonary Medicine, January 22, 2021
Clinical management of COVID-19 requires close monitoring of lung function. While computed tomography (CT) offers ideal way to identify the phenotypes, it cannot monitor the patient response to therapeutic interventions. We present a case of ventilation management for a COVID-19 patient where electrical impedance tomography (EIT) was used to personalize care. A 53-year-old male was sent to Far Eastern Memorial Hospital, Taiwan, due to shortness of breath for ~ 2 weeks and pneumonia confirmed by chest X-ray. Disease history included sleep apnoea, coronary artery disease after percutaneous occlusion balloon angioplasty and medication controlled hypertension. SARS-CoV-2 was confirmed positive. The patient developed acute respiratory distress syndrome, required invasive mechanical ventilation, and was subsequently weaned. EIT was used multiple times: to titrate the positive end-expiratory pressure, understand the influence of body position, and guide the support levels during weaning and after extubation. We show how EIT provides bedside monitoring of the patient´s response to various therapeutic interventions and helps guide treatments. EIT provides unique information that may help the ventilation management in the pandemic of COVID-19.
Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages
Cell Research, January 21, 2021
How the innate and adaptive host immune system miscommunicate to worsen COVID-19 immunopathology has not been fully elucidated. Here, we perform single-cell deep-immune profiling of bronchoalveolar lavage (BAL) samples from 5 patients with mild and 26 with critical COVID-19 in comparison to BALs from non-COVID-19 pneumonia and normal lung. We use pseudotime inference to build T-cell and monocyte-to-macrophage trajectories and model gene expression changes along them. In mild COVID-19, CD8+ resident-memory (TRM) and CD4+ T-helper-17 (TH17) cells undergo active (presumably antigen-driven) expansion towards the end of the trajectory, and are characterized by good effector functions, while in critical COVID-19 they remain more naïve. Vice versa, CD4+ T-cells with T-helper-1 characteristics (TH1-like) and CD8+ T-cells expressing exhaustion markers (TEX-like) are enriched halfway their trajectories in mild COVID-19, where they also exhibit good effector functions, while in critical COVID-19 they show evidence of inflammation-associated stress at the end of their trajectories. Monocyte-to-macrophage trajectories show that chronic hyperinflammatory monocytes are enriched in critical COVID-19, while alveolar macrophages, otherwise characterized by anti-inflammatory and antigen-presenting characteristics, are depleted. In critical COVID-19, monocytes contribute to an ATP-purinergic signaling-inflammasome footprint that could enable COVID-19 associated fibrosis and worsen disease-severity. Finally, viral RNA-tracking reveals infected lung epithelial cells, and a significant proportion of neutrophils and macrophages that are involved in viral clearance.
Integrated photothermal decontamination device for N95 respirators
Scientific Reports, January 19, 2021
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the COVID-19 global pandemic has infected over 25 million people worldwide and resulted in the death of millions. The COVID-19 pandemic has also resulted in a shortage of personal protective equipment (PPE) in many regions around the world, particularly in middle- and low-income countries. The shortages of PPE, such as N95 respirators, is something that will persist until an effective vaccine is made available. Thus, devices that while being easy to operate can also be rapidly deployed in health centers, and long-term residences without the need for major structural overhaul are instrumental to sustainably use N95 respirators. In this report, we present the design and validation of a decontamination device that combines UV-C & B irradiation with mild-temperature treatment. The device can decontaminate up to 20 masks in a cycle of < 30 min. The decontamination process did not damage or reduce the filtering capacity of the masks. Further, the efficacy of the device to eliminate microbes and viruses from the masks was also evaluated. The photothermal treatment of our device was capable of eradicating > 99.9999% of the bacteria and > 99.99% of the virus tested.
More skilled clinical management of COVID-19 patients modified mortality in an intermediate respiratory intensive care unit in Italy
Respiratory Research, January 15, 2021
Some studies investigated epidemiological and clinical features of laboratory-confirmed patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the virus causing coronavirus disease 2019 (COVID-19), but limited attention has been paid to the follow-up of hospitalized patients on the basis of clinical setting and the expertise of clinical management. In the present single-centered, retrospective, observational study, we reported findings from 87 consecutive laboratory-confirmed COVID-19 patients with moderate-to-severe acute respiratory syndrome hospitalized in an intermediate Respiratory Intensive Care Unit (RICU), subdividing the patients in two groups according to the admission date (before and after March 29, 2020). With improved skills in the clinical management of COVID-19, we observed a significant lower mortality in the T2 group compared with the T1 group and a significantly difference in terms of mortality among the patients transferred in Intensive Care Unit (ICU) from our intermediate RICU (100% in T1 group vs. 33.3% in T2 group). The average length of stay in intermediate RICU of ICU-transferred patients who survived in T1 and T2 was significantly longer than those who died (who died 3.3 ± 2.8 days vs. who survived 6.4 ± 3.3 days).
Impact of high dose prophylactic anticoagulation in critically ill patients with COVID-19 pneumonia
CHEST, January 15, 2021
Due to the high risk of thrombotic complications (TC) during SARS-CoV-2 infection, several scientific societies have proposed to increase the dose of preventive anticoagulation, although arguments in favor of this strategy are inconsistent. Our objective was to determine the incidence of TC in critically ill patients with COVID-19 and what is the relationship between the dose of anticoagulant therapy and the incidence of TC? All consecutive patients referred to eight French intensive care units (ICU) for COVID-19 were included in our observational study. Clinical and laboratory data were collected from ICU admission to day 14, including anticoagulation status and thrombotic and hemorrhagic events. The effect of high dose prophylactic anticoagulation (either at intermediate or equivalent to therapeutic dose), defined using a standardized protocol of classification, was assessed using a time-varying exposure model using inverse probability of treatment weight. Out of 538 patients included, 104 patients developed a total of 122 TC with an incidence of 22.7 % (19.2-26.3). Pulmonary embolism accounted for 52 % of the recorded TC. High dose prophylactic anticoagulation was associated with a significant reduced risk of TC (HR 0.81 [0.66-0.99]) without increasing the risk of bleeding (HR 1.11 [0.70-1.75]).
Epic Deterioration Index May Identify High- and Low-Risk COVID-19 Patients
Pulmonology Advisor, January 15, 2021
The Epic Deterioration Index (EDI) can identify subsets of high- and low-risk patients with coronavirus disease 2019 (COVID-19) with good discrimination, according to study results published in the Annals of the American Thoracic Society. The EDI is a prediction model that has been used in hospitals for medical decision-making during the COVID-19 pandemic. However, it has not been independently evaluated and other models have been shown to be biased against vulnerable populations; therefore, researchers independently evaluated the EDI in hospitalized patients with COVID-19 overall and in disproportionately affected subgroups. The researchers studied patients with COVID-19 admitted to non-intensive care units (ICUs) at Michigan Medicine from March 9 to May 20, 2020. The EDI was calculated at 15-minute intervals to predict a composite outcome of ICU-level care, mechanical ventilation, or in-hospital death. Of the 392 COVID-19 hospitalizations meeting inclusion criteria, 103 (26%) met the composite outcome at a median of 2.5 days after admission. Of all hospitalizations, 88 (22%) resulted in ICU-level care, 44 (11%) in mechanical ventilation, and 35 (8.9%) in death. Patients who experienced an adverse outcome were older, more likely to be White, and more likely to have a history of cardiac arrhythmias, chronic kidney disease, congestive heart failure, depression, diabetes, hypertension, metastatic cancer, and rheumatoid arthritis or other collagen vascular diseases (all P <.05). Disparate impact analyses demonstrated that EDI predictions did not differ by sex or race.
Diagnostic Performance of CO-RADS and the RSNA Classification System in Evaluating COVID-19 at Chest CT: A Meta-Analysis
Radiology: Cardiothoracic Imaging, January 14, 2021
The purposes of the study was to determine the diagnostic performance of the COVID-19 Reporting and Data System (CO-RADS) and the Radiological Society of North America (RSNA) categorizations in patients with clinically suspected coronavirus disease 2019 (COVID-19) infection. In this meta-analysis, studies from 2020, up to August 24, 2020 were assessed for inclusion criteria of studies that used CO-RADS or the RSNA categories for scoring chest CT in patients with suspected COVID-19. A total of 186 studies were identified. After review of abstracts and text, a total of nine studies were included in this study. Patient information (n¸ age, sex), CO-RADS and RSNA scoring categories, and other study characteristics were extracted. Study quality was assessed with the QUADAS-2 tool. Meta-analysis was performed with a random effects model. Nine studies (3283 patients) were included. Overall study quality was good, except for risk of non-performance of repeated reverse transcriptase polymerase chain reaction (RT-PCR) after negative initial RT-PCR and persistent clinical suspicion in four studies. Pooled COVID-19 frequencies in CO-RADS categories were: 1, 8.8%; 2, 11.1%; 3, 24.6%; 4, 61.9%; and 5, 89.6%. Pooled COVID-19 frequencies in RSNA classification categories were: negative 14.4%; atypical, 5.7%; indeterminate, 44.9%; and typical, 92.5%. Pooled pairs of sensitivity and specificity using CO-RADS thresholds were the following: at least 3, 92.5% (95% CI: 87.1, 95.7) and 69.2% (95%: CI: 60.8, 76.4); at least 4, 85.8% (95% CI: 78.7, 90.9) and 84.6% (95% CI: 79.5, 88.5); and 5, 70.4% (95% CI: 60.2, 78.9) and 93.1% (95% CI: 87.7, 96.2). Pooled pairs of sensitivity and specificity using RSNA classification thresholds for indeterminate were 90.2% (95% CI: 87.5, 92.3) and 75.1% (95% CI: 68.9, 80.4) and for typical were 65.2% (95% CI: 37.0, 85.7) and 94.9% (95% CI: 86.4, 98.2).
Artificial intelligence matches subjective severity assessment of pneumonia for prediction of patient outcome and need for mechanical ventilation: a cohort study
Scientific Reports, January 13, 2021
Our objective was to compare the performance of artificial intelligence (AI) and Radiographic Assessment of Lung Edema (RALE) scores from frontal chest radiographs (CXRs) for predicting patient outcomes and the need for mechanical ventilation in COVID-19 pneumonia. Our IRB-approved study included 1367 serial CXRs from 405 adult patients (mean age 65 ± 16 years) from two sites in the US (Site A) and South Korea (Site B). We recorded information pertaining to patient demographics (age, gender), smoking history, comorbid conditions (such as cancer, cardiovascular and other diseases), vital signs (temperature, oxygen saturation), and available laboratory data (such as WBC count and CRP). Two thoracic radiologists performed the qualitative assessment of all CXRs based on the RALE score for assessing the severity of lung involvement. All CXRs were processed with a commercial AI algorithm to obtain the percentage of the lung affected with findings related to COVID-19 (AI score). Independent t- and chi-square tests were used in addition to multiple logistic regression with Area Under the Curve (AUC) as output for predicting disease outcome and the need for mechanical ventilation. The RALE and AI scores had a strong positive correlation in CXRs from each site (r2 = 0.79–0.86; p < 0.0001). Patients who died or received mechanical ventilation had significantly higher RALE and AI scores than those with recovery or without the need for mechanical ventilation (p < 0.001). Patients with a more substantial difference in baseline and maximum RALE scores and AI scores had a higher prevalence of death and mechanical ventilation (p < 0.001). The addition of patients’ age, gender, WBC count, and peripheral oxygen saturation increased the outcome prediction from 0.87 to 0.94 (95% CI 0.90–0.97) for RALE scores and from 0.82 to 0.91 (95% CI 0.87–0.95) for the AI scores. AI algorithm is as robust a predictor of adverse patient outcome (death or need for mechanical ventilation) as subjective RALE scores in patients with COVID-19 pneumonia.
Recombinant tissue plasminogen activator treatment for COVID-19 associated ARDS and acute cor pulmonale
The International Journal of Infectious Diseases, January 13, 2021
The literature sources pointed out that COVID-19 patients possess altered coagulation process and are connected to respiratory and cardiovascular diseases, including acute respiratory distress syndrome and acute cor pulmonale (ACP). ACP is characterized by unexpected rise in the pulmonary vascular resistance and it was described to be associated with acute respiratory distress syndrome (ARDS). We have witnessed the pandemic spread of the novel SARS-CoV-2 infection, and some patients suffering from this disease (COVID-19) have developed ARDS. Interestingly, Creel-Bulos et al reported the development of ACP in patients with severe forms of COVID-19. Furthermore, it was suggested that altered coagulation process and augmented levels of D-dimer were important attributes of pneumonia in patients infected with SARS-CoV-2. Recent study revealed that the treatment with tissue plasminogen activator provided some initial and transient improvements in patients with COVID-19 associated ARDS. In the present case report we have described the effects of the above mentioned thrombolytic in the context of COVID-19 and ACP.
Are women with asthma at increased risk for severe COVID-19?
The Lancet, January 12, 2021
[Comment] Although adults with asthma appear to have a reduced risk of severe COVID-19 compared with younger populations, women with asthma might represent a somewhat susceptible subgroup for severe COVID-19 requiring hospitalisation. A study by Atkins and colleagues established female sex as an independent risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hospitalisation among patients with asthma in the UK.This study and three additional studies from Paris, France, Illinois, USA, and New York, NY, USA, report that 37–53% of all individuals hospitalised with SARS-CoV-2 were women.However, 56–71% of patients with asthma hospitalised for COVID-19 were women in these studies. This increased proportion might be partially explained by the higher baseline prevalence of asthma in women than in men, because data from similar geographical areas suggest 51–65% of individuals with asthma are women. Several mechanisms might increase the risk of COVID-19-related hospitalisation in women with asthma. The recognition of these mechanisms might guide targeted management strategies.
Ventilator-associated pneumonia in critically ill patients with COVID-19
Critical Care, January 11, 2021
Pandemic COVID-19 caused by the coronavirus SARS-CoV-2 has a high incidence of patients with severe acute respiratory syndrome (SARS). Many of these patients require admission to an intensive care unit (ICU) for invasive ventilation and are at significant risk of developing a secondary, ventilator-associated pneumonia (VAP). To study the incidence of VAP and bacterial lung microbiome composition of ventilated COVID-19 and non-COVID-19 patients. In this retrospective observational study, we compared the incidence of VAP and secondary infections using a combination of microbial culture and a TaqMan multi-pathogen array. In addition, we determined the lung microbiome composition using 16S RNA analysis in a subset of samples. The study involved 81 COVID-19 and 144 non-COVID-19 patients receiving invasive ventilation in a single University teaching hospital between March 15th 2020 and August 30th 2020. COVID-19 patients were significantly more likely to develop VAP than patients without COVID (Cox proportional hazard ratio 2.01 95% CI 1.14–3.54, p = 0.0015) with an incidence density of 28/1000 ventilator days versus 13/1000 for patients without COVID (p = 0.009).
Prone positioning improves oxygenation and lung recruitment in patients with SARS-CoV-2 acute respiratory distress syndrome; a single centre cohort study of 20 consecutive patients
BMC Research Notes, January 9, 2021
We aimed to characterize the effects of prone positioning on respiratory mechanics and oxygenation in invasively ventilated patients with SARS-CoV-2 ARDS. This was a prospective cohort study in the Intensive Care Unit (ICU) of a tertiary referral centre. We included 20 consecutive, invasively ventilated patients with laboratory confirmed SARS-CoV-2 related ARDS who underwent prone positioning in ICU as part of their management. The main outcome was the effect of prone positioning on gas exchange and respiratory mechanics. There was a median improvement in the PaO2/FiO2 ratio of 132 in the prone position compared to the supine position (IQR 67–228). We observed lower PaO2/FiO2 ratios in those with low (< median) baseline respiratory system static compliance, compared to those with higher (> median) static compliance (P < 0.05). There was no significant difference in respiratory system static compliance with prone positioning. Prone positioning was effective in improving oxygenation in SARS-CoV-2 ARDS. Furthermore, poor respiratory system static compliance was common and was associated with disease severity. Improvements in oxygenation were partly due to lung recruitment. Prone positioning should be considered in patients with SARS-CoV-2 ARDS.
Automatic clustering method to segment COVID-19 CT images
PLOS ONE, January 8, 2021
Coronavirus pandemic (COVID-19) has infected more than ten million persons worldwide. Therefore, researchers are trying to address various aspects that may help in diagnosis this pneumonia. Image segmentation is a necessary pr-processing step that implemented in image analysis and classification applications. Therefore, in this study, our goal is to present an efficient image segmentation method for COVID-19 Computed Tomography (CT) images. The proposed image segmentation method depends on improving the density peaks clustering (DPC) using generalized extreme value (GEV) distribution. The DPC is faster than other clustering methods, and it provides more stable results. However, it is difficult to determine the optimal number of clustering centers automatically without visualization. So, GEV is used to determine the suitable threshold value to find the optimal number of clustering centers that lead to improving the segmentation process. The proposed model is applied for a set of twelve COVID-19 CT images. Also, it was compared with traditional k-means and DPC algorithms, and it has better performance using several measures, such as PSNR, SSIM, and Entropy.
Knowledge translation tools to guide care of non-intubated patients with acute respiratory illness during the COVID-19 Pandemic
Critical Care, January 8, 2021
Providing optimal care to patients with acute respiratory illness while preventing hospital transmission of COVID-19 is of paramount importance during the pandemic; the challenge lies in achieving both goals simultaneously. Controversy exists regarding the role of early intubation versus use of non-invasive respiratory support measures to avoid intubation. This review summarizes available evidence and provides a clinical decision algorithm with risk mitigation techniques to guide clinicians in care of the hypoxemic, non-intubated, patient during the COVID-19 pandemic. Although aerosolization of droplets may occur with aerosol-generating medical procedures (AGMP), including high flow nasal oxygen and non-invasive ventilation, the risk of using these AGMP is outweighed by the benefit in carefully selected patients, particularly if care is taken to mitigate risk of viral transmission. Non-invasive support measures should not be denied for conditions where previously proven effective and may be used even while there is suspicion of COVID-19 infection. Patients with de novo acute respiratory illness with suspected/confirmed COVID-19 may also benefit. These techniques may improve oxygenation sufficiently to allow some patients to avoid intubation; however, patients must be carefully monitored for signs of increased work of breathing. Patients showing signs of clinical deterioration or high work of breathing not alleviated by non-invasive support should proceed promptly to intubation and invasive lung protective ventilation strategy. With adherence to these principles, risk of viral spread can be minimized.
Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma
Respiratory Research, January 7, 2021
Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels. ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes.
CT radiomics facilitates more accurate diagnosis of COVID-19 pneumonia: compared with CO-RADS
Journal of Translational Medicine, January 7, 2021
Limited data was available for rapid and accurate detection of COVID-19 using CT-based machine learning model. This study aimed to investigate the value of chest CT radiomics for diagnosing COVID-19 pneumonia compared with clinical model and COVID-19 reporting and data system (CO-RADS), and develop an open-source diagnostic tool with the constructed radiomics model. This study enrolled 115 laboratory-confirmed COVID-19 and 435 non-COVID-19 pneumonia patients (training dataset, n = 379; validation dataset, n = 131; testing dataset, n = 40). Key radiomics features extracted from chest CT images were selected to build a radiomics signature using least absolute shrinkage and selection operator (LASSO) regression. Clinical and clinico-radiomics combined models were constructed. The combined model was further validated in the viral pneumonia cohort, and compared with performance of two radiologists using CO-RADS. The diagnostic performance was assessed by receiver operating characteristics curve (ROC) analysis, calibration curve, and decision curve analysis (DCA). Eight radiomics features and 5 clinical variables were selected to construct the combined radiomics model, which outperformed the clinical model in diagnosing COVID-19 pneumonia with an area under the ROC (AUC) of 0.98 and good calibration in the validation cohort. The combined model also performed better in distinguishing COVID-19 from other viral pneumonia with an AUC of 0.93 compared with 0.75 (P = 0.03) for clinical model, and 0.69 (P = 0.008) or 0.82 (P = 0.15) for two trained radiologists using CO-RADS. The sensitivity and specificity of the combined model can be achieved to 0.85 and 0.90. The DCA confirmed the clinical utility of the combined model. An easy-to-use open-source diagnostic tool was developed using the combined model.
Asthma and COVID-19: a systematic review
Allergy, Asthma & Clinical Immunology, January 6, 2021
Severe coronavirus disease-19 (COVID-19) presents with progressive dyspnea, which results from acute lung inflammatory edema leading to hypoxia. As with other infectious diseases that affect the respiratory tract, asthma has been cited as a potential risk factor for severe COVID-19. However, conflicting results have been published over the last few months and the putative association between these two diseases is still unproven. Here, we systematically reviewed all reports on COVID-19 published since its emergence in December 2019 to June 30, 2020, looking into the description of asthma as a premorbid condition, which could indicate its potential involvement in disease progression. We found 372 articles describing the underlying diseases of 161,271 patients diagnosed with COVID-19. Asthma was reported as a premorbid condition in only 2623 patients accounting for 1.6% of all patients.
Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults
New England Journal of Medicine, January 6, 2021
Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P=0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed.
CDC: Anaphylaxis Rate With COVID Vax 10 Times Greater Than for Flu Shots
MedPage Today, January 6, 2021
While rare, the rate of anaphylaxis following COVID-19 mRNA vaccines appeared about 10 times that documented for flu shots, CDC officials said on Wednesday. Overall, 21 cases of anaphylaxis following COVID vaccination were reported out of about 1.9 million doses given as of Dec. 23, according to an early Morbidity and Mortality Weekly Report release. That amounts to 11.1 cases per million versus an estimated 1.3 cases per million following inactivated influenza vaccine, agency officials said on a call with the media. They noted that, as of now, 29 confirmed cases of anaphylaxis are reported with the Pfizer/BioNTech and Moderna vaccines. In addition, the officials said, the MMWR report from Dec. 14-23 focuses on the Pfizer vaccine, since the Moderna vaccine was not available until Dec. 21. Still, there is not enough data to see a difference in risk between vaccines. No deaths from anaphylaxis have been seen to date. Nancy Messonnier, MD, director of CDC’s National Center for Immunization and Respiratory Diseases, emphasized that these events were rare and that the benefits of COVID-19 vaccination outweighed the risks. Moreover, comparing these to the numbers for flu “misses the point” when there are over 2,000 deaths from COVID-19 every day in the U.S.
The role of CPAP as a potential bridge to invasive ventilation and as a ceiling-of-care for patients hospitalized with Covid-19—An observational study
PLOS ONE, December 31, 2020
Continuous positive airway pressure (CPAP) ventilation may be used as a potential bridge to invasive mechanical ventilation (IMV), or as a ceiling-of-care for persistent hypoxaemia despite standard oxygen therapy, according to UK guidelines. We examined the association of mode of respiratory support and ceiling-of-care on mortality. We conducted a retrospective cohort analysis of routinely collected de-identified data of adults with nasal/throat SARs-CoV-2 swab-positive results. Of 347 patients with SARs-CoV-2 swab-positive results, 294 (84.7%) patients admitted for Covid-19 were included in the study. Sixty-nine patients were trialled on CPAP, mostly delivered by face mask, either as an early ceiling of care instituted within 24 hours of admission (N = 19), or as a potential bridge to IMV (N = 44). Patients receiving a ceiling of care more than 24 hours after admission (N = 6) were excluded from the analysis. Two hundred and fifteen patients (73.1%) maximally received air/standard oxygen therapy, and 45 (15.3%) patients maximally received CPAP. Thirty-four patients (11.6%) required IMV, of which 24 had received prior CPAP. There were 138 patients with an early ceiling-of-care plan (pre-admission/within 24h). Overall, 103 (35.0%) patients died and 191 (65.0%) were alive at study end. Among all patients trialled on CPAP either as a potential bridge to IMV (N = 44) or as a ceiling-of-care (N = 19) mortality was 25% and 84%, respectively. Overall, there was strong evidence for higher mortality among patients who required CPAP or IMV, compared to those who required only air/oxygen (aOR 5.24 95%CI: 1.38, 19.81 and aOR 46.47 95%CI: 7.52, 287.08, respectively; p<0.001), and among patients with early ceiling-of-care compared to those without a ceiling (aOR 41.81 95%CI: 8.28, 211.17; p<0.001). Among patients without a ceiling of care (N = 137), 10 patients required prompt intubation following failed oxygen therapy, but 44 patients received CPAP. CPAP failure, defined as death (N = 1) or intubation (N = 24), occurred in 57% (N = 25) of patients. But in total, 75% (N = 33) of those started on CPAP with no ceiling of care recovered to discharge—19 without the need for IMV, and 14 following IMV.
Emergency ventilator for COVID-19
PLOS ONE, December 30, 2020
The COVID-19 pandemic disrupted the world in 2020 by spreading at unprecedented rates and causing tens of thousands of fatalities within a few months. The number of deaths dramatically increased in regions where the number of patients in need of hospital care exceeded the availability of care. Many COVID-19 patients experience Acute Respiratory Distress Syndrome (ARDS), a condition that can be treated with mechanical ventilation. In response to the need for mechanical ventilators, designed and tested an emergency ventilator (EV) that can control a patient’s peak inspiratory pressure (PIP) and breathing rate, while keeping a positive end expiratory pressure (PEEP). This article describes the rapid design, prototyping, and testing of the EV. The development process was enabled by rapid design iterations using additive manufacturing (AM). In the initial design phase, iterations between design, AM, and testing enabled a working prototype within one week. The designs of the 16 different components of the ventilator were locked by additively manufacturing and testing a total of 283 parts having parametrically varied dimensions. In the second stage, AM was used to produce 75 functional prototypes to support engineering evaluation and animal testing. The devices were tested over more than two million cycles. We also developed an electronic monitoring system and with automatic alarm to provide for safe operation, along with training materials and user guides. The final designs are available online under a free license. The designs have been transferred to more than 70 organizations in 15 countries. This project demonstrates the potential for ultra-fast product design, engineering, and testing of medical devices needed for COVID-19 emergency response.
Blood test dynamics in hospitalized COVID-19 patients: Potential utility of D-dimer for pulmonary embolism diagnosis
PLOS ONE, December 28, 2020
A higher incidence of thrombotic events, mainly pulmonary embolism (PE), has been reported in hospitalized patients with COVID-19. The main objective was to assess clinical and laboratory differences in hospitalized COVID-19 patients according to occurrence of PE. This retrospective study included all consecutive patients hospitalized with COVID-19 who underwent a computed tomography (CT) angiography for PE clinical suspicion. Clinical data and median blood test results distributed into weekly periods from COVID-19 symptoms onset, were compared between PE and non-PE patients. Ninety-two patients were included, 29 (32%) had PE. PE patients were younger (63.9 (SD 13.7) vs 69.9 (SD 12.5) years). Clinical symptoms and COVID-19 CT features were similar in both groups. PE was diagnosed after a mean of 20.0 (SD 8.6) days from the onset of COVID-19 symptoms. Corticosteroid boluses were more frequently used in PE patients (62% vs. 43%). No patients met ISTH DIC criteria. Any parameter was statistically significant or clinically relevant except for D-Dimer when comparing both groups. Median values [IQR] of D-dimer in PE vs non-PE patients were: week 2 (2010.7 [770.1–11208.9] vs 626.0 [374.0–2382.2]; p = 0.004); week 3 (3893.1 [1388.2–6694.0] vs 1184.4 [461.8–2447.8]; p = 0.003); and week 4 (2736.3 [1202.1–8514.1] vs 1129.1 [542.5–2834.6]; p = 0.01). Median fold-increase of D-dimer between week 1 and 2 differed between groups (6.64 [3.02–23.05] vs 1.57 [0.64–2.71], p = 0.003); ROC curve AUC was 0.879 (p = 0.003) with a sensitivity and specificity for PE of 86% and 80%, respectively.
Timing and clinical outcomes of tracheostomy in patients with COVID-19
British Journal of Surgery, December 28, 2020
[Letter to the Editor] Most tracheostomy guidelines for patients with COVID-19 infection recommend that tracheostomy be performed 21 days after intubation and with a negative test result to reduce the risk of tracheostomy-related COVID-19 transmission to healthcare workers. However, the practical feasibility of this recommendation regarding tracheostomy timing is questionable because positive test results can persist for several weeks. There is also a lack of comprehensive understanding about the clinical course of patients with COVID-19 who undergo tracheostomy, based on sufficient follow-up. From 17 February to 2 July 2020, 501 patients with a moderate to severe COVID-19 infection were treated in four tertiary referral hospitals in Daegu. Among these, 27 (5.4 per cent) had a tracheostomy, 19 men and 8 women of mean age 68.8 (range 26–85) years. The mean time from the onset of signs or symptoms to COVID-19 diagnosis was 3 (range 0–13) days, and the time from diagnosis to intubation was 6 (0–32) days. The results of this study demonstrated that it is not practically feasible to wait for 21 days after intubation. Moreover, this delay was helpful neither for appropriate management of acute respiratory distress nor to prevent possible tracheal stenosis resulting from prolonged intubation. Furthermore, as it took more than 6 weeks (43.1 days) to obtain a negative COVID-19 test result and there was no tracheostomy-related transmission of COVID-19, current guidelines would have provided little benefit in reducing the risk of tracheostomy-related transmission. Therefore, we believe that tracheostomy can be performed whenever indicated, regardless of time from intubation or COVID-19 test results.
D-Dimers Level as a Possible Marker of Extravascular Fibrinolysis in COVID-19 Patients
Journal of Clinical Medicine, December 24, 2020
Host defence mechanisms to counter virus infection include the activation of the broncho-alveolar haemostasis. Fibrin degradation products secondary to extravascular fibrin breakdown could contribute to the marked increase in D-Dimers during COVID-19. We sought to examine the prognostic value on lung injury of D-Dimers in non-critically ill COVID-19 patients without thrombotic events. This study retrospectively analysed hospitalized COVID-19 patients classified according to a D-Dimers threshold following the COVID-19 associated haemostatic abnormalities (CAHA) classification at baseline and at peak (Stage 1: D-Dimers less than three-fold above normal; Stage 2: D-Dimers three- to six-fold above normal; Stage 3: D-Dimers six-fold above normal). The primary endpoint was the occurrence of critical lung injuries on chest computed tomography. The secondary outcome was the composite of in-hospital death or transfer to the intensive care unit (ICU). Results: Among the 123 patients included, critical lung injuries were evidenced in 8 (11.9%) patients in Stage 1, 6 (20%) in Stage 2 and 15 (57.7%) in Stage 3 (p = 0.001). D-Dimers staging at peak was an independent predictor of critical lung injuries regardless of the inflammatory burden assessed by CRP levels (OR 2.70, 95% CI (1.50–4.86); p < 0.001) and was significantly associated with increased in-hospital death or ICU transfer (14.9 % in Stage 1, 50.0% in Stage 2 and 57.7% in Stage 3 (p < 0.001)). D-Dimers staging at peak was an independent predictor of in-hospital death or ICU transfer (OR 2.50, CI 95% (1.27–4.93); p = 0.008). In the absence of overt thrombotic events, D-Dimers quantification is a relevant marker of critical lung injuries and dismal patient outcome.
Multi-organ point-of-care ultrasound for COVID-19 (PoCUS4COVID): international expert consensus
Critical Care, December 24, 2020
COVID-19 has caused great devastation in the past year. Multi-organ point-of-care ultrasound (PoCUS) including lung ultrasound (LUS) and focused cardiac ultrasound (FoCUS) as a clinical adjunct has played a significant role in triaging, diagnosis and medical management of COVID-19 patients. The expert panel from 27 countries and 6 continents with considerable experience of direct application of PoCUS on COVID-19 patients presents evidence-based consensus using GRADE methodology for the quality of evidence and an expedited, modified-Delphi process for the strength of expert consensus. We searched Medline, Pubmed Central, Embase, Cochrane, Scopus and online pre-print databases from 01/01/2020 to 01/08/2020, and collected all English language publications on PoCUS in adult COVID-19 patients, using the MeSH query: [(“lung” AND “ultrasound”) OR “echocardiography” OR “Focused cardiac ultrasound” OR “point-of-care ultrasound” OR “venous ultrasound”] AND [“COVID-19” OR “SARS-CoV2”]. This systematic search strategy identified 214 records. The use of ultrasound is suggested in many clinical situations related to respiratory, cardiovascular and thromboembolic aspects of COVID-19, comparing well with other imaging modalities. The limitations due to insufficient data are highlighted as opportunities for future research.
COVID-19 update: the first 6 months of the pandemic
Human Genomics, December 23, 2020
The COVID-19 pandemic is sweeping the world and will feature prominently in all our lives for months and most likely for years to come. We review here the current state 6 months into the declared pandemic. Specifically, we examine the role of the pathogen, the host and the environment along with the possible role of diabetes. We also firmly believe that the pandemic has shown an extraordinary light on national and international politicians whom we should hold to account as performance has been uneven. We also call explicitly on competent leadership of international organizations, specifically the WHO, UN and EU, informed by science. Finally, we also condense successful strategies for dealing with the current COVID-19 pandemic in democratic countries into a developing pandemic playbook and chart a way forward into the future. This is useful in the current COVID-19 pandemic and, we hope, in a very distant future again when another pandemic might arise.
Effects of Tocilizumab in COVID-19 patients: a cohort study
BMC Infectious Diseases, December 22, 2020
Due to the lack of proven therapies, we evaluated the effects of early administration of tocilizumab for COVID-19. By inhibition of the IL-6 receptor, tocilizumab may help to mitigate the hyperinflammatory response associated with progressive respiratory failure from SARS-CoV-2. A retrospective, observational study was conducted on hospitalized adults who received intravenous tocilizumab for COVID-19 between March 23, 2020 and April 10, 2020. Most patients were male (66.7%), Hispanic (63.3%) or Black (23.3%), with a median age of 54 years. Tocilizumab was administered at a median of 8 days (range 1–21) after initial symptoms and 2 days (range 0–12) after hospital admission. Within 30 days from receiving tocilizumab, 36 patients (60.0%) demonstrated clinical improvement, 9 (15.0%) died, 33 (55.0%) were discharged alive, and 18 (30.0%) remained hospitalized. Successful extubation occurred in 13 out of 29 patients (44.8%). Infectious complications occurred in 16 patients (26.7%) at a median of 10.5 days. After tocilizumab was administered, there was a slight increase in PaO2/FiO2 and an initial reduction in CRP, but this effect was not sustained beyond day 10. Majority of patients demonstrated clinical improvement and were successfully discharged alive from the hospital after receiving tocilizumab. We observed a rebound effect with CRP, which may suggest the need for higher or subsequent doses to adequately manage cytokine storm.
Prognostic value of bedside lung ultrasound score in patients with COVID-19
Critical Care, December 22, 2020
Bedside lung ultrasound (LUS) has emerged as a useful and non-invasive tool to detect lung involvement and monitor changes in patients with coronavirus disease 2019 (COVID-19). However, the clinical significance of the LUS score in patients with COVID-19 remains unknown. We aimed to investigate the prognostic value of the LUS score in patients with COVID-19. The LUS protocol consisted of 12 scanning zones and was performed in 280 consecutive patients with COVID-19. The LUS score based on B-lines, lung consolidation and pleural line abnormalities was evaluated. The median time from admission to LUS examinations was 7 days (interquartile range [IQR] 3–10). Patients in the highest LUS score group were more likely to have a lower lymphocyte percentage (LYM%); higher levels of D-dimer, C-reactive protein, hypersensitive troponin I and creatine kinase muscle-brain; more invasive mechanical ventilation therapy; higher incidence of ARDS; and higher mortality than patients in the lowest LUS score group. After a median follow-up of 14 days [IQR, 10–20 days], 37 patients developed ARDS, and 13 died. Patients with adverse outcomes presented a higher rate of bilateral involvement; more involved zones and B-lines, pleural line abnormalities and consolidation; and a higher LUS score than event-free survivors. The Cox models adding the LUS score as a continuous variable (hazard ratio [HR]: 1.05, 95% confidence intervals [CI] 1.02 ~ 1.08; P < 0.001; Akaike information criterion [AIC] = 272; C-index = 0.903) or as a categorical variable (HR 10.76, 95% CI 2.75 ~ 42.05; P = 0.001; AIC = 272; C-index = 0.902) were found to predict poor outcomes more accurately than the basic model (AIC = 286; C-index = 0.866). An LUS score cut-off > 12 predicted adverse outcomes with a specificity and sensitivity of 90.5% and 91.9%, respectively.
Lung mechanics in type L CoVID-19 pneumonia: a pseudo-normal ARDS
Translational Medicine Communications, December 21, 2020
This study was conceived to provide systematic data about lung mechanics during early phases of CoVID-19 pneumonia, as long as to explore its variations during prone positioning. We enrolled four patients hospitalized in the Intensive Care Unit of “M. Bufalini” hospital, Cesena (Italy); after the positioning of an esophageal balloon, we measured mechanical power, respiratory system and transpulmonary parameters and arterial blood gases every 6 hours, just before decubitus change and 1 hour after prono-supination. Both respiratory system and transpulmonary compliance and driving pressure confirmed the pseudo-normal respiratory mechanics of early CoVID-19 pneumonia (respectively, CRS 40.8 ml/cmH2O and DPRS 9.7 cmH2O; CL 53.1 ml/cmH2O and DPL 7.9 cmH2O). Interestingly, prone positioning involved a worsening in respiratory mechanical properties throughout time (CRS,SUP 56.3 ml/cmH2O and CRS,PR 41.5 ml/cmH2O – P 0.37; CL,SUP 80.8 ml/cmH2O and CL,PR 53.2 ml/cmH2O – P 0.23). Despite the severe ARDS pattern, respiratory system and lung mechanical properties during CoVID-19 pneumonia are pseudo-normal and tend to worsen during pronation.
Most Allergic Reactions Not Enough to Nix COVID-19 Vaccine
MedPage Today, December 18, 2020
While criteria for contraindication to COVID-19 mRNA vaccines are narrow, more observation or possibly delayed vaccination may be necessary in those with a history of severe allergic reactions, CDC staff said on a call with clinicians on Friday. The only individuals who should not receive mRNA COVID-19 vaccines, such as the recently authorized Pfizer/BioNTech vaccine and Moderna’s similar product, are those with a history of severe allergic reaction, including anaphylaxis, to components of the vaccine. For example, CDC staff highlighted polyethylene glycol, which is often used in laxatives. However, those with a history of severe allergic reaction to another vaccine or an injectable therapy may receive the vaccine, but with precautions. Given recent publicity surrounding anaphylactic reactions to the Pfizer vaccine, CDC staff discussed an algorithm for the triage of individuals presenting for mRNA COVID-19 vaccines. A risk assessment and potential deferral of vaccination applies only to those with a history of these severe vaccine-related allergies or severe allergies to other injectable therapies. CDC clinical guidance recommends a 30-minute observation period for those with a history of severe allergic reaction, including anaphylaxis, due to any cause, and a 15-minute period for those with an allergic reaction, but not anaphylaxis.
Risks of ventilator-associated pneumonia and invasive pulmonary aspergillosis in patients with viral acute respiratory distress syndrome related or not to Coronavirus 19 disease
Critical Care, December 18, 2020
Data on incidence of ventilator-associated pneumonia (VAP) and invasive pulmonary aspergillosis in patients with severe SARS-CoV-2 infection are limited. We conducted a monocenter retrospective study comparing the incidence of VAP and invasive aspergillosis between patients with COVID-19-related acute respiratory distress syndrome (C-ARDS) and those with non-SARS-CoV-2 viral ARDS (NC-ARDS). We assessed 90 C-ARDS and 82 NC-ARDS patients, who were mechanically ventilated for more than 48 h. At ICU admission, there were significantly fewer bacterial coinfections documented in C-ARDS than in NC-ARDS: 14 (16%) vs 38 (48%), p < 0.01. Conversely, significantly more patients developed at least one VAP episode in C-ARDS as compared with NC-ARDS: 58 (64%) vs. 36 (44%), p = 0.007. The probability of VAP was significantly higher in C-ARDS after adjusting on death and ventilator weaning [sub-hazard ratio = 1.72 (1.14–2.52), p < 0.01]. The incidence of multi-drug-resistant bacteria (MDR)-related VAP was significantly higher in C-ARDS than in NC-ARDS: 21 (23%) vs. 9 (11%), p = 0.03. Carbapenem was more used in C-ARDS than in NC-ARDS: 48 (53%), vs 21 (26%), p < 0.01. According to AspICU algorithm, there were fewer cases of putative aspergillosis in C-ARDS than in NC-ARDS [2 (2%) vs. 12 (15%), p = 0.003], but there was no difference in Aspergillus colonization. In our experience, we evidenced a higher incidence of VAP and MDR-VAP in C-ARDS than in NC-ARDS and a lower risk for invasive aspergillosis in the former group.
Development and Prospective Validation of a Deep Learning Algorithm for Predicting Need for Mechanical Ventilation
CHEST, December 17, 2020
Can a transparent deep learning (DL) model predict the need for MV in hospitalized patients and those with COVID-19 up to 24 hours in advance? Our goal was an objective and early identification of hospitalized patients, and particularly those with novel coronavirus disease 2019 (COVID-19), who may require mechanical ventilation (MV) may aid in delivering timely treatment. We trained and externally validated a transparent DL algorithm to predict the future need for MV in hospitalized patients, including those with COVID-19, using commonly available data in electronic health records. Additionally, commonly used clinical criteria (heart rate, oxygen saturation, respiratory rate, FiO2 and pH) were used to assess future need for MV. Performance of the algorithm was evaluated using the area under receiver operating characteristic curve (AUC), sensitivity, specificity and positive predictive value. We obtained data from over 30,000 ICU patients (including over 700 patients with COVID-19) from two academic medical centers. The performance of the model with a 24-hour prediction horizon at the development and validation sites was comparable (AUC of 0.895 versus 0.882, respectively), providing significant improvement over traditional clinical criteria (p<0.001). Prospective validation of the algorithm among patients with COVID-19 yielded AUCs in the range 0.918-0.943. A transparent DL algorithm improves on traditional clinical criteria to predict the need for MV in hospitalized patients, including in those with COVID-19. Such an algorithm may help clinicians optimize timing of tracheal intubation, better allocate resources and staff, and improve patient care.
Mortality due to COVID-19 elevated in patients with preexisting ILD
Helio | Pulmonology, December 17, 2020
Mortality due to COVID-19 was higher in patients with preexisting fibrotic idiopathic interstitial lung disease compared with other interstitial lung diseases, researchers reported in a new study.
“Patients with preexisting ILD may be at high risk for severe COVID-19 disease due to impaired lung function, propensity to develop acute exacerbation of pulmonary fibrosis or immunomodulatory medications that may interact with viral clearance or pathogenesis,” Laure Gallay, MD, PhD, of the National Coordinating Reference Centre for Rare Pulmonary Diseases at Claude Bernard University Lyon 1 in France, and colleagues wrote in the American Journal of Respiratory and Critical Care Medicine. “However, whether the type of ILD may influence the outcome of COVID-19 is unknown.” Researchers conducted a multicenter, observational survey of specialized centers to analyze the survival rate in patients with COVID-19 and ILDs. Researchers reported data from 123 patients (median age, 64 years; 66% men) with COVID-19 and ILDs. Cases were collected from the outset of the COVID-19 outbreak in France through May. “Of note, the mortality among subjects with an ILD other than fibrotic ILD was comparable to that reported in the global French population hospitalized for COVID-19,” the researchers wrote. On the univariable analysis and multivariable analysis, male sex (P = .03), older age (P < .01) and chronic use of home oxygen supplementation (P < .01) were independent predictors of mortality among these patients, according to the study.
Outcomes of an intermediate respiratory care unit in the COVID-19 pandemic
PLOS ONE, December 16, 2020
Fifteen percent of COVID-19 patients develop severe pneumonia. Non-invasive mechanical ventilation and high-flow nasal cannula can reduce the rate of endotracheal intubation in adult respiratory distress syndrome, although failure rate is high. To describe the rate of endotracheal intubation, the effectiveness of treatment, complications and mortality in patients with severe respiratory failure due to COVID-19. Prospective cohort study in a first-level hospital in Madrid. Patients with a positive polymerase chain reaction for SARS-CoV-2 and admitted to the Intermediate Respiratory Care Unit with tachypnea, use of accessory musculature or SpO2 <92% despite FiO2> 0.5 were included. Intubation rate, medical complications, and 28-day mortality were recorded. Statistical analysis through association studies, logistic and Cox regression models and survival analysis was performed. Seventy patients were included. 37.1% required endotracheal intubation, 58.6% suffered medical complications and 24.3% died. Prone positioning was independently associated with lower need for endotracheal intubation (OR 0.05; 95% CI 0.005 to 0.54, p = 0.001). The adjusted HR for death at 28 days in the group of patients requiring endotracheal intubation was 5.4 (95% CI 1.51 to 19.5; p = 0.009).
Glucocorticoids with low-dose anti-IL1 anakinra rescue in severe non-ICU COVID-19 infection: A cohort study
PLOS ONE, December 16, 2020
The optimal treatment for patients with severe coronavirus-19 disease (COVID-19) and hyper-inflammation remains debated. A cohort study was designed to evaluate whether a therapeutic algorithm using steroids with or without interleukin-1 antagonist (anakinra) could prevent death/invasive ventilation. Patients with a ≥5-day evolution since symptoms onset, with hyper-inflammation (CRP≥50mg/L), requiring 3–5 L/min oxygen, received methylprednisolone alone. Patients needing ≥6 L/min received methylprednisolone + subcutaneous anakinra daily either frontline or in case clinical deterioration upon corticosteroids alone. Death rate and death or intensive care unit (ICU) invasive ventilation rate at Day 15, with Odds Ratio (OR) and 95% CIs, were determined according to logistic regression and propensity scores. A Bayesian analysis estimated the treatment effects. Of 108 consecutive patients, 70 patients received glucocorticoids alone. The control group comprised 63 patients receiving standard of care. In the corticosteroid ± stanakinra group (n = 108), death rate was 20.4%, versus 30.2% in the controls, indicating a 30% relative decrease in death risk and a number of 10 patients to treat to avoid a death (p = 0.15). Using propensity scores a per-protocol analysis showed an OR for COVID-19-related death of 0.9 (95%CI [0.80–1.01], p = 0.067). On Bayesian analysis, the posterior probability of any mortality benefit with corticosteroids ± anakinra was 87.5%, with a 7.8% probability of treatment-related harm. Pre-existing diabetes exacerbation occurred in 29 of 108 patients (26.9%).
High Prevalence of Pulmonary Sequelae at 3 Months After Hospital Discharge in Mechanically Ventilated COVID-19 Survivors
American Journal of Respiratory and Critical Care Medicine, December 15, 2020
Severe COVID-19 is characterized by acute hypoxemic respiratory failure, usually with extensive consolidations and areas with ground glass on chest computed tomography (CT). Whether long-term respiratory sequelae persist in severe COVID-19 survivors remains to be established. This report describes our findings of respiratory outcomes in mechanically ventilated COVID-19 survivors at three months following hospital discharge. We recorded clinical and follow-up data of all COVID-19 patients treated at our ICU in the Maastricht Intensive Care Covid (MaastrICCht) cohort (registered in The Netherlands Trial Register (NL8613). The institutional review board of Maastricht UMC+ approved the study and informed consent was obtained (METC2020-2287). During admission, ventilator strategies included lung-protective ventilation (tidal volumes 6 ml/kg) and PEEP titration using electrical impedance tomography (EIT). Prone positioning was considered when P/F- ratio was below 112,5 mmHg (15 kPa) and maintained for at least 12 hours. At three months after hospital discharge, survivors were screened at a multi-disciplinary post-ICU outpatient clinic for respiratory outcomes with pulmonary function testing (PFT) including spirometry, lung volumes, and diffusing capacity for carbon monoxide adjusted for hemoglobin (DLCOc), high resolution chest computed tomography (HRCT), and 6-minute walk test (6-MWT). Two experienced radiologists systematically scored chest HRCTs for the presence of pulmonary abnormalities, including ground glass opacifications, reticulation, consolidations, bronchiectasis, atelectasis, presence of new emphysematous and cystic changes and air trapping, extent of lobe involvement, and total lung involvement. The extent of lobe involvement was visually scored on a 0- 5 scale: 0= no involvement, 1= 1-5%, 2= 6-25%, 3= 26-50%, 4= 51-75%, and 5= >75% involvement. The CT Severity Score (CTSS) was calculated by adding the lobar scores. HRCTs were compared to scans performed at presentation (n=33) at the emergency department or during admission (n=5) depending on availability. All data are presented as median [interquartile range (IQR)]. Correlations between CTSS, PFT results and 6-MWT were assessed using Spearman’s rank correlation.
Increased Odds of Death for Patients with Interstitial Lung Disease and COVID-19: A Case–Control Study
American Journal of Respiratory and Critical Care Medicine, December 15, 2020
[Letter to the Editor] Coronavirus disease (COVID-19) is an international public health emergency. Although the prevalence of chronic respiratory disease in patients with COVID-19 has been reportedly low (1.5%), it is associated with increased risk of severe disease and—in chronic obstructive pulmonary disease—increased mortality. Together with numerous previously reported risk factors for severe COVID-19, it has been hypothesized that patients with interstitial lung diseases (ILDs) may have poorer outcomes from COVID-19. In this letter, we present the results of a multicenter retrospective case–control study examining outcomes from COVID-19 in patients with preexisting ILD. Adult patients (greater than 18 yr old) with preexisting ILD who had COVID-19 diagnosed by real-time PCR or with negative real-time PCR but positive IgM and/or IgG serology between March 1 and June 8, 2020, at six Mass General Brigham hospitals were identified using the electronic health record–integrated centralized clinical data registry. ILD was defined as physician diagnosis or, if no pulmonology visit existed in our system, as radiologic evidence with confirmatory histopathology. A control cohort with COVID-19 but without ILD was identified from the same registry and preliminarily matched by age ± 5 years, sex, white/nonwhite race, and comparative health using an automated method. Control subjects were confirmed not to have ILD through medical record review, and 2:1 matching was manually verified. The primary outcome of interest was death, censored on June 8, 2020. Secondary outcomes included hospital admission, ICU admission, and hospital discharge either to the home or a skilled nursing facility. Read on for results.
Corticosteroid use in COVID-19 patients: a systematic review and meta-analysis on clinical outcomes
Critical Care, December 14, 2020
In the current SARS-CoV-2 pandemic, there has been worldwide debate on the use of corticosteroids in COVID-19. In the recent RECOVERY trial, evaluating the effect of dexamethasone, a reduced 28-day mortality in patients requiring oxygen therapy or mechanical ventilation was shown. Their results have led to considering amendments in guidelines or actually already recommending corticosteroids in COVID-19. However, the effectiveness and safety of corticosteroids still remain uncertain, and reliable data to further shed light on the benefit and harm are needed. The aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of corticosteroids in COVID-19. A systematic literature search of RCTS and observational studies on adult patients was performed across Medline/PubMed, Embase and Web of Science from December 1, 2019, until October 1, 2020, according to the PRISMA guidelines. Primary outcomes were short-term mortality and viral clearance (based on RT-PCR in respiratory specimens). Secondary outcomes were: need for mechanical ventilation, need for other oxygen therapy, length of hospital stay and secondary infections. Forty-four studies were included, covering 20.197 patients. In twenty-two studies, the effect of corticosteroid use on mortality was quantified. The overall pooled estimate (observational studies and RCTs) showed a significant reduced mortality in the corticosteroid group (OR 0.72 (95%CI 0.57–0.87). Furthermore, viral clearance time ranged from 10 to 29 days in the corticosteroid group and from 8 to 24 days in the standard of care group. Fourteen studies reported a positive effect of corticosteroids on need for and duration of mechanical ventilation. A trend toward more infections and antibiotic use was present.
Suspected heparin-induced thrombocytopenia in a COVID-19 patient on extracorporeal membrane oxygenation support: a case report
Thrombosis Journal, December 14, 2020
Coronavirus disease 2019 (COVID-19), the disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is an ongoing medical problem worldwide. Patients may have different severity levels, ranging from mild dyspnea or coughing to multiorgan failure. For those with life-threatening complications, intensive interventions may be requisite. Extracorporeal membrane oxygenation (ECMO) is a potentially life-saving procedure, in which the patient’s blood is circulated through an oxygenator to provide oxygen to vital organs. In ECMO, the tubing system is usually coated with heparin to reduce to risk of thrombosis due to widespread coagulation activation throughout the set . However, this practice gives rise to an increased risk of Heparin-induced thrombocytopenia (HIT), a condition in which platelets are incessantly activated by anti-PF4/Heparin antibodies, leading to catastrophic thrombotic events. In this report, we describe a case of a COVID-19 patient on ECMO with suspected HIT who was particularly difficult to manage due to our lack of resources.
Can Natural Polyphenols Help in Reducing Cytokine Storm in COVID-19 Patients?
Molecules, December 12, 2020
SARS-CoV-2 first emerged in China during late 2019 and rapidly spread all over the world. Alterations in the inflammatory cytokines pathway represent a strong signature during SARS-COV-2 infection and correlate with poor prognosis and severity of the illness. The hyper-activation of the immune system results in an acute severe systemic inflammatory response named cytokine release syndrome (CRS). No effective prophylactic or post-exposure treatments are available, although some anti-inflammatory compounds are currently in clinical trials. Studies of plant extracts and natural compounds show that polyphenols can play a beneficial role in the prevention and the progress of chronic diseases related to inflammation. The aim of this manuscript is to review the published background on the possible effectiveness of polyphenols to fight SARS-COV-2 infection, contributing to the reduction of inflammation. Here, some of the anti-inflammatory therapies are discussed and although great progress has been made though this year, there is no proven cytokine blocking agents for COVID currently used in clinical practice. In this regard, bioactive phytochemicals such as polyphenols may become promising tools to be used as adjuvants in the treatment of SARS-CoV-2 infection. Such nutrients, with anti-inflammatory and antioxidant properties, associated to classical anti-inflammatory drugs, could help in reducing the inflammation in patients with COVID-19.
Identification of distinct immunophenotypes in critically-ill COVID-19 patients
CHEST, December 11, 2020
Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection causes direct lung damage, overwhelming endothelial activation and inflammatory reaction leading to acute respiratory failure and multi-organ dysfunction. Ongoing clinical trials are evaluating targeted therapies to hinder this exaggerated inflammatory response. Critically-ill COVID-19 patients have shown heterogeneous severity trajectories, suggesting that response to therapies is likely to vary across patients. The Research Question we wanted to answer was: Are critically-ill COVID-19 patients biologically and immunologically dissociable based on profiling of currently evaluated therapeutic targets? We did a single-center, prospective study in an ICU department in France. Ninety-six critically-ill adult patients admitted with a documented SARS-CoV-2 infection were enrolled. We conducted principal components analysis and hierarchical clustering on a vast array of immunologic variables measured on the day of ICU admission. We found that patients were distributed in three clusters bearing distinct immunologic features and associated to different ICU outcomes. Cluster 1 had a “humoral immunodeficiency” phenotype with predominant B-lymphocyte defect, relative hypogammaglobulinemia, and moderate inflammation. Cluster 2 had a “hyperinflammatory” phenotype, with high cytokine levels (IL-6, IL-1β, IL-8, TNF⍺) associated to CD4+ and CD8+ T-lymphocyte defects. Cluster 3 had a “complement-dependent” phenotype with terminal complement activation markers (elevated C3 and sC5b-9).
Maximum chest CT score is associated with progression to severe illness in patients with COVID-19: a retrospective study from Wuhan, China
BMC Infectious Diseases, December 11, 2020
The Coronavirus Disease 2019 (COVID-19) pandemic is a worldwide health crisis. Limited information is available regarding which patients will experience more severe disease symptoms. We evaluated hospitalized patients who were initially diagnosed with moderate COVID-19 for clinical parameters and radiological feature that showed an association with progression to severe/critical symptoms. This study, a retrospective single-center study at the Central Hospital of Wuhan, enrolled 243 patients with confirmed COVID¬19 pneumonia. Forty of these patients progressed from moderate to severe/critical symptoms during follow up. Demographic, clinical, laboratory, and radiological data were extracted from electronic medical records and compared between moderate- and severe/critical-type symptoms. Univariable and multivariable logistic regressions were used to identify the risk factors associated with symptom progression. Patients with severe/critical symptoms were older (p < 0.001) and more often male (p = 0.046). A combination of chronic obstructive pulmonary disease (COPD) and high maximum chest computed tomography (CT) score was associated with disease progression. Maximum CT score (> 11) had the greatest predictive value for disease progression. The area under the receiver operating characteristic curve was 0.861 (95% confidence interval: 0.811–0.902).
Identification of biological correlates associated with respiratory failure in COVID-19
BMC Medical Genomics, December 11, 2020
Coronavirus disease 2019 (COVID-19) is a global public health concern. Recently, a genome-wide association study (GWAS) was performed with participants recruited from Italy and Spain by an international consortium group. Summary GWAS statistics for 1610 patients with COVID-19 respiratory failure and 2205 controls were downloaded. In the current study, we analyzed the summary statistics with the information of loci and p-values for 8,582,968 single-nucleotide polymorphisms (SNPs), using gene ontology analysis to determine the top biological processes implicated in respiratory failure in COVID-19 patients. We considered the top 708 SNPs, using a p-value cutoff of 5 × 10− 5, which were mapped to the nearest genes, leading to 144 unique genes. The list of genes was input into a curated database to conduct gene ontology and protein-protein interaction (PPI) analyses. The top ranked biological processes were wound healing, epithelial structure maintenance, muscle system processes, and cardiac-relevant biological processes with a false discovery rate < 0.05. In the PPI analysis, the largest connected network consisted of 8 genes. Through a literature search, 7 out of the 8 gene products were found to be implicated in both pulmonary and cardiac diseases. Gene ontology and PPI analyses identified cardio-pulmonary processes that may partially explain the risk of respiratory failure in COVID-19 patients.
Corticosteroid therapy is associated with improved outcome in critically ill COVID-19 patients with hyperinflammatory phenotype
CHEST, December 11, 2020
Corticosteroid therapy is commonly used in patients with coronavirus disease 2019 (COVID-19), while its impact on outcomes and which patients could benefit from corticosteroid therapy are uncertain. Our objective was to determine whether clinical phenotypes of COVID-19 were associated with differential response to corticosteroid therapy. Critically ill patients with COVID-19 from Tongji hospital between Jan 2020 and Feb 2020 were included, and the main exposure of interest was the administration of intravenous corticosteroids. The primary outcome was 28-day mortality. Marginal structural modeling was used to account for baseline and time-dependent confounders. An unsupervised machine learning approach was carried out to identify phenotypes of COVID-19. A total of 428 patients were included, and 280/428 (65.4%) patients received corticosteroid therapy. The 28-day mortality was significantly higher in patients who received corticosteroid therapy than in those who did not (53.9% vs. 19.6%; p<0.0001). After marginal structural modeling, corticosteroid therapy was not significantly associated with 28-day mortality (HR 0.80, 95% CI 0.54-1.18; p=0.26). Our analysis identified two phenotypes of COVID-19, and compared to the hypoinflammatory phenotype, the hyperinflammatory phenotype was characterized by elevated levels of proinflammatory cytokines, higher SOFA scores and higher rates of complications. Corticosteroid therapy was associated with a reduced 28-day mortality (HR 0.45; 95% CI 0.25–0.80; p=0.0062) in patients with hyperinflammatory phenotype.
Impact of comorbid asthma on severity of coronavirus disease (COVID-19)
Scientific Reports, December 11, 2020
The severity of the coronavirus disease (COVID-19) is associated with various comorbidities. However, no studies have yet demonstrated the potential risk of respiratory failure and mortality in COVID-19 patients with pre-existing asthma. We selected 7272 adult COVID-19 patients from the Korean Health Insurance Review and Assessment COVID-19 database for this nationwide retrospective cohort study. Among these, 686 patients with asthma were assessed by their severities and evaluated by the clinical outcome of COVID-19 compared to patients without asthma. Of 7272 adult COVID-19 patients, 686 with asthma and 6586 without asthma were compared. Asthma was not a significant risk factor for respiratory failure or mortality among all COVID-19 patients (odds ratio [OR] = 0.99, P = 0.997 and OR = 1.06, P = 0.759) after adjusting for age, sex, and the Charlson comorbidity score. However, a history of acute exacerbation (OR = 2.63, P = 0.043) was significant risk factors for death among COVID-19 patients with asthma. Asthma is not a risk factor for poor prognosis of COVID-19. However, asthma patients who had any experience of acute exacerbation in the previous year before COVID-19 showed higher COVID-19-related mortality, especially in case of old age and male sex. We conducted a retrospective cohort study in South Korea to assess the risk factors of respiratory failure or mortality in COVID-19 patients with asthma. The patients with COVID-19 were defined by the following diagnostic codes using the HIRA dataset: B342, B972, B18, U181, and U071. All diagnoses were confirmed by reverse transcription-polymerase chain reaction testing for SARS-CoV-2. From the initial screening to the evaluation of the clinical outcomes of COVID-19 patients, the study period was divided into the following three different periods: 1. the premeasurement period, 2. measurement period, 3. the COVID-19 period. Read more for results.
Analyzing changes in respiratory rate to predict the risk of COVID-19 infection
PLOS ONE, December 10, 2020
COVID-19, the disease caused by the SARS-CoV-2 virus, can cause shortness of breath, lung damage, and impaired respiratory function. Containing the virus has proven difficult, in large part due to its high transmissibility during the pre-symptomatic incubation. The study’s aim was to determine if changes in respiratory rate could serve as a leading indicator of SARS-CoV-2 infections. A total of 271 individuals (age = 37.3 ± 9.5, 190 male, 81 female) who experienced symptoms consistent with COVID-19 were included– 81 tested positive for SARS-CoV-2 and 190 tested negative; these 271 individuals collectively contributed 2672 samples (days) of data (1856 healthy days, 231 while infected with COVID-19 and 585 while negative for COVID-19 but experiencing symptoms). To train a novel algorithm, individuals were segmented as follows; (1) a training dataset of individuals who tested positive for COVID-19 (n = 57 people, 537 samples); (2) a validation dataset of individuals who tested positive for COVID-19 (n = 24 people, 320 samples); (3) a validation dataset of individuals who tested negative for COVID-19 (n = 190 people, 1815 samples). All data was extracted from the WHOOP system, which uses data from a wrist-worn strap to produce validated estimates of respiratory rate and other physiological measures. Using the training dataset, a model was developed to estimate the probability of SARS-CoV-2 infection based on changes in respiratory rate during night-time sleep. The model’s ability to identify COVID-positive individuals not used in training and robustness against COVID-negative individuals with similar symptoms were examined for a critical six-day period spanning the onset of symptoms. The model identified 20% of COVID-19 positive individuals in the validation dataset in the two days prior to symptom onset, and 80% of COVID-19 positive cases by the third day of symptoms.
Nebulised surfactant for the treatment of severe COVID-19 in adults (COV-Surf): A structured summary of a study protocol for a randomized controlled trial
Trials, December 10, 2020
SARS-Cov-2 virus preferentially binds to the Angiotensin Converting Enzyme 2 (ACE2) on alveolar epithelial type II cells, initiating an inflammatory response and tissue damage which may impair surfactant synthesis contributing to alveolar collapse, worsening hypoxia and leading to respiratory failure. The objective of this study is to evaluate the feasibility, safety and efficacy of nebulised surfactant in COVID-19 adult patients requiring mechanical ventilation for respiratory failure. This study is a dose-escalating randomized open-label clinical trial of 20 COVID-19 patients. This study is conducted in two centres: University Hospital Southampton and University College London Hospitals. Eligible participants are aged ≥18, hospitalised with COVID-19 (confirmed by PCR), who require endotracheal intubation and are enrolled within 24 hours of mechanical ventilation. For patients unable to consent, assent is obtained from a personal legal representative (PerLR) or professional legal representative (ProfLR) prior to enrolment. The co-primary outcome is the improvement in oxygenation (PaO2/FiO2 ratio) and pulmonary ventilation (Ventilation Index (VI), where VI = [RR x (PIP − PEEP) × PaCO2]/1000) at 48 hours after study initiation.
Delivery system can vary ventilatory parameters across multiple patients from a single source of mechanical ventilation
PLOS ONE, December 10, 2020
Current limitations in the supply of ventilators during the Covid19 pandemic have limited respiratory support for patients with respiratory failure. Split ventilation allows a single ventilator to be used for more than one patient but is not practicable due to requirements for matched patient settings, risks of cross-contamination, harmful interference between patients and the inability to individualize ventilator support parameters. We hypothesized that a system could be developed to circumvent these limitations. A novel delivery system was developed to allow individualized peak inspiratory pressure settings and PEEP using a pressure regulatory valve, developed de novo, and an inline PEEP ‘booster’. One-way valves, filters, monitoring ports and wye splitters were assembled in-line to complete the system and achieve the design targets. This system was then tested to see if previously described limitations could be addressed. The system was investigated in mechanical and animal trials (ultimately with a pig and sheep concurrently ventilated from the same ventilator). The system demonstrated the ability to provide ventilation across clinically relevant scenarios including circuit occlusion, unmatched physiology, and a surgical procedure, while allowing significantly different pressures to be safely delivered to each animal for individualized support.
COVID-19 related concerns of people with long-term respiratory conditions: a qualitative study
BMC Pulmonary Medicine, December 9, 2020
The COVID-19 pandemic is having profound psychological impacts on populations globally, with increasing levels of stress, anxiety, and depression being reported, especially in people with pre-existing medical conditions who appear to be particularly vulnerable. There are limited data on the specific concerns people have about COVID-19 and what these are based on. The aim of this study was to identify and explore the concerns of people with long-term respiratory conditions in the UK regarding the impact of the COVID-19 pandemic and how these concerns were affecting them. We conducted a thematic analysis of free text responses to the question “What are your main concerns about getting coronavirus?”, which was included in the British Lung Foundation/Asthma UK (BLF-AUK) partnership COVID-19 survey, conducted between the 1st and 8th of April 2020. This was during the 3rd week of the UK’s initial ‘social distancing measures’ which included advice to stay at home and only go outside for specific limited reasons. 7039 responses were analysed, with respondents from a wide range of age groups (under 17 to over 80), gender, and all UK nations. Respondents reported having asthma (85%), COPD (9%), bronchiectasis (4%), interstitial lung disease (2%), or ‘other’ lung diseases (e.g. lung cancer) (1%). Four main themes were identified: (1) vulnerability to COVID-19; (2) anticipated experience of contracting COVID-19; (3) pervasive uncertainty; and (4) inadequate national response.
A multicenter randomized trial to assess the efficacy of CONvalescent plasma therapy in patients with Invasive COVID-19 and acute respiratory failure treated with mechanical ventilation: the CONFIDENT trial protocol
BMC Pulmonary Medicine, December 7, 2020
The COVID-19 pandemic reached Europe in early 2020. Convalescent plasma is used without a consistent evidence of efficacy. Our hypothesis is that passive immunization with plasma collected from patients having contracted COVID-19 and developed specific neutralizing antibodies may alleviate symptoms and reduce mortality in patients treated with mechanical ventilation for severe respiratory failure during the evolution of SARS-CoV-2 pneumonia. We plan to include 500 adult patients, hospitalized in 16 Belgian intensive care units between September 2020 and 2022, diagnosed with SARS-CoV-2 pneumonia, under mechanical ventilation for less than 5 days and a clinical frailty scale less than 6. The study treatment will be compared to standard of care and allocated by randomization in a 1 to 1 ratio without blinding. The main endpoint will be mortality at day 28. We will perform an intention to treat analysis. The number of patients to include is based on an expected mortality rate at day 28 of 40 percent and an expected relative reduction with study intervention of 30 percent with α risk of 5 percent and β risk of 20 percent. This study will assess the efficacy of plasma in the population of mechanically ventilated patients. A stratification on the delay from mechanical ventilation and inclusion will allow to approach the optimal time use. Selecting convalescent plasmas with a high titer of neutralizing antibodies against SARS-CoV-2 will allow a homogeneous study treatment. The inclusion in the study is based on the consent of the patient or his/her legal representative, and the approval of the Investigational Review Board of the University hospital of Liège, Belgium. A data safety monitoring board (DSMB) has been implemented. Interim analyses have been planned at 100, 2002, 300 and 400 inclusions in order to decide whether the trail should be discontinued prematurely for ethical issues. We plan to publish our results in a peer-reviewed journal and to present them at national and international conferences.
Corticosteroid treatment for early acute respiratory distress syndrome: a systematic review and meta-analysis of randomized trials
Journal of Intensive Care, December 7, 2020
The effect of corticosteroid treatment on survival outcome in early acute respiratory distress syndrome (ARDS) is still debated. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the efficacy of prolonged corticosteroid therapy in early ARDS. We assessed the MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science databases from inception to August 1, 2020. We included RCTs that compared prolonged corticosteroid therapy with control treatment wherein the intervention was started within 72 h of ARDS diagnosis. Two investigators independently screened the citations and conducted the data extraction. The primary outcomes were all-cause 28- or 30-day mortality and 60-day mortality. Several endpoints such as ventilator-free days and adverse events were set as the secondary outcomes. DerSimonian-Laird random-effects models were used to report pooled odds ratios (ORs). Among the 4 RCTs included, all referred to the all-cause 28- or 30-day mortality. In the corticosteroid group, 108 of 385 patients (28.1%) died, while 139 of 357 (38.9%) died in the control group (pooled OR, 0.61; 95% confidence interval [CI], 0.44–0.85). Three RCTs mentioned the all-cause 60-day mortality. In the corticosteroid group, 78 of 300 patients (26.0%) died, while 101 of 265 (38.1%) died in the control group (pooled OR, 0.57; 95% CI, 0.40–0.83). For secondary outcomes, corticosteroid treatment versus control significantly prolonged the ventilator-free days (4 RCTs: mean difference, 3.74; 95% CI, 1.53–5.95) but caused hyperglycemia (3 RCTs: pooled OR, 1.52; 95% CI, 1.04–2.21). Conclusion: Prolonged corticosteroid treatment in early ARDS improved the survival outcomes.
Did COVID Lockdowns Prevent Kids’ Asthma Flares?
MedPage Today, December 4, 2020
The coronavirus pandemic has been a particularly scary time for children with asthma and their parents, but there is growing evidence that as a group kids with asthma are not only doing OK during COVID-19, but may actually be doing better. A study in Annals of the American Thoracic Society documented a steep drop in emergency department (ED) visits for asthma exacerbations at Boston Children’s Hospital during the early months of the pandemic when citywide lockdowns were in place. While ED avoidance may have played a part in the roughly 80% decline in pediatric asthma visits in the spring and early summer, Tregony Simoneau, MD, of Boston Children’s Hospital, and colleagues said the drop may have more to do with actual declines in asthma exacerbations among kids during the period. In addition, in a separate, international investigation of asthma outcomes among kids during COVID-19, a team reported that two-thirds of the children in the study showed evidence of improved asthma control during the first wave of the pandemic, with an overall decrease in asthma exacerbations and hospitalizations. The team concluded that the improvements were “probably the result of reduced exposure to asthma triggers and increased treatment adherence.” “Exacerbations tend to drop in the summer, and they always peak again in September within about 2 weeks of school starting,” she explained. “Another factor here is that kids may be using their asthma medications more appropriately because there is a lot of anxiety and fear related to COVID-19.”
Year in Review: COPD
MedPage Today, December 4, 2020
Patient management remains a challenge in year of COVID-19. New therapies and devices for chronic obstructive pulmonary disease (COPD) were approved in 2020 and researchers continued to explore expanding the definition of disease beyond spirometry. But 2020 was dominated by the struggles managing the care of highly vulnerable COPD patients during the COVID-19 pandemic. The delivery of routine components of COPD care, such as lung function testing and pulmonary rehabilitation, came to a virtual halt in the spring as medical offices closed. Connecting patients to these services remained a challenge throughout the year even after those offices reopened. “Almost all of my COPD patients have refused to come into the office. I see them remotely if I see them at all,” said David Mannino III, MD, of the University of Kentucky HealthCare in Lexington. Pulmonary and critical care specialist MeiLan Han, MD, of Michigan Medicine in Ann Arbor, said that while telemedicine has plugged some of the gaps, remote access to key COPD services has not been available for the vast majority of patients. “I have been struggling to find remote pulmonary rehabilitation for my patients. It has been a huge problem,” she told MedPage Today.
Revisiting One of the Dreaded Outcomes of the Current Pandemic: Pulmonary Embolism in COVID-19
Medicina, December 3, 2020
Coronavirus disease 2019 (COVID-19), which first emerged towards the end of the year 2019, was declared a pandemic by the World Health organization (WHO) on March 11, 2020. With ever-increasing case counts across the globe, the whole world is grappling to control this pandemic. The spectrum of clinical manifestations in COVID-19 is varied, and this has added to the complexity of its management. Some patients remain asymptomatic, while a myriad of systemic complications unfortunately affect others. Among these, acute respiratory distress syndrome (ARDS) continues to be the main cause of mortality and morbidity during this pandemic. Myocardial injury has been reported to significantly worsen clinical outcomes in COVID-19 patients with the mortality rate being reported to be as high as 37% in those with elevated troponin levels. Besides these two entities, venous thromboembolism (VTE) due to hypercoagulability has posed substantial mortality and morbidity risks. Deep venous thrombosis (DVT) and pulmonary embolism (PE) are evident in up to 1/3 of COVID-19 patients. In this article, we attempt to succinctly, yet comprehensively, discuss PE in patients with COVID-19 with a review of the prevailing literature.
Occurrence of Invasive Pulmonary Fungal Infections in Severe COVID-19 Patients Admitted to the ICU
American Journal of Respiratory and Critical Care Medicine, December 2, 2020
Whether severe COVID-19 is a significant risk factor for the development of invasive fungal superinfections is of great medical interest and remains for now an open question. We aim to assess the occurrence of invasive fungal respiratory superinfections in patients with severe COVID-19. We conducted the study on patients with severe SARS-CoV2 related pneumonia admitted to 5 intensive care units in France, who had respiratory and serum sampling performed for specific screening of fungal complication. The study population included a total of 145 patients the median age was 55 years old, most of them were male (n=104; 72%), were overweight (n=99; 68%), suffered from hypertension (n=83; 57%) and diabetes (n=46; 32%). Few patients presented preexisting host risk factors for invasive fungal infection (n=20; 14%). Their global severity was high: all patients were on invasive mechanical ventilation and half (n= 73, 54%) were on extracorporeal membrane oxygenation support. Mycological analysis included 2815 mycological tests (culture, galactomannan, beta-glucan, PCR) performed on 475 respiratory samples and 532 sera. A probable/putative invasive pulmonary mold infection was diagnosed in 7 (4.8%) patients and linked to high mortality. Multivariate analysis indicates a significantly higher risk for solid organ transplant recipients (OR=4.66 [1.98; 7.34], p=0.004). False positive fungal test and clinically irrelevant colonization, which did not require initiation of antifungal treatment, was observed in 25 patients (17.2%). In patients with no underlying immunosuppression, severe SARS-CoV-2 related pneumonia seems at low risk of invasive fungal secondary infection, especially aspergillosis.
In silico immune infiltration profiling combined with functional enrichment analysis reveals a potential role for naïve B cells as a trigger for severe immune responses in the lungs of COVID-19 patients
PLOS ONE, December 2, 2020
COVID-19, caused by SARS-CoV-2, has rapidly spread to more than 160 countries worldwide since 2020. Despite tremendous efforts and resources spent worldwide trying to explore antiviral drugs, there is still no effective clinical treatment for COVID-19 to date. Approximately 15% of COVID-19 cases progress to pneumonia, and patients with severe pneumonia may die from acute respiratory distress syndrome (ARDS). It is believed that pulmonary fibrosis from SARS-CoV-2 infection further leads to ARDS, often resulting in irreversible impairment of lung function. If the mechanisms by which SARS-CoV-2 infection primarily causes an immune response or immune cell infiltration can be identified, it may be possible to mitigate excessive immune responses by modulating the infiltration and activation of specific targets, thereby reducing or preventing severe lung damage. However, the extent to which immune cell subsets are significantly altered in the lung tissues of COVID-19 patients remains to be elucidated. This study applied the CIBERSORT-X method to comprehensively evaluate the transcriptional estimated immune infiltration landscape in the lung tissues of COVID-19 patients and further compare it with the lung tissues of patients with idiopathic pulmonary fibrosis (IPF). We found a variety of immune cell subtypes in the COVID-19 group, especially naïve B cells were highly infiltrated. Comparison of functional transcriptomic analyses revealed that non-differentiated naïve B cells may be the main cause of the over-active humoral immune response.
Extensive DVT and Pulmonary Embolism Leading to the Diagnosis of Coronavirus Disease 2019 in the Absence of Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia
CHEST, December 1, 2020
A 31-year-old patient with no past medical history presented to the ED for an erythematous swelling of the left inferior limb. The patient had no fever, stable hemodynamic status, and oxygen saturation was 99% (room air). Notably, the heart rate was 133 beats/ min. Blood tests showed high inflammatory markers with C-reactive protein, ferritin, and fibrinogen levels of 225 mg/L, 2646 mg/L, and 7.22 g/L, respectively. Moreover, the D-dimer level was 5.0 mg/L. CT venography showed an extended femoropopliteal DVT expanding to the subrenal vena cava, and a lobar bilateral pulmonary embolism. There is growing evidence that coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. To date, all patients reported with venous thromboembolic disease and COVID-19 have shown evidence of viral pneumonia. Here, we report the case of a 31- year-old patient with unexplained extensive DVT and bilateral pulmonary embolism in the absence of COVID-19 pneumonia, leading to the diagnosis of otherwise asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the context of the COVID-19 pandemic, given the high rates of otherwise asymptomatic patients, testing for SARS-CoV-2 should be performed in all patients with unexplained VTE occurring in COVID19-endemic areas, even in the absence of other disease manifestations suggestive of SARSCoV-2 infection.
Uncontrolled Innate and Impaired Adaptive Immune Responses in Patients with COVID-19 Acute Respiratory Distress Syndrome
American Journal of Respiratory and Critical Care Medicine, December 1, 2020
Uncontrolled inflammatory innate response and impaired adaptive immune response are associated with clinical severity in patients with coronavirus disease (COVID-19). Our objective was to compare the immunopathology of COVID-19 acute respiratory distress syndrome (ARDS) with that of non–COVID-19 ARDS, and to identify biomarkers associated with mortality in patients with COVID-19 ARDS. This prospective observational monocenter study included immunocompetent patients diagnosed with RT-PCR–confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and ARDS admitted between March 8 and March 30, 2020.They were compared with patients with non–COVID-19 ARDS. The primary clinical endpoint of the study was mortality at Day 28. Flow cytometry analyses and serum cytokine measurements were performed at Days 1–2 and 4–6 of ICU admission. As compared with patients with non–COVID-19 ARDS (n = 36), those with COVID-19 (n = 38) were not significantly different regarding age, sex, and Sequential Organ Failure Assessment and Simplified Acute Physiology Score II scores but exhibited a higher Day-28 mortality (34% vs. 11%, P = 0.030). Patients with COVID-19 showed profound and sustained T CD4+ (P = 0.002), CD8+ (P < 0.0001), and B (P < 0.0001) lymphopenia, higher HLA-DR expression on monocytes (P < 0.001) and higher serum concentrations of EGF (epithelial growth factor), GM-CSF, IL-10, CCL2/MCP-1, CCL3/MIP-1a, CXCL10/IP-10, CCL5/RANTES, and CCL20/MIP-3a. After adjusting on age and Sequential Organ Failure Assessment, serum CXCL10/IP-10 (P = 0.047) and GM-CSF (P = 0.050) were higher and nasopharyngeal RT-PCR cycle threshold values lower (P = 0.010) in patients with COVID-19 who were dead at Day 28. Profound global lymphopenia and a “chemokine signature” were observed in COVID-19 ARDS.
A Survey-based Estimate of COVID-19 Incidence and Outcomes among Patients with Pulmonary Arterial Hypertension or Chronic Thromboembolic Pulmonary Hypertension and Impact on the Process of Care
Annals of the American Thoracic Society, December 1, 2020
Patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) typically undergo frequent clinical evaluation. The incidence and outcomes of coronavirus disease (COVID-19) and its impact on routine management for patients with pulmonary vascular disease is currently unknown. Our objective was to assess the cumulative incidence and outcomes of recognized COVID-19 for patients with PAH/CTEPH followed at accredited pulmonary hypertension centers, and to evaluate the pandemic’s impact on clinic operations at these centers. A survey was e-mailed to program directors of centers accredited by the Pulmonary Hypertension Association. Descriptive analyses and linear regression were used to analyze results. Seventy-seven center directors were successfully e-mailed a survey, and 58 responded (75%). The cumulative incidence of COVID-19 recognized in individuals with PAH/CTEPH was 2.9 cases per 1,000 patients, similar to the general U.S. population. In patients with PAH/CTEPH for whom COVID-19 was recognized, 30% were hospitalized and 12% died. These outcomes appear worse than the general population. A large impact on clinic operations was observed including fewer clinic visits and substantially increased use of telehealth. A majority of centers curtailed diagnostic testing and a minority limited new starts of medical therapy. Most centers did not use experimental therapies in patients with PAH/CTEPH diagnosed with COVID-19. The cumulative incidence of COVID-19 recognized in patients with PAH/CTEPH appears similar to the broader population, although outcomes may be worse. Although the total number of patients with PAH/CTEPH recognized to have COVID-19 was small, the impact of COVID-19 on broader clinic operations, testing, and treatment was substantial.
Risk Factors for Mortality Following COVID-19 in Patients with Pre-existing Interstitial Lung Disease
American Journal of Respiratory and Critical Care Medicine, November 30, 2020
Patients with pre-existing interstitial lung disease (ILD) may be at high risk for severe COVID-19 disease due to impaired lung function, propensity to develop acute exacerbation of pulmonary fibrosis, or immunomodulatory medications that may interact with viral clearance or pathogenesis. Previous studies found that patients with ILDs had an increased risk of death as compared to controls matched for age, sex, comorbidities and/or race. However, whether the type of ILD may influence the outcome of COVID-19 is unknown. Here, we aimed at comparing mortality of COVID-19 between patients with fibrotic idiopathic ILD including idiopathic pulmonary fibrosis (IPF), to those with other types of ILD. In this multicentric observational survey of specialized centers, we analyzed the survival of COVID-19 in patients with ILDs and compared mortality rates among those with fibrotic idiopathic ILDs including IPF, to other ILDs. Patients were eligible if they had preexisting ILD, and if they had COVID-19 during the study period confirmed by RT-PCR or definite clinical manifestations (acute onset of fever, flu-like symptoms, headache, and anosmia), typical features on chest CT and positive serology for SARS-CoV-2 virus. Patients with lung transplantation were excluded. Consecutive cases were collected using a deidentified case report form through the French rare lung disease network (OrphaLung) between the onset of the outbreak in France to May 28, 2020. Data collected included demographics, medical history, comorbidities, last available lung function in stable condition, and treatment received at the time of COVID-19.
How I approach membrane lung dysfunction in patients receiving ECMO
Critical Care, November 30, 2020
[Editorial] With improvements in circuit technology and expanding supportive evidence, extracorporeal membrane oxygenation (ECMO) use has grown rapidly over the past decade. Advances in pump and membrane lung (ML) design have led to simpler and more efficient circuits. Circuit-related complications, however, remain frequent and associated with considerable morbidity. Mechanisms of membrane lung dysfunction The ML is responsible for oxygen uptake and carbon dioxide removal. The non-biologic surface of the ML activates inflammatory and coagulation pathways with thrombus formation, fibrinolysis, and leukocyte activation leading to ML dysfunction. Activation of coagulation and fibrinolysis can precipitate systemic coagulopathy or hemolysis, while clot deposition can obstruct blood flow. Additionally, moisture buildup in the gas phase and protein and cellular debris accumulation in the blood phase may contribute to shunt and dead-space physiology, respectively, impairing gas exchange. These three categories—hematologic abnormalities, mechanical obstruction, and inadequate gas exchange—prompt the majority of ML exchanges. The decision to exchange a ML is complex and without clear guidelines. In this manuscript, we outline a physiologic approach to troubleshooting this common yet high-risk event.
COVID-19 vaccine developed by Moderna, NIH gets FDA review date
Helio | Infectious Disease News, November 30, 2020
The FDA’s vaccine advisory committee will meet on Dec. 17 to review an emergency use authorization (EUA) request for the COVID-19 vaccine candidate codeveloped by Moderna and the NIH, Moderna announced. It will be the second such meeting in 8 days of the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), which will review an EUA request filed by Pfizer and BioNTech for their COVID-19 vaccine candidate on Dec. 10. Moderna announced the VRBPAC date at the same time it reported that preliminary data from a primary efficacy analysis showed its messenger RNA (mRNA)-based vaccine, mRNA-1273, was 94.1% efficacious overall and 100% efficacious against severe COVID-19, with no serious safety concerns identified to date. According to a press release, the phase 3 COVE study exceeded the 2-month median follow-up following vaccination required for an EUA submission, which Moderna said it was filing Monday. “We believe that our vaccine will provide a new and powerful tool that may change the course of this pandemic and help prevent severe disease, hospitalizations and death,” Moderna CEO Stéphane Bancel said in the press release. “I want to thank the thousands of participants in our phase 1, phase 2 and phase 3 studies, as well as the staff at clinical trial sites who have been on the front lines of the fight against the virus.”
Chest CT in COVID-19 at the ED: Validation of the COVID-19 Reporting and Data System (CO-RADS) and CT severity score
CHEST, November 30, 2020
Computed tomography (CT) is thought to play a key role in COVID-19 diagnostic work-up. The possibility to compare data across different settings depends on the systematic and reproducible manner the scans are analyzed and reported. The COVID-19 Reporting and Data System (CO-RADS) and the corresponding CT severity score (CTSS) introduced by the Radiological Society of the Netherlands (NVvR) attempt to do so. However, this system has not been externally validated. We aimed to prospectively validate the CO-RADS as a COVID-19 diagnostic tool at the emergency department (ED), and evaluate if the CTSS is associated with prognosis. We conducted a prospective, observational study in two tertiary centers in The Netherlands, between March 19 and May 28, 2020. We consecutively included 741 adult patients at the ED with suspected COVID-19, who received a chest CT and SARS-CoV-2 PCR (PCR). Diagnostic accuracy measures were calculated for CO-RADS using PCR as reference. Logistic regression was performed for CTSS in relation to hospital admission, ICU admission and 30-day mortality. 741 patients were included. We found an AUC of 0.91 (CI 0.89-0.94) for CO-RADS using PCR as reference. The optimal CO-RADS cut-off was 4, with a sensitivity of 89.4% (CI 84.7-93.0) and specificity of 87.2% (CI 83.9-89.9). We found a significant association between CTSS and hospital admission, ICU admission, and 30-day mortality; adjusted odds ratios per point increase in CTSS were 1.19 (CI 1.09-1.28), 1.23 (1.15-1.32), 1.14 (1.07-1.22), respectively. Intra-class correlation coefficients for CO-RADS and CTSS were 0.94 (0.91-0.96) and 0.82 (CI 0.70-0.90).
Computational simulation to assess patient safety of uncompensated COVID-19 two-patient ventilator sharing using the Pulse Physiology Engine
PLOS ONE, November 25, 2020
The COVID-19 pandemic is stretching medical resources internationally, sometimes creating ventilator shortages that complicate clinical and ethical situations. The possibility of needing to ventilate multiple patients with a single ventilator raises patient health and safety concerns in addition to clinical conditions needing treatment. Wherever ventilators are employed, additional tubing and splitting adaptors may be available. Adjustable flow-compensating resistance for differences in lung compliance on individual limbs may not be readily implementable. By exploring a number and range of possible contributing factors using computational simulation without risk of patient harm, this paper attempts to define useful bounds for ventilation parameters when compensatory resistance in limbs of a shared breathing circuit is not possible. To be useful for clinicians, attention has been directed to clinically available parameters. These simulations show patient outcome during multi-patient ventilation is most closely correlated to lung compliance, oxygenation index, oxygen saturation index, and end-tidal carbon dioxide of individual patients. The simulated patient outcome metrics were satisfactory when the lung compliance difference between two patients was less than 12 mL/cmH2O, and the oxygen saturation index difference was less than 2 mmHg. This desperate approach to shared ventilation support would be a last resort when alternatives have been exhausted.
Bronchoalveolar Lavage in COVID-19 Patients with Invasive Mechanical Ventilation for ARDS
Annals of the American Thoracic Society, November 24, 2020
[Letter to the Editor] Bronchoalveolar lavage (BAL) is a routine bronchoscopic procedure that may provide significant information for the management of pneumonia. In critically ill patients, including those with severe acute respiratory distress syndrome (ARDS), bronchoscopy and BAL safety have been demonstrated. However, early after the novel coronavirus SARS-CoV-2 disease (COVID-19) pandemic spread, guidelines converged in recommending limiting the use of bronchoscopy and considered known or suspected COVID-19 to be a relative contraindication to bronchoscopy, as the risk of healthcare workers contamination may be increased by this aerosol-generating procedure. During the first wave of the pandemic, we rapidly observed, as highlighted by others, an increased need for bronchoscopy in COVID-19-associated ARDS patients requiring mechanical ventilation, mainly for bronchoaspiration but also, in some cases, to perform BAL for microbiological sampling. The ability of BAL to confirm COVID-19 was also demonstrated, in case of previous negative nasopharyngeal swab(s) in patients, intubated or not, with clinical concern for this diagnosis. Nevertheless, the value of BAL has not been evaluated so far for further microbiological workup after non-invasive diagnostic tests were exhausted. For this purpose, and because data on BAL performed on COVID-19 associated-ARDS patients remain scarce, we herein describe our single center experience at the Henri Mondor University Hospital (Créteil, France) on 28 consecutive BAL performed between March 31st and June 3rd, 2020, on 24 COVID-19 patients (four patients had two BAL) treated with invasive mechanical ventilation for moderate to severe ARDS. Median time [IQR] from intubation to BAL was 16 [10-21] days, and median [IQR] PaO2/FiO2 ratio, FiO2 and PEEP (H20 cm) before BAL were respectively: 122 [74-148], 0.8 [0.4-1] and 8 [5-10].
Inhaled interferon beta improves odds of recovery from COVID-19
Helio | Pulmonology, November 24, 2020
Hospitalized patients with COVID-19 who received inhaled nebulized interferon beta-1a were twice as likely to improve and recover than those who received placebo, according to data published in The Lancet Respiratory Medicine. “The findings of this trial suggest the potential utility of SNG001 in treating patients admitted to hospital with COVID-19, although SNG001 should be explored further in a phase 3 trial,” Phillip D. Monk, PhD, chief scientific officer at Synairgen Research at Southampton General Hospital, U.K., and colleagues wrote. “Currently, treatment options for COVID-19 remain limited, with the only evidence-based therapies being remdesivir and dexamethasone.” The randomized, double-blind, placebo-controlled phase 2 trial included 101 adult patients admitted to one of nine U.K. hospitals with COVID-19 infection from March 30 to May 30. Patients were randomly assigned to inhaled nebulized interferon beta-1a (SNG001, Synairgen; n = 48) or placebo (n = 50) by inhalation via mouthpiece daily for 14 days. The primary outcome was change in clinical condition on the WHO Ordinal Scale for Clinical Improvement (OSCI) during the dosing period in the intention-to-treat population.
Deep-learning algorithms for the interpretation of chest radiographs to aid in the triage of COVID-19 patients: A multicenter retrospective study
PLOS ONE, November 24, 2020
The recent medical applications of deep-learning (DL) algorithms have demonstrated their clinical efficacy in improving speed and accuracy of image interpretation. If the DL algorithm achieves a performance equivalent to that achieved by physicians in chest radiography (CR) diagnoses with Coronavirus disease 2019 (COVID-19) pneumonia, the automatic interpretation of the CR with DL algorithms can significantly reduce the burden on clinicians and radiologists in sudden surges of suspected COVID-19 patients. The aim of this study was to evaluate the efficacy of the DL algorithm for detecting COVID-19 pneumonia on CR compared with formal radiology reports. This is a retrospective study of adult patients that were diagnosed as positive COVID-19 cases based on the reverse transcription polymerase chain reaction among all the patients who were admitted to five emergency departments and one community treatment center in Korea. The CR images were evaluated with a publicly available DL algorithm. Patients with evidence of pneumonia on chest CT scans were also classified as COVID-19 pneumonia positive outcomes. The overall sensitivity and specificity of the DL algorithm for detecting COVID-19 pneumonia on CR were 95.6%, and 88.7%, respectively. The area under the curve value of the DL algorithm for the detection of COVID-19 with pneumonia was 0.921. The DL algorithm demonstrated a satisfactory diagnostic performance comparable with that of formal radiology reports in the CR-based diagnosis of pneumonia in COVID-19 patients.
Outcomes of mechanically ventilated patients with COVID-19 associated respiratory failure
PLOS ONE, November 23, 2020
The outcomes of patients requiring invasive mechanical ventilation for COVID-19 remain poorly defined. We sought to determine clinical characteristics and outcomes of patients with COVID-19 managed with invasive mechanical ventilation in an appropriately resourced US health care system. Outcomes of COVID-19 infected patients requiring mechanical ventilation treated within the Inova Health System between March 5, 2020 and April 26, 2020 were evaluated through an electronic medical record review. 1023 COVID-19 positive patients were admitted to the Inova Health System during the study period. Of these, 164 (16.0%) were managed with invasive mechanical ventilation. All patients were followed to definitive disposition. 70/164 patients (42.7%) had died and 94/164 (57.3%) were still alive. Deceased patients were older (median age of 66 vs. 55, p <0.0001) and had a higher initial d-dimer (2.22 vs. 1.31, p = 0.005) and peak ferritin levels (2998 vs. 2077, p = 0.016) compared to survivors. 84.3% of patients over 70 years old died in the hospital. Conversely, 67.4% of patients age 70 or younger survived to hospital discharge. Younger age, non-Caucasian race and treatment at a tertiary care center were all associated with survivor status. Mortality of patients with COVID-19 requiring invasive mechanical ventilation is high, with particularly daunting mortality seen in patients of advanced age, even in a well-resourced health care system.
Testing IgG antibodies against the RBD of SARS-CoV-2 is sufficient and necessary for COVID-19 diagnosis
PLOS ONE, November 23, 2020
The COVID-19 pandemic and the fast global spread of the disease resulted in unprecedented decline in world trade and travel. A critical priority is, therefore, to quickly develop serological diagnostic capacity and identify individuals with past exposure to SARS-CoV-2. In this study serum samples obtained from 309 persons infected by SARS-CoV-2 and 324 of healthy, uninfected individuals as well as serum from 7 COVID-19 patients with 4–7 samples each ranging between 1–92 days post first positive PCR were tested by an “in house” ELISA which detects IgM, IgA and IgG antibodies against the receptor binding domain (RBD) of SARS-CoV-2. Sensitivity of 47%, 80% and 88% and specificity of 100%, 98% and 98% in detection of IgM, IgA and IgG antibodies, respectively, were observed. IgG antibody levels against the RBD were demonstrated to be up regulated between 1–7 days after COVID-19 detection, earlier than both IgM and IgA antibodies. Study of the antibody kinetics of seven COVID 19 patients revealed that while IgG levels are high and maintained for at least 3 months, IgM and IgA levels decline after a 35–50 days following infection. Altogether, these results highlight the usefulness of the RBD based ELISA, which is both easy and cheap to prepare, to identify COVID-19 patients even at the acute phase. Most importantly, our results demonstrate that measuring IgG levels alone is both sufficient and necessary to diagnose past exposure to SARS-CoV-2.
Could KL-6 levels in COVID-19 help to predict lung disease?
Respiratory Research, November 24, 2020
Coronavirus disease COVID-19 has become a public health emergency of international concern. Together with the quest for an effective treatment, the question of the post-infectious evolution of affected patients in healing process remains uncertain. Krebs von den Lungen 6 (KL-6) is a high molecular weight mucin-like glycoprotein produced by type II pneumocytes and bronchial epithelial cells. Its production is raised during epithelial lesions and cellular regeneration. In COVID-19 infection, KL-6 serum levels could therefore be of interest for diagnosis, prognosis and therapeutic response evaluation. Our study retrospectively compared KL-6 levels between a cohort of 83 COVID-19 infected patients and two other groups: healthy subjects (n = 70) on one hand, and a heterogenous group of patients suffering from interstitial lung diseases (n = 31; composed of 16 IPF, 4 sarcoidosis, 11 others) on the other hand. Demographical, clinical and laboratory indexes were collected. Our study aims to compare KL-6 levels between a COVID-19 population and healthy subjects or patients suffering from interstitial lung diseases (ILDs). Ultimately, we ought to determine whether KL-6 could be a marker of disease severity and bad prognosis. Our results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects, but to a lesser extent than in patients suffering from ILD. Increased levels of KL-6 in COVID-19 patients were associated with a more severe lung disease.
Transpulmonary Pressure-guided Ventilation to Attenuate Atelectrauma and Hyperinflation in Acute Lung Injury
American Journal of Respiratory and Critical Care Medicine, November 23, 2020
The inherent appeal of using esophageal manometry to guide PEEP titration lies in its ability to distinguish lung from chest wall mechanics. Transpulmonary pressure (PL) is calculated as the pressure measured at the airway opening minus the pleural pressure, typically estimated via esophageal manometry. Lung injury termed atelectrauma may occur from high regional forces generated repeatedly during cyclic closure and reopening of small airways during tidal ventilation. Negative PL values (where pleural pressure exceeds airway pressure) predispose to small airways closure and cause lung injury that, in preclinical models, is attenuated with higher PEEP. Here, Bastia and colleagues highlight the potential for esophageal manometry to estimate PL even in asymmetric lung injury. In their study, invasively ventilated pigs were subjected to unilateral lung injury via surfactant lavage and high tidal stretch instituted with temporary endobronchial blockade occluding the contralateral lung. After injury was established, the bronchial blocker was removed and respiratory mechanics were assessed in both hemithoraces at different levels of PEEP. Pleural pressure was measured directly using air-filled balloon catheters inserted into the ventral and dorsal pleural spaces of the left and right hemithoraces, and also was estimated with esophageal manometry. Electrical impedance tomography (EIT) was used to evaluate heterogeneous insufflation.
Gov’t Prepares to Distribute Regeneron COVID-19 Drug
MedPage Today, November 23, 2020
Following the FDA’s weekend authorization of Regeneron’s monoclonal antibody cocktail for mild-moderate COVID-19, the federal government’s Operation Warp Speed (OWS) is swinging into action, officials said Monday. Department of Health and Human Services (HHS) Secretary Alex Azar said OWS would ship 30,000 doses on Tuesday — each eligible COVID-19 patient receives one dose — with thousands more to go out in the days ahead. On a phone call with reporters, he also reiterated the government’s promise that the drug would be provided to patients at no cost (Facilities may still charge for administration of the intravenous product, however). Regeneron’s CEO told CNBC on Monday that the company currently has 80,000 doses on hand and expects to ship 300,000 by early January, with 100,000 additional doses per month to come thereafter. Getting the product to patients is a major logistical challenge, officials explained, as has been the case with Eli Lilly’s bamlanivimab, another infusion therapy that received emergency authorization 2 weeks ago. Both drugs are to be used in non-hospitalized patients at risk for illness progression — meaning they are for outpatient administration. Because patients by definition have COVID-19, they need to be isolated, and sites must be prepared to provide infusions to large numbers of them given the current surge in cases.
Outcomes of mechanically ventilated patients with COVID-19 associated respiratory failure
PLOS ONE, November 23, 2020
The outcomes of patients requiring invasive mechanical ventilation for COVID-19 remain poorly defined. We sought to determine clinical characteristics and outcomes of patients with COVID-19 managed with invasive mechanical ventilation in an appropriately resourced US health care system. Outcomes of COVID-19 infected patients requiring mechanical ventilation treated within the Inova Health System between March 5, 2020 and April 26, 2020 were evaluated through an electronic medical record review. 1023 COVID-19 positive patients were admitted to the Inova Health System during the study period. Of these, 164 (16.0%) were managed with invasive mechanical ventilation. All patients were followed to definitive disposition. 70/164 patients (42.7%) had died and 94/164 (57.3%) were still alive. Deceased patients were older (median age of 66 vs. 55, p <0.0001) and had a higher initial d-dimer (2.22 vs. 1.31, p = 0.005) and peak ferritin levels (2998 vs. 2077, p = 0.016) compared to survivors. 84.3% of patients over 70 years old died in the hospital. Conversely, 67.4% of patients age 70 or younger survived to hospital discharge. Younger age, non-Caucasian race and treatment at a tertiary care center were all associated with survivor status. Mortality of patients with COVID-19 requiring invasive mechanical ventilation is high, with particularly daunting mortality seen in patients of advanced age, even in a well-resourced health care system.
FDA authorizes emergency use of casirivimab, imdevimab for COVID-19
Helio | Primary Care, November 23, 2020
The FDA granted emergency use authorization for the monoclonal antibodies casirivimab and imdevimab to be administered together intravenously for the treatment of mild to moderate COVID-19. According to a press release, this EUA pertains to adults and children aged 12 years and older with positive SARS-CoV-2 viral test results who weigh 88 pounds or more and are at high risk for progressing to severe COVID-19. Adults aged older than 65 years who have certain chronic medical conditions may also receive the treatment. The authorization does not extend to patients who are hospitalized or require oxygen therapy due to COVID-19. According to the release, the EUA for casirivimab and imdevimab is based on a randomized, double-blind, placebo-controlled clinical trial of 799 nonhospitalized adults with mild to moderate COVID-19 symptoms. The FDA said the “most important evidence” to emerge from the trial was that only 3% of the monoclonal antibody recipients were hospitalized or visited an ED compared with 9% of those who received placebo. The agency also noted that viral load reduction in patients who were treated with casirivimab and imdevimab was larger compared with patients treated with placebo at day 7. The effects on viral load, reduction in hospitalizations and ED visits were similar in patients receiving either of the two casirivimab and imdevimab doses in the study.
Effectiveness and safety of noninvasive positive pressure ventilation in the treatment of COVID-19-associated acute hypoxemic respiratory failure: a single center, non-ICU setting experience
Internal and Emergency Medicine, November 22, 2020
The role of noninvasive positive pressure ventilation (NIPPV) in COVID-19 patients with acute hypoxemic respiratory failure (AHRF) is uncertain, as no direct evidence exists to support NIPPV use in such patients. We retrospectively assessed the effectiveness and safety of NIPPV in a cohort of COVID-19 patients consecutively admitted to the COVID-19 general wards of a medium-size Italian hospital, from March 6 to May 7, 2020. Healthcare workers (HCWs) caring for COVID-19 patients were monitored, undergoing nasopharyngeal swab for SARS-CoV-2 in case of onset of COVID-19 symptoms, and periodic SARS-CoV-2 screening serology. Overall, 50 patients (mean age 74.6 years) received NIPPV, of which 22 (44%) were successfully weaned, avoiding endotracheal intubation (ETI) and AHRF-related death. Due to limited life expectancy, 25 (50%) of 50 NIPPV-treated patients received a “do not intubate” (DNI) order. Among these, only 6 (24%) were weaned from NIPPV. Of the remaining 25 NIPPV-treated patients without treatment limitations, 16 (64%) were successfully weaned, 9 (36%) underwent delayed ETI and, of these, 3 (33.3%) died. NIPPV success was predicted by the use of corticosteroids (OR 15.4, CI 1.79–132.57, p 0.013) and the increase in the PaO2/FiO2 ratio measured 24–48 h after NIPPV initiation (OR 1.02, CI 1–1.03, p 0.015), while it was inversely correlated with the presence of a DNI order (OR 0.03, CI 0.001–0.57, p 0.020). During the study period, 2 of 124 (1.6%) HCWs caring for COVID-19 patients were diagnosed with SARS-CoV-2 infection. Apart from patients with limited life expectancy, NIPPV was effective in a substantially high percentage of patients with COVID-19-associated AHRF. The risk of SARS-CoV-2 infection among HCWs was low.
Pneumomediastinum in ARDS from COVID-19 Infection
American Journal of Respiratory and Critical Care Medicine, November 20, 2020
Pneumomediastinum is an uncommon complication of acute respiratory distress syndrome (ARDS) from viral infections, including severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1). Barotrauma from SARS-CoV-2 infection (i.e. COVID-19) has been increasingly described. We report 5 patients with pneumomediastinum out of 92 critically ill, mechanically ventilated adults with ARDS from COVID-19 at our institution from March 1st through August 31st, 2020. Unlike other reports, no patient had pneumothorax or required tube thoracostomy at diagnosis, suggesting alveolar rupture occurred without disruption of visceral pleura. Pneumomediastinum developed from 24 hours prior to 9 days after initiation of mechanical ventilation without evidence of tracheal injury or use of recruitment maneuvers. Patients received low-tidal volume ventilation targeting plateau pressures less than 30 cm H2O to minimize driving pressure, with sedation and/or paralysis used to reduce initial high respiratory effort and limit dyssynchrony. Our cumulative incidence (5.4%) of pneumomediastinum without pneumothorax falls between incidences reported in other series. All patients later developed other barotrauma days after initial diagnosis, including two patients developing pneumopericardium and one developing pneumoperitoneum with severe subcutaneous emphysema from the neck to the pelvis. Four of the five patients died during hospitalization, with the remaining patient being discharged alive.
Tissue-specific Immunopathology in Fatal COVID-19
American Journal of Respiratory and Critical Care Medicine, November 20, 2020
In life-threatening COVID-19, corticosteroids reduce mortality, suggesting that immune responses have a causal role in death. Whether this deleterious inflammation is primarily a direct reaction to the presence of SARS-CoV-2 or an independent immunopathologic process is unknown. Our objective was to determine SARS-CoV-2 organotropism and organ-specific inflammatory responses, and the relationships between viral presence, inflammation, and organ injury. Tissue was acquired from eleven detailed post-mortem examinations. SARS-CoV-2 organotropism was mapped by multiplex PCR and sequencing, with cellular resolution achieved by in situ viral spike protein detection. Histological evidence of inflammation was quantified from 37 anatomical sites, and the pulmonary immune response characterized by multiplex immunofluorescence. Multiple aberrant immune responses in fatal COVID-19 were found, principally involving the lung and reticuloendothelial system, and these were not clearly topologically associated with the virus. Inflammation and organ dysfunction did not map to the tissue and cellular distribution of SARS-CoV-2 RNA and protein, both between and within tissues.
Endothelial Damage in Acute Respiratory Distress Syndrome
International Journal of Molecular Sciences, November 20, 2020
The pulmonary endothelium is a metabolically active continuous monolayer of squamous endothelial cells that internally lines blood vessels and mediates key processes involved in lung homoeostasis. Many of these processes are disrupted in acute respiratory distress syndrome (ARDS), which is marked among others by diffuse endothelial injury, intense activation of the coagulation system and increased capillary permeability. Most commonly occurring in the setting of sepsis, ARDS is a devastating illness, associated with increased morbidity and mortality and no effective pharmacological treatment. Endothelial cell damage has an important role in the pathogenesis of ARDS and several biomarkers of endothelial damage have been tested in determining prognosis. By further understanding the endothelial pathobiology, development of endothelial-specific therapeutics might arise. In this review, we will discuss the underlying pathology of endothelial dysfunction leading to ARDS and emerging therapies. Furthermore, we will present a brief overview demonstrating that endotheliopathy is an important feature of hospitalised patients with coronavirus disease-19 (COVID-19).
Computed tomography characterization and outcome evaluation of COVID-19 pneumonia complicated by venous thromboembolism
PLOS ONE, November 19, 2020
COVID-19 is frequently complicated by venous thromboembolism (VTE). Computed tomography (CT) of the chest—primarily usually conducted as low-dose, non-contrast enhanced CT—plays an important role in the diagnosis and follow-up of COVID-19 pneumonia. Performed as contrast-enhanced CT pulmonary angiography, it can reliably detect or rule-out pulmonary embolism (PE). Several imaging characteristics of COVID-19 pneumonia have been described for chest CT, but no study evaluated CT findings in the context of VTE/PE. In our retrospective study, we analyzed clinical, laboratory and CT imaging characteristics of 50 consecutive patients with RT-PCR proven COVID-19 pneumonia who underwent contrast-enhanced chest CT at two tertiary care medical centers. All patients with RT-PCR proven COVID-19 pneumonia and contrast-enhanced chest CT performed at two tertiary care hospitals between March 1st and April 20th 2020 were retrospectively identified. Patient characteristics (age, gender, comorbidities), symptoms, date of symptom onset, RT-PCR results, imaging results of CT and leg ultrasound, laboratory findings (C-reactive protein, differential blood count, troponine, N-terminal pro-B-type natriuretic peptide (NT-proBNP), fibrinogen, interleukin-6, D-dimer, lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase muscle-brain (CKmb) and lactate,) and patient outcome (positive: discharge or treatment on normal ward; negative: treatment on intensive care unit (ICU), need for mechanical ventilation, extracorporeal membrane oxygenation (ECMO), or death) were analyzed.
Insights on ventilation management, clinical outcomes in COVID-19
Helio | Pulmonology, November 18, 2020
During the first month of the COVID-19 outbreak in the Netherlands, there was broad use of lung-protective ventilation with low tidal volume and low driving pressure and prone positioning, according to results of the PRoVENT-COVID study. “[This report] provides information on ventilation practice in these patients, which can be used to improve local practices,” Michela Botta, MD, of the department of intensive care at Amsterdam University Medical Center, the Netherlands, and colleagues wrote in The Lancet Respiratory Medicine. “The data presented here could function as a basis for new hypotheses and sample size calculations for future trials of invasive ventilation in patients with COVID-19,” the researchers wrote. “Additionally, our finding that respiratory system compliance and tidal volume affect major outcomes has implications for the understanding of differences in outcomes in the cohorts of patients with COVID-19 that have been reported and will be reported in the near future.”
Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: an observational cohort study
Journal of Allergy and Clinical Immunology, November 18, 2020
Immunomodulants have been proposed to mitigate SARS-Cov-2-induced cytokine storm, which drives acute respiratory distress syndrome in COVID-19. To determine efficacy and safety of the association of IL-1 receptor antagonist anakinra plus methylprednisolone in severe COVID-19 pneumonia with hyperinflammation. Secondary analysis of prospective observational cohort studies at an Italian tertiary health-care facility. COVID-19 patients consecutively hospitalized (02/25/2020 to 03/30/2020), with hyperinflammation (ferritin ≥1000ng/mL and/or C-reactive protein >10mg/dL) and respiratory failure (oxygen therapy from 0.4 FiO2 Venturi mask to invasive mechanical ventilation) were evaluated to investigate the effect of high-dose anakinra plus methylprednisolone on survival. Patients were followed from study inclusion to day 28 or death. 120 COVID-19 patients with hyperinflammation (median age 62 years, 80.0% males, median PaO 2:FiO 2 ratio 151, 32.5% on mechanical ventilation) were evaluated. Of these, 65 were treated with anakinra and methylprednisolone and 55 were untreated historical controls. At 28 days, mortality was 13.9% in treated patients and 35.6% in controls (Kaplan-Meier plots, p=0.005). Unadjusted and adjusted risk of death was significantly lower for treated patients compared to controls (HR 0.33 (95%CI 0.15-0.74), p=0.007 and HR 0.18 (95%CI 0.07-0.50), p=0.001, respectively).
Factors associated with disease severity and mortality among patients with COVID-19: A systematic review and meta-analysis
PLOS ONE, November 18, 2020
Understanding the factors associated with disease severity and mortality in Coronavirus disease (COVID-19) is imperative to effectively triage patients. We performed a systematic review to determine the demographic, clinical, laboratory and radiological factors associated with severity and mortality in COVID-19. We searched PubMed, Embase and WHO database for English language articles from inception until May 8, 2020. We included Observational studies with direct comparison of clinical characteristics between a) patients who died and those who survived or b) patients with severe disease and those without severe disease. Data extraction and quality assessment were performed by two authors independently. Among 15680 articles from the literature search, 109 articles were included in the analysis. The risk of mortality was higher in patients with increasing age, male gender (RR 1.45, 95%CI 1.23–1.71), dyspnea (RR 2.55, 95%CI 1.88–2.46), diabetes (RR 1.59, 95%CI 1.41–1.78), hypertension (RR 1.90, 95%CI 1.69–2.15). Congestive heart failure (OR 4.76, 95%CI 1.34–16.97), hilar lymphadenopathy (OR 8.34, 95%CI 2.57–27.08), bilateral lung involvement (OR 4.86, 95%CI 3.19–7.39) and reticular pattern (OR 5.54, 95%CI 1.24–24.67) were associated with severe disease. Clinically relevant cut-offs for leukocytosis (>10.0 x109/L), lymphopenia (< 1.1 x109/L), elevated C-reactive protein (>100mg/L), LDH (>250U/L) and D-dimer (>1mg/L) had higher odds of severe disease and greater risk of mortality.
Effect of PEEP in COVID-19-Related ARDS Similar to Classical ARDS
Pulmonology Advisor, November 18, 2020
The effects of positive end expiratory pressure (PEEP) in COVID-19-related acute respiratory distress syndrome (ARDS) are similar to those reported in classical ARDS, according to study results published in the American Journal of Respiratory and Critical Care Medicine. Assessment of lung ventilation and perfusion of COVID-19-related ARDS is scarce, especially in response to positive end expiratory pressure (PEEP) and prone positioning. Therefore, researchers sought to describe the physiologic effects of PEEP and prone positioning on respiratory mechanics, ventilation, and pulmonary perfusion in patients with COVID-19-related ARDS. Of 41 patients with COVID-19-related ARDS admitted during the study period, only 9 completed full explorations and could be analyzed. The effects of PEEP in COVID-19-related ARDS were demonstrated to be close to those reported in classical ARDS. The increase in PEEP resulted in alveolar recruitment associated with a significant decrease in severe shunt, mainly in the dorsal regions, driven by the increase in dorsal ventilation. Additionally, increasing PEEP resulted in less severe alveolar dead space in the ventral regions, because ventilation decreased more than perfusion. However, the better ventilation/perfusion ratio (V/Q) matching at high PEEP was at the expense of hyperdistension, as suggested by the respiratory mechanics data and in particular by a decrease in ventral compliance and ventilation. Turning the patient from supine to prone position increased the PaO2/FiO2 ratio by 64 mm Hg, induced recruitment in the dorsal regions and collapse in ventral regions, but did not change the dorsal predominance of pulmonary perfusion. Proning also decreased ventral dead space and dorsal shunt.
T Cells May Tell Us More About COVID Immunity MedPage Today, November 18, 2020
While antibodies have been the focus of testing for past infection with COVID-19, T cells will also provide some insights — potentially better ones, experts say. These lymphocytes are the first responders that then coordinate the immune response while building an imprint, a memory, so that subsequent infections fade quickly, often unnoticed. T cell tests are more complex and typically reserved for research, but some may be coming to the clinic soon, with at least one company seeking FDA emergency use authorization (EUA). Recent studies indicate that assaying T cells can even improve diagnostic accuracy and possibly predict how COVID-19 will unfold. “Testing T cell responses can accelerate detection of an infection by as much as a week. The cells come in on day 2 and they divide very quickly, to detectable levels as early as 3 or 4 days from infection,” said Dawn Jelley-Gibbs, PhD, who investigated T cells in influenza at the Trudeau Institute in Saranac Lake, New York. The good news is that in COVID-19, T cells appear a day or two after symptoms start, bind the virus at several sites, and persist – so far. “Since we did not observe a substantial decline during the follow-up, we assume that the memory CD8 T cell response remains sustained for a longer period, more than a year. But only longitudinal studies over a long time will prove this assumption right or wrong,” said corresponding author Christoph Neumann-Haefelin, MD.
Lower respiratory tract myeloid cells harbor SARS-CoV-2 and display an inflammatory phenotype
CHEST, November 17, 2020
SARS-CoV-2 pneumonia may induce an aberrant immune response with brisk recruitment of myeloid cells into the airspaces. Although the clinical implications are unclear, others have suggested that infiltrating myeloid cells may contribute to morbidity and mortality during SARS-CoV-2 infection. However, few reports have characterized myeloid cells from the lower respiratory tract, which appears to be the primary site of viral-induced pathology, during severe SARS-CoV-2 pneumonia. Endotracheal aspirate (ETA) samples were prospectively collected from seven patients requiring mechanical ventilation for severe pneumonia due to SARS-CoV-2 infection as documented by RT-PCR during April-June 2020. The median age of the seven patients was 58 (range 56-77) and five (71.4%) were male. The median duration of reported symptoms prior to initiation of mechanical ventilation was 7 days (range 3-11). Samples were collected within a median of 5 days (range 1-14) after initiation of mechanical ventilation. Our findings suggest that lower respiratory tract myeloid cells found in endotracheal aspirate samples harbor SARS-CoV-2 virus and display an inflammatory phenotype marked by expression of CD14, CD16, IL-6, and tissue factor. While others have shown co-localization of SARS-CoV-1 and H1N1 influenza virus with human monocyte/macrophages in autopsy studies, we believe this to be the first description and confirmation of the presence of SARS-CoV-2 virions inside lower respiratory tract myeloid cells, including polymorphonuclear leukocytes, from human samples.
Early plasma IL-37 responses accompanied with low inflammatory cytokines correlate with benign clinical outcomes during SARS-CoV-2 infection
Journal of Infectious Diseases, November 17, 2020
The immune protective mechanisms during SARS-CoV-2 infection remain to be deciphered for the development of an effective intervention approach. We examined early responses of IL-37, a powerful anti-inflammatory cytokine, in 254 SARS-CoV-2-infected patients prior to any clinical intervention and determined its correlation with clinical prognosis. Our results demonstrated that SARS-CoV-2 infection causes elevation of plasma IL-37. Higher early IL-37 responses correlated with earlier viral RNA negative conversion, chest CT image improvement and cough relief, consequently resulted in earlier hospital discharge. Further assays showed that higher IL-37 was associated with lower IL-6 and IL-8 and higher IFN-α and facilitated biochemical homeostasis. Low IL-37 responses predicted severe clinical prognosis in combination with IL-8 and CRP. In addition, we observed that IL-37 administration was able to attenuate lung inflammation and alleviate respiratory tissue damage in human angiotensin-converting enzyme 2 (hACE2)-transgenic mice infected with SARS-CoV-2. Overall, we found that IL-37 plays a protective role by antagonizing inflammatory responses while retaining type I IFN, thereby maintaining the functionalities of vital organs.
Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome
BMC Pulmonary Medicine, November 16, 2020
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar inflammatory status in patients with moderate to severe COVID-19. Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n = 28) and to the Intermediate Medicine Ward (IMW) (n = 5). We analyze the differential cell count, ultrastructure of cells and Interleukin (IL)6, 8 and 10 levels. ICU patients showed a marked increase in neutrophils (1.24 × 105 ml− 1, 0.85–2.07), lower lymphocyte (0.97 × 105 ml− 1, 0.024–0.34) and macrophages fractions (0.43 × 105 ml− 1, 0.34–1.62) compared to IMW patients (0.095 × 105 ml− 1, 0.05–0.73; 0.47 × 105 ml− 1, 0.28–1.01 and 2.14 × 105 ml− 1, 1.17–3.01, respectively) (p < 0.01). Study of ICU patients BAL by electron transmission microscopy showed viral particles inside mononuclear cells confirmed by immunostaining with anti-viral capsid and spike antibodies. IL6 and IL8 were significantly higher in ICU patients than in IMW (IL6 p < 0.01, IL8 p < 0.0001), and also in patients who did not survive (IL6 p < 0.05, IL8 p = 0.05 vs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (p < 0.1) or antivirals (p < 0.05).
Bedside Electrical Impedance Tomography Unveils Respiratory “Chimera” in COVID-19
American Journal of Respiratory and Critical Care Medicine, November 16, 2020
In 1981, Reginald Greene et al. illustrated extensive pulmonary artery filling defects in patients with different severity of acute respiratory failure by bedside angiographic studies (1). More recently, perfusion distribution and regional lung ventilation can be assessed at bedside by non-invasive, radiation-free electrical impedance tomography (EIT) (2-3). In this report, we present three patients intubated for acute hypoxic respiratory failure due to COVID-19. The three patients had similar levels of oxygenation but different respiratory system compliance (Fig.1). EIT was used to determine regional ventilation and perfusion distribution. Cases 1, 2 and 3 were assessed after 2, 17 and 19 days of mechanical ventilation, respectively. All patients were assessed by computed tomography (CT) without contrast (Fig. 1). Case-1 CT shows peripheral and basilar ground-glass opacities, compatible with known COVID19 pneumonia. Cases-2 and case-3 CT images describes diffuse bilateral groundglass opacities. This report shows that clinical information of the patient coupled with real-time non-invasive bedside EIT might be helpful to characterize the etiology of hypoxemia of patients with respiratory failure with COVID-19.
Inhaled corticosteroids fail to protect against COVID-19-related death in asthma, COPD
Helio | Pulmonology, November 16, 2020
A new study found no benefit of inhaled corticosteroid use in protecting against COVID-19-related mortality in patients with asthma and COPD. Researchers conducted an observational study to analyze patient-level data for 148,557 patients with COPD and 818,490 patients with asthma culled from primary care electronic health records with death data from the OpenSAFELY platform from March to May. Risk for COVID-19-related mortality was increased among patients with COPD prescribed an ICS compared with those prescribed LABA and LAMA combination therapy (adjusted HR = 1.39; 95% CI, 1.1-1.76). Those with asthma who were prescribed high-dose ICS had an increased risk for COVID-19-related mortality compared with patients prescribed SABAs (aHR = 1.55; 95% CI, 1.1-2.18), but those prescribed low- or medium-dose ICS were not at an increased risk (aHR = 1.14; 95% CI, 0.85-1.54), according to the results. “We found no evidence of a beneficial effect of regular ICS use among people with COPD and asthma on COVID-19-related mortality. Although we report a small harmful association, the pattern of results we observed suggests this association could readily be explained by differences in underlying health between people prescribed ICS and those prescribed other respiratory medications,” Anna Schultze, PhD, research fellow in pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, and colleagues wrote in The Lancet Respiratory Medicine. “These results do not support any change to the current clinical guidelines for the routine treatment of people with COPD or asthma with ICS during outbreaks of SARS-CoV-2 infection.”
Prone-Position Ventilation in Patients with Neurologic Conditions: A Systematic Review of the Literature and Suggested Protocol
Neurosurgery, November 16, 2020
Recommendations regarding ventilation strategies in the setting of COVID-19, which may culminate in a clinical picture similar to ARDS, have not yet been well established. Prone positioning has shown benefit as an adjunct supportive measure for patients who develop ARDS. However, studies assessing the benefit of prone positioning have excluded patients with reduced intracranial compliance resulting in a unique predicament, whereby patients with concomitant neurological diagnoses and ARDS have no defined treatment algorithm or recommendations for management. A systematic review of the literature, performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2009 guidelines, yielded 10 articles for analysis. Utilizing consensus from these articles, in combination with review of multi-institutional proning protocols for patients with non-neurologic conditions, a proning protocl for patients with intracranial pathology and concomitant ARDS was developed. Among the 10 studies included in final analysis, there was consensus that prone positioning should be considered when there is evidence of acute lung injury or ARDS in patients with neurologic injury. Patients may be proned with a speciality bed or manually on a standard bed with the assistance of seven to nine personnel, in the manner described herein. Special consideration for patients requiring frequent neurologic exams and patients at risk of cardiac arrest or seizure are discussed.
Large-Scale Plasma Analysis Revealed New Mechanisms and Molecules Associated with the Host Response to SARS-CoV-2
International Journal of Molecular Sciences, November 16, 2020
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every continent, registering over 1,250,000 deaths worldwide. The effects of SARS-CoV-2 on host targets remains largely limited, hampering our understanding of Coronavirus Disease 2019 (COVID-19) pathogenesis and the development of therapeutic strategies. The present study used a comprehensive untargeted metabolomic and lipidomic approach to capture the host response to SARS-CoV-2 infection. We found that several circulating lipids acted as potential biomarkers, such as phosphatidylcholine 14:0_22:6 (area under the curve (AUC) = 0.96), phosphatidylcholine 16:1_22:6 (AUC = 0.97), and phosphatidylethanolamine 18:1_20:4 (AUC = 0.94). Furthermore, triglycerides and free fatty acids, especially arachidonic acid (AUC = 0.99) and oleic acid (AUC = 0.98), were well correlated to the severity of the disease. An untargeted analysis of non-critical COVID-19 patients identified a strong alteration of lipids and a perturbation of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, aminoacyl-tRNA degradation, arachidonic acid metabolism, and the tricarboxylic acid (TCA) cycle. The severity of the disease was characterized by the activation of gluconeogenesis and the metabolism of porphyrins, which play a crucial role in the progress of the infection. In addition, our study provided further evidence for considering phospholipase A2 (PLA2) activity as a potential key factor in the pathogenesis of COVID-19 and a possible therapeutic target.
COVID-19 vaccine developed by Moderna, NIH is 94.5% effective, early data show
Helio | Infectious Disease News, November 16, 2020
An interim review of phase 3 data showed that a COVID-19 vaccine codeveloped by Moderna Inc. and the NIH had an efficacy rate of 94.5% with no significant safety concerns, Moderna said. The efficacy and safety data were reported by an NIH-appointed data safety monitoring board and were based on 95 cases of COVID-19, of which 90 occurred in the placebo group vs. five in the vaccine group. These included 11 cases of severe COVID-19 — all in the placebo group. The announcement was more good news for COVID-19 vaccine programs following Pfizer and BioNTech’s announcement last week that its mRNA vaccine candidate was shown to be more than 90% effective based on interim phase 3 data. “Since the vaccines are very, very similar, we can conclude that repeating the experiment led to the same outcome, which increases confidence,” Florian Krammer, PhD, a professor of vaccinology at the Icahn School of Medicine at Mount Sinai in New York, told Healio.
COVID-19 Test Correlation Between Nasopharyngeal Swab and Bronchoalveolar Lavage in Asymptomatic Patients
CHEST, November 16, 2020
In this study, we report the positive and negative rates of SARS-CoV-2 RT-PCR results from NP swabs and BAL and their correlations among asymptomatic patients undergoing bronchoscopy. We found no discordance between negative initial nasopharyngeal tests and bronchoscopic BAL tests for SARS-CoV2 by RT-PCR in 206 consecutive bronchoscopies. These findings suggest that SARS-CoV-2 RT-PCR from NP swabs is an effective screening technique when compared to BAL and supports their use as the standard screening tests for patients with low clinical suspicion for COVID-19 who are undergoing bronchoscopy. Wang et al described SARS-CoV-2 detection rate from various biospecimens in 205 patients with COVID-19 and found BAL samples with a positive rate of 93%, nasal swabs with 63%, and pharyngeal swabs with 32%. However, their patient population only included patients with symptomatic COVID-19 disease, whereas our population was specifically screened to be negative for COVID-19. Thus, their report of discrepancies between NP and BAL testing is not contrary to our finding of significant concordance between paired samples of negative NP and BAL tests. We found that all patients with low clinical suspicion for COVID-19 that tested negative for SARS-CoV-2 RT-PCR from NP swabs also tested negative for COVID-19 from BAL samples, with no test discrepancy between screening NP swabs and BAL. This finding supports the use of NP swab test as an appropriate screening test for aerosol-generating procedures in the midst of the current pandemic.
Focus on the Potential Role of Lung Ultrasound in COVID-19 Pandemic: What More to Do?
International Journal of Environmental Research and Public Health, November 13, 2020
COVID-19, a novel severe acute respiratory syndrome (SARS) emerging in China’s Hubei province in late 2019, due to a new coronavirus (SARS-CoV-2), is causing a global pandemic involving many areas of the world, which so far counts more than 43 million cases and more than 1,155,000 deaths worldwide. In Italy, at the time of writing, we are facing a second wave of infections with an important pressure on hospital structures. The virus has a specific tropism for the lower respiratory tract in the early disease stage. About 20% of affected patients are at risk of developing the severe form of the disease with an acute respiratory distress syndrome (ARDS) and with high morbidity/mortality. The histopathologic aspect of initial COVID-19 pneumonia is characterized by alveolar edema and damage while inflammatory component is usually patchy and mild. Reparative processes with pneumocyte hyperplasia and/or interstitial thickening may be present while the late phases show gravitational consolidations, edema, alveolar congestion, hemorrhagic necrosis and fibrosis. Computed tomography (CT) is considered the routine imaging technique for diagnosis and monitoring of COVID-19 pneumonia. Data show a high specificity and sensitivity for diagnosis of COVID-19, even though CT chest is not inexpensive and universally available; moreover, it often requires an infected or unstable patient to be moved to the scanner or radiology unit with potential exposure of several people including staff members, needing proper sanitation of the CT room after use and personal protective equipment; lastly, it is underutilized in children and pregnant women because of concerns over radiation exposure. In this context, considering the increasing frequency of confirmed COVID-19 cases and the need of new, highly sensitive and faster diagnostic tools, the role of lung ultrasound (LUS) has become relevant.
Is the Frequency of Candidemia Increasing in COVID-19 Patients Receiving Corticosteroids?
Journal of Fungi, November 13, 2020
Corticosteroids have potent anti-inflammatory and immunosuppressive effects. Recently, these medications have gained importance in the treatment of severe COVID-19. The relationship between corticosteroid treatment and fungal infections is well established. Corticosteroids may promote fungal growth in vitro. Moreover, use of corticosteroids have been associated with increased risk for most serious fungal diseases including candidemia, invasive aspergillosis, fusariosis, and mucormycosis. We present provocative results of a series of candidemia cases following COVID-19, in which the use of steroids was suggested as the main risk factor for fungal infection. Overall mortality was 72.7%, despite antifungal therapy. Physicians should be aware of the potential risk for candidemia among severely ill COVID-19 patients receiving high-doses of corticosteroids. Here we present data demonstrating a marked (10-fold) increase in frequency of candidemia in hospitalized patients with COVID-19 receiving corticosteroids in Brazil.
Associations between blood type and COVID-19 infection, intubation, and death
Nature Communications, November 13, 2020
The rapid global spread of the novel coronavirus SARS-CoV-2 has strained healthcare and testing resources, making the identification and prioritization of individuals most at-risk a critical challenge. Recent evidence suggests blood type may affect risk of severe COVID-19. Here, we use observational healthcare data on 14,112 individuals tested for SARS-CoV-2 with known blood type in the New York Presbyterian (NYP) hospital system to assess the association between ABO and Rh blood types and infection, intubation, and death. We find slightly increased infection prevalence among non-O types. Risk of intubation was decreased among A and increased among AB and B types, compared with type O, while risk of death was increased for type AB and decreased for types A and B. We estimate Rh-negative blood type to have a protective effect for all three outcomes. Our results add to the growing body of evidence suggesting blood type may play a role in COVID-19.
Pulmonary fibrosis in critically ill patients with novel coronavirus pneumonia during the convalescent stage and a proposal for early intervention
Acta Pharmacologica Sinica, November 13, 2020
Most patients with COVID-19 have a good prognosis, but a small portion of patients become critically ill and even die (the cumulative mortality rate is ~3.7%). Critically ill patients account for ~15% of those with COVID-19, and most of them are the elderly, patients with underlying diseases or patients with obesity. Critically ill patients often experience dyspnea and/or hypoxemia 1 week after onset of the illness, and in severe cases, the patient can rapidly develop acute respiratory distress syndrome (ARDS), septic shock, uncorrectable metabolic acidosis, bleeding and coagulation dysfunction, and multiple organ failure. According to our clinical treatment experience, we previously proposed the “Huashan Model”, which is based on supportive therapy for multiple organs supplemented with anti-inflammatory and anticoagulation therapies, for the treatment of patients with severe novel coronavirus pneumonia (NCP). This model significantly improved the survival rate of critically ill NCP patients by correcting the pathophysiological state, adjusting immune system function, and promoting clearance of the virus and affected cells through symptomatic and supportive treatment. Patients with severe NCP in the convalescent stage often experience serious complications, such as multiple organ failure. In particular, prevalent pulmonary parenchymal lesions, alveolar lumen exudates, and pulmonary interstitial fibrosis can lead to poor pulmonary function in patients and seriously affect their long-term quality of life. Therefore, alleviating/reversing the process of pulmonary interstitial fibrosis, improving the pulmonary function of patients with severe NCP, and improving the quality of life of patients should be the focus of treatment for patients with severe NCP in the convalescent stage.
Transfer-to-Transfer Learning Approach for Computer Aided Detection of COVID-19 in Chest Radiographs
AI, November 13, 2020
The coronavirus disease 2019 (COVID-19) global pandemic has severely impacted lives across the globe. Respiratory disorders in COVID-19 patients are caused by lung opacities similar to viral pneumonia. A Computer-Aided Detection (CAD) system for the detection of COVID-19 using chest radiographs would provide a second opinion for radiologists. For this research, we utilize publicly available datasets that have been marked by radiologists into two-classes (COVID-19 and non-COVID-19). We address the class imbalance problem associated with the training dataset by proposing a novel transfer-to-transfer learning approach, where we break a highly imbalanced training dataset into a group of balanced mini-sets and apply transfer learning between these. We demonstrate the efficacy of the method using well-established deep convolutional neural networks. Our proposed training mechanism is more robust to limited training data and class imbalance. We study the performance of our algorithm(s) based on 10-fold cross validation and two hold-out validation experiments to demonstrate its efficacy. We achieved an overall sensitivity of 0.94 for the hold-out validation experiments containing 2265 and 2139 marked as COVID-19 chest radiographs, respectively. For the 10-fold cross validation experiment, we achieve an overall Area under the Receiver Operating Characteristic curve (AUC) value of 0.996 for COVID-19 detection. This paper serves as a proof-of-concept that an automated detection approach can be developed with a limited set of COVID-19 images, and in areas with scarcity of trained radiologists.
Pulmonary Endothelial Dysfunction and Thrombotic Complications in COVID-19 Patients
American Journal of Respiratory Cell and Molecular Biology, November 12, 2020
SARS-CoV-2, a new strain of a Coronaviridae virus which presents 79% genetic similarity to the severe acute respiratory syndrome coronavirus (SARS-CoV) has been recently recognized as the cause of a global pandemic by the World Health Organization (WHO) implying a major threat to the world public health. SARS-CoV-2 infects host human cells by binding through the viral spike proteins to the angiotensin-converting enzyme 2 (ACE-2) receptor, fuses with the cell membrane, enters and starts its replication process in order to multiply its viral load. Coronavirus disease (COVID-19) was initially considered a respiratory infection that could cause pneumonia. However, in severe cases, it extends beyond the respiratory system and becomes a multi-organ disease. This transition from localized respiratory infection to multi-organ disease is due to two main complications of COVID-19. On the one hand, the so-called cytokine storm: an uncontrolled inflammatory reaction of the immune system in which defensive molecules become aggressive for the body itself. On the other hand, the formation of a large number of thrombi that can cause myocardial infarction, stroke and pulmonary embolism (PE). The pulmonary endothelium actively participates in these two processes, becoming the last barrier before the virus spreads throughout the body. In this review, we examine the role of the pulmonary endothelium in response to COVID-19, the existence of potential biomarkers and the development of novel therapies to restore vascular homeostasis and to protect/treat these patients. Additionally, we review the thrombotic complications recently observed in COVID-19 patients and its potential threatening sequelae.
Analyzing inter-reader variability affecting deep ensemble learning for COVID-19 detection in chest radiographs
PLOS ONE, November 12, 2020
Data-driven deep learning (DL) methods using convolutional neural networks (CNNs) demonstrate promising performance in natural image computer vision tasks. However, their use in medical computer vision tasks faces several limitations, viz., (i) adapting to visual characteristics that are unlike natural images; (ii) modeling random noise during training due to stochastic optimization and backpropagation-based learning strategy; (iii) challenges in explaining DL black-box behavior to support clinical decision-making; and (iv) inter-reader variability in the ground truth (GT) annotations affecting learning and evaluation. This study proposes a systematic approach to address these limitations through application to the pandemic-caused need for Coronavirus disease 2019 (COVID-19) detection using chest X-rays (CXRs). Specifically, our contribution highlights significant benefits obtained through (i) pretraining specific to CXRs in transferring and fine-tuning the learned knowledge toward improving COVID-19 detection performance; (ii) using ensembles of the fine-tuned models to further improve performance over individual constituent models; (iii) performing statistical analyses at various learning stages for validating results; (iv) interpreting learned individual and ensemble model behavior through class-selective relevance mapping (CRM)-based region of interest (ROI) localization; and, (v) analyzing inter-reader variability and ensemble localization performance using Simultaneous Truth and Performance Level Estimation (STAPLE) methods. To the best of our knowledge, this is the first study to construct ensembles, perform ensemble-based disease ROI localization, and analyze inter-reader variability and algorithm performance for COVID-19 detection in CXRs.
Pulmonary Endothelial Dysfunction and Throhttps://www.atsjournals.org/doi/10.1165/rcmb.2020-0359PSbotic Complications in COVID-19 Patients
American Journal of Respiratory Cell and Molecular Biology, November 12, 2020
SARS-CoV-2 infects host human cells by binding through the viral spike proteins to the angiotensin-converting enzyme 2 (ACE-2) receptor, fuses with the cell membrane, enters and starts its replication process in order to multiply its viral load. Coronavirus disease (COVID-19) was initially considered a respiratory infection that could cause pneumonia. However, in severe cases, it extends beyond the respiratory system and becomes a multi-organ disease. This transition from localized respiratory infection to multi-organ disease is due to two main complications of COVID-19. On the one hand, the so-called cytokine storm: an uncontrolled inflammatory reaction of the immune system in which defensive molecules become aggressive for the body itself. On the other hand, the formation of a large number of thrombi that can cause myocardial infarction, stroke and pulmonary embolism (PE). The pulmonary endothelium actively participates in these two processes, becoming the last barrier before the virus spreads throughout the body. In this review, we examine the role of the pulmonary endothelium in response to COVID-19, the existence of potential biomarkers and the development of novel therapies to restore vascular homeostasis and to protect/treat these patients. Additionally, we review the thrombotic complications recently observed in COVID-19 patients and its potential threatening sequelae.
Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome
Journal of Translational Medicine, November 11, 2020
Foxp3+ regulatory T cells (Tregs) play essential roles in immune homeostasis and repair of damaged lung tissue. We hypothesized that patients whose lung injury resolves quickly, as measured by time to liberation from mechanical ventilation, have a higher percentage of Tregs amongst CD4+ T cells in either airway, bronchoalveolar lavage (BAL) or peripheral blood samples. We prospectively enrolled patients with ARDS requiring mechanical ventilation and collected serial samples, the first within 72 h of ARDS diagnosis (day 0) and the second 48–96 h later (day 3). We analyzed immune cell populations and cytokines in BAL, tracheal aspirates and peripheral blood, as well as cytokines in plasma, obtained at the time of bronchoscopy. The study cohort was divided into fast resolvers (FR; n = 8) and slow resolvers (SR; n = 5), based on the median number of days until first extubation for all participants (n = 13). The primary measure was the percentage of CD4+ T cells that were Tregs. The BAL of FR contained more Tregs than SR. This finding did not extend to Tregs in tracheal aspirates or blood. BAL Tregs expressed more of the full-length FOXP3 than a splice variant missing exon 2 compared to Tregs in simultaneously obtained peripheral blood.
Diagnostic Value of Initial Chest CT Findings for the Need of ICU Treatment/Intubation in Patients with COVID-19
Diagnostics, November 10, 2020
Computed tomography (CT) plays an important role in the diagnosis of COVID-19. The aim of this study was to evaluate a simple, semi-quantitative method that can be used for identifying patients in need of subsequent intensive care unit (ICU) treatment and intubation. We retrospectively analyzed the initial CT scans of 28 patients who tested positive for SARS-CoV-2 at our Level-I center. The extent of lung involvement on CT was classified both subjectively and with a simple semi-quantitative method measuring the affected area at three lung levels. Competing risks Cox regression was used to identify factors associated with the time to ICU admission and intubation. Their potential diagnostic ability was assessed with receiver operating characteristic (ROC)/area under the ROC curves (AUC) analysis. A 10% increase in the affected lung parenchyma area increased the instantaneous risk of intubation (hazard ratio (HR) = 2.00) and the instantaneous risk of ICU admission (HR 1.73). The semi-quantitative measurement outperformed the subjective assessment diagnostic ability (AUC = 85.6% for ICU treatment, 71.9% for intubation). This simple measurement of the involved lung area in initial CT scans of COVID-19 patients may allow early identification of patients in need of ICU treatment/intubation and thus help make optimal use of limited ICU/ventilation resources in hospitals.
Lung transcriptome of a COVID-19 patient and systems biology predictions suggest impaired surfactant production which may be druggable by surfactant therapy
Scientific Reports, November 10, 2020
An incomplete understanding of the molecular mechanisms behind impairment of lung pathobiology by COVID-19 complicates its clinical management. In this study, we analyzed the gene expression pattern of cells obtained from biopsies of COVID-19-affected patient and compared to the effects observed in typical SARS-CoV-2 and SARS-CoV-infected cell-lines. We then compared gene expression patterns of COVID-19-affected lung tissues and SARS-CoV-2-infected cell-lines and mapped those to known lung-related molecular networks, including hypoxia induced responses, lung development, respiratory processes, cholesterol biosynthesis and surfactant metabolism; all of which are suspected to be downregulated following SARS-CoV-2 infection based on the observed symptomatic impairments. Network analyses suggest that SARS-CoV-2 infection might lead to acute lung injury in COVID-19 by affecting surfactant proteins and their regulators SPD, SPC, and TTF1 through NSP5 and NSP12; thrombosis regulators PLAT, and EGR1 by ORF8 and NSP12; and mitochondrial NDUFA10, NDUFAF5, and SAMM50 through NSP12. Furthermore, hypoxia response through HIF-1 signaling might also be targeted by SARS-CoV-2 proteins. Drug enrichment analysis of dysregulated genes has allowed us to propose novel therapies, including lung surfactants, respiratory stimulants, sargramostim, and oseltamivir. Our study presents a distinct mechanism of probable virus induced lung damage apart from cytokine storm.
Point of care aspergillus testing in intensive care patients
Critical Care, November 10, 2020
Invasive pulmonary aspergillosis (IPA) is an increasingly recognized complication in intensive care unit (ICU) patients, especially those with influenza, cirrhosis, chronic obstructive pulmonary disease, and other diseases. The diagnosis can be challenging, especially in the ICU, where clinical symptoms as well as imaging are mostly nonspecific. Recently, Aspergillus lateral flow tests were developed to decrease the time to diagnosis of IPA. Several studies have shown promising results in bronchoalveolar lavage fluid (BALf) from hematology patients. We therefore evaluated a new lateral flow test for IPA in ICU patients. Using left-over BALf from adult ICU patients in two university hospitals, we studied the performance of the Aspergillus galactomannan lateral flow assay (LFA) by IMMY (Norman, OK, USA). Patients were classified according to the 2008 EORTC-MSG definitions, the AspICU criteria, and the modified AspICU criteria, which incorporate galactomannan results. These internationally recognized consensus definitions for the diagnosis of IPA incorporate patient characteristics, microbiology and radiology. The LFA was read out visually and with a digital reader by researchers blinded to the final clinical diagnosis and IPA classification. We included 178 patients, of which 55 were classified as cases (6 cases of proven and 26 cases of probable IPA according to the EORTC-MSG definitions, and an additional 23 cases according to the modified AspICU criteria). Depending on the definitions used, the sensitivity of the LFA was 0.88–0.94, the specificity was 0.81, and the area under the ROC curve 0.90–0.94, indicating good overall test performance.
https://www.mdpi.com/2077-0383/9/11/3624
Journal of Clinical Medicine, November 10, 2020
Viral infections are known to lead to serious respiratory complications in cystic fibrosis (CF) patients. Hypothesizing that CF patients were a population at high risk for severe respiratory complications from SARS-CoV-2 infection, we conducted a national study to describe the clinical expression of COVID-19 in French CF patients. This prospective observational study involves all 47 French CF centers caring for approximately 7500 CF patients. Between March 1st and June 30th 2020, 31 patients were diagnosed with COVID-19: 19 had positive SARS-CoV-2 RT-PCR in nasopharyngeal swabs; 1 had negative RT-PCR but typical COVID-19 signs on a CT scan; and 11 had positive SARS-CoV-2 serology. Fifteen were males, median (range) age was 31 (9–60) years, and 12 patients were living with a lung transplant. The majority of the patients had CF-related diabetes (n = 19, 61.3%), and a mild lung disease (n = 19, 65%, with percent-predicted forced expiratory volume in 1 s (ppFEV1) > 70). Three (10%) patients remained asymptomatic. For the 28 (90%) patients who displayed symptoms, most common symptoms at admission were fever (n = 22, 78.6%), fatigue (n = 14, 50%), and increased cough (n = 14, 50%). Nineteen were hospitalized (including 11 out of the 12 post-lung transplant patients), seven required oxygen therapy, and four (3 post-lung transplant patients) were admitted to an Intensive Care Unit (ICU). Ten developed complications (including acute respiratory distress syndrome in two post-lung transplant patients), but all recovered and were discharged home without noticeable short-term sequelae. Overall, French CF patients were rarely diagnosed with COVID-19.
COVID-19 vaccine more than 90% effective, Pfizer says
Helio | Infectious Disease News, November 9, 2020
A vaccine candidate developed by Pfizer and BioNTech was more than 90% effective in preventing COVID-19 and showed no serious safety concerns, according to an interim analysis of phase 3 clinical trial results released by the companies. Pfizer and BioNTech said they plan to submit the mRNA-based vaccine candidate, now called BNT162b2, to the FDA for an emergency use authorization after a required safety milestone is met, likely in the third week of November. The analysis, which was conducted by an external and independent data monitoring committee, evaluated 94 confirmed cases of COVID-19 among more than 43,000 participants enrolled in the global trial, including more than 38,000 who have received two doses of the vaccine candidate. Around 42% of participants globally and 30% in the United States are from racially and ethnically diverse backgrounds, the companies said. At 7 days after the second dose, the vaccine was more than 90% effective compared with placebo among participants with no prior exposure to SARS-CoV-2. “This means that protection is achieved 28 days after the initiation of the vaccination, which consists of a 2-dose schedule. As the study continues, the final vaccine efficacy percentage may vary,” the companies said.
Should ECMO Come Before Intubation for COVID-19?
MedPage Today, November 9, 2020
Extracorporeal membrane oxygenation (ECMO) is usually a last resort strategy for acute respiratory distress syndrome (ARDS), but for cases from COVID-19 should it come sooner? Starting awake ECMO prior to intubation for severe COVID-19 has been tried by a group led by Jeffrey DellaVolpe, MD, medical director of the adult ECMO program at Methodist Hospital in San Antonio. “Early on we were very affected by looking at the numbers and seeing the really astronomical numbers of patients who were dying who were mechanically ventilated, and we said maybe the ventilator is a piece of this,” he told MedPage Today. Their novel approach is venovenous ECMO for COVID-19 patients with single organ failure, minimal pressor requirement, young age, minimal comorbidities, good functional status before the infection, and a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen of less than 100 despite 100% inspired oxygen (and prone positioning, if clinically feasible). A multidisciplinary team selects COVID-19 patients for ECMO, with the idea of sparing patients from sedation, paralytics, high airway pressure, and high levels of inspired oxygen. That’s a provocative concept, commented Cara Agerstrand, MD, director of the medical ECMO program at New York-Presbyterian/Columbia University Irving Medical Center in New York City. COVID-19 patients have typically received mechanical ventilation following the standard of care for severe ARDS, with lung protective settings along with prone positioning and other strategies before attempting ECMO.
Studies find mixed results for tocilizumab to treat COVID-19
Helio | Infectious Diseases, November 9, 2020
Three studies recently published in JAMA Internal Medicine evaluated the effects of tocilizumab against COVID-19. The studies were conducted in the United States, France and Italy, and all involved patients who were hospitalized with COVID-19. In an editorial accompanying the studies, Jonathan B. Parr, MD, MPH, assistant professor of medicine in the division of infectious diseases at the University of North Carolina School of Medicine, wrote that the “newly released randomized trials suggest a potential role for tocilizumab in COVID-19 but do not show clear evidence of efficacy, in contrast to observational studies.”
COVID-19 ‘may not be characterized by cytokine storm’
Helio | Infectious Disease, November 7, 2020
COVID-19 may not be characterized by the presence of a cytokine storm, an abnormal strong proinflammatory response, according to results published in JAMA. “Critically ill patients with COVID-19 with acute respiratory distress syndrome (ARDS) had circulating cytokine levels that were lower compared with patients with bacterial sepsis and similar to other critically ill patients,” Matthijs Kox, PhD, of the department of intensive care medicine at Radboud University Medical Center in Nijmegen, Netherlands, and colleagues wrote. “These findings are in line with lower leukocyte counts observed in patients with COVID-19, and are possibly due to lower overall disease severity, despite the presence of severe pulmonary injury.” Kox and colleagues examined characteristics of 46 patients with COVID-19 and ARDS, 51 with septic shock with ARDS, 30 with out-of-hospital cardiac arrest and 62 with multiple traumas admitted to the ICU at Radboud University Medical Center. They excluded patients with immunological insufficiencies, which they defined as chronic or concomitant immunosuppressive medication use. “The findings of this preliminary analysis suggest COVID-19 may not be characterized by cytokine storm,” the researchers wrote. “Whether anticytokine therapies will benefit patients with COVID-19 remains to be determined.”
COVID-19 Hospitalization, Severity Risk May Not Be Higher in Patients With Asthma
Pulmonology Advisor, November 6, 2020
Patients with asthma who test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVD-19), may not have a higher risk of hospitalization or severe outcomes associated with COVID-19 compared with SARS-CoV-2-positive patients without asthma, according to study results published in the Annals of Allergy, Asthma, and Immunology. The retrospective study was an analysis of electronic medical record data of 727 patients with onfirmed SARS-CoV-2. Of these patients, a total of 105 (14.4%) patients had a diagnosis of asthma, based on International Classification of Diseases, Tenth Revision codes and confirmed by clinical history by a board-certified allergist. In the patients with asthma, a similar proportion of patients received care as an outpatient and inpatient (14.6% vs 14.2%, respectively). While the adjusted odds of hospitalization were 1.4 times higher in patients with asthma vs those without asthma, the difference was not statistically insignificant (95% CI, 0.82-2.4; P =.22). The adjusted odds of death vs hospitalization or ICU admission was 1.3 times higher for patients with asthma, but this difference was also not statistically significant (95% CI, 0.6-2.8; P =.48). Factors associated with increased odds of hospitalization included age, number of comorbidities, and race (non-white vs white, P =.01). The odds of intubation were significantly higher in patients with vs without asthma (odds ratio [OR], 2 fold; 95% CI, 1-4-fold; P =.047). There was no difference between the 2 groups, however, in terms of intubation duration (P =.44) or hospitalization (P =.44).
Accuracy of Conventional and Machine Learning Enhanced Chest Radiography for the Assessment of COVID-19 Pneumonia: Intra-Individual Comparison with CT
Journal of Clinical Medicine, November 6, 2020
Our purpose was to evaluate diagnostic accuracy of conventional radiography (CXR) and machine learning enhanced CXR (mlCXR) for the detection and quantification of disease-extent in COVID-19 patients compared to chest-CT. Real-time polymerase chain reaction (rt-PCR)-confirmed COVID-19-patients undergoing CXR from March to April 2020 together with COVID-19 negative patients as control group were retrospectively included. Two independent readers assessed CXR and mlCXR images for presence, disease extent and type (consolidation vs. ground-glass opacities (GGOs) of COVID-19-pneumonia. Further, readers had to assign confidence levels to their diagnosis. CT obtained ≤ 36 h from acquisition of CXR served as standard of reference. Inter-reader agreement, sensitivity for detection and disease extent of COVID-19-pneumonia compared to CT was calculated. McNemar test was used to test for significant differences. Results: Sixty patients (21 females; median age 61 years, range 38–81 years) were included. Inter-reader agreement improved from good to excellent when mlCXR instead of CXR was used (k = 0.831 vs. k = 0.742). Sensitivity for pneumonia detection improved from 79.5% to 92.3%, however, on the cost of specificity 100% vs. 71.4% (p = 0.031). Overall, sensitivity for the detection of consolidation was higher than for GGO (37.5% vs. 70.4%; respectively). No differences could be found in disease extent estimation between mlCXR and CXR, even though the detection of GGO could be improved. Diagnostic confidence was better on mlCXR compared to CXR (p = 0.013). In line with the current literature, the sensitivity for detection and quantification of COVID-19-pneumonia was moderate with CXR and could be improved when mlCXR was used for image interpretation.
A mutation may have made COVID-19 more contagious
Medical News Today, November 6, 2020
Between March and July 2020, a particular mutation became almost ubiquitous in SARS-CoV-2 infections in Houston, TX. This strongly suggests that it makes the virus more infectious. However, there is no evidence to suggest that it makes the virus any more deadly. Metropolitan Houston reported its first case of COVID-19, which is the illness that develops due to SARS-CoV-2, on March 5, 2020. A week later, the virus was spreading within the community. A previous study found that strains of the virus containing a particular mutation, called G614, caused 71% of cases in Houston in the early phase of this first wave of infections. A follow-up study by the same team now reveals that by summer, during the second wave, this variant accounted for 99.9% of all COVID-19 infections in the area. The researchers at Houston Methodist Hospital — in collaboration with scientists at the University of Texas at Austin and the University of Chicago, IL — discovered that one of these mutations may allow the spike to evade a neutralizing antibody produced by the human immune system. It is unclear whether or not this mutation also increases infectivity. However, the researchers report that it is currently rare and does not appear to make the disease more severe. They also found no evidence to suggest that the virus has acquired mutations that might render either the vaccines in development or existing antibody treatments ineffective. Concluding their report, the authors write, “The findings will help us to understand the origin, composition, and trajectory of future infection waves and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution.”
The Japanese version of the Fear of COVID-19 scale: Reliability, validity, and relation to coping behavior
PLOS ONE, November 5, 2020
COVID-19 is spreading worldwide, causing various social problems. The aim of the present study was to verify the reliability and validity of the Japanese version of the Fear of COVID-19 Scale (FCV-19S) and to ascertain FCV-19S effects on assessment of Japanese people’s coping behavior. After back-translation of the scale, 450 Japanese participants were recruited from a crowdsourcing platform. These participants responded to the Japanese FCV-19S, the Japanese versions of the Hospital Anxiety and Depression scale (HADS) and the Japanese versions of the Perceived Vulnerability to Disease (PVD), which assesses coping behaviors such as stockpiling and health monitoring, reasons for coping behaviors, and socio-demographic variables. Results indicated the factor structure of the Japanese FCV-19S as including seven items and one factor that were equivalent to those of the original FCV-19S. The scale showed adequate internal reliability (α = .87; ω = .92) and concurrent validity, as indicated by significantly positive correlations with the Hospital Anxiety and Depression Scale (HADS; anxiety, r = .56; depression, r = .29) and Perceived Vulnerability to Disease (PVD; perceived infectability, r = .32; germ aversion, r = .29). Additionally, the FCV-19S not only directly increased all coping behaviors (β = .21 – .36); it also indirectly increased stockpiling through conformity reason (indirect effect, β = .04; total effect, β = .31). These results suggest that the Japanese FCV-19S psychometric scale has equal reliability and validity to those of the original FCV-19S. These findings will contribute further to the investigation of various difficulties arising from fear about COVID-19 in Japan.
COVID-19 With Suspected PE Shows Lung Changes Similar to Infarct, Organizing Pneumonia
Pulmonology Advisor, November 5, 2020
Although hypercoagulability has been reported in critically ill patients with coronavirus disease 2019 (COVID-19), results from a small study revealed that patients with COVID-19 did not have a higher prevalence of pulmonary embolism (PE) compared to those without COVID-19. Findings from this study, published in PLOS ONE, did show that patients with COVID-19 and suspected PE had lung changes that resembled infarct pneumonia and organizing pneumonia (OP). Researchers conducted retrospective analysis of data of 68 adult patients with COVID-19 confirmed by real-time polymerase chain reaction who were consecutively admitted to isolation wards and intensive care units at the University Hospital Zurich in Switzerland. Patients in this study were admitted to the hospital between March and April 2020. In the 2019 and 2020 cohorts, 175 and 157 patients, respectively, underwent computed tomography (CT) pulmonary angiography (CT-PA) for PE at the institution were also included in this study as control individuals. For all 3 cohorts, independent readers assessed for the presence and location of PE. Additionally, parenchymal changes typical of COVID-19 pneumonia, infarct pneumonia, and OP were examined in the cohort of patients with COVID-19. The investigators concluded that the findings may imply that vascular pathology in COVID-19 is microangiopathic “and hence generally too small to be captured directly by CT.” They suggested that “[v]isible lung changes in CT might be a surrogate for the underlying pathology caused by [severe acute respiratory syndrome virus 2] unveiling the invisible endothelial changes within the lungs. An increased [pulmonary artery and aorta] ratio may be a hint to the underling pathology and warrant[s] further investigation.”
Deep learning-based model for detecting 2019 novel coronavirus pneumonia on high-resolution computed tomography
Scientific Reports, November 5, 2020
Computed tomography (CT) is the preferred imaging method for diagnosing 2019 novel coronavirus (COVID19) pneumonia. We aimed to construct a system based on deep learning for detecting COVID-19 pneumonia on high resolution CT. For model development and validation, 46,096 anonymous images from 106 admitted patients, including 51 patients of laboratory confirmed COVID-19 pneumonia and 55 control patients of other diseases in Renmin Hospital of Wuhan University were retrospectively collected. Twenty-seven prospective consecutive patients in Renmin Hospital of Wuhan University were collected to evaluate the efficiency of radiologists against 2019-CoV pneumonia with that of the model. An external test was conducted in Qianjiang Central Hospital to estimate the system’s robustness. The model achieved a per-patient accuracy of 95.24% and a per-image accuracy of 98.85% in internal retrospective dataset. For 27 internal prospective patients, the system achieved a comparable performance to that of expert radiologist. In external dataset, it achieved an accuracy of 96%. With the assistance of the model, the reading time of radiologists was greatly decreased by 65%. The deep learning model showed a comparable performance with expert radiologist, and greatly improved the efficiency of radiologists in clinical practice.
High SARS-CoV-2 genomic load at time of hospital admission may predict adverse outcomes
Helio | Pulmonology, November 5, 2020
The amount of RNA, or genomic load, of SARS-CoV-2 detected in swab tests of patients admitted to the hospital with viral pneumonia is associated with more severe outcomes, researchers reported in the Annals of the American Thoracic Society. “We demonstrated that for patients admitted to the hospital with COVID-19 pneumonia, SARS-CoV-2 load, as reflected by the cycle threshold value of the polymerase chain reaction, should be looked at as a predictor of adverse outcomes,” Ioannis M. Zacharioudakis, MD, infectious disease specialist in the department of medicine at the New York University Grossman School of Medicine, said in a press release. “High viral load was shown to be a predictor of poor outcomes above and beyond age, other medical problems and severity of illness on presentation, indicating that it can be used to risk-stratify, or triage, patients.” The primary outcome was the association between genomic load and COVID-19-related pneumonia outcomes such as death, discharge to hospice care, mechanical ventilation use or extracorporeal membrane oxygenation use.
Global Initiative for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: The 2020 GOLD Science Committee Report on COVID-19 & COPD
American Journal of Respiratory and Critical Care Medicine, November 4, 2020
The SARS-CoV-2 pandemic has raised many questions about the management of COPD patients and whether modifications of their therapy are required. It has raised questions about recognising and differentiating COVID-19 from COPD given the similarity of the symptoms. It is unclear whether COPD patients are at increased risk of becoming infected with SARS-CoV-2. During periods of high prevalence of COVID-19, spirometry should be used when essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery. COPD patients should follow basic infection control measures including social distancing, hand washing and wearing a mask or face covering. Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management. Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications. Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an COPD exacerbation may be challenging. If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered. Patients who developed moderate to severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches, as appropriate, including remdesivir, dexamethasone, and anticoagulation. Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung ventilation in patients with ARDS. Patients who develop mild COVID-19 should be followed as normal. Patients who developed moderate or worse COVID-19 should be monitored more frequently than normally with particular attention to the need for oxygen therapy.
https://www.tandfonline.com/doi/abs/10.1080/1744666X.2021.1847084?journalCode=ierm20
Expert Review of Clinical Immunology, November 4, 2020
The mortality of coronavirus disease 2019 (COVID-19) is frequently driven by an injurious immune response characterized by the development of acute respiratory distress syndrome (ARDS), endotheliitis, coagulopathy, and multi-organ failure. This spectrum of hyperinflammation in COVID-19 is commonly referred to as cytokine storm syndrome (CSS). For review, Medline and Google Scholar were searched up until 15th of August 2020 for relevant literature. Evidence supports a role of dysregulated immune responses in the immunopathogenesis of severe COVID-19. CSS associated with SARS-CoV-2 shows similarities to the exuberant cytokine production in some patients with viral infection (e.g.SARS-CoV-1) and may be confused with other syndromes of hyperinflammation like the cytokine release syndrome (CRS) in CAR-T cell therapy. Interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha have emerged as predictors of COVID-19 severity and in-hospital mortality. Despite similarities, COVID-19-CSS appears to be distinct from HLH, MAS, and CRS, and the application of HLH diagnostic scores and criteria to COVID-19 is not supported by emerging data. While immunosuppressive therapy with glucocorticoids has shown a mortality benefit, cytokine inhibitors may hold promise as “rescue therapies” in severe COVID-19. Given the arguably limited benefit in advanced disease, strategies to prevent the development of COVID-19-CSS are needed.
Low-dose chest CT for diagnosing and assessing the extent of lung involvement of SARS-CoV-2 pneumonia using a semi quantitative score
PLOS ONE, November 3, 2020
The purpose is to assess the ability of low-dose CT (LDCT) to determine lung involvement in SARS-CoV-2 pneumonia and to describe a COVID19-LDCT severity score. Patients with SARS-CoV-2 infection confirmed by RT-PCR were retrospectively analysed. Clinical data, the National Early Warning Score (NEWS) and imaging features were recorded. Lung features included ground-glass opacities (GGO), areas of consolidation and crazy paving patterns. The COVID19-LDCT score was calculated by summing the score of each segment from 0 (no involvement) to 10 (severe impairment). Univariate analysis was performed to explore predictive factor of high COVID19-LDCT score. The nonparametric Mann-Whitney test was used to compare groups and a Spearman correlation used with p<0.05 for significance. Eighty patients with positive RT-PCR were analysed. The mean age was 55 years ± 16, with 42 males (53%). The most frequent symptoms were fever (60/80, 75%) and cough (59/80, 74%), the mean NEWS was 1.7±2.3. All LDCT could be analysed and 23/80 (28%) were normal. The major imaging finding was GGOs in 56 cases (67%). The COVID19-LDCT score (mean value = 19±29) was correlated with NEWS (r = 0.48, p<0.0001). No symptoms were risk factor to have pulmonary involvement. Univariate analysis shown that dyspnea, high respiratory rate, hypertension and diabetes are associated to a COVID19-LDCT score superior to 50.
Eosinophilia in critically ill COVID-19 patients: a French monocenter retrospective study
Critical Care, November 3, 2020
As reported in bacterial sepsis, the early phase of SARS-CoV-2 infection seems to be accompanied by eosinopenia. Conversely, our team noticed that several of our critically ill COVID-19 patients developed unexpected and unexplained eosinophilia during their ICU stay. Indeed, as white blood cells count is performed almost daily, monitoring and studying eosinophil course is simple in the ICU setting. To our knowledge, no study has focused on eosinophilia in COVID-19 although eosinophil recovery seven days after initial eosinopenia seems to be associated with a better outcome. We aimed to assess the incidence and to describe eosinophilia in critically ill COVID-19 patients, as well as to compare the outcome between patients developing or not eosinophilia during their ICU stay. We retrospectively reviewed all daily white blood cells counts performed in adult COVID-19 patients (RT-PCR positive for SARS-CoV-2) admitted to our 40-bed COVID-19 ICU between March 6 and July 30, 2020. Eosinophilia was defined by an eosinophil count higher than 500/mm3 and was considered as severe when exceeding 1500/mm3. Eosinopenia was defined by an eosinophil count lower than 40/mm3. Among the 26 patients who developed eosinophilia, 22 (85%) had eosinopenia at ICU admission. Eosinophilia occurred 19 [13–28] days after ICU admission and lasted 5 [3–12] days. Median eosinophil count was 900 [678–1350]/mm3. Six patients (23%) developed severe eosinophilia. Seven patients (29%) had a biphasic eosinophilia. Ten (38%) patients were treated with a β-lactam antibiotic when eosinophilia occurred.
Erythrocyte, Platelet, Serum Ferritin, and P-Selectin Pathophysiology Implicated in Severe Hypercoagulation and Vascular Complications in COVID-19
International Journal of Molecular Sciences, November 3, 2020
Progressive respiratory failure is seen as a major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection. Relatively little is known about the associated morphologic and molecular changes in the circulation of these patients. In particular, platelet and erythrocyte pathology might result in severe vascular issues, and the manifestations may include thrombotic complications. These thrombotic pathologies may be both extrapulmonary and intrapulmonary and may be central to respiratory failure. Previously, we reported the presence of amyloid microclots in the circulation of patients with coronavirus disease 2019 (COVID-19). Here, we investigate the presence of related circulating biomarkers, including C-reactive protein (CRP), serum ferritin, and P-selectin. These biomarkers are well-known to interact with, and cause pathology to, platelets and erythrocytes. We also study the structure of platelets and erythrocytes using fluorescence microscopy (using the markers PAC-1 and CD62PE) and scanning electron microscopy. Thromboelastography and viscometry were also used to study coagulation parameters and plasma viscosity. We conclude that structural pathologies found in platelets and erythrocytes, together with spontaneously formed amyloid microclots, may be central to vascular changes observed during COVID-19 progression, including thrombotic microangiopathy, diffuse intravascular coagulation, and large-vessel thrombosis, as well as ground-glass opacities in the lungs. Consequently, this clinical snapshot of COVID-19 strongly suggests that it is also a true vascular disease and considering it as such should form an essential part of a clinical treatment regime.
Chest CT Findings after 4 Months from the Onset of COVID-19 Pneumonia: A Case Series
Diagnostics, November 3, 2020
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the reference standard for SARS-CoV-2 diagnosis is real-time reverse transcription polymerase chain reaction (RT-PCR), computed tomography (CT) is recommended for both initial evaluation and follow-up. There is a growing body of published evidence about CT evolution during the course of COVID-19 pneumonia. Here, we report six confirmed cases of COVID-19 patients who underwent unenhanced chest CT on admission and after 4 months from the onset of symptoms. Chest-CT at first admission showed the typical CT features of COVID-19. Interestingly, the follow-up CT revealed the persistence of lung abnormalities in five cases even if all the patients were completely asymptomatic. Our six confirmed COVID-19 cases presented with mild symptoms such as asthenia, myalgia, cough, and fever. Chest CT, performed at first assessment, revealed the presence of the typical CT features of COVID-19 pneumonia: focal rounded pure GGOs or GGOs with smooth septal thickening located in both the costal and mediastinal subpleural peripheral parenchyma. The patients underwent a chest CT after 3 months from the onset of symptoms and about after 2 months from the hospital discharge.
Q&A: Is convalescent plasma effective for COVID-19?
Helio | Infectious Disease, November 2, 2020
Researchers reported recently in The BMJ that convalescent plasma was not associated with a reduction in progression to severe COVID-19 or all-cause mortality in adults with moderate disease. The results were from a phase 2 randomized controlled trial conducted at 39 hospitals in India. Healio spoke with Shmuel Shoham, MD, an associate professor of medicine at Johns Hopkins University School of Medicine, about the clinical implications of the new study, and how convalescent plasma has been used since receiving emergency use authorization (EUA) from the FDA in August.
Corticosteroids plus tocilizumab superior to standard of care in COVID-19 cytokine storm
Helio | Rheumatology, November 2, 2020
Corticosteroids plus tocilizumab demonstrated superior survival outcomes compared with standard or care and corticosteroids alone, or alongside anakinra, in patients with COVID-19 cytokine storm, according to data published in Chest. “Uncontrolled and unabated cytokine release and a hyperinflammatory response termed as COVID-19 ‘cytokine storm’ (CCS), was described as a major determinant of poor survival,” Sonali Narain, MBBS, of the Barbara Zucker School of Medicine at Hofstra University and Northwell Health, and colleagues wrote. “Limited data existed to guide clinical decision-making in the absence of FDA-approved COVID-19 specific therapies. Faced with rapidly increasing rates of infection and hospitalizations, physicians repurposed immunomodulatory treatments in an attempt to curtail morbidity and mortality. The use of immunomodulatory drugs decreases mortality in the population of COVID-19 patients with evidence of hyperinflammatory response,” Narain told Healio Rheumatology. “The decreased mortality was especially seen in those receiving tocilizumab plus steroids when compared to no steroids, but even when compared to the group who received steroids alone. This role for combinations of immunomodulatory therapies needs to be elucidated in prospective clinical trials comparing combinations to steroids alone.”
CXCL10 could drive longer duration of mechanical ventilation during COVID-19 ARDS
Critical Care, November 2, 2020
COVID-19-related ARDS has unique features when compared with ARDS from other origins, suggesting a distinctive inflammatory pathogenesis. Data regarding the host response within the lung are sparse. The objective is to compare alveolar and systemic inflammation response patterns, mitochondrial alarmin release, and outcomes according to ARDS etiology (i.e., COVID-19 vs. non-COVID-19). In this study, bronchoalveolar lavage fluid and plasma were obtained from 7 control, 7 non-COVID-19 ARDS, and 14 COVID-19 ARDS patients. Clinical data, plasma, and epithelial lining fluid (ELF) concentrations of 45 inflammatory mediators and cell-free mitochondrial DNA were measured and compared. COVID-19 ARDS patients required mechanical ventilation (MV) for significantly longer, even after adjustment for potential confounders. There was a trend toward higher concentrations of plasma CCL5, CXCL2, CXCL10, CD40 ligand, IL-10, and GM-CSF, and ELF concentrations of CXCL1, CXCL10, granzyme B, TRAIL, and EGF in the COVID-19 ARDS group compared with the non-COVID-19 ARDS group. Plasma and ELF CXCL10 concentrations were independently associated with the number of ventilator-free days, without correlation between ELF CXCL-10 and viral load. Mitochondrial DNA plasma and ELF concentrations were elevated in all ARDS patients, with no differences between the two groups. ELF concentrations of mitochondrial DNA were correlated with alveolar cell counts, as well as IL-8 and IL-1β concentrations.
Anomalous asthma and chronic obstructive pulmonary disease Google Trends patterns during the COVID-19 pandemic
Clinical and Translational Allergy, November 2, 2020
An increase in online searches on health topics may either mirror epidemiological changes or reflect media coverage. In the context of COVID-19, this is particularly relevant, as COVID-19 symptoms may be mistaken for those of respiratory disease exacerbations. Therefore, we aimed to assess Internet search patterns on asthma and chronic obstructive pulmonary disease (COPD) in the context of COVID-19, as compared to searches on other chronic diseases. We retrieved Google Trends (GTs) data on two respiratory (asthma and COPD) and three non-respiratory (diabetes, hypertension, and Crohn’s disease) chronic diseases over the past 5 years (up to May 31, 2020). For 54 countries, and for each disease, we built autoregressive integrated moving average (ARIMA) models to predict GTs for 2020 based on 2015–2019 search patterns. In addition, we estimated the proportion of searches in which COVID-19-related terms were used. To assess the potential impact of media coverage on online searches, we assessed whether weekly “asthma” GTs correlated with the number of Google News items on asthma. Over the past 5 years, worldwide search volumes for asthma and COPD reached their maximum values in March 2020. Such was not observed for diabetes, hypertension and Crohn’s disease. In 38 (70%) countries, GTs on asthma were higher in March 2020 than the respective maximum predicted values. This compares to 19 countries for COPD, 23 for hypertension, 11 for Crohn’s disease, and 9 for diabetes. Queries with COVID-19-related terms represented up to 47.8% of the monthly searches on asthma, and up to 21.3% of COPD searches. In most of the assessed countries, moderate-strong correlations were observed between “asthma” GTs and the number of news items on asthma.
Compliance Phenotypes in Early Acute Respiratory Distress Syndrome before the COVID-19 Pandemic
American Journal of Respiratory and Critical Care Medicine, November 1, 2020
A novel model of phenotypes based on set thresholds of respiratory system compliance (Crs) was recently postulated in context of coronavirus disease (COVID-19) acute respiratory distress syndrome (ARDS). In particular, the dissociation between the degree of hypoxemia and Crs was characterized as a distinct ARDS phenotype. Our objective was to determine whether such Crs-based phenotypes existed among patients with ARDS before the COVID-19 pandemic and to closely examine the Crs–mortality relationship. We undertook a secondary analysis of patients with ARDS, who were invasively ventilated on controlled modes and enrolled in a large, multinational, epidemiological study. We assessed Crs, degree of hypoxemia, and associated Crs-based phenotypic patterns with their characteristics and outcomes. Among 1,117 patients with ARDS who met inclusion criteria, the median Crs was 30 (interquartile range, 23–40) ml/cm H2O. One hundred thirty-six (12%) patients had preserved Crs (≥50 ml/cm H2O; phenotype with low elastance [“phenotype L”]), and 827 (74%) patients had poor Crs (<40 ml/cm H2O; phenotype with high elastance [“phenotype H”]). Compared with those with phenotype L, patients with phenotype H were sicker and had more comorbidities and higher hospital mortality (32% vs. 45%; P < 0.05). A near complete dissociation between PaO2/FiO2 and Crs was observed. Of 136 patients with phenotype L, 58 (43%) had a PaO2/FiO2 < 150. In a multivariable-adjusted analysis, the Crs was independently associated with hospital mortality (adjusted odds ratio per ml/cm H2O increase, 0.988; 95% confidence interval, 0.979–0.996; P = 0.005).
Lung Ultrasound Beats X-Rays in COVID Pneumonia Screening
MedPage Today, November 1, 2020
Portable ultrasound scans were more sensitive than x-rays at the preliminary detection of atypical pneumonia in patients who may have COVID-19, a researcher reported. In a study of possible COVID-19 patients who presented to the emergency department (ED), ultrasound sensitivity was 97.6% (95% CI 91.6-99.7) versus 69.9% (95% CI 58.8-79.5) for x-ray, reported Ryan C. Gibbons, MD, of the Lewis Katz School of Medicine at Temple University in Philadelphia, in a presentation at the virtual American College of Emergency Physicians meeting. Gibbons urged an “ultrasound first” approach to screening. “It’s a valuable tool to quickly separate the lower-risk from higher-risk patients and move those lower-risk patients out,” he told MedPage Today following his online presentation. Ultrasound scans, which can easily be performed at bedside with handheld devices, are also more convenient than x-rays, Gibbons said. Physicians use “a handheld probe that plugs into an iPad. You can be in and out of a room in under a few minutes and sanitization is very quick. And we’re not transporting a patient to and from x-ray or having to wait for a portable x-ray machine,” he said. Gibbons said that at his hospital, patients who may have COVID-19 are now routinely screened via ultrasound scans instead of x-rays. Patients with negative results typically go home, while those with positive scans are sent for CT scans and usually admitted, he said.
The α7 nicotinic acetylcholine receptor agonist GTS-21 improves bacterial clearance in mice by restoring hyperoxia-compromised macrophage function
Molecular Medicine, October 30, 2020
Mechanical ventilation, in combination with supraphysiological concentrations of oxygen (i.e., hyperoxia), is routinely used to treat patients with respiratory distress, such as COVID-19. However, prolonged exposure to hyperoxia compromises the clearance of invading pathogens by impairing macrophage phagocytosis. Previously, we have shown that the exposure of mice to hyperoxia induces the release of the nuclear protein high mobility group box-1 (HMGB1) into the pulmonary airways. Furthermore, extracellular HMGB1 impairs macrophage phagocytosis and increases the mortality of mice infected with Pseudomonas aeruginosa (PA). The aim of this study was to determine whether GTS-21 (3-(2,4-dimethoxybenzylidene) anabaseine), an α7 nicotinic acetylcholine receptor (α7nAChR) agonist, could (1) inhibit hyperoxia-induced HMGB1 release into the airways; (2) enhance macrophage phagocytosis and (3) increase bacterial clearance from the lungs in a mouse model of ventilator-associated pneumonia. In this study, GTS-21 (0.04, 0.4, and 4 mg/kg) or saline were administered by intraperitoneal injection to mice that were exposed to hyperoxia (≥ 99% O2) and subsequently challenged with PA. Our results indicate that GTS-21 is efficacious in improving bacterial clearance and reducing acute lung injury via enhancing macrophage function by inhibiting the release of nuclear HMGB1. Therefore, the α7nAChR represents a possible pharmacological target to improve the clinical outcome of patients on ventilators by augmenting host defense against bacterial infections.
Osmotic Adaptation by Na+-Dependent Transporters and ACE2: Correlation with Hemostatic Crisis in COVID-19
Biomedicines, October 30, 2020
COVID-19 symptoms, including hypokalemia, hypoalbuminemia, ageusia, neurological dysfunctions, D-dimer production, and multi-organ microthrombosis reach beyond effects attributed to impaired angiotensin-converting enzyme 2 (ACE2) signaling and elevated concentrations of angiotensin II (Ang II). Although both SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus) and SARS-CoV-2 utilize ACE2 for host entry, distinct COVID-19 pathogenesis coincides with the acquisition of a new sequence, which is homologous to the furin cleavage site of the human epithelial Na+ channel (ENaC). This review provides a comprehensive summary of the role of ACE2 in the assembly of Na+-dependent transporters of glucose, imino and neutral amino acids, as well as the functions of ENaC. Data support an osmotic adaptation mechanism in which osmotic and hemostatic instability induced by Ang II-activated ENaC is counterbalanced by an influx of organic osmolytes and Na+ through the ACE2 complex. We propose a paradigm for the two-site attack of SARS-CoV-2 leading to ENaC hyperactivation and inactivation of the ACE2 complex, which collapses cell osmolality and leads to rupture and/or necrotic death of swollen pulmonary, endothelial, and cardiac cells, thrombosis in infected and non-infected tissues, and aberrant sensory and neurological perception in COVID-19 patients. This dual mechanism employed by SARS-CoV-2 calls for combinatorial treatment strategies to address and prevent severe complications of COVID-19.
nSARS-Cov-2, pulmonary edema and thrombosis: possible molecular insights using miRNA-gene circuits in regulatory networks
https://exrna.biomedcentral.com/articles/10.1186/s41544-020-00057-y ExRNA, October 30, 2020
Given the worldwide spread of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (nSARS-CoV-2) infection pandemic situation, research to repurpose drugs, identify novel drug targets, vaccine candidates have created a new race to curb the disease. While the molecular signature of nSARS-CoV-2 is still under investigation, growing literature shows similarity among nSARS-CoV-2, pulmonary edema, and thromboembolic disorders due to common symptomatic features. A network medicine approach is used to explore the molecular complexity of the disease and to uncover common molecular trajectories of edema and thrombosis with nSARS-CoV-2. A comprehensive nSARS-CoV-2 responsive miRNA: Transcription Factor (TF): gene co-regulatory network was built using host-responsive miRNAs and it’s associated tripartite, Feed-Forward Loops (FFLs) regulatory circuits were identified. These regulatory circuits regulate signaling pathways like virus endocytosis, viral replication, inflammatory response, pulmonary vascularization, cell cycle control, virus spike protein stabilization, antigen presentation, etc. A unique miRNA-gene regulatory circuit containing a consortium of four hub FFL motifs is proposed to regulate the virus-endocytosis and antigen-presentation signaling pathways. These regulatory circuits also suggest potential correlations/similarity in the molecular mechanisms during nSARS-CoV-2 infection, pulmonary diseases and thromboembolic disorders and thus could pave way for repurposing of drugs. Some important miRNAs and genes have also been proposed as potential candidate markers. A detailed molecular snapshot of TGF signaling as the common pathway, that could play an important role in controlling common pathophysiologies among diseases, is also put forth.
Q&A: Navigating ‘the COVID literature tsunami’
Helio | Infectious Disease News, October 29, 2020
As COVID-19 continues to surge across the United States, researchers have been analyzing developments to determine what areas of research should be explored next. In a recent journal article, Ferric C. Fang, MD, professor of laboratory medicine, pathology and microbiology at the University of Washington, and other editors of Clinical Infectious Diseases explored previous research related to COVID-19 virology, epidemiology, presentation, diagnosis, complications, treatment and prevention and summarized the results from several related studies to help researchers and clinicians “surf the COVID literature tsunami.” Healio spoke with Fang about the state of COVID-19 diagnostic and vaccine research, and the role of peer-reviewed studies during the pandemic.
Case Fatality Rates for COVID-19 Patients Requiring Invasive Mechanical Ventilation: A Meta-analysis
American Journal of Respiratory and Critical Care Medicine, October 29, 2020
Initial reports of case fatality rates (CFR) among adults with coronavirus diease-19 (COVID-19) receiving invasive medical ventilation (IMV) are highly variable. Our objective was to examine the CFR of patients with COVID-19 receiving IMV. Two authors independently searched PubMed, Embase, medRxiv, bioRxiv, the COVID-19 living systematic review, and national registry databases. The primary outcome was the “reported CFR” for patients with confirmed COVID-19 requiring IMV. “Definitive hospital CFR” for patients with outcomes at hospital discharge was also investigated. Finally, CFR was analyzed by patient age, geographic region, and study quality based on the Newcastle-Ottawa Scale. Sixty-nine studies were included, describing 57,420 adult patients with COVID-19 who received IMV. Overall reported CFR was estimated as 45% (95% CI 39-52%). Fifty-four out of 69 studies stated whether hospital outcomes were available but provided a definitive hospital outcome on only 13,120 (22.8%) of the total IMV patient population. Among studies where age stratified CFR was available, pooled CFR estimates ranged from 47.9% (95% CI 46.4-49.4%) in younger patients (age ≤40) to 84.4% (95% CI 83.3-85.4) in older patients (age >80). CFR was also higher in early COVID-19 epicenters. Overall heterogeneity is high (I2>90%) with non-significant Egger’s regression test suggesting no publication bias.
Predictive criteria identifies patients at risk for cytokine storm in COVID-19
Helio | Rheumatology, October 28, 2020
New criteria comprising inflammation, cell death and tissue damage, and prerenal electrolyte imbalance may predict cytokine storm in COVID-19 at an early stage, according to findings published in the Annals of the Rheumatic Diseases. “A significant number of patients hospitalized with COVID-19 infection develop an hyperinflammatory response called cytokine storm,” Roberto Caricchio, MD, FACR, of the Temple University School of Medicine, in Philadelphia, told Healio Rheumatology. “These patients tend to have longer length of hospital stay and importantly are at greater risk of complications and death. There are no criteria to identify these patients.” According to the researchers, the criteria for macrophage activation syndrome, hemophagocytic lymphohistiocytosis and the HScore failed to identify cytokine storm associated with COVID-19. Instead, Caricchio and colleagues used new criteria that included three clusters of laboratory results. These involved inflammation, cell death and tissue damage, and prerenal electrolyte imbalance. These criteria demonstrated a sensitivity of 0.85 and a specificity of 0.8. In addition, they were able to identify patients with longer hospitalization and increased mortality.
Renin–Angiotensin System: An Important Player in the Pathogenesis of Acute Respiratory Distress Syndrome
International Journal of Molecular Science, October 28, 2020
Acute respiratory distress syndrome (ARDS) is characterized by massive inflammation, increased vascular permeability and pulmonary edema. Mortality due to ARDS remains very high and even in the case of survival, acute lung injury can lead to pulmonary fibrosis. The renin–angiotensin system (RAS) plays a significant role in these processes. The activities of RAS molecules are subject to dynamic changes in response to an injury. Initially, increased levels of angiotensin (Ang) II and des-Arg9-bradykinin (DABK), are necessary for an effective defense. Later, augmented angiotensin converting enzyme (ACE) 2 activity supposedly helps to attenuate inflammation. Appropriate ACE2 activity might be decisive in preventing immune-induced damage and ensuring tissue repair. ACE2 has been identified as a common target for different pathogens. Some Coronaviruses, including SARS-CoV-2, also use ACE2 to infiltrate the cells. A number of questions remain unresolved. The importance of ACE2 shedding, associated with the release of soluble ACE2 and ADAM17-mediated activation of tumor necrosis factor-α (TNF-α)-signaling is unclear. The roles of other non-classical RAS-associated molecules, e.g., alamandine, Ang A or Ang 1–9, also deserve attention. In addition, the impact of established RAS-inhibiting drugs on the pulmonary RAS is to be elucidated. The unfavorable prognosis of ARDS and the lack of effective treatment urge the search for novel therapeutic strategies. In the context of the ongoing SARS-CoV-2 pandemic and considering the involvement of humoral disbalance in the pathogenesis of ARDS, targeting the renin–angiotensin system and reducing the pathogen’s cell entry could be a promising therapeutic strategy in the struggle against COVID-19.
Coronavirus Update With Anthony Fauci
JN Learning, October 28, 2020
[Video, 29:50] View/listen in as Howard Bauchner, MD, Editor in Chief, JAMA, interviews Anthony S. Fauci, MD, to discuss the latest developments in the COVID-19 pandemic, including the continued importance of nonpharmaceutical interventions (masking, handwashing, physical distancing) for managing rising case numbers in the US and globally.
Universal face shield use significantly reduces SARS-CoV-2 infections among HCP
Helio | Primary Care, October 28, 2020
Universal use of face shields by health care personnel at a Texas hospital led to a significant reduction in SARS-CoV-2 infections, data presented at IDWeek show. Mayar Al Mohajer, MD, MBA, FIDSA, FSHEA, an infectious disease specialist at Baylor Saint Luke’s Medical Center, told Healio Primary Care that in April, his institution began requiring health care professionals (HCPs) and patients to wear masks. It simultaneously implemented surveillance testing every 2 weeks for high-risk HCP and for all patients upon admission and prior to undergoing invasive procedures. “Around the end of June, we noticed an increase in the rate of health care personnel testing positive for COVID-19, even though we were implementing all of the basic methods to prevent it,” Al Mohajer said. Consequently, Baylor Saint Luke’s — a quaternary health care system with more than 500 beds and 8,000 HCP — added a requirement that all HCP wear face shields upon entry to the facility, he said. The researchers found that from April 17 to July 5, before face shields were required, Baylor Saint Luke’s weekly positive SARS-CoV-2 infection rates among HCP rose from 0% to 12.9%, and health care-associated infections increased from 0 to 5. From July 6 to July 26, the first few weeks after face shields were required, the positive SARS-CoV-2 infection rate dropped to 2.3%, and health care-associated infections decreased to 0.
“Impact of Corticosteroids in COVID-19 Outcomes: Systematic Review and Meta-Analysis”
CHEST, October 28, 2020
Since its appearance in late 2019, infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have created unprecedented challenges for health systems worldwide. Multiple therapeutic options have been explored including corticosteroids (CS); preliminary results of CS in coronavirus disease 2019 (COVID-19) are encouraging, however, the role of CS is still controversial. Our objective was to answer the questions: What is the impact of CS in mortality, ICU admission, mechanical ventilation and viral shedding in COVID-19 cases? We conducted a systematic review of literature on CS and COVID-19 in major databases (PubMed, MEDLINE, and EMBASE) of published literature until July 22, 2020, that report outcomes of interest in COVID-19 patients receiving CS with a comparative group. A total of 73 studies with 21,350 COVID-19 cases were identified. CS use was widely reported in mechanically ventilated (35.3%), ICU (51.3%) and severe COVID-19 cases (40%). CS showed mortality benefit in severely ill COVID-19 cases (OR 0.65, 95%CI 0.51-0.83, P=0.0006), however, no beneficial or harmful effects were noted amongst high- or low-dose CS regimens. Emerging evidence shows that low-dose CS do not have a significant impact in the duration of SARS-CoV-2 viral shedding. Our results show evidence of mortality benefit in severely-ill COVID-19 treated with CS. CS are widely used in COVID-19 cases worldwide and a rapidly developing global pandemic warrants further high-quality clinical trials to define the most beneficial timing and dosing for CS.
Top in ID: COVID-19 case counts, spike in US death rate
Helio | Infectious Diseases, October 27, 2020
During a special session at IDWeek, Anthony S. Fauci, MD, said many countries, including the United States, are experiencing a surge in COVID-19 cases. It was the top story in infectious disease last week. Another top story was about new data showing a 20% spike in mortality during a 4-month period in the U.S. Many countries are seeing a spike in COVID-19, including the U.S., where a third wave has pushed the number of cases above 8.2 million, including 220,000 deaths. The U.S. had a mortality rate that was 20% higher than expected between March and July, and it experienced high COVID-19-related mortality and excess all-cause deaths into September, according to results from two JAMA studies. As scientists test treatments and vaccines against COVID-19, Healio spoke with Infectious Disease News Editorial Board Member Peter Chin-Hong, MD, about which populations are being left out of COVID-19 research and what needs to happen to make the process more inclusive.
Allergy & Asthma Network Announces National Trusted Messengers Project to Address Health Inequities
BioSpace, October 27, 2020
As part of Respiratory Care Week, Allergy & Asthma Network (AAN) and partners Sanofi and Self Care Catalysts will launch Not One More Life Trusted Messengers, a holistic project built on trust to address health inequities, increase access to important health information and screenings for people of color and improve long-term health outcomes, especially for those with respiratory conditions. The COVID-19 pandemic has further exposed health disparities and interconnected, systemic barriers faced by people of color, as evidenced by the disproportionate infection and death rates in these communities. These disparities can be observed at all ages, but are especially prevalent in younger age groups. Among those aged 45-54, Black and Hispanic/Latino death rates are at least six times higher than whites. To address this need, the Trusted Messengers project mobilizes leaders from the community, health advocacy and pharmaceutical organizations to drive community engagement, expand health care access and accelerate digital innovation in order to correct disparities in health that go well beyond COVID-19. AAN piloted the Trusted Messengers project model in Atlanta, hosting two community screening events on September 19 and 26. “Hundreds of patients in Atlanta were screened for COVID-19, asthma, COPD and were able to consult with healthcare professionals,” said Keisha Lance Bottoms, Mayor of Atlanta. “It’s encouraging to see people coming out and getting tested, and to know that the Trusted Messengers project will continue to help them throughout their health journey.”
Dedicated tracheostomy team, planning avoided delays in care for COVID-19 pneumonia
Helio | Pulmonology, October 26, 2020
A dedicated tracheostomy team and following standard of care for timing of tracheostomy avoided delaying necessary procedures in patients with COVID-19 pneumonia, without increasing risk for transmission to the care team. “With the recent COVID-19 pandemic, an unprecedented surge in patients requiring prolonged mechanical ventilation led to an increase in the need for tracheostomies,” Ella Illuzzi, NP, adult care nurse practitioner at Mount Sinai Health System, New York, said during a presentation at the virtual CHEST Annual Meeting. “Tracheostomy is an aerosol-generating procedure that raises potential risk to the proceduralist. Therefore, international professional total laryngology and surgical organizations published guidelines, which recommended delaying tracheostomy to after 21 days in order to assure viral clearance prior to the procedure. In the setting of well-intended practice guidelines, intensivists are faced with a new dilemma: following the standard of care for tracheostomy planning vs. delaying the procedure without evidence to support the new recommended guidelines.” Of the 111 tracheostomy procedures for COVID-19 prolonged respiratory failure, 35 patients were discharged to home alive, 23 patients were weaned from mechanical ventilation but remained hospitalized on a non-ICU floor, 33 patients died, and 20 patients remained in the ICU or were undergoing active weaning in a designated weaning unit at the time of data collection.
Performance of 5 Immunoassays for SARS-CoV-2 Compared
Pulmonology Advisor, October 26, 2020
A comparative assessment of the performance of 4 widely available antibody immunoassays and 1 novel immunoassay showed that these assays can be used for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologic testing to achieve sensitivity and specificity of at least 98%, according to study results published in The Lancet Infectious Diseases. Study authors conducted a head-to-head assessment of the following 4 commercial antibody assays, with the aim of evaluating the performance of each assay:
- SARS-CoV-2 IgG assay (Abbott, Chicago, IL, USA)
- LIAISON SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Saluggia, Italy)
- Elecsys Anti-SARS-CoV-2 assay (Roche, Basel, Switzerland)
- SARS-CoV-2 Total assay (Siemens, Munich, Germany)
The Abbott and Roche assays are known to detect antibodies to the nucleoprotein, whereas the DiaSorin and Siemens assays detect antibodies to the spike glycoprotein. The Abbott and Diasorin assays detect immunoglobulin (Ig)G only, whereas the Roche and Siemens assays detect total antibody. Study authors compared these 4 assays and a novel 384-well ELISA (the Oxford immunoassay) that detects total IgG to a trimeric spike protein.
Eosinophilic pulmonary vasculitis as a manifestation of the hyperinflammatory phase of COVID-19
Journal of Allergy and Clinical Immunology, October 26, 2020
[Letter to the Editor] The role of eosinophils in coronavirus disease 2019 (COVID-19) is still a matter of debate and eosinopenia is regarded as a negative predictive factor. A 60-year-old male patient with severe COVID-19 was mechanically ventilated for 6 days before transfer to our hospital. Comorbidities were hypertension and diabetes, but no allergic disorders or asthma. Body mass index was 26.3 kg/m2. He was a former smoker. Initially, C-reactive protein was 202 mg/L, procalcitonin 0.693 ng/mL, and white blood cell count 9.45 gpt/L, with normal percentages of eosinophils and lymphocytes. He received antibiotics and fluid management. Computed tomography on day 5 postintubationem (PI) showed bipulmonary ground glass opacities and basal consolidations, with marked progression on day 16 PI, necessitating extracorporeal membrane oxygenation starting on day 22 PI. Severe acute respiratory syndrome coronavirus 2 PCR was still positive on day 33 PI and negative from day 37 PI. He showed only a very slight increase in anti–severe acute respiratory syndrome coronavirus 2 antibodies in plasma, about one-third in comparison to other patients with a severe course of COVID-19. The arbitrary result of the assay amounted to 13 on day 16 PI with no significant increase in the following month. Bronchoalveolar lavage on day 32 PI yielded 30% lymphocytes (97% CD3+ T cells, 53% cytotoxic CD8+ CD3+ T cells), 25% neutrophils, and 36% eosinophils as well as 130 pg/mL IL-6, 2.4 pg/mL IL-5, and 4.5 pg/mL TNF-α.
Operational challenges of a low-dose CT lung cancer screening program during the COVID-19 pandemic
CHEST, October 26, 2020
The coronavirus disease 2019 (COVID-19) pandemic has had tremendous impact on healthcare systems, requiring diversion of resources to focus on the immediate needs of critically ill patients while postponing “non-essential” services, including lung cancer screening (LCS) low dose CT (LDCT). Although annual LCS is recommended for high-risk individuals, the risk of COVID9 19 exposure for both patients and healthcare workers may outweigh the benefits amidst the pandemic. As a result, multiple organizations recommended delaying LCS. Postponement of baseline and follow up examinations, especially for high risk patients with Lung-RADS (LR) categories 3 (1-2% probability of malignancy) and 4 (5-15% probability of malignancy), may result in delayed diagnosis and treatment of lung cancer. The purpose of our study was to assess how LCS LDCT volume was impacted by the COVID-19 pandemic. This is a single-institution, retrospective review compliant with the Health Insurance Portability and Accountability Act and approved with exemption by our Institutional Review Board.
6% of US adults hospitalized with COVID-19 work in health care
Helio | Infectious Disease News, October 26, 2020
In the United States, 6% of adults hospitalized with COVID-19 are health care personnel, an analysis indicated. Almost 30% of health care personnel (HCP) with COVID-19 were admitted to the ICU, according to results published in MMWR. “Findings from this analysis of data from a multisite surveillance network highlight the prevalence of severe COVID-19-associated illness among HCP and potential for transmission of SARS-CoV-2 among HCP, which could decrease the workforce capacity of the health care system,” Anita K. Kambhampati, MPH, and colleagues from the CDC’s COVID-NET Surveillance Team, wrote. “HCP, regardless of any patient contact, should adhere strictly to recommended infection prevention and control guidance at all times in health care facilities to reduce transmission of SARS-CoV-2, including proper use of recommended personal protective equipment, hand hygiene, and physical distancing.” According to Kambhampati and colleagues, among 6,760 adults hospitalized with COVID-19 in 13 states between March 1 and May 31, 5.9% were HCP. Among the infected HCP, 36.3% worked in nursing-related occupations and 67.4% were expected to have direct contact with patients. A total of 89.8% of HCP had an underlying medical condition, with obesity being the most common one (72.5%).
Limiting Outward Flow From the Patient’s Airways to the Airway Operator: Head Chamber for Intubation of COVID-19 Patients
Cureus, October 25, 2020
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 2019 (COVID-19), a potentially fatal disease affecting a growing number of individuals worldwide. The number of infected patients has been increasing alarmingly according to the Coronavirus Resource Center of Johns Hopkins University of Medicine. Exposure of healthcare personnel to the virus is a major problem. Adding an extra layer of protection separating the patient from the airway operator during tracheal intubation and redirecting droplets and bio-aerosols to a filtered suction system may reduce contamination. The aim of this study was to develop and test the effectiveness of a new device to achieve this goal. We present the prototype of an adjunct to personal protective equipment (PPE) for intubation of patients with coronavirus disease 2019 (COVID-19). Acknowledging the risk of infection for the airway operator and personnel in the room when tracheal intubation is required for a COVID-19 patient, we designed a chamber that creates a microenvironment around the patient’s head that limits the outward flow from a patient’s airways to the airway operator with a filtered suction system in order to limit viral spread and lower contamination risk during intubation in non-negative-pressure rooms. The device was successfully tested in a simulation setting.
Stem cell therapy for COVID‐19, ARDS and pulmonary fibrosis
Cell Proliferation, October 24, 2020
Coronavirus disease 2019 (COVID‐19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). COVID‐19 mainly causes damage to the lung, as well as other organs and systems such as the hearts, the immune system and so on. Although the pathogenesis of COVID‐19 has been fully elucidated, there is no specific therapy for the disease at present, and most treatments are limited to supportive care. Stem cell therapy may be a potential treatment for refractory and unmanageable pulmonary illnesses, which has shown some promising results in preclinical studies. In this review, we systematically summarize the pathogenic progression and potential mechanisms underlying stem cell therapy in COVID‐19, and registered COVID‐19 clinical trials. Of all the stem cell therapies touted for COVID‐19 treatment, mesenchymal stem cells (MSCs) or MSC‐like derivatives have been the most promising in preclinical studies and clinical trials so far. MSCs have been suggested to ameliorate the cytokine release syndrome (CRS) and protect alveolar epithelial cells by secreting many kinds of factors, demonstrating safety and possible efficacy in COVID‐19 patients with acute respiratory distress syndrome (ARDS). However, considering the consistency and uniformity of stem cell quality cannot be quantified nor guaranteed at this point, more work remains to be done in the future.
Ventilation management and clinical outcomes in invasively ventilated patients with COVID-19 (PRoVENT-COVID): a national, multicentre, observational cohort study
The Lancet | Respiratory Medicine, October 23, 2020
Large differences in outcomes for invasively ventilated patients with COVID-19 have been reported for different countries—eg, mortality rates for these patients in China were reported to be two-times higher than those in Italy and the USA—and even within a single country, such as the UK. Several ventilatory interventions, such as lung-protective ventilation with a low tidal volume and a low driving pressure, high positive end-expiratory pressure (PEEP) with recruitment manoeuvers, prone positioning, and extracorporeal membrane oxygenation (ECMO) affect case fatality in patients with acute respiratory distress syndrome (ARDS). It is not clear how these interventions are applied in routine practice in patients with ARDS related to COVID-19. Differences in outcomes motivate urgent comparative research to characterise between-country differences to inform best practice in the context of a surge of cases. We did the PRactice of VENTilation in COVID-19 study (PRoVENT-COVID) to describe ventilation management, epidemiological characteristics, and outcomes in invasively ventilated patients with COVID-19 in the Netherlands. The primary objective was to compare invasive ventilation settings and parameters over the first 4 days of ventilation in the ICUs of hospitals across the country. We also aimed to establish whether some ventilation settings and parameters have an independent association with the duration of ventilation and clinical outcomes.
Acute kidney injury associated with COVID-19: a prognostic factor for pulmonary embolism or co-incidence?
European Heart Journal, October 23, 2020
[Case Study] An 81-year-old gentleman presented with fever (39.1°C), cough, dysuria, and urinary tract infection, which warranted antibiotic therapy. Medical history included insulin-dependent type 2 diabetes mellitus, arterial hypertension, and third-degree atrioventricular block with an implanted pacemaker. The patient was intubated and required mechanical ventilation for severe respiratory failure (Horowitz index of 64.2 mmHg) 6 days after hospitalization. SARS-CoV-2 polymerase chain reaction (PCR) test on nasopharyngeal swabs was positive and chest computed tomography (CT) illustrated bilateral ground-glass opacities (Panel A). Laboratory tests showed a remarkable increase in the inflammatory cytokine interleukin-6 (270.6 pg/mL) and C-reactive protein (CRP; 222.7 mg/L). In the second week, he developed acute kidney injury (AKI) [creatinine, 296 μmol/L; blood urea nitrogen (BUN), 14.6 μmol/L, and estimated glomerular filtration rate (eGFR) 16 mL/min/1.73 m2], and consequently continuous haemodialysis was initiated. Fifteen days later, D-dimer levels were strikingly elevated (15 293 μg/L), and CT pulmonary angiography revealed segmental pulmonary embolism (PE) in the right upper lobe (Panel B) without signs of right ventricular failure (Supplementary material online, Video 1). ECG showed new onset of atrial fibrillation. Anticoagulation with unfractionated heparin was implemented. The patient remained in the intensive care unit until recovery of pulmonary function, but dialysis continued for 24 days to be prepared for discharge.
FDA OKs Remdesivir, First Drug for COVID-19
MedPage Today, October 22, 2020
The FDA approved remdesivir (Veklury) on Thursday for treating hospitalized COVID-19 patients, a first for the disease that started a global pandemic. Remdesivir, an antiviral that works by limiting SARS-CoV-2 replication, is indicated for hospitalized patients age 12 and up (and at least 40 kg [88.2 lbs]). Previously, the intravenous drug was solely available under an emergency use authorization (EUA) from the agency. FDA also announced a new EUA for remdesivir in hospitalized kidsage 12 and older weighing at least 3.5 kg (7.7 lbs) but less than 40 kg, and in kids under age 12 weighing at least 3.5 kg. The news comes exactly a week after a major international trial led by the World Health Organization (WHO) found no survival improvement for hospitalized COVID-19 patients treated with the drug, and no improvement in time to recovery. Approval was based on three randomized trials, including the National Institutes of Health-led ACTT-1 trial, a phase III trial that showed that patients with mild, moderate, and severe disease who were treated with up to 10 days of remdesivir recovered a median 5 days quicker than those on placebo (10 vs 15 days; rate ratio [RR] 1.29, 95% CI 1.12-1.49, P<0.001), and a median 7 days quicker in those requiring oxygen at baseline (11 vs 18 days; RR 1.31, 95% CI 1.12-1.52).
Bedside Evaluation of Pulmonary Embolism by Saline Contrast Enhanced Electrical Impedance Tomography: Considerations for Future Research
American Journal of Respiratory and Critical Care Medicine, October 22, 2020
[Letter to the Editor] We read with great interest the article by Huaiwu He et al. entitled “bedside evaluation of pulmonary embolism (PE) by saline contrast electrical impedance tomography method: A prospective observational study”. The authors found PE-envoked regional perfusion defection could be detected with saline-contrasted EIT and claimed that the method showed high sensitivity and specificity for diagnosis of PE. However, several factors potentially affecting the reported findings should be discussed. For measurement of pulmonary perfusion, a short apnea is needed during bolus injection of 10ml 10% NaCl to eliminate the interruption from cyclic breath. The conscious patients were required to hold their breath at the end of expiration for 8 seconds or longer. Although the shorter the apnea, the more feasible for conscious patients to hold their breath, it needs imperative time to allow blood mixed with saline to travel through the whole pulmonary circulation. Slutsky, et al. found mean pulmonary transit time (PTT) ranged from 4.3 to 12.6 seconds (mean 7.7 ±1.5 seconds) in human. In this context, it’s questionable that a period with a lower level of 8 seconds is enough for saline to pass through the lung in patients with PE. On the other hand, for those intubated, holding breath for even 8 seconds might be challenging as dyspnea is common among patients with PE, manual expiratory hold is likely to trigger spontaneous breath, which would dramatically impact the intrathoracic electric impedance. To avoid spontaneous breath, sometimes neuromuscular relaxant is needed, which was not detailed in this article. Recently, Mauri et al published a study exploring the ventilation-perfusion ratio in patients with COVID-19, in which a lower concentration (5%) of saline and end-inspiration occlusion for 20 seconds were implemented for determination of pulmonary perfusion.
The Impact of COVID-19 on Physician Burnout Globally: A Review
Healthcare, October 22, 2020
The current pandemic, COVID-19, has added to the already high levels of stress that medical professionals face globally. While most health professionals have had to shoulder the burden, physicians are not often recognized as being vulnerable and hence little attention is paid to morbidity and mortality within this group. Our objective was to analyse and summarise the current knowledge on factors/potential factors contributing to burnout amongst healthcare professionals amidst the pandemic. This review also makes a few recommendations on how best to prepare intervention programmes for physicians. In August 2020, a systematic review was performed using the database Medline and Embase (OVID) to search for relevant papers on the impact of COVID-19 on physician burnout–the database was searched for terms such as “COVID-19 OR pandemic” AND “burnout” AND “healthcare professional OR physician”. A manual search was done for other relevant studies included in this review. Results: Five primary studies met the inclusion criteria. A further nine studies were included which evaluated the impact of occupational factors (n = 2), gender differences (n = 4) and increased workload/sleep deprivation (n = 3) on burnout prior to the pandemic. Additionally, five reviews were analysed to support our recommendations. Results from the studies generally showed that the introduction of COVID-19 has heightened existing challenges that physicians face such as increasing workload, which is directly correlated with increased burnout. However, exposure to COVID-19 does not necessarily correlate with increased burnout and is an area for more research.
Simple risk score may predict need for mechanical ventilation in COVID-19
Helio | Pulmonology, October 22, 2020
Researchers developed a novel risk score to predict risk for mechanical ventilation among hospitalized patients with COVID-19. Thresholds for three common clinical variables were used: admission heart rate, any position initial troponin level and ratio of oxygen saturation to fraction of inspired oxygen (SpO2/FiO2). Muhtadi Alnababteh, MD, chief resident at MedStar Washington Hospital Center, and colleagues conducted a retrospective study of adults with laboratory-confirmed COVID-19 who were admitted to the tertiary care center from March 15 to April 15. Among 265 patients, 54 (20.4%) required invasive mechanical ventilation, the overall mean age was 59 years, 55% were men and 75% were Black. The researchers found that three common clinical variables independently predicted the need for mechanical ventilation in this population:
- admission heart rate (OR = 1.032; 95% CI, 1.013-1.015; P < .001);
- SpO2/FiO2 ratio (OR = 0.619; 95% CI, 95% CI, 0.463-0.829; P = .001); and
- any position initial troponin (OR = 4.18; 95% CI, 1.93-9.036; P < .001).
Alnababteh and colleagues also determined the best cutoff points for two of the variables: admission heart rate higher than 101.5 beats per minute (area under the curve = 0.686; 68.5% sensitivity; 66.4% specificity) and SpO2/FiO2 ratio less than 4.4 (AUC = 0.714; 72.2% sensitivity; 61.6% specificity).
Prognostic Tool May Improve COVID-19 Management
MedPage Today, October 21, 2020
A score developed in China to quantify COVID-19 pneumonia severity appeared to predict mortality in U.S. patients, and may help to eventually guide treatment decisions, a researcher said. When applied to a small cohort of U.S. patients at the time of hospitalization, the MuLBSTA score was associated with in-hospital death with an area under the receiver operating curve of 0.813, reported Jurgena Tusha, MD, of Wayne State University School of Medicine in Detroit. “An influx of SARS-CoV-2 infection has led to unanswered questions. One such question raised was how to risk stratify these patients in order to direct further management,” Tusha said at a presentation at the annual meeting of the American College of Chest Physicians.
She explained the components of the MuLBSTA score, which are weighted according to importance:
- Multilobe infiltrate (Yes +5)
- Absolute lymphocyte count less than 0.8 (Yes +4)
- Bacterial coinfection detected by sputum or blood culture (Yes +4)
- Smoking history (Active smoker +3, Prior smoker +2)
- History of hypertension (Yes +2)
- Age older than 60 (Yes +2)
Earlier work with the MuLBSTA score indicated it could predict 90-day mortality in patients, at rates of 0.47% for patients with a score of 0 to around 69% with a score of 20.
Pulmonary Vascular Changes in Acute Respiratory Distress Syndrome Due to COVID-19
American Journal of Respiratory and Critical Care Medicine, October 21, 2020
[Letter to the Editor] This letter is in response to an article published by Patel et al in the recent issue of the American Journal of Respiratory and Critical Care Medicine. 1 The author’s observation is consistent with previous report suggesting varying grade of pulmonary thromboembolism, pulmonary vascular micothrombosis and pulmonary vascular dilatation in advance stage of acute hypoxemic failure due to COVID-19. In the current study, radiologic findings were obtained when nearly 50% of patients were on extracorporeal membrane oxygenation (ECMO). Therefore, interpretation and generalization of the findings become somewhat more intriguing due to complexities arising from hemodynamic, oxygenation and hematologic alterations induced by ECMO. Venoarterial ECMO is known to increase afterload, left ventricular (LV) end diastolic pressure, left atrial pressure and post-capillary venous dilatation. Furthermore, femoral arterial oxygenated flow may not reach the coronary circulation due to watershed effect (north south syndrome) and may induce LV ischemia and aggravates LV dysfunction. Additionally, venous return diversion to ECMO circuit may induce stagnation in pulmonary circulation, which may further get aggravated by increase in pulmonary vascular resistance (PVR) due to positive end expiratory pressure (PEEP). However, total lung blood volume may get reduced and there is a lesser hydrostatic pressure gradient for pulmonary edema formation.
Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients’ performance: a prospective observational cohort study
Respiratory Research, October 21, 2020
Two hallmarks of severe COVID-19 are hyperinflammation, most typically involving a “cytokine storm” with massive interleukin 6 (IL6) expression, and hyperferritinemia. Ferritin is the most relevant cellular iron storage protein and is regulated by both, iron availability and inflammation. Accordingly, IL6 is a key mediator of inflammation-driven iron handling, as it induces the production of hepcidin, the master regulator of iron homeostasis. Hepcidin regulates cellular iron efflux via degradation of the sole cellular iron exporter ferroportin 1 (FPN1), which induces cellular iron retention in macrophages and reduces duodenal iron absorption. Inflammation, therefore, causes alterations of iron homeostasis hallmarked by functional iron deficiency (ID) as reflected by high iron content in reticuloendothelial cells and consequently high serum ferritin levels whereas circulating iron levels are low. Subsequently, inflammation limits this metal’s availability for erythropoiesis, thus causing anemia, termed as anemia of inflammation (AI). AI is highly prevalent in patients with infections since the underlying immune-mediated iron restriction is considered as an important host defense mechanism to limit microbial proliferation and pathogenicity. Indeed, iron is not only essential for multiple cellular processes for eucaryotes but also for microbes including viruses. Of importance, over 80% of hospitalized patients with COVID-19 presented with inflammation-driven imbalances of iron homeostasis upon admission, which predicted an adverse clinical course. As ferritin also has pro-inflammatory properties, it has been speculated whether or not hyperferritinemia in COVID-19 might contribute to its pathogenesis and severity. Accordingly, we herein analysed for persisting alterations of iron metabolism in survivors of COVID-19 aiming to evaluate their prevalence and their association with persisting pathologic processes linked to COVID-19.
COVID-19: What Iodine Maps From Perfusion CT can reveal—A Prospective Cohort Study
Critical Care, October 21, 2020
Subtraction CT angiography (sCTA) is a technique used to evaluate pulmonary perfusion based on iodine distribution maps. The aim of this study is to assess lung perfusion changes with sCTA seen in patients with COVID-19 pneumonia and correlate them with clinical outcomes. This prospective cohort study was carried out with 45 RT-PCR-confirmed COVID-19 patients that required hospitalization at three different hospitals, between April and May 2020. In all cases, a basic clinical and demographic profile was obtained. Lung perfusion was assessed using sCTA. Evaluated imaging features included: Pattern predominance of injured lung parenchyma in both lungs (ground-glass opacities, consolidation and mixed pattern) and anatomical extension; predominant type of perfusion abnormality (increased perfusion or hypoperfusion), perfusion abnormality distribution (focal or diffuse), extension of perfusion abnormalities (mild, moderate and severe involvement); presence of vascular dilatation and vascular tortuosity. All participants were followed-up until hospital discharge searching for the development of any of the study endpoints. These endpoints included intensive-care unit (ICU) admission, initiation of invasive mechanical ventilation (IMV) and death. Forty-one patients (55.2 ± 16.5 years, 22 men) with RT-PCR-confirmed SARS-CoV-2 infection and an interpretable iodine map were included. Patients with perfusion anomalies on sCTA in morphologically normal lung parenchyma showed lower Pa/Fi values (294 ± 111.3 vs. 397 ± 37.7, p = 0.035), and higher D-dimer levels (1156 ± 1018 vs. 378 ± 60.2, p < 0.01). The main common patterns seen in lung CT scans were ground-glass opacities, mixed pattern with predominant ground-glass opacities and mixed pattern with predominant consolidation in 56.1%, 24.4% and 19.5% respectively.
Fauci: Case counts ‘stunning’ as many places see COVID-19 surge
Helio | Infectious Diseases, October 21, 2020
Many countries are seeing a spike in COVID-19, including the United States, where a third wave has pushed the number of cases above 8.2 million, including 220,000 deaths. “The numbers throughout the globe have been stunning, making this already the most disastrous pandemic that we have experienced in our civilization in over 102 years, since the 1918 influenza pandemic,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said during a special session at IDWeek focused on COVID-19. Fauci noted the global case count: “40 million cases and over 1.1 million deaths.” “Unfortunately, for the United States, we have been hit harder than virtually any other country on the planet,” he said. The Johns Hopkins coronavirus resource center, which tracks state-level trends, has reported recent sharp increases in daily cases in states like North Dakota (803 cases per 100,000 people), Wisconsin (3,317 per 100,000 people), Rhode Island (293 per 100,000 people) and Wyoming (230 per 100,000 people), and declines in states including Arkansas, Kentucky and South Dakota.
The Costs of Coronavirus
Journal of the American Medical Association, October 20, 2020
[Video, 38:44] View/listen in as Howard Bauchner, MD, Editor in Chief, JAMA, interviews authors of three recent features in JAMA:
- David M. Cutler, PhD, of Harvard University discusses financial costs: the $16 trillion virus.
- Lisa Cooper, MD, MPH, of Johns Hopkins University discusses the costs to communities of color in excess deaths and bereavement.
- Charles R. Marmar, MD, of NYU Grossman School of Medicine discusses the mental health costs.
Follow up of patients with severe coronavirus disease 2019 (COVID-19): Pulmonary and extrapulmonary disease sequelae
Respiratory Medicine, October 20, 2020
Since December 2019 the novel coronavirus disease 2019 (COVID-19) has been burdening all health systems worldwide. However, pulmonary and extrapulmonary sequelae of COVID-19 after recovery from the acute disease are unknown. Hospitalized COVID-19 patients not requiring mechanical ventilation were included and followed 6 weeks after discharge. Body plethysmography, lung diffusion capacity (DLco), blood gas analysis (ABG), 6-min walk test (6MWT), echocardiography, and laboratory tests were performed. Quality of life (QoL), depression, and anxiety were assessed using validated questionnaires. 33 patients with severe disease were included. Patients were discharged without prophylactic anticoagulation. At follow-up there were no thromboembolic complications in any patient. 11 patients (33%) had dyspnea, 11 (33%) had cough, and 15 (45%) suffered from symptoms of fatigue. Pulmonary function tests including ABG did not reveal any limitations (TLC: median = 94% of predicted [IQR:85–105]; VC: 93% [78–101]; FEV1: 95% [72–103]; FEV1/FVC 79% [76–85]; PaO2: 72 mmHg [67–79]; PaCO2: 38 mmHg (Xu et al., 2020; Tian et al., 2020; Huang et al., 2020; Ware, 2013) [35-38], except for slightly reduced DLco (77% [69–95]). There were no echocardiographic impairments. 6MWT distance was reduced in most patients without oxygen desaturation. According to standardized questionnaires, patients suffered from reduced QoL, mainly due to decreased mobility (SGRQ activity score: 54 [19–78]). There were no indicators for depression or anxiety.
COVID-19 With COPD: Fewer Hospitalizations, But Greater Mortality
Pulmonology Advisor, October 20, 2020
Chronic obstructive pulmonary disease (COPD) may be associated with higher rates of mortality in patients with coronavirus disease 2019 (COVID-19), according to research presented at the CHEST Annual Meeting, held virtually, October 18 to 21. However, COPD is also associated with a lower prevalence of COVID-19-related hospitalizations. Investigators evaluated results from 22 studies conducted across 8 countries that included more than 11,000 patients. They noted that prior diabetes and hypertension diagnoses were significantly more prevalent than COPD in patients hospitalized with COVID-19, which only accounted for 5% of the patients analyzed. Hypertension, by contrast, was noted in 42% of patients hospitalized for COVID-19 while 23% had a diabetes diagnosis. The prevalence for COVID-19 hospitalization among the general population is approximately 9% (in patients older than 40 years). Because the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has a prominent respiratory element, researchers expected patients with prior lung disease to have greater mortality. The lower prevalence of COVID-19 in patients with COPD “may reflect greater measures taken by COPD patients to avoid coronavirus exposure.”
Expression of SARS-CoV-2 entry factors in lung epithelial stem cells and its potential implications for COVID-19
Scientific Reports, October 20, 2020
SARS-CoV-2 can infiltrate the lower respiratory tract, resulting in severe respiratory failure and a high death rate. Normally, the airway and alveolar epithelium can be rapidly reconstituted by multipotent stem cells after episodes of infection. Here, we analyzed published RNA-seq datasets and demonstrated that cells of four different lung epithelial stem cell types express SARS-CoV-2 entry factors, including Ace2. Thus, stem cells can be potentially infected by SARS-CoV-2, which may lead to defects in regeneration capacity partially accounting for the severity of SARS-CoV-2 infection and its consequences. We found that epithelial stem cells (basal cells, AEPs, BASCs and H2-K1high cells) express Ace2 and other SARS-CoV-2 entry factors, making these cells probable targets of SARS-CoV-2 infection. The expression of these factors in different stem cells was relatively low, but, for example, among cells expressing markers that are specific to the gas-exchanging alveoli, AEPs exhibited higher expression of SARS-CoV-2 entry factors than differentiated AT1 and AT2 cells. These results are in agreement with the observations that cell differentiation is accompanied by depletion of the ACE2 protein. Multipotent stem cells can reconstitute lung epithelium after episodes of infection or other injuries, and it was demonstrated that stem cells could proliferate in COVID-19 patients. However, the expression of SARS-CoV-2 entry factors makes them potentially infectable by SARS-CoV-2, which may in turn result in a decreased capacity for lung epithelial regeneration and potentially complicate recovery from the disease.
https://www.healio.com/news/infectious-disease/20201016/deaths-spike-20-in-us-during-4month-period?M_BT=5615057921030
Helio | Infectious Disease News, October 19, 2020
The United States had a mortality rate that was 20% higher than expected between March and July, and it experienced high COVID-19-related mortality and excess all-cause deaths into September, according to results from two JAMA studies. The first study explored excess deaths and their relationship to states’ reopening and easing of restrictions. “The number of deaths that are occurring as a result of the pandemic is larger than the COVID-19 death count that is being reported,” Steven Woolf, MD, MPH, director emeritus of the Center on Society and Health at Virginia Commonwealth University, told Healio. “Some of that excess is being produced by people who are dying from causes other than COVID-19 but from disruptions produced by the pandemic itself and our response to it.” In a separate study, Alyssa Bilinski, MSc, a health policy PhD candidate at Harvard University, and Ezekiel J. Emanuel, MD, PhD, vice provost for global initiatives at the University of Pennsylvania, compared COVID-19 deaths and excess all-cause mortality in the U.S. with that of 18 other countries. “The U.S. has experienced more deaths from COVID-19 than any other country and has one of the highest cumulative per capita death rates,” the researchers wrote. “An unanswered question is to what extent high U.S. mortality was driven by the early surge of cases prior to improvements in prevention and patient management vs. a poor longer-term response.”
https://www.atsjournals.org/doi/abs/10.1164/rccm.202008-3058LE
American Journal of Respiratory and Clinical Care Medicine
Assessment of lung ventilation and perfusion of C-ARDS is still scarce, especially in response to positive end expiratory pressure (PEEP) and prone positioning. The objective of this study was to describe the physiological effects of PEEP and prone position on respiratory mechanics, ventilation and pulmonary perfusion in patients with C-ARDS. Methods ARDS was defined according to the Berlin definition, and SARS-CoV-2 infection was confirmed by positive nasopharyngeal polymerase chain reaction. Patients were included consecutively, within 72 hours of intubation, if the EIT device was available. Patients with a contraindication to esophageal catheter and/or impedancemetry were excluded. Patients were deeply sedated and paralyzed. An electrical impedance tomography assessed regional ventilation and perfusion. Lung perfusion was recorded during an expiratory pause by injecting a 10 cc bolus of 7.5% hypertonic saline solution into a central venous catheter. Respiratory mechanics, ventilation, and perfusion EIT data were recorded at three arbitrary levels of PEEP (18, 12, and 6 cmH2O) in the supine position and at PEEP 12 cmH2O after 3 hours of prone position. Arterial blood gases were collected prior to exploration, prior to prone positioning, and at the end of proning. The following parameters were collected in each phase: expiratory tidal volume, peak pressure, plateau pressure, total PEEP, end-inspiratory and end-expiratory esophageal pressure, pulse oximetry, end-tidal expired carbon dioxide pressure, respiratory rate, heart rate, blood pressure, and cardiac output.
Fauci: No Quick End to Pandemic
MedPage Today, October 19, 2020
In a sobering message to physicians and their patients, the United States’ top infectious disease official suggests the rampaging SARS-CoV-2 pandemic is going to be with us for a while. “We are now in the middle of an explosive pandemic of historic proportions, the likes of which we have not experienced in the last 102 years with over a million deaths worldwide and 38 million cases – and the end is not in sight,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said as keynote speaker at the virtual annual meeting of the American College of Chest Physicians. “Unfortunately for the United States, we are the worst hit country in the world,” Fauci said in his pre-recorded speech. The U.S. case count surpassed 8 million and the death count was nearing 220,000 over the weekend. Fauci noted that the U.S. government is deeply involved in vaccine development, supporting six different candidate vaccines, including five now in phase III trials. “Our strategic approach means we are harmonizing these vaccine trials so they have a common data monitoring and safety board, common primary and secondary endpoints, and common immunological parameters,” he said.
One in five young adults hospitalized for COVID-19 require intensive care
Helio | Infectious Diseases, October 19, 2020
Approximately one-fifth of young adults hospitalized with COVID-19 required intensive care, according to research published in JAMA Internal Medicine. “We think the vast majority of people in this age range have self-limited disease and don’t require hospitalization,” Scott Solomon, MD, director of noninvasive cardiology in the Division of Cardiovascular Medicine at the Brigham and Women’s Hospital, said in a press release. “But if you do, the risks are really substantial.” Solomon and colleagues evaluated data from the Premier Healthcare Database, which includes 1,030 U.S. hospitals and health care systems, on adults aged 18 to 34 years with COVID-19 who were discharged from the hospital between April 1 and June 30. They identified 3,222 young adults with COVID-19 who were hospitalized at 419 U.S. hospitals. Among them, 36.8% were obese, 24.5% were morbidly obese, 18.2% had diabetes and 16.1% had hypertension. Solomon and colleagues identified a greater risk for death or mechanical ventilation among patients with morbid obesity (adjusted OR = 2.30; 95% CI, 1.77-2.98) and hypertension (adjusted OR = 2.36; 95% CI, 1.79-3.12) compared with those without such conditions. They also found that male patients had a greater risk for death or mechanical ventilation compared with female patients (adjusted OR = 1.53; 95% CI, 1.20-1.95).
How does risk vary for Black and Asian patients with COVID-19?
Medical News Today, October 18, 2020
New research suggests that people of Black, mixed, and Asian ethnicity are more at risk of COVID-19, but these risks vary as the disease progresses. A new study finds that COVID-19 risks for people of Black, mixed, or Asian ethnicity vary over the course of the disease. The research also suggests that even after accounting for socioeconomic status and other comorbidities, these populations are more at risk of contracting COVID-19. For the authors of the research, which appears in the journal EClinicalMedicine, this suggests that other yet-to-be-identified factors associated with ethnicity are likely to be at play. As Dr. Winston Morgan, a Reader in Toxicology and Clinical Biochemistry at the University of East London, United Kingdom, argues, “there is as much genetic variation within racialized groups as there is between the whole human population.” For the researchers, while genetic differences can, at times, be associated with specific ethnicities and linked to particular health issues, how this could work in the context of COVID-19 is far from clear. Indeed, for Dr. Morgan: “The evidence suggests that the new coronavirus does not discriminate but highlights existing discriminations. The continued prevalence of ideas about race today – despite the lack of any scientific basis – shows how these ideas can mutate to justify the power structures that have ordered our society since the 18th century.”
SARS-CoV-2 detection in the lower respiratory tract of invasively ventilated ARDS patients
Critical Care, October 16, 2020
The SARS-CoV-2 disseminated in Europe in late February 2020, causing the largest pandemic due to any respiratory viruses in recent history. Several authors suggested that viral shedding and severity of disease might be correlated, but they mostly focused on viral presence in upper respiratory secretions. Viral shedding from upper respiratory tract appeared to be higher soon after symptoms’ onset, but during the course of disease, the shedding originates predominantly from the lower respiratory tract (LRT). To date, data on viral replication in distal airways are scarce. Only one small study partly investigated the role of viral presence into LRT. Moreover, the association between SARS-CoV-2 viral load in LRT and mortality remains unevaluated. Our objectives were (1) to describe the viral shedding and the viral load in LRT and (2) to determine THE ASSOCIATION BETWEEN VIRAL PRESENCE AND MORTALITY in critically ill COVID-19 patients.
Association Between Anticoagulation and Survival in Interstitial Lung Disease: An Analysis of the Pulmonary Fibrosis Foundation (PFF) Registry
CHEST, October 16, 2020
Aberrations in the coagulation system have been implicated in the pathogenesis of interstitial lung disease (ILD). Anticoagulants have been proposed as a potential therapy in ILD; however, a randomized control trial examining warfarin as a treatment for IPF was terminated early for harm. This has led some to speculate that warfarin specifically may be harmful in ILD, and use of direct oral anticoagulants (DOACs) may result in superior outcomes. We sought to delineate the relationship between anticoagulation and outcomes in patients with ILD through an analysis of the Pulmonary Fibrosis Foundation (PFF) registry. An analysis of all patients in the PFF registry was performed. Patients were stratified into three groups: no anticoagulation (AC), DOAC use, or warfarin use. Survival was analyzed using both Kaplan Meier curves and Cox proportional hazards models. Of 1,911 patients included in the analysis, 174 (9.1%) were anticoagulated, 93 (4.9%) with DOACs, and 81 (4.2%) with warfarin. There was a two-fold increased risk of death or transplant for patients receiving DOACS, while for warfarin this was over a two and half times greater risk. DOACs were not associated with an increased risk of mortality after adjustment for confounding variables. However, even after adjustment, patients anticoagulated with warfarin remained at increased risk of mortality. In patients with IPF, warfarin was associated with reduced transplant free survival, but DOACs were not. There was no statistically significant difference in survival between those receiving warfarin and those receiving a DOAC.
Change in Allergy Practice during the COVID-19 Pandemic
International Archives of Allergy and Immunology, October 15, 2020
International guidelines in asthma and allergy has been updated for COVID-19 pandemic and pandemic has caused dramatic changes in allergy and immunology services. However, it is not known whether specialty-specific recommendations for COVID-19 are followed by allergists. By conducting this study, we aimed to determine the attitudes and experiences of adult/pediatric allergists on allergy management during COVID-19. We used a 20-question survey to elicit data from allergists (residents and pediatric and adult allergists registered to the Turkish National Society of Allergy and Clinical Immunology) across Turkey via e-mail. We analyzed the data statistically for frequency distributions and descriptive analysis. A total of 183 allergists participated in the survey. Telemedicine was used for management of asthma (73%), allergic rhinitis (53%), atopic dermatitis (51%), chronic urticaria/angioedema (59%), drug hypersensitivity (45%), food allergy (48%), venom allergy (30%), anaphylaxis (22%), and hereditary angioedema (28%). Thirty-one percent of the respondents discontinued subcutaneous immunotherapy (SCIT) during the COVID-19 pandemic. Thirty-four percent of the physicians reported interruption of systemic steroid use in asthma patients, and 25% of the respondents discontinued biological therapy.
High Respiratory Drive and Excessive Respiratory Efforts Predict Relapse of Respiratory Failure in Critically Ill Patients with COVID-19
American Journal of Respiratory and Critical Care Medicine, October 15, 2020
Since the first reported cases in December 2019 in Wuhan, China, coronavirus disease (COVID-19) outbreak has rapidly spread around the world. This infection often requires ICU admissions and invasive mechanical ventilation. To prevent diaphragmatic atrophy and to enhance weaning, the early use of ventilatory modes allowing spontaneous breathing is usually recommended as soon as possible but should be balanced with potential harmful effects. Indeed, a high respiratory drive is sometimes observed in patients with acute respiratory distress syndrome (ARDS), and thus, spontaneous breathing could lead to uncontrolled transpulmonary pressures and possibly to patient self-inflicted lung injuries (P-SILI). Strong efforts could also simply reflect the nonresolution of the underlying disease and thus invite to delay the weaning process of mechanical ventilation. Lacking specific respiratory monitoring, surrogate measures of respiratory drive should be assessed. We hypothesized that mechanically ventilated patients with COVID-19 with ARDS often present high respiratory drive and excessive inspiratory efforts (as suggested by elevated P0.1 and ΔPocc measurements) and that this could rapidly lead to a relapse of respiratory failure during the weaning process of mechanical ventilation. Therefore, the aim of this study was to assess the threshold values of P0.1 and ΔPocc predicting the occurrence of relapse in the following 24-hour period after measurements in intubated and mechanically ventilated patients with COVID-19 pneumonia.
Scientific consensus on the COVID-19 pandemic: we need to act now
The Lancet, October 15, 2020
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 35 million people globally, with more than 1 million deaths recorded by WHO as of Oct 12, 2020. As a second wave of COVID-19 affects Europe, and with winter approaching, we need clear communication about the risks posed by COVID-19 and effective strategies to combat them. Here, we share our view of the current evidence-based consensus on COVID-19.
Venous thromboembolism and COVID-19: a case report and review of the literature
Journal of Medical Case Reports, October 15, 2020
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), continues to desolate a significant portion of the world’s population, and health care providers continue to see new and frightening displays of its pathogenicity. Currently, there is minimal data available highlighting the prevalence of venous thromboembolism in patients infected with COVID-19. This case report with a literature review emphasizes a unique presentation of COVID-19 that is highly important for health care providers to consider when treating their patients. We report an atypical case involving a 65-year-old male patient with an acute saddle pulmonary embolism and a deep vein thrombosis (DVT) associated with COVID-19.
Detection of Invasive Pulmonary Aspergillosis in COVID-19 with Nondirected BAL
American Journal of Respiratory and Critical Care Medicine, October 15, 2020
[Letter to the Editor] Invasive pulmonary aspergillosis (IPA) can complicate influenza pneumonia in critically ill patients owing to viral destruction of bronchial mucosa, facilitating invasion of Aspergillus species, and compromised host defenses to Aspergillus. Given the association between IPA and increased mortality in influenza, rapid diagnostic investigations and early (preemptive) treatment of IPA are recommended in critically ill patients with influenza. In ICU patients with coronavirus disease (COVID-19), the same principles may apply as in influenza. A high incidence of IPA in patients with COVID-19 admitted to the ICU has been reported in small cohorts of patients, some of which appeared online. However, in these studies, a bronchoscopy with BAL was not consistently applied, which may hamper estimation of the IPA incidence in COVID-19, as a BAL to obtain material for culture and for galactomannan (GM) measurement is generally recommended for IPA diagnosis in the critically ill. However, owing to risk of aerosolization, only a restricted role for bronchoscopy with BAL is recommended in patients with COVID-19. We have applied a diagnostic approach by performing a nondirected BAL via a closed-circuit suction catheter, which we describe in this letter. Using this nondirected BAL technique as a standard approach, we aimed to determine the proportion of patients with IPA in a cohort of patients with COVID-19 (PCR confirmed) requiring mechanical ventilation who were consecutively admitted to the ICU of our teaching hospital during a 3-week time frame in April 2020.
Paired nasopharyngeal and deep lung testing for SARS-CoV2 reveals a viral gradient in critically ill patients: a multi-centre study
CHEST, October 14, 2020
Since the start of the COVID19 pandemic, arising from SARS-CoV-2 viral infection, approximately 13000 patients have been admitted to critical care in the United Kingdom, the majority have required advanced respiratory support. Samples for SARS-CoV-2 detection can be obtained from the upper (nasopharyngeal/oropharyngeal swabs) or lower respiratory tract (sputum/endotracheal aspirate/broncho-alveolar lavage (BAL)). Viral ribonucleic acid (RNA) is detected using reverse transcriptase polymerase chain reaction (RT-PCR). The Cycle threshold (Ct) has a simple negative linear correlation with the logarithm of the number of gene copies in the original sample and thus can be used to provide a semiquantitative estimate of the viral RNA in a specimen. It has been suggested that SARS-CoV-2 is predominantly shed from upper respiratory tract, distinguishing it from SARS-CoV-1, where replication occurs mainly in the lower respiratory tract. A recent multi-site viral detection study indicated higher nasopharyngeal (NP) viral loads in some patients early in the course of disease, although they generally detected viral RNA in sputum for longer. However, this study was conducted on patients with mild disease, and it is unclear whether the results pertain to critically ill patients. Our objective was to evaluate SARS-CoV-2 RNA loads between paired NP and deep lung (endotracheal aspirate or BAL) samples from critically ill patients.
Two Major COVID Trials Paused for Safety Issues
WebMD, October 14, 2020
Johnson & Johnson paused dosing and enrollment in all of its COVID-19 vaccine clinical trials due to an unexplained illness in a study participant, the company announced Monday. Later in the day, Eli Lilly had to acknowledge a pause of a clinical trial of antibody treatment because of a “potential safety concern,” The New York Times reported, citing emails U.S. government officials sent to researchers. In a statement to the Times, Eli Lily spokesperson Molly McCully confirmed the pause in the trial and said, “Safety is of the upmost importance to Lilly. Lilly is supportive of the decision by the independent (safety monitoring board) to cautiously ensure the safety of the patients participating in this study.” But that wasn’t the only challenge facing Eli Lilly. Reuters reported late Monday that FDA inspectors found serious quality control problems at the Lilly plant where the antibody drugs are manufactured. Meanwhile, in the Johnson & Johnson trial, the patient’s illness is being reviewed and evaluated by an independent monitoring board and the company’s doctors that investigate safety data. “Adverse events — illnesses, accidents, etc. — even those that are serious, are an expected part of any clinical study, especially large studies,” according to the announcement.
Methyl-Prednisolone Pulses May Improve COVID-19 Pneumonia Prognosis
Pulmonology Advisor, October 14, 2020
Patients with severe coronavirus disease 2019 (COVID-19) pneumonia had improved prognosis after receiving a short course of methyl-prednisolone pulses during the second week of disease, according to study results published in PLoS One. Clinical end points of time to death and time to endotracheal intubation were monitored in patients with severe COVID-19 pneumonia. Comparisons were made between patients who received a short course of methyl-prednisolone pulses during the second week of disease and those who only received standard care. Methyl-prednisolone pulses were defined as 125 to 250 mg per day for 3 consecutive days. “This study confirms that [methyl-prednisolone], 125-250 mg/d for 3 consecutive days given during the second week of disease without subsequent tapering, improve the prognosis of patients with COVID-19 pneumonia, features of inflammatory activity and respiratory deterioration,” the study authors wrote. “Our results open the door to a more rational and planned management of patients with COVID-19.”
Global impact of COVID-19 infection requiring admission to the intensive care unit: a systematic review and meta-analysis
CHEST, October 14, 2020
SARS-CoV-2 has placed an unprecedented burden on intensive care units (ICUs) around the world. A striking feature of COVID-19 is rapidly progressive respiratory failure, which develops in approximately 5% of infected adults. At the time of writing (28 August 2020) there have been over 24 million confirmed cases of COVID-19 and more than three quarters of a million deaths worldwide. In early case series, mortality rates for critically ill patients with COVID-19 were between 40-61% despite advanced ICU supports. This mortality rate is substantially greater than in previous viral pneumonitis pandemics, such as the 2009 H1N1 influenza pandemic with morality rates between 10-30%. Usual provision of ICU level supports has also been strained during the current pandemic by the natural history of severe COVID-19 with reports of protracted ICU lengths of stay. More recent ICU series from regions with lesser COVID-19 population prevalence have reported lower ICU mortality rates of ~15 %. Whilst there is a need to measure the international burden of critical illness, there is limited understanding of the global impact and outcomes of COVID-19 infection requiring ICU admission. The objective of this systematic review and meta-analysis was to provide a contemporary and global assessment of the point estimate of mortality and risk factors for severe disease in patients admitted to an ICU with COVID-19.
Antibody Therapy VIR-7831 Enters Phase 3 for Outpatient COVID-19 Treatment
Pulmonology Advisor, October 14, 2020
The study evaluating the antibody therapy VIR-7831 (GSK4182136) for the early treatment of patients with coronavirus disease 2019 (COVID-19) has moved into phase 3, according to GlaxoSmithKline and Vir Biotechnology, Inc. By binding to an epitope on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the fully human monoclonal antibody has been shown to neutralize the virus. The investigational treatment is expected to achieve high concentrations in the lungs and was designed to have an extended half-life. The multicenter, double-blind, placebo-controlled phase 2/3 COMET-ICE study consists of 2 parts investigating VIR-7831 in non-hospitalized patients with mild to moderate COVID-19 who are at high risk of hospitalization. The first part assessed the safety and tolerability of VIR-7831 over a 14-day period. Following a positive assessment by an independent data monitoring committee, the trial will now expand globally to additional sites. The second part of the study will assess the efficacy and safety of a single intravenous infusion of VIR-7831 in approximately 1300 patients. The primary efficacy end point will be the proportion of patients who have progression of COVID-19, defined as the need for hospitalization or death within 29 days of randomization.
NIH trial will test existing drugs against COVID-19
Helio | Infectious Disease News, October 14, 2020
The National Institute of Allergy and Infectious Diseases will repurpose approved or late-stage investigational therapies and test them against COVID-19 to determine if they warrant larger trials, the NIH said. The ACTIV-5 Big Effect Trial (ACTIV-5/BET) will be conducted in partnership with NIH’s public-private partnership Accelerating COVID-19 Therapeutic Innovations and Vaccines (ACTIV) program. The phase 2 adaptive, randomized, double-blind, placebo-controlled trial will recruit adult patients hospitalized with COVID-19 in up to 40 sites across the United States. Each study group will have approximately 100 volunteers, and each testing site will investigate up to three treatments. The NIH said the trial will test two monoclonal antibodies — risankizumab (Boehringer Ingelheim, AbbVie) and lenzilumab (Humanigen) — in combination with remdesivir (Gilead Sciences), compared with control groups that will receive placebo and remdesivir. The goal of the new trial “is to identify as quickly as possible the experimental therapeutics that demonstrate the most clinical promise as COVID-19 treatments and move them into larger scale testing,” NIAID Director Anthony S. Fauci, MD, said in the release. “This study design is both an efficient way of finding those promising treatments and eliminating those that are not.”
Combination Antibody Therapy Reduces Viral Load, COVID-19 Hospitalizations
Pulmonology Advisor, October 13, 2020
New data from the BLAZE-1 clinical trial showed that treatment with 2 of Lilly’s severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies (bamlanivimab [LY-CoV555] plus etesevimab [LY-CoV016]) reduced viral load as well as symptoms, hospitalizations and emergency room (ER) visits among patients with coronavirus disease 2019 (COVID-19). An interim analysis of the phase 2 study evaluated the combination therapy in recently diagnosed patients with mild to moderate COVID-19. Patients were randomized to receive 2800mg of each antibody (n=112) or placebo (n=156). The primary end point of the study was change from baseline to day 11 in SARS-CoV-2 viral load; additional end points included the percentage of patients who experienced COVID-related hospitalization, ER visits or death from baseline through day 29. Results showed that the combination therapy significantly reduced viral load (P =.011), with most patients demonstrating near complete viral clearance by day 11. Additionally, the antibody treatment was associated with reduced viral levels at both days 3 (P =.016) and 7 (P <.001).
Update Alert 2: Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19 Annals of Internal Medicine, October 13, 2020
We have updated the protocol of our living systematic review (PROSPERO registration: CRD42020178187). This most recent search update, which was done on 11 July 2020, identified 2756 citations. Of these, we included 3 observational cohort studies of patients with coronavirus disease 2019 (COVID-19) in the updated quantitative synthesis. One of the new studies compared bilevel positive airway pressure (BiPAP) with continuous positive airway pressure (CPAP), 1 compared high-flow oxygen by nasal cannula (HFNC) with invasive mechanical ventilation (IMV), and the last compared noninvasive ventilation (NIV) with IMV. In summary, the results suggest no change in the findings of the original systematic review. Noninvasive ventilation may have similar effects to IMV on mortality, but the evidence is uncertain.
A systematic review of SARS-CoV-2 vaccine candidates
Nature, October 13, 2020
The coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to public health. SARS-CoV-2 belongs to the Betacoronavirus of the family Coronaviridae, and commonly induces respiratory symptoms, such as fever, unproductive cough, myalgia, and fatigue. To better understand the virus, numerous studies have been performed, and strategies have been established with the aim to prevent further spread of COVID-19, and to develop efficient and safe drugs and vaccines. For example, the structures of viral proteins, such as the spike protein (S protein), main protease (Mpro), and RNA-dependent RNA polymerase (RdRp), have been uncovered, providing information for the design of drugs against SARS-CoV-2. In addition, elucidating the immune responses induced by SARS-CoV-2 is accelerating the development of therapeutic approaches. In essence, diverse small molecule drugs and vaccines are being developed to treat COVID-19. According to the World Health Organization (WHO), as of September 17, 2020, 36 vaccine candidates were under clinical evaluation to treat COVID-19, and 146 candidate vaccines were in preclinical evaluation. Given that vaccines can be applied for prophylaxis and the treatment for SARS-CoV-2 infection, in this review, we introduce the recent progress of therapeutic vaccines candidates against SARS-CoV-2. Furthermore, we summarize the safety issues that researchers may be confronted with during the development of vaccines. We also describe some effective strategies to improve the vaccine safety and efficacy that were employed in the development of vaccines against other pathogenic agents, with the hope that this review will aid in the development of therapeutic methods against COVID-19.
Spontaneous pneumothorax as unusual presenting symptom of COVID-19 pneumonia: surgical management and pathological findings
Journal of Cardiothoracic Surgery, October 12, 2020
Spontaneous pneumothorax has been reported as a possible complication of novel coronavirus associated pneumonia (COVID-19). We report two cases of COVID-19 patients who developed spontaneous and recurrent pneumothorax as a presenting symptom, treated with surgical procedure. An insight on pathological finding is given. Two patients presented to our hospital with spontaneous pneumothorax associated with Sars-Cov2 infection onset. After initial conservative treatment with chest drain, both patients had a recurrence of pneumothorax during COVI-19 disease, contralateral (patient 1) or ipsilateral (patient 2) and therefore underwent lung surgery with thoracoscopy and bullectomy. Intraoperative findings of COVID-19 pneumonia were parenchymal atelectasis and vascular congestion. Lung tissue was very frail and prone to bleeding. Histological examination showed interstitial infiltration of lymphocytes and plasma cells, as seen in non specific interstitial pneumonia, together with myo-intimal thickening of vessels with blood extravasation and microthrombi.
Characteristics and Prognosis of COVID-19 in Patients with COPD
Journal of Clinical Medicine, October 12, 2020
Patients with Chronic Obstructive Pulmonary Disease (COPD) have a higher prevalence of coronary ischemia and other factors that put them at risk for COVID-19-related complications. We aimed to explore the impact of COVID-19 in a large population-based sample of patients with COPD in Castilla-La Mancha, Spain. We analyzed clinical data in electronic health records from 1 January to 10 May 2020 by using Natural Language Processing through the SAVANA Manager® clinical platform. Out of 31,633 COPD patients, 793 had a diagnosis of COVID-19. The proportion of patients with COVID-19 in the COPD population (2.51%; 95% CI 2.33–2.68) was significantly higher than in the general population aged >40 years (1.16%; 95% CI 1.14–1.18); p < 0.001. Compared with COPD-free individuals, COPD patients with COVID-19 showed significantly poorer disease prognosis, as evaluated by hospitalizations (31.1% vs. 39.8%: OR 1.57; 95% CI 1.14–1.18) and mortality (3.4% vs. 9.3%: OR 2.93; 95% CI 2.27–3.79). Patients with COPD and COVID-19 were significantly older (75 vs. 66 years), predominantly male (83% vs. 17%), smoked more frequently, and had more comorbidities than their non-COPD counterparts. Pneumonia was the most common diagnosis among COPD patients hospitalized due to COVID-19 (59%); 19% of patients showed pulmonary infiltrates suggestive of pneumonia and heart failure. Mortality in COPD patients with COVID-19 was associated with older age and prevalence of heart failure (p < 0.05). COPD patients with COVID-19 showed higher rates of hospitalization and mortality, mainly associated with pneumonia. This clinical profile is different from exacerbations caused by other respiratory viruses in the winter season.
Excess Deaths From COVID-19 and Other Causes, March-July 2020
Journal of the American Medical Association, October 12, 2020
Previous studies of excess deaths (the gap between observed and expected deaths) during the coronavirus disease 2019 (COVID-19) pandemic found that publicly reported COVID-19 deaths underestimated the full death toll, which includes documented and undocumented deaths from the virus and non–COVID-19 deaths caused by disruptions from the pandemic. A previous analysis found that COVID-19 was cited in only 65% of excess deaths in the first weeks of the pandemic (March-April 2020); deaths from non–COVID-19 causes increased sharply in 5 states with the most COVID-19 deaths. This study updates through August 1, 2020, the estimate of excess deaths and explores temporal relationships with state reopenings (lifting of coronavirus restrictions). Although total US death counts are remarkably consistent from year to year, US deaths increased by 20% during March-July 2020. COVID-19 was a documented cause of only 67% of these excess deaths. Some states had greater difficulty than others in containing community spread, causing protracted elevations in excess deaths that extended into the summer. US deaths attributed to some noninfectious causes increased during COVID-19 surges. Excess deaths attributed to causes other than COVID-19 could reflect deaths from unrecognized or undocumented infection with severe acute respiratory syndrome coronavirus 2 or deaths among uninfected patients resulting from disruptions produced by the pandemic.
Use of Ivermectin is Associated with Lower Mortality in Hospitalized Patients with COVID-19 (ICON study)
CHEST, October 12, 2020
Ivermectin was shown to inhibit SARS-CoV-2 replication in-vitro, which has led to off-label use, but clinical efficacy has not been previously described. The objective of the study was to determine if ivermectin benefits hospitalized COVID-19 patients. Charts of consecutive patients hospitalized at four Broward Health hospitals in Florida with confirmed COVID-19 between March 15 through May 11, 2020 treated with or without ivermectin were reviewed. The primary outcome was all-cause in-hospital mortality. Secondary outcomes included mortality in patients with severe pulmonary involvement, extubation rates for mechanically ventilated patients, and length of stay. Severe pulmonary involvement was defined as need for FiO2 ≥50%, noninvasive ventilation, or invasive ventilation at study entry. Logistic regression and propensity score matching were used to adjust for confounders. 280 patients, 173 treated with ivermectin and 107 without ivermectin, were reviewed. Most patients in both groups also received hydroxychloroquine and/or azithromycin. Univariate analysis showed lower mortality in the ivermectin group (15.0% versus 25.2%, OR 0.52, CI 0.29-0.96, P=0.03). Mortality was also lower among ivermectin-treated patients with severe pulmonary involvement (38.8% vs 80.7%, OR 0.15, CI 0.05-0.47, p=0.001). There were no significant differences in extubation rates (36.1% vs 15.4%, OR 3.11 (0.88-11.00), p=0.07) or length of stay. After multivariate adjustment for confounders and mortality risks, the mortality difference remained significant (OR 0.27, CI 0.09-0.80, p=0.03). 196 patients were included in the propensity-matched cohort. Mortality was significantly lower in the ivermectin group (13.3% vs 24.5%, OR 0.47, CI 0.22-0.99, p<0.05); an 11.2% (CI 0.38%-22.1%) absolute risk reduction, with a number needed to treat of 8.9 (CI 4.5-263).
Immunopathogenesis of SARS-CoV-2-induced pneumonia: lessons from influenza virus infection
Inflammation and Regeneration, October 12, 2020
Factors determining the progression of frequently mild or asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection into life-threatening pneumonia remain poorly understood. Viral and host factors involved in the development of diffuse alveolar damage have been extensively studied in influenza virus infection. Influenza is a self-limited upper respiratory tract infection that causes acute and severe systemic symptoms and its spread to the lungs is limited by CD4+ T-cell responses. A vicious cycle of CCL2- and CXCL2-mediated inflammatory monocyte and neutrophil infiltration and activation and resultant massive production of effector molecules including tumor necrosis factor (TNF)-α, nitric oxide, and TNF-related apoptosis-inducing ligand are involved in the pathogenesis of progressive tissue injury. SARS-CoV-2 directly infects alveolar epithelial cells and macrophages and induces foci of pulmonary lesions even in asymptomatic individuals. Mechanisms of tissue injury in SARS-CoV-2-induced pneumonia share some aspects with influenza virus infection, but IL-1β seems to play more important roles along with CCL2 and impaired type I interferon signaling might be associated with delayed virus clearance and disease severity. Further, data indicate that preexisting memory CD8+ T cells may play important roles in limiting viral spread in the lungs and prevent progression from mild to severe or critical pneumonia. However, it is also possible that T-cell responses are involved in alveolar interstitial inflammation and perhaps endothelial cell injury, the latter of which is characteristic of SARS-CoV-2-induced pathology.
News from virtual ERS: Novel inhaled therapies, long-term COVID-19 follow-up and more
Helio | Pulmonology, October 12, 2020
The Healio editors have compiled a list of the most-read pulmonology news from the recent virtual European Respiratory Society International Congress. Highlights from the virtual meeting including the later-life impact of childhood bronchitis, gefapixant for refractory or unexplained chronic cough and the benefit of inhaled molgramostim in autoimmune pulmonary alveolar proteinosis. Other presentations focused on persisting pulmonary impairment in COVID-19 survivors, short-course oral dexamethasone in patients with community-acquired pneumonia and asthma prescribing based on genetic differences.
Genomic evidence for reinfection with SARS-CoV-2: a case study
The Lancet, October 12, 2020
The degree of protective immunity conferred by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently unknown. As such, the possibility of reinfection with SARS-CoV-2 is not well understood. We describe an investigation of two instances of SARS-CoV-2 infection in the same individual. A 25-year-old man who was a resident of Washoe County in the US state of Nevada presented to health authorities on two occasions with symptoms of viral infection, once at a community testing event in April, 2020, and a second time to primary care then hospital at the end of May and beginning of June, 2020. Nasopharyngeal swabs were obtained from the patient at each presentation and twice during follow-up. Nucleic acid amplification testing was done to confirm SARS-CoV-2 infection. We did next-generation sequencing of SARS-CoV-2 extracted from nasopharyngeal swabs. Sequence data were assessed by two different bioinformatic methodologies. A short tandem repeat marker was used for fragment analysis to confirm that samples from both infections came from the same individual. The patient had two positive tests for SARS-CoV-2, the first on April 18, 2020, and the second on June 5, 2020, separated by two negative tests done during follow-up in May, 2020. Genomic analysis of SARS-CoV-2 showed genetically significant differences between each variant associated with each instance of infection. The second infection was symptomatically more severe than the first.
An aberrant STAT pathway is central to COVID-19
Cell Death & Differentiation, October 9, 2020
COVID-19 is caused by SARS-CoV-2 infection and characterized by diverse clinical symptoms. Type I interferon (IFN-I) production is impaired and severe cases lead to ARDS and widespread coagulopathy. We propose that COVID-19 pathophysiology is initiated by SARS-CoV-2 gene products, the NSP1 and ORF6 proteins, leading to a catastrophic cascade of failures. These viral components induce signal transducer and activator of transcription 1 (STAT1) dysfunction and compensatory hyperactivation of STAT3. In SARS-CoV-2-infected cells, a positive feedback loop established between STAT3 and plasminogen activator inhibitor-1 (PAI-1) may lead to an escalating cycle of activation in common with the interdependent signaling networks affected in COVID-19. Specifically, PAI-1 upregulation leads to coagulopathy characterized by intravascular thrombi. Overproduced PAI-1 binds to TLR4 on macrophages, inducing the secretion of proinflammatory cytokines and chemokines. The recruitment and subsequent activation of innate immune cells within an infected lung drives the destruction of lung architecture, which leads to the infection of regional endothelial cells and produces a hypoxic environment that further stimulates PAI-1 production. Acute lung injury also activates EGFR and leads to the phosphorylation of STAT3. COVID-19 patients’ autopsies frequently exhibit diffuse alveolar damage (DAD) and increased hyaluronan (HA) production which also leads to higher levels of PAI-1. COVID-19 risk factors are consistent with this scenario, as PAI-1 levels are increased in hypertension, obesity, diabetes, cardiovascular diseases, and old age. We discuss the possibility of using various approved drugs, or drugs currently in clinical development, to treat COVID-19. This perspective suggests to enhance STAT1 activity and/or inhibit STAT3 functions for COVID-19 treatment. This might derail the escalating STAT3/PAI-1 cycle central to COVID-19.
Development and evaluation of an artificial intelligence system for COVID-19 diagnosis
Nature Communications, October 9, 2020
Early detection of COVID-19 based on chest CT enables timely treatment of patients and helps control the spread of the disease. We proposed an artificial intelligence (AI) system for rapid COVID-19 detection and performed extensive statistical analysis of CTs of COVID-19 based on the AI system. We developed and evaluated our system on a large dataset with more than 10 thousand CT volumes from COVID-19, influenza-A/B, non-viral community acquired pneumonia (CAP) and non-pneumonia subjects. In such a difficult multi-class diagnosis task, our deep convolutional neural network-based system is able to achieve an area under the receiver operating characteristic curve (AUC) of 97.81% for multi-way classification on test cohort of 3,199 scans, AUC of 92.99% and 93.25% on two publicly available datasets, CC-CCII and MosMedData respectively. In a reader study involving five radiologists, the AI system outperforms all of radiologists in more challenging tasks at a speed of two orders of magnitude above them. Diagnosis performance of chest x-ray (CXR) is compared to that of CT. Detailed interpretation of deep network is also performed to relate system outputs with CT presentations.
ILD a risk factor for poor outcomes from COVID-19
Helio | Pulmonology, October 9, 2020
Older adults with interstitial lung disease and COVID-19 have increased risk for severe disease, hospitalization and death, researchers reported in the American Journal of Respiratory and Critical Care Medicine. “In this case-control study, patients with ILD who contracted COVID-19 had a greater than fourfold increased adjusted odds of death, were more likely to be hospitalized and require ICU level of care, and were less likely to be discharged, particularly to home, compared to a matched cohort of COVID-19 patients without ILD,” Anthony J. Esposito, MD, research fellow in the department of medicine in the division of pulmonary and critical care medicine at Brigham and Women’s Hospital, and colleagues wrote. “Accordingly, this study suggests that comorbid ILD is a risk factor for poor outcomes from COVID-19.” The multicenter, case-control study included 46 adults with pre-existing ILD and a COVID-19 diagnosis from March to June at six Mass General Brigham hospitals. For comparison, the researchers also analyzed a control cohort of 92 patients with COVID-19 without ILD. Patients with ILD and COVID-19 were more likely to be admitted to the hospital and require ICU care than those without COVID-19, and were less likely to be discharged from the hospital.
Improving Prone Positioning for Severe ARDS during the COVID-19 Pandemic: An Implementation Mapping Approach
Annals of the American Thoracic Society, October 9, 2020
Prone positioning reduces mortality in patients with severe acute respiratory distress syndrome (ARDS), a feature of severe COVID-19. Despite this, most patients with ARDS do not receive this life-saving therapy. The objective of the study was to identify determinants of prone positioning utilization, to develop specific implementation strategies, and to incorporate strategies into an overarching response to the COVID-19 crisis. We used an implementation mapping approach guided by implementation science frameworks. We conducted semi-structured interviews with 30 ICU clinicians who staffed 12 ICUs within the Penn Medicine health system and the University of Michigan Medical Center. We performed thematic analysis utilizing the Consolidated Framework for Implementation Research (CFIR). We then conducted three focus groups with a task force of ICU leaders to develop an implementation menu, using the Expert Recommendations for Implementing Change (ERIC) framework. The task force developed five specific implementation strategies: educational outreach, learning collaborative, clinical protocol, prone positioning team, and automated alerting, elements of which were rapidly implemented at Penn Medicine.
Safety and Efficacy of Bronchoscopy in Critically Ill Patients with COVID-19
CHEST, October 8, 2020
Coronavirus disease 2019 (COVID-19) can progress to severe respiratory failure requiring intubation and mechanical ventilation, with a grim prognosis in this subset of patients. Despite the perceived increased risk from aerosol-generating procedures, data from prior severe acute respiratory syndrome suggests no increased transmission from bronchoscopy. There is a paucity of data regarding the actual risk and benefit of bronchoscopy for patients with COVID-19, leading to uncertainty regarding recommendations. The hypothesis of this report is that bronchoscopy with intermittent apnea is safe for both patients and healthcare providers. This study reports our experience with therapeutic bronchoscopy in patients with severe COVID-19. This is a retrospective analysis of all patients admitted to the New York University Langone Health (NYULH) Manhattan campus between March 13th-April 24th, 2020 with COVID19 and respiratory failure requiring mechanical ventilation that underwent bronchoscopy. COVID-19 was diagnosed by nasal pharyngeal swab for reverse transcriptase polymerase chain reaction (rtPCR) assays. Indications were concern for superimposed pneumonia, thick secretions with decreasing tidal volumes, evidence of endotracheal tube obstruction not resolved by suctioning, or significant bloody secretions. The NYULH institutional review board approved this human subjects study.
CDC: Multisystem Inflammatory Syndrome Reported in Adults With SARS-CoV-2
Pulmonology Advisor, October 8, 2020
Adult patients with current or previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can develop a hyperinflammatory syndrome, which resembles multisystem inflammatory syndrome in children (MIS-C), according to a case series published in the Oct. 2 early-release issue of the U.S. Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report. Sapna Bamrah Morris, M.D., from the CDC COVID-19 Response Team, and colleagues present reports of 27 patients with cardiovascular, gastrointestinal, dermatologic, and neurologic symptoms without severe respiratory illness who concurrently received positive test results for SARS-CoV-2. The researchers highlight recognition of multisystem inflammatory syndrome in adults (MIS-A), which resembles MIS-C. The patients described had minimal respiratory symptoms, hypoxemia, or radiographic abnormalities. In case reports describing MIS-A, only eight of 16 patients had any documented respiratory symptoms before onset of MIS-A. All 16 patients had evidence of cardiac effects, 13 had gastrointestinal symptoms on admission, and five had dermatologic manifestations. Ten of the patients had pulmonary ground-glass opacities, and six had pleural effusions on chest imaging, despite minimal respiratory symptoms.
Elective Intubation Not a COVID Risk?
MedPage Today, October 8, 2020
Intubation and extubation didn’t generate as much risky aerosol as expected, a real-world operating room study showed. A second study suggested that bedside tracheotomy was pretty safe, too. Aerosol recordings performed under the operating theater “clean zone” canopy at the typical distance between practitioner and patient’s mouth during the intubation sequence turned up an average of 7 and maximum 77 particles per liter of air over a 5-min period during anesthesia induction and intubation. That was higher than the background of 2 particles/L per 5 minutes in the empty operating theater but far lower than the average 732 particles by the same measure created by a voluntary cough (P<0.0001), reported Anthony Pickering, MBChB, PhD, of the University of Bristol in England, and colleagues. The results were virtually the same with the ultraclean ventilation system flow turned off as when it was on, they wrote in Anaesthesia. None of the patients had COVID-19, and the particle concentration was only a “plausible but unproven surrogate” for infection risk, the researchers cautioned. “When considering the risk of transmission of SARS-CoV-2, it is helpful to reflect on the definition of an aerosol-generating procedure that has been expressly stated as ‘aerosol generating procedures are considered to have a greater likelihood of producing aerosols compared to coughing,'” the group wrote.
Two distinct immunopathological profiles in autopsy lungs of COVID-19
Nature Communications, October 8, 2020
Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. Immune mediated damage has been proposed as a pathogenic factor, but immune responses in lungs of COVID-19 patients remain poorly characterized. Here we show transcriptomic, histologic and cellular profiles of post mortem COVID-19 (n = 34 tissues from 16 patients) and normal lung tissues (n = 9 tissues from 6 patients). Two distinct immunopathological reaction patterns of lethal COVID-19 are identified. One pattern shows high local expression of interferon stimulated genes (ISGhigh) and cytokines, high viral loads and limited pulmonary damage, the other pattern shows severely damaged lungs, low ISGs (ISGlow), low viral loads and abundant infiltrating activated CD8+ T cells and macrophages. ISGhigh patients die significantly earlier after hospitalization than ISGlow patients. Our study may point to distinct stages of progression of COVID-19 lung disease and highlights the need for peripheral blood biomarkers that inform about patient lung status and guide treatment.
Remdesivir Distribution Transitioned to Gilead Under Revised EUA
Pulmonology Advisor, October 7, 2020
The Food and Drug Administration (FDA) has revised the Emergency Use Authorization (EUA) for remdesivir (Veklury; Gilead Sciences) removing the US government’s role in directing the allocation of the investigational coronavirus disease 2019 (COVID-19) treatment. Remdesivir is a nucleotide analogue with broad-spectrum antiviral activity. It is currently available in the US under an EUA for hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19, regardless of disease severity. Since the COVID-19 pandemic began, the US Department of Health and Human Services (HHS) was responsible for the allocation and distribution of remdesivir to COVID-19 patients. By increasing manufacturing capacity, Gilead has been able to expand the supply of remdesivir, which now exceeds market demand based on recent allocation numbers from HHS’ Office of the Assistant Secretary for Preparedness and Response. Under the revised EUA, Gilead Sciences will resume control of the distribution of remdesivir in the US. To ensure stable management of drug supply, AmerisourceBergen will remain the sole US distributor of the product through the end of this year and will sell directly to hospitals. The Company is now able to meet real-time demand for remdesivir and potential future surges of COVID-19.
COVID-19 Infection versus Influenza (Flu) and Other Respiratory Illnesses
American Journal of Respiratory and Critical Care Medicine, October 6, 2020
Consider providing this patient education information series, which explains that SARS-CoV-2 is the virus that causes the COVID-19 infection. It further identifies for patients that they can be ill with more than one virus at the same time. As the SARS-CoV-2 virus pandemic continues, influenza and other respiratory infections will also emerge in the community. Respiratory infections may present with similar symptoms and all can spread from person to person. It is hard to tell which virus or bacteria is causing a person’s illness based on symptoms alone. At times testing is needed to see which virus(es) or bacteria are present. These tests usually involve getting a nose and/or throat swab sample, as most of these viruses are present in large amounts in the back of the nose and throat. There is still a lot to learn about the COVID-19 infection and research is ongoing.
Lung Histopathology in COVID-19 as Compared to SARS and H1N1 Influenza: A Systematic Review
CHEST, October 6, 2020
Patients with severe Coronavirus Disease 2019 (COVID-19) have respiratory failure with hypoxemia and acute bilateral pulmonary infiltrates, consistent with acute respiratory distress syndrome (ARDS). It has been suggested that respiratory failure in COVID-19 represents a novel pathologic entity. So, how does the lung histopathology described in COVID-19 compare to the lung histopathology described in SARS and H1N1 influenza? We conducted a systematic review to characterize the lung histopathologic features of COVID-19 and compare them against findings of other recent viral pandemics, H1N1 influenza and SARS. We systematically searched MEDLINE and PubMed for studies published up to June 24, 2020 using search terms for COVID-19, H1N1 influenza and SARS with keywords for pathology, biopsy, and autopsy. Using PRISMA-IPD guidelines, our systematic review analysis included 26 articles representing 171 COVID-19 patients; 20 articles representing 287 H1N1 patients; and eight articles representing 64 SARS patients. In COVID-19, acute phase diffuse alveolar damage (DAD) was reported in 88% of patients, which was similar to the proportion of cases with DAD in both H1N1 (90%) and SARS (98%). Pulmonary microthrombi were reported in 57% of COVID-19 and 58% of SARS patients, as compared to 24% of H1N1 influenza patients.
Deep phenotyping of 34,128 adult patients hospitalised with COVID-19 in an international network study
Nature Communications, October 6, 2020
Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 shares similarities with influenza to the extent that both cause respiratory disease which can vary markedly in its severity and present with a similar constellation of symptoms, including fever, cough, myalgia, malaise, fatigue and dyspnoea. Early reports do, however, indicate that the proportion of severe infections and mortality rate is higher for COVID-19. Older age and a range of underlying health conditions, such as immune deficiency, cardiovascular disease, chronic lung disease, neuromuscular disease, neurological disease, chronic renal disease and metabolic diseases, have been associated with an increased risk of severe influenza and associated mortality. Here we first aimed to describe the characteristics of patients hospitalised with COVID-19. In particular, we set out to summarise individuals’ demographics, medical conditions, and medication use.
Systemic Complement Activation Associated With Respiratory Failure in COVID-19
Pulmonology Advisor, October 5, 2020
Systemic complement activation is associated with respiratory failure in patients with coronavirus disease 2019 (COVID-19), according to the results of a recent study published in the journal PNAS. According to the researchers, the complement system plays a key role in the innate immune response, and has been previously associated with respiratory failure, acute respiratory distress syndrome development, and severity in bacterial and viral pneumonia. Therefore, the investigators sought to identify the degree and specific time point of systemic complement activation in COVID-19, particularly as the activation relates to the clinical course of disease. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data from were abstracted from electronic medical records from patients hospitalized with COVID-19. Blood samples were obtained at hospital admission (within 48 hours), at days 3 to 5, and days 7 to 10. Patients were divided according to the presence of respiratory failure, and associations for outcomes were examined between the 2 groups. Of the 39 patients who were positive for SARS-CoV-2 included in the study, respiratory failure was either prominent at admission or developed while hospitalized in 23 patients. Baseline characteristics revealed significant differences in myalgia, fatigue, arterial oxygen partial pressure /fractional inspired oxygen ratio, need for oxygen therapy, and Sequential Organ Failure Assessment (SOFA) score between patients with and without respiratory failure.
Mist begins to clear for lung delivery of RNA
Nature Biotechnology, October 5, 2020
In August, Vir Biotechnology and Alnylam Pharmaceuticals announced that lung-targeted small interfering RNA (siRNA) conjugates against SARS-CoV-2 and other coronaviruses delivered to the lung are scheduled for preclinical studies by the end of the year. The collaboration inked in March involves Alnylam, the RNA interference (RNAi) pioneer, providing Vir with over 350 siRNAs targeting all available SARS-CoV-1 and SARS-CoV-2 genomes. Vir has been screening these molecules in vitro for potent lead siRNA candidates; if any are taken forward, Alnylam retains a 50–50 option for participation. Around the same time, Translate Bio closed a licensing deal with French pharmaceutical giant Sanofi Pasteur for use of its mRNA platform to develop vaccines for infectious diseases. Under the partnership, the mRNA vaccines will be delivered by intramuscular injection and are not targeted to specific organs or tissues. But the multibillion-dollar deal highlights the potential of Translate Bio’s expertise in mRNA delivery. That includes a tissue-specific mRNA delivery platform that the company is using to target the lung in cystic fibrosis and idiopathic pulmonary fibrosis. RNA delivery into the lungs, if successful, would be a boon for drug and vaccine makers. Other advances in lipid nanoparticle (LNP) formulations, inhalation devices, carrier particles and customized chemical modifications are making strides toward the goal of delivering RNA candidates — including mRNA, antisense RNA and siRNA — into the lung. Success could open treatment doors for lung disorders in COVID-19 and beyond.
Long-term Health Consequences of COVID-19
Journal of the American Medical Association, October 5, 2020
With more than 30 million documented infections and 1 million deaths worldwide, the coronavirus disease 2019 (COVID-19) pandemic continues unabated. The clinical spectrum of severe acute respiratory syndrome coronavirus (SARS-CoV) 2 infection ranges from asymptomatic infection to life-threatening and fatal disease. Current estimates are that approximately 20 million people globally have “recovered”; however, clinicians are observing and reading reports of patients with persistent severe symptoms and even substantial end-organ dysfunction after SARS-CoV-2 infection. Because COVID-19 is a new disease, much about the clinical course remains uncertain—in particular, the possible long-term health consequences, if any. Currently, there is no consensus definition of postacute COVID-19. Based on the COVID Symptom Study, in which more than 4 million people in the US, UK and Sweden have entered their symptoms after a COVID-19 diagnosis, postacute COVID-19 is defined as the presence of symptoms extending beyond 3 weeks from the initial onset of symptoms and chronic COVID-19 as extending beyond 12 weeks. It is possible that individuals with symptoms were more likely to participate in this study than those without them. In a study of 55 patients with COVID-19, at 3 months after discharge, 35 (64%) had persistent symptoms and 39 (71%) had radiologic abnormalities consistent with pulmonary dysfunction such as interstitial thickening and evidence of fibrosis. Three months after discharge, 25% of patients had decreased diffusion capacity for carbon monoxide. In another study of 57 patients, abnormalities in pulmonary function test results obtained 30 days after discharge, including decreased diffusion capacity for carbon monoxide and diminished respiratory muscle strength, were common and occurred in 30 patients (53%) and 28 patients (49%), respectively.
COVID-19 pneumonia: high diagnostic accuracy of chest CT in patients with intermediate clinical probability
European Radiology, October 3, 2020
If a definite diagnosis of COVID-19 infection requires real-time reverse transcription polymerase chain reaction (RT-PCR) of viral nucleic acids, chest CT scan has proved to be of clinical importance and the main tool for screening. The Fleischner Society recently validated the use of imaging in patients suspected of having COVID-19 presenting with mild clinical features and at risk for disease progression, and as a help for medical triage of patients suspected of having COVID-19 in a resource-constrained environment, in case of moderate-to-severe clinical features and high pre-test probability of disease. A recent meta-analysis by Kim et al showed that the diagnostic value of chest CT depends on the prevalence of COVID-19 infection in the studied population. In areas where the prevalence is low, chest CT screening of patients with suspected disease has a low positive predictive value. On the other hand, in the case of epidemic surge of patients at the emergency department, the clinicians will face a difficult challenge of rapid triage depending on disease presentation and severity. Patients with typical clinical symptoms and bilateral radiographic opacities may be hospitalized without a diagnostic CT scan. The patients for whom the diagnosis is unclear represent the group with intermediate probability and may benefit from a chest CT scan, looking for evidence of COVID versus other pathologies. The objective of this study was to evaluate the inter-observer agreement and diagnostic accuracy including positive and negative predictive values of chest CT to identify COVID-19 pneumonia in patients with intermediate clinical probability during an acute disease outbreak in a European country.
Outcome of Hospitalization for COVID-19 in Patients with Interstitial Lung Disease: An International Multicenter Study
American Journal of Respiratory and Critical Care Medicine, October 2, 2020
The impact of COVID-19 on patients with Interstitial Lung Disease (ILD) has not been established. The objective was to assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age, sex and comorbidity matched population. An international multicenter audit of patients with a prior diagnosis of ILD admitted to hospital with COVID-19 between 1 March and 1 May 2020 was undertaken and compared with patients, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished IPF from non-IPF ILD and used lung function to determine the greatest risks of death. Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity-score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching ILD patients with COVID-19 had higher mortality (HR 1.60, Confidence Intervals 1.17-2.18 p=0.003) compared with age, sex and co-morbidity matched controls without ILD. Patients with a FVC of <80% had an increased risk of death versus patients with FVC ≥80% (HR 1.72, 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR 2.27, 1.39−3.71). Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD.
Rehabilitation Trends in Patients With COVID-19 Requiring Invasive Ventilation
Pulmonology Advisor, October 2, 2020
In patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU) with a high acuity of illness and a prolonged period of mechanical ventilation, the time to commencement of rehabilitation was often delayed because of the severity of an individual’s condition. Researchers conducted a single-center, prospective, noninterventional, observational study in patients with a COVID-19 diagnosis admitted to the ICU at the Queen Elizabeth Hospital Birmingham (QEHB) in Birmingham, United Kingdom. Results of the analysis were published in the Annals of the American Thoracic Society. Investigators sought to describe the clinical status, demographics, level of rehabilitation, and mobility status at ICU discharge in individuals with COVID-19. Adult patients were enrolled who had been admitted to the ICU at QEHB from March through April 2020 with a confirmed diagnosis of COVID-19 and had received mechanical ventilation for more than 24 hours. The rehabilitation status of all participants was measured daily with use of the Manchester Mobility Score (MMS) to identify the time taken to first mobilize (defined as an MMS of ≥2, ie, sitting on the edge of the bed or higher) and the location of hospital discharge, as 1 of the following categories: home with no rehabilitation; home with rehabilitation; or inpatient rehabilitation facility. A total of 177 patients were identified, with 110 of them surviving to ICU discharge and thus included in the analysis. The mean participant age of those who survived to ICU discharge was 53±12 years. Overall, 75% of the participants were men; the majority of the patients were of White (48%) or Asian (35%) ethnicity. In the patient cohort, 87% were classified as overweight or obese (body mass index [BMI], 25).
NNU report: 1,700+ HCWs died from COVID-19 in US
Helio | Primary Care, October 2, 2020
As of Sept. 16, there have been 1,718 deaths from COVID-19 and related complications among health care workers in the U.S., significantly more than the 690 deaths reported by the CDC, according to a report released by National Nurses United. “Nurses and health care workers were forced to work without personal protective equipment they needed to do their job safely,” Zenei Cortez, RN, a president of National Nurses United, said in a press release. “It is immoral and unconscionable that they lost their lives.” The report follows survey results released by the American Nurses Association last month, which found that many nurses across the United States were still facing PPE shortages, with many reusing essential N-95 masks for 5 days or longer. Researchers collected information on registered nurses and other health care workers using media reports, obituaries, union memorial pages, GoFundMe and social media platforms, including Facebook, Twitter and Reddit. They assessed deaths from COVID-19 and related complications among health care workers, which they defined as all workers in care settings, including nursing homes, hospitals, medical practices, congregate-living and home health care settings. They found that among the 1,718 health care worker deaths attributed to COVID-19-related illness, 213 deaths occurred among registered nurses.
Global Death Toll From COVID-19 Passes 1 Million
Pulmonology Advisor, October 2, 2020
The global COVID-19 pandemic reached a grim new milestone on Tuesday: 1 million dead. Americans made up more than 200,000 of those deaths, or one in every five, according to a running tally compiled by Johns Hopkins University. “It’s not just a number. It’s human beings. It’s people we love,” Howard Markel, M.D., a professor of medical history at the University of Michigan, told the Associated Press. He is an adviser to government officials on how best to handle the pandemic – and he lost his 84-year-old mother to COVID-19 in February. “It’s people we know,” Markel said. “And if you don’t have that human factor right in your face, it’s very easy to make it abstract.” It has taken the newly emerged severe acute respiratory syndrome coronavirus 2 virus just eight months to reach a worldwide death toll that has meant personal and economic tragedy for billions. Right now, more than 33 million people worldwide are known to have been infected with the new coronavirus, the Hopkins tally showed.
Effect of Face Masks on Gas Exchange in Healthy Persons and Patients with COPD
Annals of American Thoracic Society, October 2, 2020
Current evidence, from observational studies to systematic reviews and epidemiologic modeling, supports the use of masks by the public, especially surgical masks, on mitigating COVID-19 transmission and deaths. However, public mask use has been heavily politicized with inconsistent recommendations by authorities leading to divided public opinion. Despite evidence to the contrary, an online UK/US survey found that only 29.7-37.8% of participants thought that wearing a surgical mask was “highly effective” in protecting them from acquiring COVID-19. To evaluate whether gas exchange abnormalities occur with the use of surgical masks in subjects with and without lung function impairment. Methods and Findings In order to demonstrate the changes in end-tidal CO2 (ETCO2) and oxygen saturation (SpO2) before and after wearing a surgical mask, we used a convenience sample of 15 housestaff physicians without lung conditions (aged 31.1 1.9 years, 60% male) and 15 veterans with severe COPD (aged 71.6 8.7 years, FEV1 44.0 22.2%, 100% male). The patients needed to have a post-bronchodilator FEV1 <50% and FEV1/FVC <0.7 and were enrolled from the pulmonary function laboratory during a scheduled 6-minute walk test ordered to assess the need for supplemental oxygen. Due to the COVID-19 pandemic, the 6-minute walk tests are done with subjects using a surgical mask. Baseline measures on room air without a mask were performed non-invasively using a Life Sense monitor, followed by continuous monitoring using a surgical mask. At 5 and 30 minutes, no major changes in ETCO2 or SpO2 of clinical significance were noted at any time point in either group at rest. With the 6-minute walk, subjects with severe COPD decreased oxygenation as expected (with 2 qualifying for supplemental oxygen).
Nomogram to identify severe coronavirus disease 2019 (COVID-19) based on initial clinical and CT characteristics: a multi-center study
BMC Medical Imaging, October 2, 2020
The objective of the study was to develop and validate a nomogram for early identification of severe coronavirus disease 2019 (COVID-19) based on initial clinical and CT characteristics. The initial clinical and CT imaging data of 217 patients with COVID-19 were analyzed retrospectively from January to March 2020. Two hundred seventeen patients with 146 mild cases and 71 severe cases were randomly divided into training and validation cohorts. Independent risk factors were selected to construct the nomogram for predicting severe COVID-19. Nomogram performance in terms of discrimination and calibration ability was evaluated using the AUC, calibration curve, decision curve, clinical impact curve and risk chart. In the training cohort, the severity score of lung in the severe group (7, interquartile range [IQR]:5–9) was significantly higher than that of the mild group (4, IQR, 2–5) (P < 0.001). Age, density, mosaic perfusion sign and severity score of lung were independent risk factors for severe COVID-19. The nomogram had a AUC of 0.929 (95% CI, 0.889–0.969), sensitivity of 84.0% and specificity of 86.3%, in the training cohort, and a AUC of 0.936 (95% CI, 0.867–1.000), sensitivity of 90.5% and specificity of 88.6% in the validation cohort. The calibration curve, decision curve, clinical impact curve and risk chart showed that nomogram had high accuracy and superior net benefit in predicting severe COVID-19.
Analysis of the clinical characteristics of 77 COVID-19 deaths
Scientific Reports, October 2, 2020
The COVID-19 outbreak is becoming a public health emergency. Data are limited on the clinical characteristics and causes of death. A retrospective analysis of COVID-19 deaths were performed for patients’ clinical characteristics, laboratory results, and causes of death. In total, 56 patients (72.7%) of the decedents (male–female ratio 51:26, mean age 71 ± 13, mean survival time 17.4 ± 8.4 days) had comorbidities. Acute respiratory failure (ARF) and sepsis were the main causes of death. Increases in C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer and lactic acid and decreases in lymphocytes were common laboratory results. Intergroup analysis showed that (1) most female decedents had cough and diabetes. (2) The proportion of young- and middle-aged deaths was higher than elderly deaths for males, while elderly decedents were more prone to myocardial injury and elevated CRP. (3) CRP and LDH increased and cluster of differentiation (CD) 4+ and CD8+ cells decreased significantly in patients with hypertension. The majority of COVID-19 decedents are male, especially elderly people with comorbidities. The main causes of death are ARF and sepsis. Most female decedents have cough and diabetes. Myocardial injury is common in elderly decedents. Patients with hypertension are prone to an increased inflammatory index, tissue hypoxia and cellular immune injury.
Subcutaneous injection of IFN alpha-2b for COVID-19: an observational study
BMC Infectious Diseases, October 2, 2020
The global pandemic of coronavirus disease 2019 (COVID-19) infection is ongoing and associated with high mortality. The aim of this study was to investigate the efficacy and safety of subcutaneous injection of interferon alpha-2b (IFN alpha-2b) combined with lopinavir/ritonavir (LPV/r) in the treatment of COVID-19 infection, compared with that of using LPV/r alone. The study included patients diagnosed with laboratory-confirmed COVID-19 infection in Wuhan Red Cross hospital during the period from January 23, 2020 to March 19, 2020. The length of stay, the time to viral clearance and adverse reactions during hospitalization were compared between patients using oral LPV/r and combined therapy of LPV/r and subcutaneous injection of IFN alpha-2b. A total of 22 patients were treated with LPV/r alone and 19 with combined therapy with subcutaneous injection of IFN alpha-2b. The average length of hospitalization in the combination group was shorter than that of LPV/r group (16 ± 9.7 vs 23 ± 10.5 days; P = 0.028). Moreover, the days of hospitalization in early intervention group decreased from 25 ± 8.5 days to 10 ± 2.9 days compared with delayed intervention group (P = 0.001). Combined therapy with IFN alpha-2b also significantly reduced the duration of detectable virus in the upper respiratory tract.
President and First Lady Test Positive for COVID-19
MedPage Today, October 2, 2020
In the dark of night, in a tweet retweeted over 600,000 times in the first three hours in which it posted, Trump announced both he and first lady Melania Trump have tested positive for COVID-19, the disease he has publicly downplayed since the start of the pandemic and which has now killed over 207,000 people in the U.S. “@FLOTUS and I tested positive for COVID-19. We will begin our quarantine and recovery process immediately. We will get through this TOGETHER!” he tweeted. The potential ramifications to this are many: At the very least, Trump will be required to temporarily halt his campaign while he quarantines, and will miss the next presidential debate, planned for October 15. Longer term, should the President exhibit symptoms, under the 25th Amendment he would have the option to transfer power to Vice President Mike Pence while he recovers.
The Structural and Social Determinants of the Racial/Ethnic Disparities in the U.S. COVID-19 Pandemic. What’s Our Role?
American Journal of Respiratory and Critical Care Medicine, October 1, 2020
The coronavirus disease (COVID-19) pandemic has crippled the United States, halting normal social and economic activities and overstretching the health system. As of June 12, 2020, the United States had over 2 million cases and 113,900 deaths. For historically disadvantaged populations, who experience fractured access to health care under standard conditions and who are more dependent on low-wage or hourly paid employment, the pandemic has had a disproportionate impact. Reports from state and city health departments have illuminated what many already knew: Black, Latinx, and Native Americans test positive for and die of COVID-19 at higher proportion than other racial and ethnic groups. In part as a consequence of the increased prevalence of COVID-19 in minority populations, the mortality rates among Black, Latinx, and Native Americans far exceeds the proportion of the population that these groups represent. As health-disparity researchers and educators and critical care and pulmonary providers on the front line caring for these patients, we believe it is imperative to report on the root causes that have led to these sobering statistics. Applying the World Health Organization Conceptual Framework for Action on Social Determinants of Health, we also identify potential avenues for policy action. This framework differentiates how the socioeconomic and political contexts manifest broadly as structural determinants, which shape exposure to intermediary social determinants, including healthcare access, that ultimately create an individual’s unique social circumstances that shape behavior and risk for disease. For this Perspective, we focus on action steps that we, as members of the American Thoracic Society (ATS), should take to actively change the status quo and influence policies that address root causes.
Comparison of inspiratory and expiratory lung and lobe volumes among supine, standing, and sitting positions using conventional and upright CT
Scientific Reports, October 1, 2020
Currently, no clinical studies have compared the inspiratory and expiratory volumes of unilateral lung or of each lobe among supine, standing, and sitting positions. In this prospective study, 100 asymptomatic volunteers underwent both low-radiation-dose conventional (supine position, with arms raised) and upright computed tomography (CT) (standing and sitting positions, with arms down) during inspiration and expiration breath-holds and pulmonary function test (PFT) on the same day. We compared the inspiratory/expiratory lung/lobe volumes on CT in the three positions. The inspiratory and expiratory bilateral upper and lower lobe and lung volumes were significantly higher in the standing/sitting positions than in the supine position (5.3–14.7% increases, all P < 0.001). However, the inspiratory right middle lobe volume remained similar in the three positions (all P > 0.15); the expiratory right middle lobe volume was significantly lower in the standing/sitting positions (16.3/14.1% decrease) than in the supine position (both P < 0.0001). The Pearson’s correlation coefficients (r) used to compare the total lung volumes on inspiratory CT in the supine/standing/sitting positions and the total lung capacity on PFT were 0.83/0.93/0.95, respectively. The r values comparing the total lung volumes on expiratory CT in the supine/standing/sitting positions and the functional residual capacity on PFT were 0.83/0.85/0.82, respectively. The r values comparing the total lung volume changes from expiration to inspiration on CT in the supine/standing/sitting positions and the inspiratory capacity on PFT were 0.53/0.62/0.65, respectively.
Management of the patient with allergic and immunological disorders in the pandemic COVID-19 era
Clinical and Molecular Allergy, October 1, 2020
The pandemic COVID-19 abruptly exploded, taking most health professionals around the world unprepared. Italy, the first European country to be hit violently, was forced to activate the lockdown in mid-February 2020. At the time of the spread, a high number of victims were quickly registered, especially in the regions of Northern Italy which have a high rate of highly-polluting production activities. The need to hospitalize the large number of patients with severe forms of COVID-19 led the National Health System to move a large number of specialists from their disciplines to the emergency hospital departments for the treatment of COVID-19. Furthermore, the lockdown itself has limited the possibility for general practitioners and pediatricians to be able to make outpatient visits and/or home care for patients with chronic diseases. Among them, the patient with atopic diseases, such as asthma, rhinitis and atopic dermatitis, is worthy of particular attention as she/he is immersed in a studded negative scenario with the onset of spring, a factor that should not be underestimated for those who suffer from pollen allergy. The Italian Society of Asthma Allergology and Clinical Immunology, to quickly deal with the lack of references and specialist medical procedures, has produced a series of indications for immunologic patient care that are reported in this paper, and can be used as guidelines by specialists of our discipline.
Positive Bubble Study in Severe COVID-19 Indicates the Development of Anatomical Intra-pulmonary Shunts in Response to Microvascular Occlusion
American Journal of Respiratory and Critical Care Medicine, September 30, 2020
We read with interest the recent article by Reynolds et al(1) describing the transcranial doppler bubble study findings in COVID-19 patients with ARDS. The authors conclude that pulmonary vascular dilatation may be present in COVID-19, analogous to the microvascular changes that occur in hepatopulmonary syndrome (HPS), as a contributory mechanism of hypoxemia in COVID-19 ARDS. Though the findings on bubble study are indisputable, we share several concerns with the conclusions in the article. The positive shunt study in severe COVID-19 indicates that abnormal arteriovenous communications open up in response to extensive small vessel occlusion, as the disease progresses. The findings fail to explain the initial severe hypoxemia in COVID-19 with preserved lung mechanics, as the degree of transpulmonary microbubble transit directly correlates with worsening lung compliance. The comparison with HPS is not appropriate due to the evidence against microcirculatory dilatation in COVID-19. To conclude, anatomical pulmonary shunts do not contribute significantly to hypoxemia in early atypical COVID-19 respiratory failure and the distinct clinical features are best explained by progressive pulmonary vascular occlusion and subsequent diffuse lung injury due to various natural (infarction and oxidative damage) and iatrogenic sequelae.
Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers – A Randomized Clinical Trial
JAMA Internal Medicine, September 30, 2020
Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our knowledge, there is no effective pharmacologic prophylaxis for individuals at risk. The objective of the study was to evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy. This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants.
Computer model unravels mystery behind severe inflammation in people with COVID-19
News Medical, September 29, 2020
A study from the University of Pittsburgh School of Medicine and Cedars-Sinai addresses a mystery first raised in March: Why do some people with COVID-19 develop severe inflammation? The research shows how the molecular structure and sequence of the SARS-CoV-2 spike protein–part of the virus that causes COVID-19–could be behind the inflammatory syndrome cropping up in infected patients. The study, published this week in the Proceedings of the National Academy of Sciences, uses computational modeling to zero in on a part of the SARS-CoV-2 spike protein that may act as a “superantigen,” kicking the immune system into overdrive as in toxic shock syndrome–a rare, life-threatening complication of bacterial infections. Symptoms of a newly identified condition in pediatric COVID-19 patients, known as Multisystem Inflammatory Syndrome in Children (MIS-C), include persistent fever and severe inflammation that can affect a host of bodily systems. While rare, the syndrome can be serious or even fatal. The first reports of this condition coming out of Europe caught the attention of study co-senior author Moshe Arditi, M.D., director of the Pediatric Infectious Diseases and Immunology Division at Cedars-Sinai and an expert on another pediatric inflammatory disease–Kawasaki disease. The investigator’s labs are now using the ideas generated by this study to search for and test antibodies specific to the SARS-CoV-2 superantigen, with the goal of developing therapies that specifically address MIS-C and cytokine storm in COVID-19 patients.
Pulmonary Artery Thrombi Located in Opacitated Lung Segments in COVID-19
Pulmonology Advisor, September 28, 2020
In patients hospitalized with coronavirus disease 2019 (COVID-19), thrombi in segmental pulmonary arteries are common and are located in opacitated lung segments, which may suggest local clot formation, according to the results of a retrospective study published in Respiratory Medicine. Respiratory failure is a common complication in hospitalized patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is frequently complicated by pulmonary embolism in segmental pulmonary arteries. The distribution of pulmonary embolism with regard to lung parenchymal opacifications has not been investigated; therefore, researchers in Germany investigated whether pulmonary embolism manifestations are limited to lung segments affected by COVID-19-pneumonia. Of 22 patients with severe COVID-19 treated between March 8 and April 15, 2020 in the hospital intensive care unit (ICU), 16 (age, 60.4±10.2 years) underwent computed tomography (CT) and a total of 288 lung segments were analyzed. Thrombi were detectable in 56.3% (9 of 16) patients with 4.4±2.9 segments occluded per patient, and 13.9% (40 of 288) segments were affected in the whole cohort. The researchers noted that patients with thrombi had significantly worse segmental opacifications on CT (P <.05) and that all thrombi were located in opacitated segments. There was no correlation between D-dimer level and number of occluded segmental arteries.
MAIT cell activation and dynamics associated with COVID-19 disease severity
Science Immunology, September 28, 2020
Severe COVID-19 is characterized by excessive inflammation of the lower airways. The balance of protective versus pathological immune responses in COVID-19 is incompletely understood. Mucosa-associated invariant T (MAIT) cells are antimicrobial T cells that recognize bacterial metabolites, and can also function as innate-like sensors and mediators of antiviral responses. Here, we investigated the MAIT cell compartment in COVID-19 patients with moderate and severe disease, as well as in convalescence. We show profound and preferential decline in MAIT cells in the circulation of patients with active disease paired with strong activation. Furthermore, transcriptomic analyses indicated significant MAIT cell enrichment and pro-inflammatory IL-17A bias in the airways. Unsupervised analysis identified MAIT cell CD69high and CXCR3low immunotypes associated with poor clinical outcome. MAIT cell levels normalized in the convalescent phase, consistent with dynamic recruitment to the tissues and later release back into the circulation when disease is resolved. These findings indicate that MAIT cells are engaged in the immune response against SARS-CoV-2 and suggest their possible involvement in COVID-19 immunopathogenesis.
COVID-19 Cases Going Up in Half of States
WebMD, September 28, 2020
Two dozen states are reporting an increase in new daily coronavirus infections, including several states that are breaking record numbers. Cases mostly trended downward throughout August and most of September after major peaks in July, and now the numbers are moving back up again. Overall, the U.S. reported more than 55,000 new cases on Friday, and the total tally pushed above 7 million this week. The national 7-day average is also increasing, according to NPR. In Wisconsin, more than 2,800 new cases were reported on Saturday, marking a new record and breaking the previous high of 2,500 cases on Sept. 18, according to Fox 11 in Madison. More than 2,000 cases were reported three days in a row. In New York, daily cases passed 1,000 on Saturday for the first time since June 5, according to Bloomberg News. South Dakota also reported its highest daily total on Saturday with more than 500 new cases. North Dakota, Utah, and Montana set records as well. New Hampshire reported its first coronavirus-related death in 11 days on Saturday, which was associated with a long-term care facility, according to WMUR. The state reported 38 new cases, and health officials say community-based transmission is happening in every county. Public health officials expect cases to increase even more throughout the fall, and state leaders are urging people to continue measures to slow the spread of the virus. “Continue to practice the basic behaviors that drive our ability to fight COVID-19 as we move into the fall and flu season,” New York Gov. Andrew Cuomo said in a Saturday update. “Wearing masks, socially distancing and washing hands make a critical difference.”
Asthma-associated risk for COVID-19 development
Journal of Allergy and Clinical Immunology
The newly described severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is responsible for a pandemic (Corona virus-induced disease -19, COVID-19). It is now well established that certain comorbidities define high risk patients. They include hypertension, diabetes, and coronary artery disease. In contrast, the context with bronchial asthma is controversial and shows marked regional differences. Since asthma is the most prevalent chronic inflammatory lung disease worldwide and SARS-CoV-2 primarily affects the upper and lower airways leading to marked inflammation, the question arises about the possible clinical and pathophysiological association between asthma and SARS-CoV-2/COVID-19. Here we analyze the global epidemiology of asthma among COVID-19 patients and propose the concept that patients suffering from different asthma endotypes (type 2 asthma versus non-type 2 asthma) present with a different risk profile in terms of SARS-CoV-2 infection, development of COVID-19 and progression to severe COVID-19 outcomes. This concept may have important implications for future COVID-19 diagnostics and immune-based therapy developments.
Modeling lung perfusion abnormalities to explain early COVID-19 hypoxemia
Nature Communications, September 28, 2020
Early stages of the novel coronavirus disease (COVID-19) are associated with silent hypoxia and poor oxygenation despite relatively minor parenchymal involvement. Although speculated that such paradoxical findings may be explained by impaired hypoxic pulmonary vasoconstriction in infected lung regions, no studies have determined whether such extreme degrees of perfusion redistribution are physiologically plausible, and increasing attention is directed towards thrombotic microembolism as the underlying cause of hypoxemia. Herein, a mathematical model demonstrates that the large amount of pulmonary venous admixture observed in patients with early COVID-19 can be reasonably explained by a combination of pulmonary embolism, ventilation-perfusion mismatching in the noninjured lung, and normal perfusion of the relatively small fraction of injured lung. Although underlying perfusion heterogeneity exacerbates existing shunt and ventilation-perfusion mismatch in the model, the reported hypoxemia severity in early COVID-19 patients is not replicated without either extensive perfusion defects, severe ventilation-perfusion mismatch, or hyperperfusion of nonoxygenated regions.
ECMO Survival Rate ‘Reasonable’ in COVID-19
MedPage Today, September 28, 2020
Most patients who require extracorporeal membrane oxygenation (ECMO) for severe COVID-19 survive, according to an international registry. Estimated 90-day in-hospital mortality was 37.4%, and mortality among those who completed their hospitalization (final disposition of death or discharge) was 39%. “These data from 213 hospitals worldwide provide a generalizable estimate of ECMO mortality in the setting of COVID-19,” wrote Ryan Barbaro, MD, of the University of Michigan in Ann Arbor, and colleagues reporting the findings in The Lancet. The data were also presented at the virtual Extracorporeal Life Support Organization meeting. Early reports of ECMO use in COVID-19 suggested that mortality could be greater than 90%, leading some to recommend withholding it, the group noted. More recent reports have suggested higher success rates, albeit with small numbers. “Considering the severity of hypoxemia in patients requiring ECMO, I’m intrigued by noting that at least 40% (if probably not more) had some reasonable recovery,” commented Behnood Bikdeli, MD, of Brigham and Women’s Hospital and Harvard in Boston. The findings were “consistent with previously reported survival rates in acute hypoxaemic respiratory failure, supporting current recommendations that centres experienced in ECMO should consider its use in refractory COVID-19-related respiratory failure,” the researchers concluded.
Immune dysfunction following COVID-19, especially in severe patients
Scientific Reports, September 28, 2020
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has been spread worldwide. Because it brought so much damage and negative effects, the World Health Organization (WHO) declared the outbreak a public health emergency of international concern on January 31, 2020. This disease has progressed rapidly, and patients who are in the severe stage could develop acute respiratory distress syndrome, sepsis, and even multiple organ dysfunction syndrome in just a short time. Severe cases had unfavorable outcomes according to the latest epidemiological statistics, which means that early identification and intervention for severe patients were very important, especially because no effective treatment has been made yet directly targeting at SARS-CoV-2. So, we collected and compared data of healthy people and laboratory-confirmed SARS-CoV-2 infected patients. The aim of this study was to know the clinical characteristics of COVID-19 and then identify the independent risk factors related to disease severity and so help clinicians distinguish severe cases by using clinical data in the early stage.
The potential indicators for pulmonary fibrosis in survivors of severe COVID-19
Journal of Infection, September 27, 2020
[Letter to Editor] We read great interest in the risk factors of critical or mortal COVID-19 cases, recently reported by Ye, et al in this journal. Here we paid more attention about the long-term lung sequelae among survivors of severe COVID-19. With more than 21 million people worldwide recovered from COVID-19, early analysis suggested a high rate of patients had residual abnormal lung function and fibrotic remodeling on CT, especially in survivors of severe SARS-CoV-2 associated pneumonia. These might contribute to long-term impairment of lung function or even lung transplants. The early identification of patients at higher risk of lung injury and fibrotic damage is critical. Therefore, we performed an observational cohort study that compared fibrosis and non-fibrosis group to investigate the potential indicators for post-fibrosis. The two-center retrospective study was approved by the institutional review board, and a total of 430 consecutive patients with positive RT-PCR were reviewed. Finally 81 survivors who recovered from severe COVID-19 pneumonia were enrolled. The median hospitalization was 26 days; all had at least three follow-up CT scans after discharge, and the median period between the discharge and the latest CT scan was 58 days (IQR: 25-46). Pulmonary fibrosis was diagnosed based on the extensive and persistent fibrotic changes, including parenchymal bands, irregular interfaces, reticular opacities, and traction bronchiectasis with or without honeycombing on the follow-up CT scans.
Lessons from an ICU recovery clinic: two cases of meralgia paresthetica after prone positioning to treat COVID-19-associated ARDS and modification of unit practices
Critical Care, September 27, 2020
Prone positioning is one of the few interventions in acute respiratory distress syndrome (ARDS) which has a proven mortality reduction. Due to the coronavirus disease 2019 (COVID-19) pandemic, severe ARDS cases have sharply increased worldwide, increasing the need for proning. Some centers have also encouraged non-intubated patients with hypoxemia due to COVID-19 to self-prone. Although generally considered low risk, pressure-related complications can occur during proning and differ from those that occur in supine patients. We present two cases of COVID-19-associated ARDS treated with prone positioning who developed meralgia paresthetica that was diagnosed in our ICU recovery clinic. Meralgia paresthetica (MP) results from compression injury of the lateral femoral cutaneous nerve between the anterior superior iliac spine and the inguinal ligament; this mononeuropathy results in sensory abnormalities in the anterolateral thigh. To our knowledge, there is only one other reported case of MP in prone positioning for ARDS, although it has been reported after surgical prone positioning in up to 24% of cases. “Identifying otherwise unseen targets for ICU quality improvement” has been postulated as one way that ICU recovery clinics might improve care, yet there are few published examples. If these patients returned to their primary care physicians, it is less likely that the cause of the MP would be known, nor would practice change. Lessons like these show the potential value of ICU recovery clinics, not only in treating post-intensive care syndrome, but in changing its underlying causes.
First RCT in COVID Anticoagulation Says Go Full Dose
MedPage Today, September 25, 2020
Respiratory outcomes were better, but 20-person trial far from conclusive. Therapeutic-level dosing of enoxaparin (Lovenox) improved respiratory outcomes in severe COVID-19, a pilot randomized trial showed. Gas exchange measured by the PaO2/FiO2 ratio improved significantly over time in the 10-patient therapeutic group (from 163 at baseline to 209 at 7 days and 261 at 14 days, P=0.0004) but not in the 10-patient control group receiving lower prophylactic-level doses in the open-label study (184, 168, and 195, respectively, P=0.487). Compared with prophylactic dosing of the drug, therapeutic dosing also led to four-fold more patients being weaned off of mechanical ventilation (P=0.031) and more ventilator-free days (15 vs 0 days, P=0.028), Carlos Henrique Miranda, MD, PhD, of São Paulo University in Brazil, and colleagues reported in Thrombosis Research. “It’s a remarkable step forward in the sense that now for the first time we are having randomized trial data related to antithrombotic therapy for COVID-19,” commented Behnood Bikdeli, MD, of Brigham and Women’s Hospital and Harvard in Boston. While the study couldn’t address the mechanism, “hypothetically, it’s reducing the risk and/or severity of macrothrombi and microthrombi in the lung,” he told MedPage Today.
Coronavirus Q&A With Anthony Fauci, MD
JAMA Network Learning, September 25, 2020
[Video] Anthony S. Fauci, MD, returns to JAMA’s Q&A series to discuss the latest developments in the COVID-19 pandemic, hosted by Howard Bauchner, MD, Editor in Chief, JAMA.
Risk of COVID-19-related death among patients with chronic obstructive pulmonary disease or asthma prescribed inhaled corticosteroids: an observational cohort study using the OpenSAFELY platform
The Lancet, September 24, 2020
Early descriptions of patients admitted to hospital during the COVID-19 pandemic showed a lower prevalence of asthma and chronic obstructive pulmonary disease (COPD) than would be expected for an acute respiratory disease like COVID-19, leading to speculation that inhaled corticosteroids (ICSs) might protect against infection with severe acute respiratory syndrome coronavirus 2 or the development of serious sequelae. We assessed the association between ICS and COVID-19-related death among people with COPD or asthma using linked electronic health records (EHRs) in England, UK. In this observational study, we analysed patient-level data for people with COPD or asthma from primary care EHRs linked with death data from the Office of National Statistics using the OpenSAFELY platform. For the COPD cohort, individuals were eligible if they were aged 35 years or older, had COPD, were a current or former smoker, and were prescribed an ICS or long-acting β agonist plus long-acting muscarinic antagonist (LABA–LAMA) as combination therapy within the 4 months before the index date. For the asthma cohort, individuals were eligible if they were aged 18 years or older, had been diagnosed with asthma within 3 years of the index date, and were prescribed an ICS or short-acting β agonist (SABA) only within the 4 months before the index date. We compared the outcome of COVID-19-related death between people prescribed an ICS and those prescribed alternative respiratory medications.
Asthma disparities during the COVID-19 pandemic: a survey of patients and physicians
Journal of Allergy and Clinical Immunology, September 24, 2020
The COVID-19 pandemic has demonstrated significantly worse outcomes for Minority (Black and Hispanic) individuals. Understanding the reasons for COVID-19-related disparities among asthma patients has important public health implications. The objective of this survey was to determine factors contributing to health disparities in those with asthma during the COVID-19 pandemic. The anonymous survey was sent through social media to adult patients with asthma, and a separate survey was sent to physicians who provide asthma care. The patient survey addressed demographic information including socioeconomic status (SES), asthma control, and attitudes/health behaviors during COVID-19. A total of 1171 patients (10.1% Minority individuals) and 225 physicians completed the survey. Minority patients were more likely to have been affected by COVID-19 (e.g., became unemployed, lived in a community with high COVID-19 cases). They had worse asthma control (increased emergency visits for asthma, lower ACT score), were more likely to live in urban areas, and had a lower household income. Initial differences in attitudes and health behaviors disappeared after controlling for baseline demographic features. Institutional racism was demonstrated by findings that Minority individuals were less likely to have a primary care physician, had more trouble affording asthma medications due to COVID-19, were more likely to have lost health insurance due to COVID-19, and that 25% of physicians found it more challenging to care for Black individuals with asthma during COVID-19.
Tocilizumab Reduces Need for Mechanical Ventilation in COVID-19 Pneumonia Trial
Pulmonology Advisor, September 23, 2020
Genentech announced that a phase 3 study assessing tocilizumab (Actemra®) plus standard of care for the treatment of hospitalized adults with coronavirus disease 2019 (COVID-19) associated pneumonia met its primary end point. The multicenter, randomized, double-blind, placebo-controlled EMPACTA study included hospitalized COVID-19 patients with oxygen saturation less than 94% while on ambient air who did not require noninvasive or invasive mechanical ventilation. Patients were randomized to receive 1 intravenous infusion of tocilizumab or placebo plus standard of care, and could be given up to 1 additional infusion. The primary end point was the cumulative proportion of patients dying or requiring mechanical ventilation by day 28. Results showed that patients treated with tocilizumab were 44% less likely to progress to mechanical ventilation or death compared with placebo (hazard ratio [HR] 0.56; 95% CI, 0.32-0.97; log-rank P =.0348). The cumulative proportion of patients who progressed to mechanical ventilation or death by day 28 was 12.2% in the tocilizumab arm compared with 19.3% in the placebo arm.
Routine blood test may predict mortality risk in patients with COVID-19
Helio | Primary Care, September 23, 2020
A standard test that evaluates blood cells can help identify patients hospitalized with COVID-19 who are at an elevated risk for death, according to research published in JAMA Network Open. “We were surprised to find that one standard test that quantifies the variation in size of red blood cells — called red cell distribution width, or RDW — was highly correlated with patient mortality, and the correlation persisted when controlling for other identified risk factors like patient age, some other lab tests, and some pre-existing illnesses,” Jonathan Carlson, MD, PhD, an instructor in medicine at Massachusetts General Hospital, said in a press release. In their cohort study, Carlson and colleagues retrospectively analyzed adult patients with SARS-CoV-2 infection who were admitted to one of four participating hospitals in the Boston area from March 4 through April 28. As part of standard critical care, all patients had their RDW, absolute lymphocyte count and dimerized plasmin fragment D levels collected daily. According to the researchers, RDW reflects cellular volume variation, and elevated RDW (more than 14.5%) has previously been associated with an increased risk for morbidity and mortality in a variety of diseases, including heart disease, pulmonary diseases, influenza, cancer and sepsis. A total of 1,641 patients were included in the analyses. The final discharge among these patients was June 26, and there were no COVID-19-related readmissions through July 25.
Risk Factors for Hospitalization, Mechanical Ventilation, or Death Among 10 131 US Veterans With SARS-CoV-2 Infection
JAMA Network Open, September 23, 2020
Identifying independent risk factors for adverse outcomes in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can support prognostication, resource utilization, and treatment. The objective of this study was to identify excess risk and risk factors associated with hospitalization, mechanical ventilation, and mortality in patients with SARS-CoV-2 infection. In this national cohort study of 88 747 veterans tested for SARS-CoV-2, hospitalization, mechanical ventilation, and mortality were significantly higher in patients with positive SARS-CoV-2 test results than among those with negative test results. Significant risk factors for mortality included older age, high regional coronavirus disease 2019 burden, higher Charlson Comorbidity Index score, fever, dyspnea, and abnormal results in many routine laboratory tests; however, obesity, Black race, Hispanic ethnicity, chronic obstructive pulmonary disease, hypertension, and smoking were not associated with mortality.
COVID Death Toll Hits 200,000 in the U.S.
WebMD, September 22, 2020
Just over 6 months after the World Health Organization declared COVID-19 a pandemic, the United States has reached a grim milestone: the novel coronavirus death toll has climbed to a staggering 200,000. “It’s sobering. It’s a large number, and clearly it tells us that everything we’re doing right now to contain it needs to continue,” says Erica Shenoy, MD, associate chief of the Infection Control Unit at Massachusetts General Hospital. “Especially heading into the fall, where we don’t know if there will be a second surge, or if this will be compounded by other respiratory illnesses.” Doctors and scientists say the number sends a clear message: Although people are itching to return to pre-pandemic life, Americans should continue to wear masks, practice hand-washing hygiene, and keep physical distance from others. While the high death toll is a bleak glimpse into how severe the illness is, there are two silver linings: The numbers seem to be trending in the right direction, and researchers have had time to discover more about a virus that at first baffled even the world’s leading scientists.
Pneumothorax Reported as Complication of COVID-19
Pulmonology Advisor, September 22, 2020
Pneumothorax is being reported as a complication of COVID-19, and has higher incidence among men and lower survival among older patients, according to a study published online Sept. 9 in the European Respiratory Journal. Anthony W. Martinelli, Ph.D., from Addenbrooke’s Hospital in Cambridge, England, and colleagues retrospectively collected cases from U.K. hospitals limited to patients with a diagnosis of COVID-19 and presence of pneumothorax or pneumomediastinum. Data were included for 71 patients, 60 of whom had pneumothoraces (six with pneumomediastinum) and 11 had pneumomediastinum alone. Two of the patients with pneumomediastinum alone had distinct episodes of pneumothorax, resulting in a total of 62 pneumothoraces. The researchers observed no difference in survival at 28 days following pneumothorax or isolated pneumomediastinum (63.1 ± 6.5 percent and 53.0 ± 18.7 percent, respectively). Men had higher incidence of pneumothorax. Survival at 28 days did not differ for men versus women (62.5 ± 7.7 percent versus 68.4 ± 10.7 percent). Compared with younger patients, those aged 70 years and older had significantly lower 28-day survival (41.7 ± 13.5 percent versus 70.9 ± 6.8 percent survival).
ACIP Mulls Priority Groups for COVID-19 Vaccines
MedPage Today, September 22, 2020
Members of the CDC’s Advisory Committee on Immunization Practices (ACIP) meeting Tuesday appeared to agree that healthcare workers should be first in line to receive a COVID-19 vaccine when one is approved, followed by some combination of essential workers, those with high-risk medical conditions, and older adults. However, with no formal vote taken — that won’t happen until one or more vaccines are authorized or approved by the FDA for clinical use — it’s not yet official policy, and not much was settled about priorities for later rounds of immunizations. ACIP chair José Romero, MD, said once data is available from phase III clinical trials, an ACIP work group will conduct an independent review of its safety and efficacy. “If and when the FDA authorizes or approves vaccines, ACIP will have an emergency meeting and then vote on recommendations and populations for use,” he said.
Hydrocortisone Did Not Reduce Mortality, Respiratory Support Need in COVID-19
Pulmonology Advisor, September 22, 2020
Low-dose hydrocortisone was not associated with a significant reduction in death or need for persistent respiratory support by day 21 of treatment compared with placebo in critically ill patients with coronavirus disease 2019 (COVID-19), according to study results published in the Journal of the American Medical Association. A total of 149 patients (mean age, 62.2 years) admitted to the intensive care unit (ICU) for COVID-19-related acute respiratory failure from March 7 to June 1, 2020, were recruited into this French multicenter, randomized double-blind trial. Last available follow-up data were for June 29, 2020. Researchers planned to enroll up to 290 patients, but recommendations from the data and safety monitoring board resulted in early termination of the study. Approximately 81.2% of patients in this cohort were mechanically ventilated. Patients were randomly assigned to either continuous infusion of low-dose hydrocortisone (n=76) or placebo (n=73). The initial dose of hydrocortisone was 200 mg/d and continued at this dose until day 7, after which the dose was decreased to 100 mg/d for 4 days and 50 mg/d for 3 days. A short treatment regimen comprising 200 mg/d for 4 days, followed by 100 mg/d for 2 days and then 50 mg/d for the next 2 days was administered if the patient’s respiratory and generally status sufficiently improved by 4 days of treatment.
COVID-19 mortality rates higher among men than women
Science Daily, September 22, 2020
A new review article from Beth Israel Deaconess Medical Center (BIDMC) shows people who are biologically male are dying from COVID-19 at a higher rate than people who are biologically female. In a review published in Frontiers in Immunology, researcher-clinicians at BIDMC explore the sex-based physiological differences that may affect risk and susceptibility to COVID-19, the course and clinical outcomes of the disease and response to vaccines. “The COVID-19 pandemic has revealed a striking gender bias with increased mortality rates in men compared with women across the lifespan,” said corresponding author Vaishali R. Moulton, MD, PhD, an assistant professor of medicine in the Division of Rheumatology and Clinical Immunology at BIDMC. “Apart from behavioral and lifestyle factors that differ between men and women, sex chromosome-linked genes, sex hormones and the microbiome control aspects of the immune responses to infection and are potentially important biological contributors to the sex-based differences we’re seeing in men and women in the context of COVID-19.”
Most COVID-19 infections are spread through respiratory droplets or aerosols and not surfaces: study
Medical Xpress, September 18, 2020
COVID-19 is spread most often through respiratory droplets or aerosols and little evidence exists supporting transmission through surfaces. As such, social distance and proper ventilation are key determinants of transmission risk. Findings from a review of published research, articles, and reports is published in Annals of Internal Medicine. Researchers from Montefiore Medical Center, Hospital of the University of Pennsylvania, Massachusetts General Hospital, Harvard Medical School, and Brigham and Women’s Hospital studied scientific articles published between January and September 2020, as well as relevant articles and institutional or governmental reports, to determine the viral, host, and environmental factors that contribute to transmission of COVID-19. They found that although several experimental studies suggest that virus particles could live for hours after inoculation in aerosols or on surfaces, the real-world studies that detect viral RNA in the environment report very low levels on surfaces, and few have isolated viable virus. Strong evidence from case and cluster reports indicates that respiratory transmission is dominant, with proximity and ventilation being key determinants of transmission risk. In the few cases where direct contact or transmission from materials or surfaces was presumed, respiratory transmission could still not be ruled out.
Histopathological findings in fatal COVID-19 severe acute respiratory syndrome: preliminary experience from a series of 10 Spanish patients
BMJ Journals | Thorax, September 18, 2020
In December 2019, an outbreak of severe acute respiratory syndrome associated to SARS-CoV2 was reported in Wuhan, China. To date, little is known on histopathological findings in patients infected with the new SARS-CoV2. Lung histopathology shows features of acute and organising diffuse alveolar damage. Subtle cellular inflammatory infiltrate has been found in line with the cytokine storm theory. Medium-size vessel thrombi were frequent, but capillary thrombi were not present. Despite the elevation of biochemical markers of cardiac injury, little histopathological damage could be confirmed. Viral RNA from paraffin sections was detected at least in one organ in 90% patients. Novel coronavirus-associated disease (COVID-19) was first detected in Spain on 31 January 2020, with more than 204 178 cases subsequently identified in 3 months. Severe COVID-19 is associated with high circulating levels of inflammatory cytokines akin to a cytokine release syndrome that frequently results in respiratory failure. To date, scant histopathological information of infected patients is available. Few descriptions of histopathological findings have mainly reported pneumonitis and diffuse alveolar damage (DAD). To advance in the knowledge of COVID-19-associated tissue damage is important to understand the mechanisms of damage caused by SARS-COV-2. Postmortem multiorgan biopsies in 10 patients who died with SARS COV-2 infection were performed after oral authorisation of a first-degree relative. Biopsies were obtained without ultrasound guidance with the patient‘s corpse still on the hospital bed.
Lung ultrasonography for risk stratification in patients with COVID-19: a prospective observational cohort study
Clinical Infectious Diseases, September 17, 2020
Point-of-care lung ultrasound (LUS) is a promising pragmatic risk stratification tool in COVID-19. This study describes and compares LUS characteristics between patients with different clinical outcomes. This prospective observational study included PCR-confirmed COVID-19 adults with symptoms of lower respiratory tract infection presenting in the emergency department (ED) of Lausanne University Hospital. A trained physician recorded LUS images using a standardized protocol. Two experts reviewed images blinded to patient outcome. We describe and compare early LUS findings (acquired within 24hours of presentation to the ED) between patient groups based on their outcome at 7 days after inclusion: 1) outpatients, 2) hospitalised and 3) intubated/death. Normalized LUS score was used to discriminate between groups. We included 80 patients (17 outpatients, 42 hospitalized and 21 intubated/dead). 73 patients (91%) had abnormal LUS (70% outpatients, 95% hospitalised and 100% intubated/death; p=0.003). The proportion of involved zones was lower in outpatients compared with other groups (median 30% [IQR 0-40%], 44% [31-70%] and 70% [50-88%], p<0.001). Predominant abnormal patterns were bilateral and multifocal spread thickening of the pleura with pleural line irregularities (70%), confluent B lines (60%) and pathologic B lines (50%). Posterior inferior zones were more often affected. Median normalized LUS score had a good level of discrimination between outpatients and others with area under the ROC of 0.80 (95% CI 0.68-0.92).
HHS Outlines COVID Vax Distribution Strategy
MedPage Today, September 17, 2020
The Health and Human Services (HHS) department on Wednesday unveiled general outlines for how the first COVID-19 vaccine doses will be shipped and administered. Developed with the Department of Defense (DOD), the four-part strategy addresses engagement with state and local partners and other stakeholders; distribution under a “phased allocation methodology” still to be developed; safe vaccine administration and availability of auxiliary supplies; and data gathering via information technology to track distribution and administration. The strategy gives January 2021 as the target to begin distribution of an FDA-approved or authorized vaccine. Also released Wednesday was a COVID-19 Vaccination Program Interim Playbook from the CDC to assist local, state, tribal and territorial partners in rolling out their COVID-19 vaccination programs. The playbook identifies healthcare personnel and other essential workers as among the “critical populations,” although final decisions remain to be made by the CDC’s Advisory Committee on Immunization Practices.
Six traits predict need for mechanical ventilation in patients with COVID-19
Helio | Critical Care, September 17, 2020
Among patients hospitalized for COVID-19 in the United States, male sex, age 60 years and older, obesity, chronic kidney disease, cardiovascular disease and living in the Northeast were associated with an increased risk for mechanical ventilation, data show. The findings, published in Clinical Infectious Diseases, also indicated that the same characteristics, except for obesity, were linked to an increased risk for mortality. “This was the first attempt to try and get a broader sense of the risk factors for adverse outcome and how they interacted with one another in a much more specific manner,” Robert S. Brown, Jr., MD, MPH, clinical chief of the division of gastroenterology and hepatology at Weill Cornell Medicine Center, told Healio Primary Care. Researchers reviewed data from 11,721 patients with COVID-19 who were admitted to 245 hospitals across 38 states between Feb. 15 and April 20. Among all patients, 48 received remdesivir (Gilead) and 4,232 received hydroxychloroquine. Researchers also identified a benefit to early mechanical ventilation vs. later mechanical ventilation, suggesting that perhaps there should be a lower threshold for initiating mechanical ventilation. However, this last point is very case specific and should be based on a physician’s observations, not the findings of a descriptive study.
Flu, COVID-19 or Both? Don’t Overlook Co-Infection, CDC Urges
MedPage Today, September 17, 2020
With overlapping signs and symptoms, surveillance, testing more important than ever. When a patient presents with acute respiratory symptoms this fall, clinicians should consider three options: influenza, COVID-19, or co-infection, CDC experts said. And given the likelihood that influenza and SARS-CoV-2 will be co-circulating in the community, clinicians should pay special attention to local surveillance data about each virus. On a CDC Clinician Outreach and Communication Activity call, CDC officials reminded clinicians that not only do influenza and COVID-19 have overlapping signs and symptoms, but co-infection with both has been documented in both case reports and case series. Co-infection, or even distinguishing SARS-CoV-2 from influenza, is particularly important because of the implications of treatment. For example, Uyeki noted that dexamethasone is recommended for severe COVID-19 infection in hospitalized patients, but corticosteroids actually prolong viral replication in influenza. Testing then becomes key in distinguishing the viruses, and Uyeki said that, as noted by Department of Health and Human Services officials, there are several kinds of “multiplex” assays that received FDA emergency use authorization (EUA), including some that received EUAs “this week,” he added.
Efforts to prevent COVID-19 led to global decline in flu
Infectious Disease News, September 17, 2020
Interventions to prevent SARS-CoV-2 transmission have led to a global decline in influenza during the COVID-19 pandemic, researchers reported in MMWR. In addition to causing a significant drop in the percentage of respiratory specimens that tested positive for influenza in the early days of the pandemic in the United States, measures such as mask wearing, social distancing, school closures and telework have kept positive tests at “historically low interseasonal levels,” the researchers said. The Southern Hemisphere has experienced a similar effect. If the measures continue through the fall, the influenza season in the U.S. “might be blunted or delayed,” according to the report. “The global decline in influenza virus circulation appears to be real and concurrent with the COVID-19 pandemic and its associated community mitigation measures,” Sonja J. Olsen, PhD, an epidemiologist in the CDC’s Influenza Division, and colleagues wrote. Olsen and colleagues reviewed data from around 300 U.S. laboratories in all 50 states, Puerto Rico, Guam and the District of Columbia. They also analyzed influenza laboratory data from surveillance platforms in Australia, Chile and South Africa to determine viral activity in the Southern Hemisphere.
Characterization of the Inflammatory Response to Severe COVID-19 Illness
American Journal of Respiratory and Critical Care Medicine, September 15, 2020
Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood. The objective here, was to define the cytokine profile ofCOVID-19 and to identify evidence of immunometabolic alterations in those with severe illness. Levels of IL-1b, IL-6, IL-8, IL-10, and sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed in plasma from healthy volunteers, hospitalized but stable patients with COVID-19 (COVID stable patients), patients with COVID-19 requiring ICU admission (COVIDICU patients), and patients with severe community acquired pneumonia requiring ICU support (CAPICU patients). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of AAT (alpha-1 antitrypsin) to COVID-19 was also evaluated. Measurements and Main Results: IL-1b, IL-6, IL-8, and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVID stable patients, and demonstrated higher levels of IL-1b, IL-6, and sTNFR1 but lower IL-10 than CAPICU patients. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, HIF-1a (hypoxia-inducible factor1a), and lactate. The production and sialylation of AAT increased in COVID-19, but this antiinflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P , 0.0001). In critically unwell patients with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6:AAT was associated with clinical resolution (P , 0.0001).
Post COVID-19, Lung Function Improves Over Time
WebMD, September 15, 2020
Patients who have long-term effects for weeks or months after they contract the coronavirus may see improvements in their lung function after 12 weeks, according to a new study. The study, which tracked 86 COVID-19 “long-haulers” in Austria, was presented at the European Respiratory Society International Congress last week. “The bad news is that people show lung impairment from COVID-19 weeks after discharge. The good news is that the impairment tends to ameliorate over time, which suggests the lungs have a mechanism for repairing themselves,” Sabina Sahanic, one of the study authors and a PhD student at the University Clinic in Innsbruck, said in a statement. The research team evaluated the patients between April and June at the 6-week and 12-week points after being released from a hospital. At 6 weeks, about 88% had observable lung damage on CT scans. In addition, 47% had trouble with breathing and 15% had a persistent cough. At 12 weeks, about 56% had lung damage, 39% had trouble with breathing, and the persistent cough remained about the same. CT scans also showed that lung damage severity decreased by the 12-week mark. The damage, which occurs from inflammation and fluid in the lungs, shows up on scans as white patches known as “ground glass.” At 6 weeks, the patches showed up in nearly all of the patients, and by 12 weeks, was observable in about half of the patients. Tests showed an improvement in lung function, too. At 6 weeks, about 28% of patients had less than 80% of normal functioning, but at 12 weeks, that dropped to 19%. The 24-week checkup is underway now.
Convalescent plasma treatment of severe COVID-19: a propensity score–matched control study
Nature Medicine, September 15, 2020
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new human disease with few effective treatments. Convalescent plasma, donated by persons who have recovered from COVID-19, is the acellular component of blood that contains antibodies, including those that specifically recognize SARS-CoV-2. These antibodies, when transfused into patients infected with SARS-CoV-2, are thought to exert an antiviral effect, suppressing virus replication before patients have mounted their own humoral immune responses. Virus-specific antibodies from recovered persons are often the first available therapy for an emerging infectious disease, a stopgap treatment while new antivirals and vaccines are being developed. This retrospective, propensity score–matched case–control study assessed the effectiveness of convalescent plasma therapy in 39 patients with severe or life-threatening COVID-19 at The Mount Sinai Hospital in New York City. Oxygen requirements on day 14 after transfusion worsened in 17.9% of plasma recipients versus 28.2% of propensity score–matched controls who were hospitalized with COVID-19 (adjusted odds ratio (OR), 0.86; 95% confidence interval (CI), 0.75–0.98; chi-square test P value = 0.025). Survival also improved in plasma recipients (adjusted hazard ratio (HR), 0.34; 95% CI, 0.13–0.89; chi-square test P = 0.027).
How COVID-19 can damage the brain
Nature, September 15, 2020
In the early months of the COVID-19 pandemic, doctors struggled to keep patients breathing, and focused mainly on treating damage to the lungs and circulatory system. But even then, evidence for neurological effects was accumulating. Some people hospitalized with COVID-19 were experiencing delirium: they were confused, disorientated and agitated. In April, a group in Japan published the first report of someone with COVID-19 who had swelling and inflammation in brain tissues. Another report described a patient with deterioration of myelin, a fatty coating that protects neurons and is irreversibly damaged in neurodegenerative diseases such as multiple sclerosis. “The neurological symptoms are only becoming more and more scary,” says Alysson Muotri, a neuroscientist at the University of California, San Diego, in La Jolla. The list now includes stroke, brain haemorrhage and memory loss. It is not unheard of for serious diseases to cause such effects, but the scale of the COVID-19 pandemic means that thousands or even tens of thousands of people could already have these symptoms, and some might be facing lifelong problems as a result. Yet researchers are struggling to answer key questions — including basic ones, such as how many people have these conditions, and who is at risk. Most importantly, they want to know why these particular symptoms are showing up.
Immunomodulators in COVID-19 – Two Sides to Every Coin
American Journal of Respiratory and Critical Care Medicine, September 14, 2020
The COVID-19 pandemic has triggered precipitous entry of multiple novel therapeutic candidates into clinical trials often without control groups, randomisation, or adequate statistical power. To this long list can be added a re-purposing of existing therapeutic strategies used for other inflammatory or viral illnesses. Our still incomplete understanding of the COVID-19 disease process, including temporal change, has driven arguably inappropriate, ill-timed or ill-judged interventions, either within trials or compassionate use. Description of the ‘cytokine storm’ epithet to COVID-19 has driven the application of immunosuppressive therapies. At the time of writing, 47 registered RCTs were evaluating inhibition of interleukin-6 (IL-6), mostly recruiting on clinical criteria alone and without incorporating measurement of circulating IL-6 levels. Although circulating IL-6 levels are higher among COVID-19 non-survivors compared to survivors, circulating IL-6 levels in COVID-19 are often 1-2 log-orders lower than other causes of ARDS or viral influenza. While there may indeed be benefit from inhibiting IL-6, timing, dosing and patient selection are key. Outcome improvements in some subsets may be diluted or counterbalanced by lack of effect or harm in others. An acceptable toxicity profile for use in other inflammatory conditions does not necessarily translate to COVID-19, especially in the critically ill subset where both the severity of the disease process and multiple iatrogenic factors magnify immunosuppression and the risk of secondary nosocomial infection. A single dose of the IL-6 inhibitor, tociluzimab, can significantly dampen any C-reactive protein and temperature response for a week.
The lasting misery of coronavirus long-haulers
Nature, September 14, 2020
Months after infection with SARS-CoV-2, some people are still battling crushing fatigue, lung damage and other symptoms of ‘long COVID’. People with more severe infections might experience long-term damage not just in their lungs, but in their heart, immune system, brain and elsewhere. Evidence from previous coronavirus outbreaks, especially the severe acute respiratory syndrome (SARS) epidemic, suggests that these effects can last for years. And although in some cases the most severe infections also cause the worst long-term impacts, even mild cases can have life-changing effects — notably a lingering malaise similar to chronic fatigue syndrome. Many researchers are now launching follow-up studies of people who had been infected with SARS-CoV-2, the virus that causes COVID-19. Several of these focus on damage to specific organs or systems; others plan to track a range of effects. In the United Kingdom, the Post-Hospitalisation COVID-19 Study (PHOSP-COVID) aims to follow 10,000 patients for a year, analysing clinical factors such as blood tests and scans, and collecting data on biomarkers. A similar study of hundreds of people over 2 years launched in the United States at the end of July. What they find will be crucial in treating those with lasting symptoms and trying to prevent new infections from lingering.
A reminder about choosing the proper code for a telehealth visit
Helio | Infectious Diseases in Children, September 14, 2020
Telehealth has helped immensely during the COVID-19 crisis. Insurance companies, although slow to approve payments, joined in to allow us to aid and interact with our patients and their families. How long this arrangement will last and how long they will waive coinsurance payments is a moving target. The AAP continues to discuss these matters with insurers. Rules have changed, confusion over which modifiers to use have been resolved and by now we are all familiar with telephone-only CPT codes 99441-3 and our old friends 99212-5 that we used for our “sick visits.” One thing has not changed, though — our fear to use 99214 and 99215, particularly when we cannot actually physically examine our patients. However, we can still use time as the main factor in choosing the proper code — 10 minutes for 99212, 15 minutes for 99213, 25 minutes for 99214 and 40 minutes for 99215. Remember, you must write down the time: For example, either 9:00 to 9:25, or 25 minutes (99214). On the other hand, do not forget that until Jan. 1, 2021, if you fulfill two-thirds of the key factors — history, physical examination and medical decision-making — you can still use 99214 with proper documentation.
Type I IFN deficiency: an immunological characteristic of severe COVID-19 patients
Signal Transduction and Targeted Therapy, September 14, 2020
Recently, a paper published in Science by Hadjadj et al. reported that type I interferon (IFN) deficiency, could be a hallmark of severe coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe COVID-19 was also associated with a lymphocytopenia, persistent blood viral load, and an exacerbated inflammatory response. These findings provide insights into the treatment of severe COVID-19 patients with type I IFN. The immunological features and mechanisms involved in COVID-19 severity are unclear. In order to test whether the severity disease can be caused by SARS-CoV-2 viral infection and hyperinflammation, Hadjadj et al. conducted a comprehensive immune analysis of grouped 50 COVID-19 patients with different disease severity. First, to identify whether the severe disease induced lymphocytopenia, Hadjadj et al. compared the peripheral blood leukocytes density of variously severe patients by combining mass cytometry with visualization of high-dimensional single-cell data based on t-distributed stochastic neighbor embedding. There is a significantly decreased density of NK cells and CD3+ T cells in severe and critical patients, while the density of B cells and monocytes was increased. The authors determined the functional status of specific T-cell subsets (CD4+/CD8+) and NK cells based on the expression of activation (CD38, HLA-DR) and exhaustion (PD-1, Tim-3) markers. They observed that the activated NK and CD4+/CD8+ T cells were increased in all infected patients, while the exhausted CD4+/CD8+ T cells and NK cells were increased in only severity patients. This result supported lymphocytopenia correlates with disease severity.
Low-Cost, Open-Source Mechanical Ventilator with Pulmonary Monitoring for COVID-19 Patients
Actuators, September 12, 2020
Since mechanical ventilators potentially expose the patient’s lungs to damage, all initiatives of constructing low-cost mechanical ventilators must provide the regulation of not only the lung’s pressure but also the positive end-expiratory pressure (PEEP). This paper shows the construction of a low-cost, open-source mechanical ventilator. The motivation for constructing this kind of ventilator comes from the worldwide shortage of mechanical ventilators for treating COVID-19 patients—the COVID-19 pandemic has been striking hard in some regions, especially the deprived ones. Constructing a low-cost, open-source mechanical ventilator aims to mitigate the effects of this shortage on those regions. The equipment documented here employs commercial spare parts only. This paper also shows a numerical method for monitoring the patients’ pulmonary condition. The method considers pressure measurements from the inspiratory limb and alerts clinicians in real-time whether the patient is under a healthy or unhealthy situation. Experiments carried out in the laboratory that had emulated healthy and unhealthy patients illustrate the potential benefits of the derived mechanical ventilator.
COVID-19 Storms: Bradykinin In, Cytokine Out?
MedPage Today, September 11, 2020
In the last week, questions have been raised about whether cytokine storm is indeed a culprit in severe COVID-19, while a paper from a government lab has made an intriguing and much-discussed case for a new mechanism, bradykinin storm. While the concepts are not necessarily mutually exclusive, scientists trying to understand how COVID-19 wreaks its damage on the human body have been buzzing about the new possibilities. The theory connects many of the disparate symptoms of COVID-19, from a loss of sense of smell and taste, to a gel-like substance forming in the lungs, and abnormal coagulation. It posits that SARS-CoV-2 disrupts both the renin-angiotensin system (RAS) and the kinin-kallikrein pathways, sending bradykinin — a peptide that dilates blood vessels and makes them leaky — out of whack. The process impedes the transfer of oxygen from the lung to the blood and subsequently to all other tissues, a common abnormality in COVID-19 patients. They found the COVID-19 cases had extremely high levels (increased nearly 200-fold) of angiotensin-converting enzyme 2 (ACE2), the surface protein used by the coronavirus to enter the cell. When the virus interacts with ACE2, it triggers an abnormal response in the bradykinin pathway, Jacobson said. At the same time, levels of angiotensin-converting enzyme, which is involved in the breakdown of bradykinin, were lower in COVID-19 patients than in controls.
Rehabilitation Levels in COVID-19 Patients Admitted to Intensive Care Requiring Invasive Ventilation: An Observational Study
Annals of the American Thoracic Society, September 11, 2020
Patients with severe COVID-19 have complex organ support needs that necessitate prolonged stays in the intensive care, likely to result in a high incidence of neuromuscular weakness and loss of well being. Early and structured rehabilitation has been associated with improved outcomes for patients requiring prolonged periods of mechanical ventilation, but at present no data are available to describe similar interventions or outcomes in COVID-19 populations. The objective of this observational study was to describe the demographics, clinical status, level of rehabilitation and mobility status at ICU discharge of patients with COVID-19. Study participants were adults admitted to ICU with a confirmed diagnosis of COVID-19 and mechanically ventilated for >24 hours. Rehabilitation status was measured daily using the Manchester Mobility Score (MMS) to identify the time taken to first mobilise (defined as sitting on the edge of the bed or higher) and highest level of mobility achieved at ICU discharge.
Low glycosylated ferritin is a sensitive biomarker of severe COVID-19
Cellular & Molecular Immunology, September 11, 2020
Severe forms of coronavirus disease 2019 (COVID-19) have been associated with a cytokine storm mainly involving interleukin (IL)-6, IL-1β, and TNF. Several authors have reported features of macrophage activation, thus comparing the cytokine storm of COVID-19 to reactive hemophagocytic lymphohistiocytosis (reHLH). However, these data have been balanced by other studies primarily involving IL-6 and, therefore, a mechanism closer to the complex immune dysregulation observed in sepsis. Considering these discrepancies, serum cytokine profiling may not be the best option for assessing COVID-19 severity and prognosis. Serum ferritin, an inflammatory biomarker, is elevated in most COVID-19 patients and has been correlated with severity and mortality. The measurement of the glycosylated fraction of ferritin (GF), which could be readily implemented in routine diagnosis, is of great interest in the diagnosis of reHLH (and in Still’s disease, which is frequently associated with macrophage activation syndrome). Indeed, a GF rate < 25% has a positive predictive value of 88% and a negative predictive value of 100% for reHLH. This study assessed whether the GF rate could serve as a biomarker for COVID-19 severity and prognosis.
In Pursuit of Microbiome-based Therapies for Acute Respiratory Failure
American Journal of Respiratory and Critical Care Medicine, September 10, 2020
A presumably overly robust inflammatory response has been associated with poor clinical outcomes in patients with acute respiratory failure including patients with acute respiratory distress syndrome (ARDS) and sepsis. Likewise, both abnormal gut and respiratory microbiota patterns (termed “dysbiosis”) are also predictive of increased mortality among critically ill patients. The ambitious aim of the study by Kitsios and colleagues, here, is to better define the interplay between the host inflammatory response and the lung microbiome, and the impact of this relationship on clinical outcomes in a heterogenous population of critically ill patients with acute respiratory failure. The results of this investigation represent an important step in the process of developing a microbiome-guided or based treatment for critically ill patients with acute respiratory failure. The cohort characteristics in the study by Kitsios and colleagues were typical of an intensive care unit (ICU) population with acute respiratory failure patients requiring mechanical ventilation: extrapulmonary sepsis (18%), ARDS (24%), pneumonia (40%) were common diagnoses and 32% of the patients received antibiotics prior to admission to the ICU.
Single-cell transcriptomic atlas of primate cardiopulmonary aging
Cell Research, September 10, 2020
Aging is a major risk factor for many diseases, especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Disease 2019 (COVID-19). Resolving cellular and molecular mechanisms associated with aging in higher mammals is therefore urgently needed. Here, we created young and old non-human primate single-nucleus/cell transcriptomic atlases of lung, heart and artery, the top tissues targeted by SARS-CoV-2. Analysis of cell type-specific aging-associated transcriptional changes revealed increased systemic inflammation and compromised virus defense as a hallmark of cardiopulmonary aging. With age, expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) was increased in the pulmonary alveolar epithelial barrier, cardiomyocytes, and vascular endothelial cells. We found that interleukin 7 (IL7) accumulated in aged cardiopulmonary tissues and induced ACE2 expression in human vascular endothelial cells in an NF-κB-dependent manner. Furthermore, treatment with vitamin C blocked IL7-induced ACE2 expression. Altogether, our findings depict the first transcriptomic atlas of the aged primate cardiopulmonary system and provide vital insights into age-linked susceptibility to SARS-CoV-2, suggesting that geroprotective strategies may reduce COVID-19 severity in the elderly.
New Recovery Programs Target COVID Long-Haulers
MedPage Today, September 10, 2020
Pulmonologists, cardiologists, neurologists, psychiatrists, and more join to get patients on their feet for good. Zijian Chen, MD, leads Mount Sinai’s COVID-19 recovery program, which is currently treating about 400 patients. At their first visit, patients are evaluated by a primary care physician for symptoms and referred to the appropriate specialists, Chen said. “Right now, we have almost every medical specialty working with the program,” Chen told MedPage Today. “We’re looking at a broad spectrum of disease. Some may have permanent lung fibrosis … that may last for the rest of their lives. Others have reactive airway or inflammatory problems that will subside over time. It’s unpredictable. It’s the same for cardiac symptoms and neurological symptoms.” At Hackensack Meridian’s COVID Recovery Center, primary care physicians develop a customized care plan and connect patients with specialists. Pulmonologists there have been treating patients with shortness of breath and exertional fatigue; cardiologists are treating heart function and rhythm disorders, and neurologists are treating comorbidities arising from strokes and clotting disorders, as well as neuropathy and cognitive impairment, according to program chair Laurie Jacobs, MD.
Aldeyra to undertake phase 2 trial of ADX-629 in patients hospitalized with COVID-19
Helio | Ocular Surgery News, September 10, 2020
Aldeyra Therapeutics has received a “study may proceed” letter from the FDA for a phase 2 clinical trial evaluating ADX-629 as a treatment for adult patients hospitalized with COVID-19, according to a press release. “What’s exciting about ADX-629 is its potential to act like a dimmer switch to modulate the aggressive immune response that is a hallmark of SARS-CoV-2, the virus that causes COVID-19,” Todd C. Brady, MD, PhD, president and CEO of Aldeyra, told Healio/OSN. “We’re still in the early innings in terms of clinical testing, but in animal models, ADX-629 has demonstrated a broad and highly statistically significant reduction in cytokine levels, which are critical mediators of inflammation in COVID-19. As a first-in-class, orally available inhibitor of RASP, ADX-629 has the potential to be clinically relevant not only for treating COVID-19 but also an array of inflammatory diseases that are not being adequately addressed by currently available therapies.” The trial will enroll about 30 patients with COVID-19. Enrollment will occur upon hospitalization, and patients will be treated for up to 28 days with orally administered ADX-629 or placebo twice daily. The trial’s key endpoints will include the National Institute of Allergy and Infectious Diseases COVID-19 scale, in addition to levels of cytokines and RASP.
Low Prevalence of Lung Obstruction, Restriction in COVID-19 After ICU Discharge
Pulmonology Advisor, September 9, 2020
Researchers observed a low prevalence of lung obstruction and restriction and either mild or no cognitive impairment in patients with coronavirus disease 2019 (COVID-19) approximately 6 weeks after discharge from the intensive care unit (ICU), according to findings from a small case series published in CHEST. A total of 102 patients who were admitted to a university medical center ICU with COVID-19 as of July 30, 2020, were included in this case series. All patients in underwent follow up at a post-COVID-19 ICU clinic around 6 weeks following discharge. Spirometry was used to assess lung function and exercise capacity. Lung volumes, diffusion capacity, and the 6-minute walking distance (6MWD) were also assessed. The Patient-Reported Outcomes Measurement Information System depression 8a-short score, Quality of Life in Neurological Disorders (Neuro-QoL™) adult cognitive function v2.0 score, the Montreal Cognitive assessment (MOCA) scores, and insomnia severity index were used to assess depression, cognitive function, and insomnia. The majority of patients (85.71%) required mechanical ventilation; the median number of days on ventilation was 11. The median ICU length of stay was 14 days and the median hospital length of stay was 22 days. Additionally, the median days to postdischarge clinic follow-up was 39.5 days.
AstraZeneca halts COVID-19 vaccine trial following adverse reaction in UK participant
Helio | Infectious Disease News, September 9, 2020
AstraZeneca’s phase 3 trial of a COVID-19 vaccine candidate has been put on hold because of a “suspected serious adverse reaction” in a participant from the United Kingdom, according to a report by STAT. AstraZeneca began the phase 3 trial in the United States on August 17. According to information available on clinicaltrials.gov, the trial is being held at 62 sites across the U.S., although not all locations have started enrolling participants. According to STAT, the trials were halted at all locations after a participant in the U.K. trial developed a suspected serious adverse reaction during the trial. In a statement from AstraZeneca issued to STAT, representatives said this is a “routine action” that happens whenever an unexplained illness occurs during a trial. “We are working to expedite the review of the single event to minimize any potential impact on the trial timeline,” they wrote. “We are committed to the safety of our participants and the highest standards of conduct in our trials.”
Abnormal Respiratory Vital Signs, ECG Findings May Predict Early Deterioration in COVID-19
Pulmonology Advisor, September 9, 2020
Abnormal respiratory vital signs coupled with electrocardiogram (ECG) findings of atrial fibrillation (AF)/flutter, right ventricular (RV) strain, or ST-segment abnormalities were found to predict early deterioration in patients with coronavirus disease 2019 (COVID-19), according to a study published in the Mayo Clinic Proceedings. Early triage is crucial for hospitalized patients with COVID-19 who require a higher level of care. In this study, researchers examined medical record data from 3 hospitals in New York City, New York to determine whether early data at emergency department presentation could predict the composite outcome of mechanical ventilation or death within the next 48 hours. The data of 1258 adults with COVID-19 (mean age, 61.6 years) who were hospitalized in March and April 2020 were examined. Electrophysiologists systematically read each patient’s ECG recordings conducted at presentation. A model adjusted for demographics, comorbidities, and vital signs was used to assess the prognostic value of ECG abnormalities. The most common comorbidities in this cohort included hypertension (57%), diabetes (37%), obesity (34%), primary lung disease (17%), and chronic kidney disease (16%). In this cohort, 73 patients (6%) died within 48 hours of presentation, and 14% of patients (n=174) were still alive at this time but were receiving mechanical ventilation. Another 277 patients (22%) died by 30 days. A total of 53% of all intubations occurred within 48 hours of presentation.
Pediatric COVID-19 cases surpass half-million
Infectious Diseases in Children, September 9, 2020
The AAP announced that a total of 513,415 pediatric cases of COVID-19 have been reported, according to an analysis of state-level data. The report found 70,630 new pediatric cases from August 20 to September 3 — a 16% increase from the total case count of 442,785 that was reported on August 19. “These numbers are a chilling reminder of why we need to take this virus seriously,” AAP President Sally Goza, MD, FAAP, said in a statement. “While much remains unknown about COVID-19, we do know that the spread among children reflects what is happening in the broader communities. A disproportionate number of cases are reported in Black and Hispanic children and in places where there is high poverty. We must work harder to address societal inequities that contribute to these disparities.” As of September 3, the total number of pediatric COVID-19 cases represents 9.8% of all reported cases.
Long-Term Lung, Health Issues Common in COVID-19
MedPage Today, September 8, 2020
Persistent lung issues are common following hospital discharge for COVID-19, but recovery is more the rule than the exception, according to two studies presented at the virtual European Respiratory Society International Congress. Among 86 patients admitted for COVID-19 at three hospitals in the Tyrolean Alps from late April through early June, 39% and 15% of patients, respectively, were still experiencing shortness of breath and coughing after 12 weeks, reported Sabrina Sahanic of the University Clinic of Internal Medicine in Innsbruck. Moreover, 56% showed evidence of COVID-19-related lung damage on CT scans. “COVID-19 survivors had persistent lung impairment weeks after recovery. Yet, over time, a moderate improvement is detectable,” Sahanic said at a press briefing. That was documented in a second study led by doctoral candidate Yara Al Chikhanie of Grenoble Alps University in France — another international ski destination — examining outcomes in 19 patients who had required mechanical ventilation for COVID-19.
Increased Odds of Death for Patients with Interstitial Lung Disease and COVID-19: A Case-Control Study
American Journal of Respiratory and Critical Care Medicine, September 8, 2020
Coronavirus disease 2019 (COVID-19) is an international public health emergency. While the prevalence of chronic respiratory disease in patients with COVID-19 has been reportedly low (1.5%), it is associated with increased risk of severe disease and—in chronic obstructive pulmonary disease—increased mortality. Along with numerous previously reported risk factors for severe COVID-19, it has been hypothesized that patients with interstitial lung diseases (ILD) may have poorer outcomes from COVID-19. In this letter, we present the results of a multicenter retrospective case-control study examining outcomes from COVID-19 in patients with pre-existing ILD. Adult patients (>18 years) with pre-existing ILD diagnosed with COVID-19 by real-time polymerase chain reaction (RT-PCR) or with negative RT-PCR but positive immunoglobulin M (IgM) and/or G (IgG) serology between March 1 and June 8, 2020 at six Mass General Brigham hospitals (Boston, MA) were identified using the electronic health record-integrated centralized clinical data registry. ILD was defined as physician diagnosis or, if no pulmonology visit existed in our system, ILD was defined as radiologic evidence with confirmatory histopathology.
Bedside MRI Feasible in ICU, for COVID-19
MedPage Today, September 8, 2020
A bedside low-field MRI scanner proved its mettle in Yale New Haven Hospital’s ICU, including for COVID-19 patients, clinicians there reported. Among 50 patients scanned in their ICU, the Hyperfine’s Swoop portable MRI system identified neuroimaging abnormalities for eight of the 20 on ventilation for COVID-19 (40%) and 29 of the 30 without COVID-19 (97%) reported in JAMA Neurology. No adverse events or complications occurred with the device or in-room scanning. No ICU equipment had to be removed from the room; the MRI imaging operator and bedside nurse remained in the room for the 0.064-T scans. The Swoop MRI device, which was cleared by the FDA last month for bedside use, wheels to the patient’s bedside, plugs into a standard electrical outlet, and is controlled through a wireless tablet.
The coronavirus is mutating — does it matter?
Nature, September 8, 2020
When COVID-19 spread around the globe this year, David Montefiori wondered how the deadly virus behind the pandemic might be changing as it passed from person to person. Montefiori is a virologist who has spent much of his career studying how chance mutations in HIV help it to evade the immune system. The same thing might happen with SARS-CoV-2, he thought. In March, Montefiori, who directs an AIDS-vaccine research laboratory at Duke University in Durham, North Carolina, contacted Bette Korber, an expert in HIV evolution and a long-time collaborator. Korber, a computational biologist at the Los Alamos National Laboratory (LANL) in Sante Fe, New Mexico, had already started scouring thousands of coronavirus genetic sequences for mutations that might have changed the virus’s properties as it made its way around the world. Compared with HIV, SARS-CoV-2 is changing much more slowly as it spreads. But one mutation stood out to Korber. It was in the gene encoding the spike protein, which helps virus particles to penetrate cells. Korber saw the mutation appearing again and again in samples from people with COVID-19. At the 614th amino-acid position of the spike protein, the amino acid aspartate (D, in biochemical shorthand) was regularly being replaced by glycine (G) because of a copying fault that altered a single nucleotide in the virus’s 29,903-letter RNA code. Virologists were calling it the D614G mutation.
Developing a COVID-19 mortality risk prediction model when individual-level data are not available
Nature Communications, September 7, 2020
At the COVID-19 pandemic onset, when individual-level data of COVID-19 patients were not yet available, there was already a need for risk predictors to support prevention and treatment decisions. Here, we report a hybrid strategy to create such a predictor, combining the development of a baseline severe respiratory infection risk predictor and a post-processing method to calibrate the predictions to reported COVID-19 case-fatality rates. With the accumulation of a COVID-19 patient cohort, this predictor is validated to have good discrimination (area under the receiver-operating characteristics curve of 0.943) and calibration (markedly improved compared to that of the baseline predictor). At a 5% risk threshold, 15% of patients are marked as high-risk, achieving a sensitivity of 88%. We thus demonstrate that even at the onset of a pandemic, shrouded in epidemiologic fog of war, it is possible to provide a useful risk predictor, now widely used in a large healthcare organization.
T cells in COVID-19 — united in diversity Nature Immunology, September 7, 2020
Comprehensive mapping reveals that functional CD4+ and CD8+ T cells targeting multiple regions of SARS-CoV-2 are maintained in the resolution phase of both mild and severe COVID-19, and their magnitude correlates with the antibody response. CD4+ and CD8+ T cells work with other constituents of a coordinated immune response to first resolve acute viral infections and then to provide protection against reinfection. Careful delineation of the frequency, specificity, functionality and durability of T cells during COVID-19 is vital to understanding how to use them as biomarkers and targets for immunotherapies or vaccines. In this issue of Nature Immunology, Peng et al. take a comprehensive approach to characterizing circulating SARS-CoV-2-specific CD4+ and CD8+ T cells following resolution of COVID-19. They report a robust and diverse T cell response targeting multiple structural and non-structural regions of SARS-CoV-2 in most resolved cases, irrespective of whether the individual had mild or severe infection. While the most frequent responses were against peptides spanning spike, membrane and nucleoprotein antigens, all eight regions tested were recognized by multiple individuals, with a maximum of 23 reactive pools in two individuals. Such multispecific T cell responses are well suited to providing a failsafe form of multilayered protection, mitigating against viral escape by mechanisms such as mutation or variable antigen presentation.
PICS: A Serious Issue for COVID-19 Survivors
MedPage Today, September 6, 2020
Even healthcare professionals may not be aware of and prepared for a condition called post-intensive care unit (ICU) syndrome (PICS) that can occur in the aftermath of COVID-19. What about those who were hospitalized for COVID-19, treated in the ICU, and are unaware of the possible long-term impact and rehabilitation phase? There is a tendency to think that once the patient is discharged from the hospital, has tested negative, and looks well, the problem is resolved. However, the struggle of COVID-19 survivors and family members or caregivers may not end there. PICS is an ongoing challenge that may potentially present a public health crisis. PICS is a term used to describe the group of impairments faced by ICU survivors. It can persist for months or years. PICS encompasses a combination of physical, neurological, social, and psychological decline. The physical impairments include intensive care-acquired weakness, classified as critical illness myopathy, neuropathy, and neuromyopathy. Cognitive and psychological impairments involve impaired memory, language, delirium, depression, anxiety, and post-traumatic stress disorder (PTSD). During the COVID-19 pandemic, critically ill clients are considered the most vulnerable to PICS. Among these, 30% suffer from depression and 70% experience anxiety and PTSD after ICU discharge. Moreover, survivors can experience additional stress as a result of isolation and limited contact with loved ones and reduced contact with staff due to precautionary measures such as personal protective equipment.
CDC: Weekly COVID-19 Deaths Down, but Still Above Epidemic Threshold
Infectious Disease Special Edition, September 4, 2020
As of Sept 4, almost 190,000 people in the United States have died from COVID-19, according to the Johns Hopkins COVID-19 Dashboard, but the weekly numbers appear to be slowing. The deaths attributed to COVID-19 during the last week of August are down, but the percentage still exceeds the epidemic threshold, according to the National Center for Health Statistics (NCHS) database. Provisional data from across the United States show that based on death certificates available on Aug. 27, the percentage of deaths attributed to COVID-19, pneumonia or influenza for week 34 was 7.9%. During week 33, it was 23.3%. In addition, the statistics show that only 6% of deaths listed just COVID-19 as a cause of death. Most certificates list comorbid conditions, such as respiratory and cardiovascular conditions, as contributors to the deaths. “In 94% of deaths with COVID-19, other conditions are listed in addition to COVID-19,” the NCHS told Infectious Disease Special Edition. “These causes may include chronic conditions like diabetes or hypertension. They may also include acute conditions that occurred as a result of COVID-19, such as pneumonia or respiratory failure.”
Invasive fungal disease common among critically ill COVID-19 patients, study finds
Helio | Infectious Disease News, September 4, 2020
Invasive fungal disease occurs often in critically ill patients with COVID-19 on mechanical ventilation, according to a study published in Clinical Infectious Diseases. “With the COVID-19 pandemic far from over, it is paramount that our understanding of the risk from associated invasive fungal disease is enhanced,” P. Lewis White, PhD, FECMM, FRCPath, consultant clinical scientist and head of the mycology reference laboratory for Public Health Wales, told Healio. White and colleagues screened 135 patients with COVID-19 for invasive fungal disease to evaluate an enhanced testing strategy. The patients were from a national, multicenter cohort in Wales. The incidence of invasive fungal disease was 26.7% — 14.1% aspergillosis and 12.6% yeast infections. The overall mortality rate was 38%, including 53% in patients with fungal disease and 31% in patients without it (P = .0387). The overall mortality rate declined when antifungal therapy was used. It was 38.5% in patients who received antifungal therapy vs. 90% in patients who did not (P = .008). White said they did not expect the high rate of invasive yeast infections.
Will Labor Day Weekend Bring Another Holiday COVID Surge?
Kaiser Health News, September 4, 2020
Hopefully, summer won’t end the way it began. Memorial Day celebrations helped set off a wave of coronavirus infections across much of the South and West. Gatherings around the Fourth of July seemed to keep those hot spots aflame. And now Labor Day arrives as those regions are cooling off from COVID-19. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, warned Wednesday that Americans should be cautious to avoid another surge in infection rates. But travelers are also weary of staying home — and tourist destinations are starved for cash. “Just getting away for an hour up the street and staying at a hotel is like a vacation, for real,” says Kimberly Michaels, who works for NASA in Huntsville, Alabama, and traveled to Nashville, Tennessee, with her boyfriend to celebrate his birthday last weekend. In time for the tail end of summer, many local governments are lifting restrictions to resuscitate tourism activity and rescue small businesses.
COVID-19 impact on treatment for chronic illness revealed
UN News, September 4, 2020
The four most common NCDs are cardiovascular disease, cancer, diabetes and chronic respiratory diseases; together, they contribute to more than 40 million deaths a year, said Dr Bente Mikkelsen, Director, WHO Division of Noncommunicable Diseases. “The most recent study shows that there is a disruption in healthcare services including NCD diagnosis and treatments in 69 per cent of cases”, she said. “In cancer, there are the highest numbers, with 55 per cent of people living with cancer (having) their health services disrupted.” Dr Mikkelsen noted that those living with one or more NCDs were among the most likely to become severely ill and die from the new coronavirus. Studies from several countries had indicated this, she said, highlighting how data on indigenous communities in Mexico, showed that diabetes was the most commonly found disease among COVID-19 fatalities. Research also found that in Italy, of those who succumbed to COVID-19 in hospital, 67 per cent suffered from hypertension and 31 per cent had type 2 diabetes.
Early outcomes show survival benefit with ECMO support in severe COVID-19
Helio | Pulmonology, September 3, 2020
Early outcomes of a single-center study demonstrate clinical benefit of extracorporeal membrane oxygenation support in patients with severe COVID-19, according to a study published in The Annals of Thoracic Surgery. “Our experience differs from other published data which suggested that ECMO is of limited value for patients with COVID-19. Although still early in many of these patients’ clinical courses, these initial outcomes are encouraging with an overall current survival of 96%, with nearly half of the patients already weaned from ECMO support, mechanical ventilation and supplemental oxygen. Furthermore, a significant number of these patients have been discharged from the hospital,” Zachary N. Kon, MD, cardiothoracic surgeon in the department of cardiothoracic surgery at NYU Langone Health, and colleagues wrote. Researchers conducted a retrospective analysis of 321 endotracheal-intubated patients with COVID-19 from March 10 to April 24, 2020. Of those, 77 (24%) were evaluated for ECMO support. ECMO support was selected based on patients’ partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio less than 150 mm Hg or pH less than 7.25 with an arterial partial pressure of carbon dioxide greater than 60 mm Hg. Patients were cannulated and managed with protective lung ventilation, early tracheostomy, bronchoscopies and proning in NYU Langone Health’s Manhattan campus ICU.
FDA Could Issue EUA for COVID-19 Vaccine Before Clinical Trials Are Completed
Pulmonology Advisor, September 3, 2020
Emergency use authorization (EUA) or approval for a COVID-19 vaccine before phase 3 clinical trials are complete could be considered by the U.S. Food and Drug Administration, according to the agency’s commissioner, Stephen Hahn, M.D. “It is up to the sponsor [vaccine developer] to apply for authorization or approval, and we make an adjudication of their application,” he told the Financial Times, CNN reported. “If they do that before the end of phase 3, we may find that appropriate. We may find that inappropriate, we will make a determination.” An EUA is not the same as full-fledged approval, Hahn noted. “Our emergency use authorization is not the same as a full approval,” he said. “The legal, medical, and scientific standard for that is that the benefit outweighs the risk in a public health emergency.” Two vaccines are currently in phase 3 trials in the United States and two more are expected to begin phase 3 trials by mid-September, CNN reported.
Technology Aids Fight Against COVID-19 — Nine innovations in health tech that help to manage the pandemic
MedPage Today, September 3, 2020
As the COVID-19 cases continue to rise across the globe, companies are working hard to develop innovative solutions to fight the coronavirus pandemic. Chinese companies such as Alibaba have led the way using artificial intelligence, data science, and technology. Startups are teaming up with clinicians, engineers, and government entities to reduce the spread of COVID-19. As we continue our fight in the management and eventual eradication of the virus, read about nine innovative ways companies are helping on the front lines.
Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19 – The CoDEX Randomized Clinical Trial
Journal of the American Medical Association, September 2, 2020
In patients with coronavirus disease 2019 (COVID-19) and moderate or severe acute respiratory distress syndrome (ARDS), does intravenous dexamethasone plus standard care compared with standard care alone increase the number of days alive and free from mechanical ventilation? ARDS due to COVID-19 is associated with substantial mortality and use of health care resources. Dexamethasone use might attenuate lung injury in these patients. The objective of the clinical trial was to determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19–associated ARDS. This multicenter, randomized, open-label, clinical trial was conducted in 41 intensive care units (ICUs) in Brazil. Patients with COVID-19 and moderate to severe ARDS, according to the Berlin definition, were enrolled from April 17 to June 23, 2020. Final follow-up was completed on July 21, 2020. The trial was stopped early following publication of a related study before reaching the planned sample size of 350 patients. Twenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n =151) or standard care alone (n = 148).
Fewer serious asthma events in Philadelphia after COVID-19 stay-at-home orders
Helio | Pulmonology, September 2, 2020
Public health interventions and stay-at-home orders issued in March in the Philadelphia region to limit the transmission of COVID-19 also led to a marked decrease in health care visits for outpatient and hospitalized patients with asthma. Researchers with the Children’s Hospital of Philadelphia and the Hospital of the University of Pennsylvania reviewed electronic health records to analyze asthma-related encounters and weekly summaries of respiratory viral testing in the 60 days leading up to March 17, when Philadelphia issued a series of stay-at-home orders, compared with the 60 days following stay-at-home orders. They found a 60% decrease in total daily asthma health care visits across CHOP’s hospital and Care Network, according to data published in The Journal of Allergy and Clinical Immunology: In Practice. Further, fewer rhinovirus infections due to mask wearing, social distancing and hygiene measures may have contributed to these findings, the researchers reported. After March, in-person asthma encounters decreased by 87% in the outpatient setting and by 84% in the emergency and inpatient settings, according to the findings. During the pandemic, video telemedicine was the most-utilized modality for asthma encounters and was used in 61% of all visits, while telephone encounters increased by 19%. During the same period, the researchers observed decreases in asthma-related systemic steroid prescriptions and the frequency of rhinovirus test positivity.
Understanding the Association Between COVID-19, Thromboembolism, and Therapeutic Anticoagulation
Pulmonology Advisor, September 2, 2020
Among hospitalized patients with coronavirus disease 2019 (COVID-19), those who receive anticoagulation treatment have lower adjusted risk of mortality and intubation compared with in-hospital patients who do not receive anticoagulation, according to study results published in the Journal of the American College of Cardiology. A team of investigators at Icahn School of Medicine at Mount Sinai in New York, New York, expanded on previous findings that suggested an association between in-hospital anticoagulation and reduced mortality. In the present investigation, the researchers compared the effects of therapeutic and prophylactic anticoagulation treatment with the absence of such treatment. Choice of agent, survival outcomes, intubation, and major bleeding were also analyzed. In addition, the study authors also reviewed the first consecutive autopsies performed at their institution to characterize the premortem management of this patient population as it relates to anticoagulation therapy. The primary outcome was in-hospital mortality, and secondary outcomes included intubation and major bleeding. Participants were all older than 18 years, had clinically confirmed severe acute respiratory syndrome coronavirus 2 infection between March 1, 2020, and April 30, 2020, and were admitted to 1 of 5 New York City hospitals included in the study.
Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19 – A Meta-analysis
Journal of the American Medical Association, September 2, 2020
Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support. The objective of this analysis was to estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality. Prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The trials were conducted in 12 countries from February 26, 2020, to June 9, 2020, and the date of final follow-up was July 6, 2020. Pooled data were aggregated from the individual trials, overall, and in predefined subgroups. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance–weighted fixed-effect meta-analysis of overall mortality, with the association between the intervention and mortality quantified using odds ratios (ORs). Random-effects meta-analyses also were conducted (with the Paule-Mandel estimate of heterogeneity and the Hartung-Knapp adjustment) and an inverse variance–weighted fixed-effect analysis using risk ratios. Patients had been randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients).
Kevzara fails to meet endpoints in ex-US phase 3 trial for severe COVID-19
Helio | Rheumatology, September 2, 2020
Sanofi announced that its IL-6 inhibitor Kevzara failed to meet primary and secondary endpoints in a phase 3 trial of patients outside the United States hospitalized with severe COVID-19. “Although this trial did not yield the results we hoped for, we are proud of the work that was achieved by the team to further our understanding of the potential use of Kevzara for the treatment of COVID-19,” John Reed, MD, PhD, global head of research and development at Sanofi, said in a company press release. The randomized trial included 420 patients who were severely or critically ill with COVID-19, recruited from hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia and Spain. Among the participants, 161 received 200 mg of Kevzara (sarilumab), 173 were treated with 400 mg and 86 received a placebo. According to the press release, although not statistically significant, the researchers observed numerical trends toward a decrease in hospital stay duration as well as faster time to better clinical outcomes, defined as a two-point improvement on a seven-point scale. In addition, the researchers noted a trend toward reduced mortality in the critical patient group, but not in the severe group. Lastly, the time to discharge was reduced by 2 to 3 days among patients who received sarilumab within the first 2 weeks of treatment, although, again, this was not statistically significant.
Safety, Immunogenicity of Investigational Inactivated Whole-Virus COVID-19 Vaccine
Pulmonology Advisor, September 1, 2020
An investigational inactivated whole-virus coronavirus disease 2019 (COVID-19) vaccine has demonstrated safety and immunogenicity, according to the results of an interim analysis published in JAMA. The study authors examined safety outcomes 28 days, and immunogenicity outcomes 14 days after 3 doses in a phase 1 trial and 2 doses in a phase 2 trial of an inactivated COVID-19 vaccine candidate in healthy adults in China. The double-blind, randomized, placebo-controlled study was designed by the Wuhan Institute of Biological Products Co Ltd, and Henan Provincial Center for Disease Control and Prevention (CDC). Healthy adults aged 18 to 59 years without a history of severe acute respiratory syndrome coronavirus (SARS-CoV) or SARS-CoV-2 infection were eligible for enrollment. Currently, there are 160 COVID-19 candidate vaccines in various stages of development, with 25 in different phases of clinical trials. This is the first report of phase 1 and 2 clinical trials of a whole virus-inactivated COVID-19 vaccine in adults.
Comparing Asthma Complications in COVID-19 With Flu
ContagionLive, August 31, 2020
A research letter published in Annals of the American Thoracic Society has challenged US Centers for Disease Control and Prevention (CDC) assumptions that those with asthma are at higher risk for severe SARS-CoV-2 infection. Research was led by Fernando Holguin, MD, MPH, of the Pulmonary Division at University of Colorado’s Anschutz Medical Campus. People living with asthma often make up more than 20 percent of those hospitalized in the United States during the annual influenza season. For SARS-CoV-2, several noteworthy risk factors for hospitalization such as hypertension, diabetes, chronic obstructive pulmonary disease, and obesity have been demonstrated. Amid the outbreak of Middle East Respiratory Syndrome (MERS), there was sparse evidence asthma patients may be at higher risk. But the underwhelming proportion of people with asthma among patients across several international studies raises questions about asthma as a particular risk factor when it comes to being hospitalized for coronavirus disease 2019 (COVID-19). The study team examined asthma prevalence among patients hospitalized for COVID-19 reported in 15 studies with population asthma prevalence and a 4-year average of asthma prevalence in influenza hospitalizations across the United States.
Coronavirus in Context: Do Antibodies Provide Protection?
WebMD, August 31, 2020
[Video] What’s the role of antibodies against coronavirus infection? It’s one of the biggest questions over the past six months. WebMD’s Chief Medical Officer, Dr. John Whyte, speaks with Alexander Greninger, MD, PhD, Assistant Director of the UW Medicine Clinical Virology Laboratory, University of Washington, about the effectives of antibodies for COVID-19 immunity and transmission.
1st U.S. COVID-19 Reinfection Reported in Nevada Patient
WebMD, August 31, 2020
The first U.S. case of a confirmed coronavirus reinfection looks to be a patient in Nevada. The U.S. case comes a few days after the first reinfection in the world was announced in Hong Kong. The Nevada case is detailed in a new paper published in The Lancet on an online preprint server. The study has not yet been reviewed by peers. Reinfection is rare, researchers said, but people should still be cautious. “If you’ve had it, you can’t necessarily be considered invulnerable to the infection,” Mark Pandori, one of the authors and director of the Nevada State Public Health Laboratory, told NBC. According to the report, the 25-year-old man from Reno, Nevada, first tested positive for COVID-19 in mid-April after experiencing a sore throat, cough, headache, nausea, and diarrhea. He recovered but got sick again in late May, marking 48 days between two positive tests after two negative tests in between the infections. During the second round, his illness was more severe, and he was hospitalized with pneumonia. Researchers found that the genetic sequencing of the virus varied, and the patient was infected with slightly different strains of the coronavirus. They aren’t sure why he was reinfected, which could be related to the virus itself or the patient’s immune system.
Management of pneumothorax in mechanically ventilated COVID-19 patients: early experience
Interactive CardioVascular and Thoracic Surgery, August 31, 2020
Pneumothorax, a major and potential fatal complication of mechanical ventilation, can further complicate the management of COVID-19 patients, whilst chest drain insertion may increase the risk of transmission of attending staff. The rate of pneumothorax in such patients has not yet been quantified. However, previous experience from the SARS outbreak, also caused by a coronavirus, suggests a high incidence (20–34%) of pneumothorax in mechanically ventilated SARS patients. Mechanical ventilation is the most common cause of iatrogenic pneumothoraces in the ICU setting; however, it is a rare occurrence in intubated patients who have relatively normal lung parenchyma. Most pneumothoraces related to mechanical ventilation are associated with a combination of high ventilation pressures and underlying chronic lung pathology such as emphysema. Previous studies have suggested that high inspiratory airway pressures and positive end-expiratory pressure were correlated with increased incidence of barotrauma. Currently, there is limited literature on how to manage pneumothoraces in mechanically ventilated COVID-19 patients. We present a case series (nine patients) and a suggested protocol for how to manage and treat pneumothoraces in COVID-19 patients in an ICU setting.
Duration of COVID-19: Data from an Italian Cohort and Potential Role for Steroids
Microorganisms, August 31, 2020
The diffusion of SARS-CoV-2, starting from China in December 2019, has led to a pandemic, reaching Italy in February 2020. Previous studies in Asia have shown that the median duration of SARS-CoV-2 viral shedding was approximately 12–20 days. We considered a cohort of patients recovered from COVID-19 showing that the median disease duration between onset and end of COVID-19 symptoms was 27.5 days (interquartile range (IQR): 17.0–33.2) and that the median duration between onset of symptoms and microbiological healing, defined by two consecutive negative nasopharyngeal swabs, was 38 days (IQR: 31.7–50.2). A longer duration of COVID-19 with delayed clinical healing (symptom-free) occurred in patients presenting at admission a lower PaO2/FiO2 ratio (p < 0.001), a more severe clinical presentation (p = 0.001) and a lower lymphocyte count (p = 0.035). Moreover, patients presenting at admission a lower PaO2/FiO2 ratio and more severe disease showed longer viral shedding (p = 0.031 and p = 0.032, respectively). In addition, patients treated with corticosteroids had delayed clinical healing (p = 0.013).
New insights into the cell- and tissue-specificity of glucocorticoid actions
Cellular & Molecular Immunology, August 31, 2020
Glucocorticoids (GCs) are endogenous hormones that are crucial for the homeostasis of the organism and adaptation to the external environment. Because of their anti-inflammatory effects, synthetic GCs are also extensively used in clinical practice. However, almost all cells in the body are sensitive to GC regulation. As a result, these mediators have pleiotropic effects, which may be undesirable or detrimental to human health. This articles summarizes the recent findings that contribute to deciphering the molecular mechanisms downstream of glucocorticoid receptor activation. Also discussed, is the complex role of GCs in infectious diseases such as sepsis and COVID-19, in which the balance between pathogen elimination and protection against excessive inflammation and immunopathology needs to be tightly regulated. An understanding of the cell type- and context-specific actions of GCs from the molecular to the organismal level would help to optimize their therapeutic use. Here, we highlight the many levels of GR-mediated regulation that have been identified so far and may help to predict the effect of GCs from the molecular to the organismal level. Taking this complexity into account, we also summarize the pathways regulated by endogenous and synthetic GCs in lymphocytes and myeloid cells. Finally, we use sepsis as an example of a pathological condition for which molecular and cellular studies can improve predictions regarding the systemic response to GCs. We stress the need for cell-targeted GC therapy to prevent not only the well-known adverse effects of GCs but also those effects that may reduce treatment efficacy.
Fad or future? Telehealth expansion eyed beyond pandemic
Modern Healthcare, August 30, 2020
Consultations via tablets, laptops and phones linked patients and doctors when society shut down in early spring. Telehealth visits dropped with the reopening, but they’re still far more common than before and now there’s a push to make them widely available in the future. Permanently expanding access will involve striking a balance between costs and quality, dealing with privacy concerns and potential fraud, and figuring out how telehealth can reach marginalized patients, including people with mental health problems. “I don’t think it is ever going to replace in-person visits, because sometimes a doctor needs to put hands on a patient,” said CMS Administrator Seema Verma, the Trump administration’s leading advocate for telehealth. Caveats aside, “it’s almost a modern-day house call,” she added. “It’s fair to say that telemedicine was in its infancy prior to the pandemic, but it’s come of age this year,” said Murray Aitken of the data firm IQVIA, which tracks the impact. In the depths of the coronavirus shutdown, telehealth accounted for more than 40% of primary care visits for patients with traditional Medicare, up from a tiny 0.1% sliver before the public health emergency. As the government’s flagship health care program, Medicare covers more than 60 million people, including those age 65 and older, and younger disabled people.
Findings from a probability-based survey of U.S. households about prevention measures based on race, ethnicity, and age in response to SARS-CoV-2
Journal of Infectious Diseases, August 29, 2020
There are 21.7 million reported cases of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and over 776,000 deaths due to the coronavirus disease 2019 (COVID-19) worldwide through August 17, 2020. Over one-fourth of cases are in the U.S., with African American and Latinos being disproportionately impacted in case counts and death rates. Prevention control messages and efforts, such as sheltering in place and quarantining, may not have been as successful among African Americans and Latinos for numerous reasons, such as needing to work outside of the home, living in large households in close quarters, and including the effects of structural racism (i.e., access to health insurance and care, limited health literacy). Little is known about individual prevention measures that were taken in response to COVID-19 or how people may engage with surveillance/reporting strategies as we enter phase two of the pandemic. We investigated individual behaviors taken by White, African American, and Latino U.S. households in response to SARS-CoV-2, and likelihood of using digital tools for symptom surveillance/reporting. We analyzed cross-sectional week one data (April 2020) of the COVID Impact Survey in a large, nationally-representative sample of U.S. adults. In general, all groups engaged in the same prevention behaviors, but Whites reported being more likely to use digital tools to report/act on symptoms and seek testing, versus African Americans and Latinos.
Fauci on ‘Highly Specific, Direct’ Therapy for COVID-19
MedPage, August 28, 2020
Monoclonal antibodies could hold promise in COVID-19 treatment and prevention if the results bear out in clinical trials for efficacy, the nation’s leading infectious diseases expert told MedPage Today. “There’s a lot of activity and it’s a highly concentrated, highly specific, direct antiviral approach to a number of diseases. The success in Ebola was very encouraging,” said National Institute of Allergy and Infectious Diseases (NIAID) Director Anthony Fauci, MD. Most recently thrust into the spotlight as effective treatments for Ebola, monoclonal antibodies are currently being researched as a potential treatment for HIV, as well as COVID-19. This month, the NIH highlighted trials of monoclonal antibodies being conducted among several different COVID-19 patient populations: outpatients with COVID-19, patients hospitalized with the disease, and even a trial in household contacts of confirmed cases, where the therapy was used as prophylaxis. Fauci explained how the mechanism of monoclonal antibodies “is really one of a direct antiviral. It’s like getting a neutralizing antibody that’s highly, highly concentrated and highly, highly specific. So, the mechanism involved is blocking of the virus from essentially entering its target cell in the body and essentially interrupting the course of infection,” he said.
The FIB-4 Index Is Associated with Need for Mechanical Ventilation and 30-day Mortality in Patients Admitted with COVID-19
Journal of Infectious Diseases, August 28, 2020
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), can be associated with a severe systemic disease leading to respiratory failure and the need for mechanical ventilation. Patients with underlying medical comorbidities, such as respiratory, cardiac, and liver disease, diabetes mellitus (DM), and obesity are at higher risk for respiratory failure. Therefore, prediction factors are needed to help front line providers to identify who might be at higher risk for intensive care and ventilator support for respiratory failure. The fibrosis-4 index (FIB-4), developed to predict fibrosis in liver disease, was used to identify patients with COVID-19 who will require ventilator support as well as associated with 30-day mortality. Multivariate analysis found obesity (OR 4.5), diabetes (OR 2.55), and FIB-4 ≥ 2.67 (OR 3.09) independently associated with need for mechanical ventilation. When controlling for ventilator use, gender, and comorbid conditions, FIB-4 ≥ 2.67 was also associated with increased 30-day mortality (OR 8.4; 95% CI 2.23-31.7). While it may not be measuring hepatic fibrosis, its components suggest that increases in FIB-4 may be reflecting systemic inflammation associated with poor outcomes.
Sudden Cardiac Arrest in a Patient with Myxedema Coma and COVID-19
Journal of the Endocrine Society, August 28, 2020
SARS-CoV-2 infection is associated with significant lung and cardiac morbidity but there is a limited understanding of the endocrine manifestations of COVID-19. We present the first case of myxedema coma in COVID-19 and we discuss how SARS-CoV-2 may have precipitated multi-organ damage and sudden cardiac arrest in our patient. A 69-year-old female with a history of small cell lung cancer presented with hypothermia, hypotension, decreased respiratory rate, and a Glasgow Coma Scale score of 5. The patient was intubated and administered vasopressors. Laboratory investigation showed elevated thyroid stimulating hormone, very low free thyroxine, elevated thyroid peroxidase antibody, and markedly elevated inflammatory markers. SARS-CoV-2 test was positive. Computed tomography showed pulmonary embolism and peripheral ground glass opacities in the lungs. The patient was diagnosed with myxedema coma with concomitant COVID-19. While treatment with intravenous hydrocortisone and levothyroxine were begun the patient developed a junctional escape rhythm. Eight minutes later, the patient became pulseless and was eventually resuscitated. Echocardiogram following the arrest showed evidence of right heart dysfunction. She died two days later from multi-organ failure. This is the first report of SARS-CoV-2 infection with myxedema coma. Sudden cardiac arrest likely resulted from the presence of viral pneumonia, cardiac arrhythmia, pulmonary emboli, and myxedema coma – all of which were associated with the patient’s SARS-CoV-2 infection.
The coronavirus is most deadly if you are older and male — new data reveal the risks
Nature, August 28, 2020
For every 1,000 people infected with the coronavirus who are under the age of 50, almost none will die. For people in their fifties and early sixties, about five will die — more men than women. The risk then climbs steeply as the years accrue. For every 1,000 people in their mid-seventies or older who are infected, around 116 will die. These are the stark statistics obtained by some of the first detailed studies into the mortality risk for COVID-19. Trends in coronavirus deaths by age have been clear since early in the pandemic. Research teams looking at the presence of antibodies against SARS-CoV-2 in people in the general population — in Spain, England, Italy and Geneva in Switzerland — have now quantified that risk, says Marm Kilpatrick, an infectious-disease researcher at the University of California, Santa Cruz. The studies reveal that age is by far the strongest predictor of an infected person’s risk of dying — a metric known as the infection fatality ratio (IFR), which is the proportion of people infected with the virus, including those who didn’t get tested or show symptoms, who will die as a result. “COVID-19 is not just hazardous for elderly people, it is extremely dangerous for people in their mid-fifties, sixties and seventies,” says Andrew Levin, an economist at Dartmouth College in Hanover, New Hampshire, who has estimated that getting COVID-19 is more than 50 times more likely to be fatal for a 60-year-old than is driving a car. But “age cannot explain everything”, says Henrik Salje, an infectious-disease epidemiologist at the University of Cambridge, UK. Gender is also a strong risk factor, with men almost twice more likely to die from the coronavirus than women.
Heparin may neutralize virus that causes COVID-19
Helio | HemOnc Today, August 28, 2020
The COVID-19 pandemic has prompted a flurry of scientific studies of various potential treatments and vaccines for the novel coronavirus. One such study, conducted by researchers at Rensselaer Polytechnic Institute and published in Antiviral Research, showed the FDA-approved anticoagulant heparin may neutralize SARS-CoV-2, the virus that causes COVID-19. SARS-CoV-2 uses a surface spike protein to attach to human cells and infect them, according to the study background. However, because heparin binds tightly with the surface spike protein, it potentially could serve as a decoy and prevent infection from occurring. “We’ve known for quite some time that heparin possesses the ability to be antiviral; it has the ability to bind to very specific proteins on the surfaces of viruses,” Jonathan S. Dordick, PhD, the Howard P. Isermann Professor of Chemical and Biological Engineering at Rensselaer and one of the study authors, said in an interview with Healio. “So that wasn’t really a surprise. The other reason we studied heparin had nothing to do with its antiviral properties.”
Trial Evaluating Half-Life Extended Monoclonal Antibodies for COVID-19 Begins
Pulmonary Advisor, August 27, 2020
A phase 1 study of AstraZeneca’s investigational monoclonal antibody AZD7442 for the prevention and treatment of coronavirus disease 2019 (COVID-19) has been initiated. AZD7442 is a combination of 2 monoclonal antibodies derived from convalescent patients who were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The monoclonal antibodies have been optimized with an extended half-life to afford at least 6 months of protection from COVID-19. According to preclinical data recently published in Nature, the monoclonal antibodies protect against infection by blocking SARS-CoV-2 virus from binding to host cells. The randomized, double-blind, placebo-controlled phase 1 study will evaluate the safety, tolerability, and pharmacokinetics of AZD7442 in up to 48 healthy participants aged 18 to 55 years. The study is funded by the Defense Advanced Research Projects Agency (DARPA) and the Biomedical Advanced Research and Development Authority (BARDA) at the US Department of Health and Human Services.
Sex differences in immune responses that underlie COVID-19 disease outcomes
Nature, August 26, 2020
A growing body of evidence reveals that male sex is a risk factor for a more severe disease, including death. Globally, ~60% of deaths from COVID-19 are reported in men, and a cohort study of 17 million adults in England reported a strong association between male sex and risk of death from COVID-19 (hazard ratio 1.59, 95% confidence interval 1.53-1.65. .53-1.65). Past studies have demonstrated that sex has a significant impact on the outcome of infections and has been associated with underlying differences in immune response to infection. For example, prevalence of hepatitis A and tuberculosis are significantly higher in men compared with women. Viral loads are consistently higher in male patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Conversely, women mount a more robust immune response to vaccines. However, the mechanism by which SARS-CoV-2 causes more severe disease in male patients than in female patients remains unknown. To elucidate the immune responses against SARS-CoV-2 infection in men and women, we performed detailed analysis on the sex differences in immune phenotype via the assessment of viral loads, SARS-CoV-2 specific antibody levels, plasma cytokines/chemokines, and blood cell phenotypes.
The Transformational Effects of COVID-19 on Medical Education
JAMA Network, August 26, 2020
[Podcast] The onset of the COVID-19 pandemic and the public health response required to minimize the catastrophic spread of the disease required an immediate change in the traditional approach to medical education and clearly amplified the need for expanding the competencies of the US physician workforce. Medical educators responded at the local and national levels to outline concerns and offer guiding principles so that academic health systems could support a robust public health response while ensuring that physician graduates are prepared to contribute to addressing current and future threats to the health of communities. While each school approached their response somewhat differently, several common themes have emerged. Join Howard Bauchner, MD, Editor in Chief of JAMA, as he interviews Catherine Lucey, MD, FACP, Department of Medicine, University of California San Francisco School of Medicine and author of The Transformational Effects of COVID-19 on Medical Education.
HF Nasal Cannula Oxygen Reduces Mechanical Ventilation Rates in Severe COVID-19
Pulmonology Advisor, August 26, 2020
High flow nasal cannula oxygen (HFNC) significantly reduced intubation and subsequent invasive mechanical ventilation, but did not affect case fatality in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU) for acute respiratory failure, according to study results published in the American Journal of Respiratory and Critical Care Medicine. Symptomatic management to restore oxygenation of severe acute respiratory failure is key during the COVID-19 pandemic, according to the authors of this retrospective study. HFNC has been shown to improve oxygenation, and reduce minute ventilation and the work of breathing in severe de novo acute hypoxemic respiratory failure. Thus, researchers in Paris, France, tested the hypothesis that HFNC reduces the rates of intubation and mortality in 379 critically ill patients admitted to the ICU for acute respiratory failure between February 21 and April 24, 2020. Overall, 146 (39%) patients received HFNC (all within the first 24 hours following ICU admission) and were compared with 233 patients who did not. The percentage of patients requiring invasive mechanical ventilation at day 28 was 56% in the HFNC group vs 75% in those who did not receive HFNC (P <.0001), and mortality at day 28 was 21% vs 30%, respectively.
Spontaneous subcutaneous emphysema and pneumomediastinum in non-intubated patients with COVID-19
Clinical Imaging, August 26, 2020
Subcutaneous emphysema (SE) and pneumomediastinum refer to the presence of air in the subcutaneous tissue and mediastinum, respectively. Spontaneous pneumomediastinum (SPM) results from a sudden rise in intra-alveolar pressure (such as in the setting of reactive airways disease, Valsalva maneuver, cough, emesis, and barotrauma), resulting in the rupture of alveoli and subsequent dissection of air along the bronchovascular sheath into the mediastinum (Macklin effect). Air may then enter the pleural, pericardial, and peritoneal spaces or the soft tissues of the chest wall, neck, or face causing subcutaneous cervicothoracic emphysema. On their own, these conditions are not typically life-threatening and often resolve with conservative treatment. However, they may indicate the presence of severe underlying pathology. While SE and SPM have been observed in patients with a variety of viral pneumonias as a complication of mechanical ventilation, the development of these conditions in non-intubated patients suggests an alternative etiology. A total of 11 non-intubated COVID-19 patients (8 male and 3 female, median age 61 years) developed SE and SPM. Demographics (age, gender, smoking status, comorbid conditions, and body-mass index), clinical variables (temperature, oxygen saturation, and symptoms), and laboratory values (white blood cell count, C-reactive protein, D-dimer, and peak interleukin-6) were collected. Chest radiography (CXR) and computed tomography (CT) were analyzed for SE, SPM, and pneumothorax by a board-certified cardiothoracic-fellowship trained radiologist.
Professional Quality of Life and Mental Health Outcomes among Health Care Workers Exposed to Sars-Cov-2 (Covid-19)
International Journal of Environmental Research and Public Health, August 26, 2020
Healthcare workers (HCWs) facing COVID-19 pandemic represented an at-risk population for new psychosocial COVID-19 strain and consequent mental health symptoms. The aim of the present study was to identify the possible impact of working contextual and personal variables (age, gender, working position, years of experience, proximity to infected patients) on professional quality of life, represented by compassion satisfaction (CS), burnout, and secondary traumatization (ST), in HCWs facing COVID-19 emergency. Further, two multivariable linear regression analyses were fitted to explore the association of mental health selected outcomes, anxiety and depression, with some personal and working characteristics that are COVID-19-related. A sample of 265 HCWs of a major university hospital in central Italy was consecutively recruited at the outpatient service of the Occupational Health Department during the acute phase of COVID-19 pandemic. HCWs were assessed by Professional Quality of Life-5 (ProQOL-5), the Nine-Item Patient Health Questionnaire (PHQ-9), and the Seven-Item Generalized Anxiety Disorder scale (GAD-7) to evaluate, respectively, CS, burnout, ST, and symptoms of depression and anxiety. Females showed higher ST than males, while frontline staff and healthcare assistants reported higher CS rather than second-line staff and physicians, respectively. Burnout and ST, besides some work or personal variables, were associated to depressive or anxiety scores.
Prediction and Analysis of SARS-CoV-2-Targeting MicroRNA in Human Lung Epithelium
Genes, August 26, 2020
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus, is responsible for the coronavirus disease 2019 (COVID-19) pandemic of 2020. Experimental evidence suggests that microRNA can mediate an intracellular defence mechanism against some RNA viruses. The purpose of this study was to identify microRNA with predicted binding sites in the SARS-CoV-2 genome, compare these to their microRNA expression profiles in lung epithelial tissue and make inference towards possible roles for microRNA in mitigating coronavirus infection. We hypothesize that high expression of specific coronavirus-targeting microRNA in lung epithelia may protect against infection and viral propagation, conversely, low expression may confer susceptibility to infection. We have identified 128 human microRNA with potential to target the SARS-CoV-2 genome, most of which have very low expression in lung epithelia. Six of these 128 microRNA are differentially expressed upon in vitro infection of SARS-CoV-2. Additionally, 28 microRNA also target the SARS-CoV genome while 23 microRNA target the MERS-CoV genome. We also found that a number of microRNA are commonly identified in two other studies. Further research into identifying bona fide coronavirus targeting microRNA will be useful in understanding the importance of microRNA as a cellular defence mechanism against pathogenic coronavirus infections.
Compartmentalized Replication of SARS-Cov-2 in Upper vs. Lower Respiratory Tract Assessed by Whole Genome Quasispecies Analysis
Microorganisms, August 26, 2020
We report whole-genome and intra-host variability of SARS-Cov-2 assessed by next generation sequencing (NGS) in upper (URT) and lower respiratory tract (LRT) from COVID-19 patients. The aim was to identify possible tissue-specific patterns and signatures of variant selection for each respiratory compartment. Six patients, admitted to the Intensive Care Unit, were included in the study. Thirteen URT and LRT were analyzed by NGS amplicon-based approach on Ion Torrent Platform. Bioinformatic analysis was performed using both realized in-house and supplied by ThermoFisher programs. Phylogenesis showed clade V clustering of the first patients diagnosed in Italy, and clade G for later strains. The presence of quasispecies was observed, with variants uniformly distributed along the genome and frequency of minority variants spanning from 1% to ~30%. For each patient, the patterns of variants in URT and LRT were profoundly different, indicating compartmentalized virus replication. No clear variant signature and no significant difference in nucleotide diversity between LRT and URT were observed. SARS-CoV-2 presents genetic heterogeneity and quasispecies compartmentalization in URT and LRT. Intra-patient diversity was low. The pattern of minority variants was highly heterogeneous and no specific district signature could be identified, nevertheless, analysis of samples, longitudinally collected in patients, supported quasispecies evolution.
After Care of Survivors of COVID-19—Challenges and a Call to Action
JAMA Health Forum, August 26, 2020
For most patients with severe illness requiring hospitalization, COVID-19 has been a frightening and life-changing experience. At the peak of the pandemic, the attention of health care teams was focused on saving lives and protecting health services from being overwhelmed. Those who survived were often discharged without a robust process of follow-up. The prevalence of post–COVID-19 complications is not yet fully known and may only become apparent in the months and years to come. Data from previous coronavirus (severe acute respiratory syndrome coronavirus [SARS-CoV] and Middle East respiratory syndrome coronavirus [MERS-CoV]) outbreaks indicate that between 20% and 40% of survivors experience long-term complications. In a recent report of 143 patients with COVID-19 who were evaluated a mean of 2 months after hospital discharge at a follow-up clinic in Rome, Italy, many patients reported persistent fatigue (53.1%), dyspnea (43.4%), joint pain (27.3%), and chest pain (21.7%). Drawing on these experiences, respiratory, cardiovascular, neurologic, metabolic, and psychosocial complications may be important long-term sequelae of COVID-19. It is therefore essential that systems are in place for timely and thorough identification of such sequelae followed by appropriate interventions. We discuss the challenges we have addressed in establishing a multidisciplinary COVID-19 follow-up clinic in a secondary care setting at the University Hospital of Birmingham, England.
Inhaled steroids reduce SARS-CoV-2-related genes in COPD
News Medical, August 25, 2020
The chronic lung condition called COPD (chronic obstructive pulmonary disease) increases the risk of severe COVID-19. Inhaled corticosteroids (ICS) are commonly prescribed to stabilize respiratory function in these patients, but the associated risk of bacterial infection has daunted some healthcare professionals from using them. Moreover, in vitro, studies show that they have an immunosuppressive effect on cells exposed to viruses. There is no evidence to reveal the effects of ICS on either susceptibility to COVID-19 or the severity of infection in patients with COPD. A new study published on the preprint server medRxiv* aims to explore the effects of treatment with ICS on the expression of specific genes related to SARS-CoV-2 infection in bronchial epithelial cells in a prospective interventional design. It is known that COPD can upregulate the expression of angiotensin-converting enzyme (ACE2) in the human lungs. However, in vitro, studies show that ICS reduces ACE2 expression. Observational studies have shown that in both asthma and COPD, the use of ICS reduces the concentration of ACE2 mRNA in sputum. In the DISARM study, the researchers randomized 68 volunteers with mild to very severe COPD to receive either ICS along with a long-acting beta-agonist (LABA) or the LABA alone. Most were male, and the degree of blockage of the airways ranged from moderate to severe. The regimens in the two groups consisted of formoterol/budesonide 12/400 μg twice daily or salmeterol/fluticasone propionate 25/250 μg twice daily), for the first group, and formoterol 12 μg twice daily for the second.
Respiratory distress the cause of most post-COVID hospital readmissions
McKinght’s Long-term Care News, August 25, 2020
Respiratory distress is the most common cause of near-term hospital readmission for patients with COVID-19, investigators have found. Among nearly 2,900 discharged patients studied, 103 returned to the emergency department within two weeks of discharge. Fully 56 of these required hospital readmittance. Respiratory complications were the chief complaint in half of these patients. They also had higher rates of chronic obstructive pulmonary disease and hypertension than their peers who did not return to the hospital, reported Girish Nadkarni, M.D., and colleagues from the Mount Sinai COVID Informatics Center. Hospital readmittance also was tied to shorter length of initial hospital stay, lower rates of anticoagulation treatment, and lower incidence of intensive care. There were no differences in age, sex or race/ethnicity in readmitted patients compared with those who did not return, the researchers wrote. The results show that some patients have substantial lingering effects from COVID-19, corresponding author Anuradha Lala, M.D., said. “As we move into a phase where COVID-19 is no longer a novel disease, we must transition our attention to the post-acute phase to understand how to keep patients well and out of the hospital,” she concluded.
Pulmonary Thrombosis or Embolism in a Large Cohort of Hospitalized Patients With Covid-19
Frontiers in Medicine, August 25, 2020
We set out to analyze the incidence and predictive factors of pulmonary embolism (PE) in hospitalized patients with Covid-19. We prospectively collected data from all consecutive patients with laboratory-confirmed Covid-19 admitted to the Hospital de la Santa Creu i Sant Pau, a university hospital in Barcelona, between March 9 and April 15, 2020. Patients with suspected PE, according to standardized guidelines, underwent CT pulmonary angiography (CTPA). A total of 1,275 patients with Covid-19 were admitted to hospital. CTPA was performed on 76 inpatients, and a diagnosis of PE was made in 32 (2.6% [95%CI 1.7–3.5%]). Patients with PE were older, and they exhibited lower PaO2:FiO2 ratios and higher levels of D-dimer and C-reactive protein (CRP). They more often required admission to ICU and mechanical ventilation, and they often had longer hospital stays, although in-hospital mortality was no greater than in patients without PE. High CRP and D-dimer levels at admission (≥150 mg/L and ≥1,000 ng/ml, respectively) and a peak D-dimer ≥6,000 ng/ml during hospital stay were independent factors associated with PE. Prophylactic low molecular weight heparin did not appear to prevent PE. Increased CRP levels correlated with increased D-dimer levels and both correlated with a lower PaO2:FiO2.
AstraZeneca starts trial of COVID-19 antibody treatment
Reuters, August 25, 2020
British drugmaker AstraZeneca has begun testing an antibody-based cocktail for the prevention and treatment of COVID-19, adding to recent signs of progress on possible medical solutions to the disease caused by the novel coronavirus. The London-listed firm, already among the leading players in the global race to develop a successful vaccine, said the study would evaluate if AZD7442, a combination of two monoclonal antibodies (mAbs), was safe and tolerable in up to 48 healthy participants between the ages of 18 and 55 years. If the UK-based early-stage trial, which has dosed its participants, shows AZD7442 is safe, AstraZeneca said it would proceed to test it as both a preventative treatment for COVID-19 and a medicine for patients who have it, in larger, mid-to-late-stage studies. Development of mAbs to target the virus, an approach already being tested by Regeneron, ELi Lilly, Roche and Molecular Partners, has been endorsed by leading scientists. mAbs mimic natural antibodies generated in the body to fight off infection and can be synthesised in the laboratory to treat diseases in patients. Current uses include treatment of some types of cancers.
U.S. Public Health Resources for COVID-19 That Are Relevant to Allergy/Immunology
Annals of Allergy, Asthma & Immunology, August 24, 2020
U.S. public health responses to emerging infections have involved public health agencies, healthcare systems, community leaders, and others. This Perspective will focus on providing an overview of U.S. public health resources (as of August 2020) related to the coronavirus disease 2019 (COVID-19) pandemic that might be most relevant to allergists/immunologists. A novel coronavirus was first reported in January 2020. This virus, subsequently named SARS-CoV-2, is thought to spread mainly from person to person through respiratory droplets among people who are in close contact (within about 6 feet). SARS-CoV-2 infection can result in mild to severe symptoms, which can include but are not limited to fever, chills, cough, difficulty breathing, fatigue, body aches, headache, new loss of taste or smell, sore throat, nasal congestion, rhinorrhea, nausea, vomiting, or diarrhea. Among >1.3 million laboratory-confirmed, adult and pediatric COVID-19 cases reported in the United States during January 22–May 30, 2020, 14% of cases were hospitalized, 2% were admitted to an intensive care unit, and 5% died. Limited available data suggest that among adults with severe COVID-19, dysregulated innate and adaptive immune responses contribute to host tissue damage.
COVID-19 Not Likely to Trigger Asthma Exacerbations in Hospitalized Patients
Pulmonology Advisor, August 24, 2020
People with asthma were not overrepresented in patients with severe pneumonia because of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who required hospitalization, according to study results published in the European Respiratory Journal. Researchers evaluated patient demographics, clinical history, asthma control history, and comorbid conditions from adult patients hospitalized with a diagnosis of SARS-CoV-2 infection and reporting a history of asthma. The outcomes of interest were mortality, length of intensive care unit (ICU) stay, and total length of hospital stay, which were compared with a random control group of individuals without asthma hospitalized for COVID-19 pneumonia. Of the 768 hospitalized patients with COVID-19, 37 reported a history of asthma, and 75 were randomly assigned to the nonasthma control group. Of the 37 patients with asthma, 70% were women, the mean age was 54 years, and body mass index was 28.3 kg/m², respectively. The median time from onset of symptoms to admission in the emergency room was 6 days. Compared with the control group, all differences between groups pointed to worse COVID-19 pneumonia in individuals without asthma. None of the patients with asthma presented with an exacerbation while in the hospital.
Scientists say Hong Kong man got coronavirus a second time
Modern Healthcare, August 24, 2020
University of Hong Kong scientists claim to have the first evidence of someone being reinfected with the virus that causes COVID-19. Genetic tests revealed that a 33-year-old man returning to Hong Kong from a trip to Spain in mid-August had a different strain of the coronavirus than the one he’d previously been infected with in March, said Dr. Kelvin Kai-Wang To, the microbiologist who led the work. The man had mild symptoms the first time and none the second time; his more recent infection was detected through screening and testing at the Hong Kong airport. “It shows that some people do not have lifelong immunity” to the virus if they’ve already had it, To said. “We don’t know how many people can get reinfected. There are probably more out there.” Whether people who have had COVID-19 are immune to new infections and for how long are key questions that have implications for vaccine development and decisions about returning to work, school and social activities.
How to Prepare Patients for the New Influenza Season During COVID-19 Pandemic
Pulmonology Advisor, August 24, 2020
Every influenza season brings with it uncertainty about what strain will predominate and how severe it will be. While much of the world still is focusing on COVID-19, the potential for another serious influenza season can’t be ignored, and the strain on the health care system of 2 epidemics could be severe. As the SARS–CoV-2 virus continues to spread across the country, the 2020-2021 influenza season will be particularly challenging. Recent influenza seasons have been particularly serious: 2017-2018 was one of the deadliest in decades, with an estimated 61,000 deaths, and 2018-2019 was one of the longest flu seasons, lasting 21 weeks. In March 2019, the World Health Organization (WHO) announced a Global Influenza Strategy for 2019-2030 aimed at “protecting people in all countries from the threat of influenza.” The goals include the prevention of seasonal influenza, the control of spread from animals to humans, and preparation for the next influenza pandemic.
An inflammatory cytokine signature predicts COVID-19 severity and survival
Nature Medicine, August 24, 2020
Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1β in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death.
DARE-19: Dapagliflozin could target key mechanisms activated in COVID-19
Helio | Endocrine Today, August 22, 2020
SGLT2 inhibitors could potentially target key mechanisms activated in COVID-19, increasing lipolysis, reducing glycolysis, inflammation and oxidative stress, and improving endothelial function to reduce organ damage, according to a speaker. “We know that favorable effects on mechanisms such as endothelial function, a key driver of adverse outcomes in COVID-19, can occur very quickly after treatment with SGLT2 inhibitors,” Mikhail Kosiborod, MD, FACC, FAHA, cardiologist at Saint Luke’s Mid America Heart Institute, professor of medicine at the University of Missouri-Kansas City School of Medicine, said during an online presentation during the virtual Heart in Diabetes conference. “If you think through these mechanisms and the fact that SGLT2 inhibitors can have a positive impact on many of them, what becomes clear is that testing SGLT2 inhibitors as potential agents for organ protection in COVID-19 may be one of the key hypotheses.” The concept is relatively simple, Kosiborod said. Viral replication and spread after COVID-19 infection trigger metabolic derangements that lead to inflammatory “overdrive,” endothelial injury and, ultimately, organ damage leading to complications and death. Data suggest antiviral treatments can work in the early phase of the disease; anti-inflammatory medications show promise during the mid-phase of the disease.
Noninvasive Respiratory Support Outside of ICU Feasible for COVID-19
Pulmonary Advisor, August 21, 2020
Patients hospitalized with coronavirus disease 2019 (COVID-19) who were treated with noninvasive respiratory support outside of the intensive care unit (ICU) had favorable outcomes, but a risk of staff contamination persisted, according to study results published in The European Respiratory Journal. Medication, mode, and usage of noninvasive respiratory support were evaluated from hospitalized patients with COVID-19 treated outside of the ICU. The primary study outcomes were the length of stay in hospital, rate of endotracheal intubation, deaths, and staff infection rates. Of the 670 consecutive patients with confirmed COVID-19 referred to pulmonology units in 9 hospitals, 69.3% were men and the mean age was 68 years. Nearly half of the patients (49.3%) were treated with continuous positive airway pressure. The overall 30-day mortality rate was 26.9%, with specific rates of 16%, 30%, and 30%, for high-flow nasal cannula, continuous positive airway pressure, and noninvasive ventilation, respectively. The rates of endotracheal intubation and the length of stay in hospital were not different among the groups.
Pulmonary Pathobiology Distinct in Lungs of People Who Died From COVID-19 vs Influenza
Pulmonology Advisor, August 21, 2020
The pulmonary pathobiology of patients who died from respiratory failure caused by coronavirus disease 2019 (COVID-19) vs influenza was found to be distinct, according to a study published in the New England Journal of Medicine. A total of 24 lungs were obtained during the autopsy of patients who died from COVID-19 (n=7), from acute respiratory distress syndrome (ARDS) caused by influenza A (H1N1; n=7), or from causes other than infection (n=10). The lungs from patients infected with H1N1 were collected in 2009 and the lungs from control individuals were matched for age. Lungs were examined using a 7-color immunohistochemical analysis, micro-computed tomographic imaging, scanning electron microscopy, corrosion casting, and gene expression analysis through direct multiplexed measurement. The lungs from patients who died from COVID-19 were from 2 women (mean age, 68±9.2 years) and 5 men (mean age, 80±11.5 years). The H1N1 lungs were from 2 women (mean age, 62.5±4.9 years) and 5 men (mean age, 55.4±10.9 years). The control lungs were from 5 women (mean age, 68.2±6.9 years) and 5 men (mean age, 79.2±3.3 years). The lungs from patients with COVID-19 vs H1N1 were (2404±560 g vs 1681±49 g, respectively; P =.04), and lungs from control individuals (1045±91 g) were lighter compared with those from patients with COVID-19 and H1N1 vs (P <.001 and P =.003, respectively).
Corticosteroids in the Treatment of Severe Covid-19 Lung Disease: The Pulmonology Perspective From the First United States Epicenter
International Journal of Infectious Diseases, August 21, 2020
The SARS-CoV-2 pandemic has introduced the medical community to a lung disease heretofore unknown to most clinicians. In much of the discourse about COVID-19 lung disease, the more familiar clinical entity of ARDS has been used as the guiding paradigm. Reflecting on studies in ARDS, particularly that due to influenza, and on data from the SARS-CoV and MERS epidemics, many authorities, including within the discipline of infectious diseases, were initially passionate in their opposition to the use of corticosteroids for lung involvement in COVID-19. The voice of the pulmonology community—the community of lung experts—has continued to be among the quietest in this conversation. Herein we offer our perspective as academic pulmonologists who encountered COVID-19 in its first United States epicenter of New York City. We encourage a conceptual separation between early COVID-19 lung involvement and ARDS. We draw on history with other immune cell-mediated lung diseases, on insights from the SARS-CoV experience, and on frontline observations in an attempt to allay the skepticism towards corticosteroids in COVID-19 lung disease that is likely to persist even as favorable study results emerge.
Performance of a multiplex polymerase chain reaction panel for identifying bacterial pathogens causing pneumonia in critically ill patients with COVID-19
Diagnostic Microbiology and Infectious Disease, August 21, 2020
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has rapidly spread worldwide. Several studies have reported complications of COVID-19, such as bacterial pneumonia, acute respiratory distress syndrome (ARDS) and multiple organ failure syndromes. Recent guidelines for the management of adults critically ill with COVID-19 have suggested the empiric use of antimicrobial agents in patients with respiratory failure. The accurate and timely diagnosis of bacterial pneumonia, particularly in cases of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), is particularly challenging, and this condition remains a major cause of morbidity and mortality. Molecular tests provide a rapid turnaround time (TAT), together with identifications and semi-quantitative results for many pathogens responsive to antimicrobial therapy. Multiplex testing may provide additional information concerning the presence of antibiotic resistance genes, thereby improving antibiotic management. We performed a prospective single-center study on critically ill patients with COVID-19, in which we conducted parallel tests of blind bronchoalveolar lavage (BBAL) by conventional culture and FilmArray® Pneumonia Plus (FA-PP) panel. The aim of this study was to evaluate the performance of FA-PP and to compare its TAT with that of conventional cultures.
Environmental contamination in the isolation rooms of COVID-19 patients with severe pneumonia requiring mechanical ventilation or high-flow oxygen therapy
Journal of Hospital Infection, August 21, 2020
Identifying the extent of environmental contamination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for infection control and prevention. The extent of environmental contamination has not been fully investigated in the context of severe coronavirus disease (COVID-19) patients. Our objective was to investigate environmental SARS-CoV-2 contamination in the isolation rooms of severe COVID-19 patients requiring mechanical ventilation or high-flow oxygen therapy. We collected environmental swab samples and air samples from the isolation rooms of three COVID-19 patients with severe pneumonia. Patient 1 and Patient 2 received mechanical ventilation with a closed suction system, while Patient 3 received high-flow oxygen therapy and noninvasive ventilation. Real-time reverse transcription polymerase chain reaction (rRT-PCR) was used to detect SARS-CoV-2; viral cultures were performed for samples not negative on rRT-PCR.
Evidence mounts for ECMO in patients with severe COVID-19 respiratory failure
Helio | Pulmonology, August 20, 2020
Two recently published studies report success with extracorporeal membrane oxygenation support in patients with acute respiratory distress syndrome associated with COVID-19. In a retrospective cohort study published in The Lancet Respiratory Medicine, researchers analyzed clinical characteristics and outcomes of 492 patients treated with ECMO for COVID-19-associated ARDS at five ICUs within the Paris-Sorbonne University Hospital Network from March 8 to May 2. The researchers reported complete day-60 follow-up for 83 patients (median age, 49 years; 73% men) who received ECMO. Before ECMO, 94% of patients were prone positioned (median driving pressure, 18 cm H2O; ratio of arterial oxygen partial pressure to fractional inspired oxygen, 60 mm Hg). Sixty days after initiation of ECMO, the researchers’ estimated probability of death was 31% and the probability of being alive and out of the ICU was 45%.
Asthma-COPD overlap strong risk factor for COVID-19 hospitalization
Helio | Pulmonology, August 19, 2020
It is important to distinguish asthma from chronic pulmonary diseases to elucidate COVID-19 risk, researchers reported in The Journal of Allergy and Clinical Immunology. “U.S.-based studies report that approximately 7% to 9% of hospitalized patients with COVID-19 had chronic lung disease, with asthma more prevalent than COPD. Recent analyses of COVID-19 cohorts suggest that chronic respiratory disease may unexpectedly be less of a risk factor for COVID-19 infection and severity than nonrespiratory diseases. However, most studies to date do not distinguish asthma from COPD within chronic respiratory disease, limiting identification of asthma-specific risk factors,” Liqin Wang, PhD, postdoctoral research fellow at the division of general internal medicine and primary care at Brigham and Women’s Hospital, Boston, and colleagues wrote in a letter to the editor. The researchers reported data from a case series of patients in the Mass General Brigham health system with a positive diagnosis of COVID-19, aged at least 18 years and a previous diagnosis of asthma. Wang and colleagues analyzed data on demographics, socioeconomic markers, BMI, insurance, smoking status, asthma medications, comorbidities and course of COVID-19 care. Patients were followed for 14 days from COVID-19 diagnosis for hospitalization and/or ICU admission, or by June 8, for death.
Post COVID -19 Pneumonia Pulmonary Fibrosis
QJM: An International Journal of Medicine, August 19, 2020
Clinical manifestations of COVID-19 have ranged from asymptomatic/mild symptoms to severe illness and mortality. Most of the mild and moderate cases are recovered completely but a small proportion of severe cases with acute respiratory distress syndrome continued to remain hypoxemic despite adequate treatment. Chest imaging of this subset of patients revealed fibrotic changes in the form of traction bronchiectasis, architectural distortion and septal thickening similar to the changes seen in other fibrotic lung diseases. The pathogenesis of post infective pulmonary fibrosis include dysregulated release of matrix metalloproteinases during the inflammatory phase of ARDS causing epithelial and endothelial injury with unchecked fibroproliferation. There is also a vascular dysfunction which is a key component of the switch from ARDS to fibrosis, with VEGF and cytokines such as IL-6 and TNFα being implicated. Although the role of presently available antifibrotic drugs (pirfenidone and nintedanib) for fibrotic lung diseases beyond idiopathic pulmonary fibrosis have been evaluated by some authors their role in post COVID-19 pneumonia pulmonary fibrosis need further research in the present pandemic.
Ex-CDC director Tom Frieden provides strategies for protecting HCWs amid COVID-19
Helio | Primary Care, August 19, 2020
Former CDC director Tom Frieden, MD, MPH, recently described a hierarchy of controls — elimination, substitution, engineering, administration and personal protective equipment — that may help prevent COVID-19 among health care workers. His remarks came during the National Medical Association’s Annual Meeting, held virtually due to the pandemic. Frieden said the “most effective” step is eliminating the hazard or infection. This can be accomplished by not allowing people who are ill to enter nursing homes and other congregate facilities. It can also be accomplished by ensuring that all hospitals and nursing home staffs have paid sick leave, so that there is no economic incentive to work while ill. If patients with COVID-19 cannot be separated from other patients and staff by engineering and substitution, PPE becomes necessary, Frieden said. When PPE is necessary, supply has to be ensured.
As U.S. schools reopen, concerns grow that kids spread coronavirus
Reuters, August 19, 2020
U.S. students are returning to school in person and online in the middle of a pandemic, and the stakes for educators and families are rising in the face of emerging research that shows children could be a risk for spreading the new coronavirus. Several large studies have shown that the vast majority of children who contract COVID-19, the disease caused by the virus, have milder illness than adults. And early reports did not find strong evidence of children as major contributors to the deadly virus that has killed more than 780,000 people globally. But more recent studies are starting to show how contagious infected children, even those with no symptoms, might be. “Contrary to what we believed, based on the epidemiological data, kids are not spared from this pandemic,” said Dr. Alessio Fasano, director of the Mucosal Immunology and Biology Research Center at Massachusetts General Hospital and author of a new study.
The Physicians Foundation 2020 Physician Survey
Physicians Foundation, August 18, 2020
The Physicians Foundation’s 2020 Survey of America’s Physicians finds that the majority of physicians believe COVID-19 won’t be under control until January 2021, with nearly half not seeing the virus being under control until after June 1, 2021. Furthermore, a majority of physicians believe that the virus will severely impact patient health outcomes due to delayed routine care during the pandemic. Read and download the findings. The survey, conducted in July with more than 3,500 respondents, asked physicians how the pandemic is affecting their practices and patients. Nearly three-quarters of those surveyed said COVID-19 would have serious consequences for health in their communities because many are delaying needed care. Health insurance is another problem; 76% cited changes in employment and insurance status is a primary cause of harm to patients caused by COVID-19. But 59% believed opening schools, businesses and other public places posed a greater risk to their patients than continued social isolation. “The data reveals a near-consensus among America’s physicians about COVID-19’s immediate and lasting impact on our healthcare system,” said Dr. Gary Price, president of The Physicians Foundation, in a prepared statement.
FDA flags accuracy issue with widely used coronavirus test
Associated Press, August 18, 2020
Potential accuracy issues with a widely used coronavirus test could lead to false results for patients, U.S. health officials warned. The Food and Drug Administration issued the alert Monday to doctors and laboratory technicians using Thermo Fisher’s TaqPath genetic test. Regulators said issues related to laboratory equipment and software used to run the test could lead to inaccuracies. The agency advised technicians to follow updated instructions and software developed by the company to ensure accurate results. The warning comes nearly a month after Connecticut public health officials first reported that at least 90 people had received false positive results for the coronavirus. Most of those receiving the false results were residents of nursing homes or assisted living facilities. A spokeswoman for Thermo Fisher said the company was working with FDA “to make sure that laboratory personnel understand the need for strict adherence to the instructions for use.” She added that company data shows most users “follow our workflow properly and obtain accurate results.”
Assessment of COVID-19 Hospitalizations by Race/Ethnicity in 12 States
JAMA Internal Medicine, August 17, 2020
Given the reported health disparities in coronavirus disease 2019 (COVID-19) infection and mortality by race/ethnicity, there is an immediate need for increased assessment of the prevalence of COVID-19 across racial/ethnic subgroups of the population in the US. We examined the racial/ethnic prevalence of cumulative COVID-19 hospitalizations in the 12 states that report such data and compared how this prevalence differs from the racial/ethnic composition of each state’s population. Using data extracted from the University of Minnesota COVID-19 Hospitalization Tracking Project, we identified the 12 states that reported the race/ethnicity of individuals hospitalized with COVID-19 between April 30 and June 24, 2020. We calculated the percentage of cumulative hospitalizations by racial/ethnic categories averaged over the study period and then calculated the difference between the percentage of cumulative hospitalizations for each subgroup and the corresponding percentage of the state’s population for each racial/ethnic subgroup as reported in the US Census. The race/ethnicity categories included were White, Black, American Indian and/or Alaskan Native, Asian, and Hispanic. Descriptive statistical analyses were conducted using Stata/MP, version 14 (Stata Corp). The University of Minnesota Institutional Review Board reviewed the study data and deemed it exempt from review and informed consent requirements because the study was not human subjects research. This analysis of COVID-19 hospitalizations in 12 US states during nearly a 2-month period represented a total of 48 788 cumulative hospitalizations among a total population of 66 796 666 individuals in 12 US states.
COVID-19: Utility of Antibiotic Therapy for Nosocomial Coinfection Unclear
Pulmonary Advisor, August 17, 2020
Patients diagnosed with coronavirus disease 2019 (COVID-19) who are not admitted to the intensive care unit (ICU) may not require antibiotic therapy due to the low frequency of community-acquired coinfection, according to the results of a single-center study published in Clinical Infectious Diseases. Current literature estimates that coinfection in COVID-19 could range from 0% to 40% of patients. As such, concerns have been raised on whether coinfection could be a significant complication in COVID-19. However, only a few studies were designed to assess co-infection and differentiate between community- and hospital-acquired coinfection, coinfection definitions are variable, and microbiologic data are inconsistently reported. As a result of these challenges, the current guidelines on antibiotic use in COVID-19 patients are not strong. This retrospective, observational study described the rates of community-acquired coinfection in patients with COVID-19. In total, 321 patients with COVID-19 (³18 years of age) were admitted to the University of Chicago Medical Center in Chicago, Illinois during the evaluation period (March 1, 2020-April 11, 2020). The date of hospital admission, ICU admission, mortality, antibiotic administration, and microbiologic test results were examined. If positive test results were collected after the fifth day of hospital admission, patients were excluded to make sure only community-acquired coinfection was captured.
AANP National Survey Reveals Progress, Challenges as Nurse Practitioners (NPs) Combat COVID-19
Cision, August 17, 2020
The findings of a second, nationwide trend survey of NPs assessing COVID-19’s impacts on NP professional practice demonstrate both significant progress and lingering challenges as health care providers work to stem the tide of the pandemic in communities nationwide. More than 80% of the profession reports their practices are better prepared to manage COVID-19 patients than at the start of the pandemic, with 35% indicating they are ready for a surge in COVID-19 cases. Despite marked progress in practice readiness and improving supplies of PPE, the number of NPs now testing positive for COVID-19 has increased three-fold since the early days of the pandemic. While acknowledging improvements in access, NPs identify testing as the most significant barrier to combatting COVID-19 in their communities, with one-third of NPs reporting patients being turned away from centralized testing sites for failure to meet pre-determined criteria, and 78% of NPs citing significant delays in receiving patients’ viral test results. Test result delays range from a low-end range of seven to 10 business days to a high-end of up to 20 days. This is the second national survey fielded by the American Association of Nurse Practitioners® (AANP), the largest national association of NPs of all specialties, aimed at understanding how COVID-19 is affecting the clinical practice of NPs across settings, specialties, and geographic location.
CDC: Sorry, People Do Not Have COVID-19 ‘Immunity’ for 3 Months
MedPage Today, August 17, 2020
People infected with COVID-19 do not necessarily have immunity to reinfection for three months, the CDC said late Friday night, trying to squelch speculation the agency had inadvertently stimulated. While people can continue to test positive for SARS-CoV-2 for up to three months after diagnosis and not be infectious to others, that does not imply that infection confers immunity for that period, the agency said. The confusion stemmed from an August 3 update to CDC’s isolation guidance, which stated: Who needs to quarantine? People who have been in close contact with someone who has COVID-19 — excluding people who have had COVID-19 within the past 3 months. People who have tested positive for COVID-19 do not need to quarantine or get tested again for up to 3 months as long as they do not develop symptoms again. People who develop symptoms again within 3 months of their first bout of COVID-19 may need to be tested again if there is no other cause identified for their symptoms. These statements could be read as suggesting that those recovering from COVID-19 will likely be safe from reinfection for three months even with close exposure to infected people. Media reports took this as a tacit acknowledgment of immunity from the agency.
Household Transmission of SARS-CoV-2 in the United States
Clinical Infectious Diseases, August 16, 2020
Although many viral respiratory illnesses are transmitted within households, the evidence base for SARS-CoV-2 is nascent. We sought to characterize SARS-CoV-2 transmission within US households and estimate the household secondary infection rate (SIR) to inform strategies to reduce transmission. We recruited laboratory-confirmed COVID-19 patients and their household contacts in Utah and Wisconsin during March 22–April 25, 2020. We interviewed patients and all household contacts to obtain demographics and medical histories. At the initial household visit, 14 days later, and when a household contact became newly symptomatic, we collected respiratory swabs from patients and household contacts for testing by SARS-CoV-2 rRT-PCR and sera for SARS-CoV-2 antibodies testing by enzyme-linked immunosorbent assay (ELISA). We estimated SIR and odds ratios (OR) to assess risk factors for secondary infection, defined by a positive rRT-PCR or ELISA test. Thirty-two (55%) of 58 households had evidence of secondary infection among household contacts. The SIR was 29% (n = 55/188; 95% confidence interval [CI]: 23–36%) overall, 42% among children (<18 years) of the COVID-19 patient and 33% among spouses/partners. Household contacts to COVID-19 patients with immunocompromised conditions had increased odds of infection (OR: 15.9, 95% CI: 2.4–106.9). Household contacts who themselves had diabetes mellitus had increased odds of infection (OR: 7.1, 95% CI: 1.2–42.5).
FDA clears Masimo device for ventilated patients
Mass Device, August 14, 2020
Masimo announced today that it received FDA clearance for its PVi for fluid responsiveness indication in ventilated adult patients. PVi (pleth variability index) now has indication as a continuous, non-invasive, dynamic indicator of responsiveness in select populations of mechanically ventilated adult patients, as it measures dynamic changes in the perfusion index that occur during the respiratory cycle, according to a news release. Irvine, Calif.-based Masimo’s PVi is available alongside its SET pulse oximetry and Rainbow pulse co-ocimetry on a variety of sensors, using a proprietary algorithm based on the relative variability of the pleth waveform. In an 18,716-patient study in France, researchers found that using PVi alongside Masimo’s SpHb continuous hemoglobin monitoring technology led to earlier transfusion and fewer units of blood transfused, as well as a 33% lower mortality rate 30 days after surgery, which trickled down to a 29% rate 90 days after surgery.
Outcomes Associated With Use of a Kinin B2 Receptor Antagonist Among Patients With COVID-19
JAMA Network Open, August 13, 2020
Pulmonary edema is a prominent feature in patients with severe COVID-19. SARS-CoV-2 enters the cell via ACE2. ACE2 is involved in degrading the kinin des-Arg9-bradykinin, a potent vasoactive peptide that can cause vascular leakage. Loss of ACE2 might lead to plasma leakage and further activation of the plasma kallikrein-kinin system with more bradykinin formation that could contribute to pulmonary angioedema via stimulation of bradykinin 2 receptors. We investigated whether treatment with the bradykinin 2 receptor antagonist icatibant in patients with COVID-19 could be used as a treatment strategy. This case-control study was approved by CMO region Arnhem-Nijmegen, the local ethical committee, which granted a waiver of consent because treatment concerned a licensed drug that would be given in an off-label setting. Informed consent was obtained in all patients. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. We included 10 patients for treatment with 3 doses of 30 mg of icatibant by subcutaneous injection at 6-hour intervals. Patients were eligible for icatibant treatment if they had confirmed SARS-CoV-2 by polymerase chain reaction assay, an oxygen saturation of less than 90% without supplemental oxygen, needed 3 L/min supplemental oxygen or more, and had a computed tomography severity score of 7 or greater. Patients with acute ischemic events at time of eligibility were excluded. For 9 patients who received icatibant on the ward, 2 matched control patients admitted prior to approval of this treatment were selected. Control patients with COVID-19 were matched on the factors sex, age, body mass index, and day of illness.
The Impact of COVID-19 on Pulmonary Hypertension
American College of Cardiology, August 13, 2020
COVID-19 has had a significant impact on all aspects of PH, from diagnosis and management to observing an increased risk of death in patients with PAH. In addition, because of the vulnerable nature of this population, the pandemic has impacted the very manner in which care is delivered in PH. The risks associated with COVID-19 in patients with PH are significant. In a US survey of 77 PAH Comprehensive Care Centers, the incidence of COVID-19 infection was 2.1 cases per 1,000 patients with PAH, which is similar to the incidence of COVID-19 infection in the general US population. But although COVID-19 did not seem to be more prevalent in patients with PAH, the mortality did appear to be higher at 12%. In addition, 33% of patients with PAH who were infected with COVID-19 ended up being hospitalized. With the outbreak of COVID-19, it became necessary to revisit the manner in which patients receive care to decrease risk of contracting the virus.
Venous thromboembolism in hospitalized patients with COVID-19 receiving prophylactic anticoagulation
Mayo Clinic Proceedings, August 13, 2020
Venous thromboembolism (VTE) has been reported in mechanically ventilated patients with severe SARS-CoV-2 infection (COVID-19). Two of the first 31 non-mechanically ventilated patients with moderate severity COVID-19 admitted to our hospital developed VTE while receiving uninterrupted prophylactic anticoagulation. Both non-mechanically ventilated patients hospitalized with COVID-19 developed symptomatic VTE while receiving uninterrupted standard prophylactic dose unfractionated or low molecular weight heparin. Reports linking severe COVID-19 and increased risk for VTE have emerged, including a high incidence of abnormal D-dimer levels among patients with COVID-19, an association between COVID-19-associated disturbances in the coagulation pathway and increased mortality, and lower 28-day mortality among patients with COVID-19 who received prophylactic heparin if they had D-dimer >3.0 mg/L or sepsis-induced coagulopathy score >4. Experts also have published interim summaries and guidance for managing VTE risk in patients with COVID-19, although the optimal approach for inpatient VTE risk stratification and prophylaxis remains uncertain. Our observations suggest that moderate severity COVID-19 might also predispose hospitalized patients to higher VTE risk than standard RAMS would predict and might even precipitate acute VTE despite use of standard prophylactic-dose anticoagulant medications.
Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes – Interim Analysis of 2 Randomized Clinical Trials
Journal of the American Medical Association, August 13, 2020
What are the safety and immunogenicity of an inactivated vaccine against coronavirus disease 2019 (COVID-19)? This was an interim analysis of 2 randomized placebo-controlled trials. In 96 healthy adults in a phase 1 trial of patients randomized to aluminum hydroxide (alum) only and low, medium, and high vaccine doses on days 0, 28, and 56, 7-day adverse reactions occurred in 12.5%, 20.8%, 16.7%, and 25.0%, respectively; geometric mean titers of neutralizing antibodies at day 14 after the third injection were 316, 206 and 297 in the low-, medium-, and high-dose groups, respectively. In 224 healthy adults randomized to the medium dose, 7-day adverse reactions occurred in 6.0% and 14.3% of the participants who received injections on days 0 and 14 vs alum only, and 19.0% and 17.9% who received injections on days 0 and 21 vs alum only, respectively; geometric mean titers of neutralizing antibodies in the vaccine groups at day 14 after the second injection were 121 vs 247, respectively.
Model-based Prediction of Critical Illness in Hospitalized Patients with COVID-19
Radiology, August 13, 2020
The prognosis of hospitalized patients with severe coronavirus disease 2019 (COVID-19) is difficult to predict, while the capacity of intensive care units (ICUs) is a limiting factor during the peak of the pandemic and generally dependent on a country’s clinical resources. The purpose of the study was to determine the value of chest radiographic findings together with patient history and laboratory markers at admission to predict critical illness in hospitalized patients with COVID-19. In this retrospective study including patients from 7th March 2020 to 24th April 2020, a consecutive cohort of hospitalized patients with RT-PCR-confirmed COVID-19 from two large Dutch community hospitals was identified. After univariable analysis, a risk model to predict critical illness (i.e. death and/or ICU admission with invasive ventilation) was developed, using multivariable logistic regression including clinical, CXR and laboratory findings. Distribution and severity of lung involvement was visually assessed using an 8-point scale (chest radiography score). Internal validation was performed using bootstrapping. Performance is presented as an area under the receiver operating characteristic curve (AUC). Decision curve analysis was performed, and a risk calculator was derived. The cohort included 356 hospitalized patients (69 ±12 years, 237 male) of whom 168 (47%) developed critical illness.
Researchers Strive to Recruit Hard-Hit Minorities Into COVID-19 Vaccine Trials
Journal of the American Medical Association, August 13, 2020
Seldom does a vaccine researcher’s job include calling city hall, big-box stores like Walmart and Target, and the US Postal Service. But Ann Falsey, MD, had those tasks on her to-do list in June as she prepared to recruit volunteers to test potential vaccines for coronavirus disease 2019 (COVID-19). Falsey, of the University of Rochester School of Medicine, hoped large employers in her area would publicize vaccine trials to their essential workers, many of whom are Black or Hispanic. “We are thinking very hard about not only how to get a diverse population that reflects the US population but also people at high risk—postal workers, home health workers, you name it,” she said. COVID-19’s startling toll on minorities has drawn widespread attention to the need for diversity in large-scale phase 3 vaccine trials. Two 30 000-person trials, led by Moderna and a joint effort of Pfizer and BioNTech, began on July 27. AstraZeneca was expected to start US recruitment to test its vaccine, developed with Oxford University, in August, followed by Johnson & Johnson in September and Novavax later this fall.
A SARS-CoV-2 Prediction Model from Standard Laboratory Tests
Clinical Infectious Diseases, August 12, 2020
With the limited availability of testing for the presence of the SARS-CoV-2 virus and concerns surrounding the accuracy of existing methods, other means of identifying patients are urgently needed. Previous studies showing a correlation between certain laboratory tests and diagnosis suggest an alternative method based on an ensemble of tests. Here, a machine learning model was trained to analyze the correlation between SARS-CoV-2 test results and 20 routine laboratory tests collected within a 2-day period around the SARS-CoV-2 test date. We used the model to compare SARS-CoV-2 positive and negative patients. In a cohort of 75,991 veteran inpatients and outpatients who tested for SARS-CoV-2 in the months of March through July, 2020, 7,335 of whom were positive by RT-PCR or antigen testing, and who had at least 15 of 20 lab results within the window period, our model predicted the results of the SARS-CoV-2 test with a specificity of 86.8%, a sensitivity of 82.4%, and an overall accuracy of 86.4% (with a 95% confidence interval of [86.0%, 86.9%]). While molecular-based and antibody tests remain the reference standard method for confirming a SARS-CoV-2 diagnosis, their clinical sensitivity is not well known. The model described herein may provide a complementary method of determining SARS-CoV-2 infection status, based on a fully independent set of indicators, that can help confirm results from other tests as well as identify positive cases missed by molecular testing.
Global COVID-19 Cases Top 20 Million
WebMD, August 12, 2020
The total of number of confirmed COVID-19 cases worldwide went over the 20 million mark on Tuesday, the Johns Hopkins Coronavirus Resource Center reported. The number of us cases has grown exponentially since the virus was first reported in China about 6-and-a-half months ago. Total cases hit the 1 million mark on April 2, CNN reported. Ten million cases were recorded in late June. It took less than 6 weeks to double that figure as case counts surged in the United States and Latin America. The number of cases is probably much higher because of testing limitations and a high number of infected people who show no symptoms. Deaths have also gone up. More than 737,000 have people died worldwide, Johns Hopkins said. The nations with the most cases are the United States (almost 5.1 million with more than 163,000 deaths), Brazil (3 million cases and 101,000 deaths), India (2.2 million cases and 45,000 deaths), Russia (895,000 cases and 15,000 deaths), and South Africa (563,000 cases and 10,600 deaths). Africa recorded its 1 millionth case last week. The 7-day average of new cases has been more than 250,000 for two weeks, CNN said.
Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With COVID-19 (Metcovid): A Randomised, Double-Blind, Phase IIb, Placebo-Controlled Trial
Clinical Infectious Diseases, August 12, 2020
Steroid use for COVID-19 is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by SARS-Co-2. This study aimed at evaluating at evaluating the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19. This parallel, double-blind, placebo-controlled, randomized, phase IIb clinical trial was performed with hospitalized patients aged ≥ 18 years with clinical, epidemiological and/or radiological suspected COVID-19, at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution), twice daily, for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality. During the study, 647 patients were screened, 416 randomized, and 393 analyzed as mITT, MP in 194 and placebo in 199 individuals. SARS-CoV-2 infection was confirmed by RT-PCR in 81.3%. Mortality at day 28 was not different between groups. A subgroup analysis showed that patients over 60 years in the MP group had a lower mortality rate at day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until day 7.
Annals On Call – Diagnosing SARS-CoV-2 Infection: Symptoms or No Symptoms?
Annals of Internal Medicine, August 12, 2020
[Podcast] In this episode of Annals On Call, Dr. Centor discusses challenges to diagnosing COVID-19 with Dr. Jeanne Marrazzo. Annals On Call focuses on a clinically influential article published in Annals of Internal Medicine. Dr. Robert Centor shares his own perspective on the material and interviews topic area experts to discuss, debate, and share diverse insights about patient care and health care delivery.
COVID-19 surge moves to Midwest, as young people fuel US case rise
Center for Infectious Disease Research and Policy, August 12, 2020
Many states initially spared from the COVID-19 pandemic is March, April, and May, are now reporting increasing transmission rates in non-metropolitan counties fueled by community spread. According to the Wall Street Journal, in Ohio, Missouri, Wisconsin, and Illinois, the weekly change in COVID-19 cases has been higher in rural regions compared to metro areas, and outbreaks are linked to social events, rather than workplace exposure or congregate living situations. A summer of waning social distancing restrictions has made bars and restaurants common COVID-19 outbreak sites, on par with nursing homes and prisons states across the country. In Louisiana, the New York Times reports bars and restaurants are linked to 25% of the state’s cases, and in Maryland, that percentage was 12%. Fueling these outbreaks are the twin forces of a national “quarantine fatigue” and young adults, who are more likely than older, more at-risk Americans, to be both patrons and employees in dining and drinking establishments. Young adults are driving outbreaks in many states, and experts worry those with mild or asymptomatic cases are spreading the disease to more vulnerable household members.
This Fall Could Be ‘Worst’ We’ve Seen
WebMD, August 12, 2020
We are in a war against COVID-19, and this fall could be one of the worst from a public health standpoint that the U.S. has ever faced, says CDC Director Robert Redfield, MD. The surging coronavirus pandemic, paired with the flu season, could create the “worst fall” that “we’ve ever had,” he said during an interview on “Coronavirus in Context,” a video series hosted by John Whyte, MD, WebMD’s chief medical officer. Redfield also said the agency’s efforts to understand the virus were hampered by a lack of cooperation from China. He reached out to China CDC Director George Gao on Jan. 3 to see if the agency could work with health officials in Wuhan to better understand the outbreak. But he never received an invitation, Redfield said. “I think if we had been able to get in at that time, we probably would have learned quicker than we learned here,” Redfield said.
Extracorporeal Membrane Oxygenation for Patients With COVID-19 in Severe Respiratory Failure
JAMA Surgery, August 11, 2020
Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS), necessitating prolonged mechanical ventilation. In some cases, even ventilatory support fails. Venovenous extracorporeal membrane oxygenation (ECMO) has been used in severe cases of respiratory failure. However, the need for prolonged ventilation, sedation, and immobility may limit its long-term benefits. The application of ECMO in patients with COVID-19 whose condition has rendered mechanical ventilatory support insufficient is not fully established. Data were collected retrospectively from 40 consecutive patients with COVID-19 who were in severe respiratory failure and supported with ECMO. Each diagnosis of COVID-19 was confirmed using polymerase chain reaction–based assays. Patients were treated at 2 tertiary medical centers in Chicago, Illinois. The research protocol was approved by the institutional review boards of the Advocate Christ Medical Center and the Rush University Medical Center with a waiver for consent because of the inability of patients to give consent. A single-access, dual-stage right atrium–to-pulmonary artery cannula was implanted, following which ventilation was discontinued while the patient continued to receive ECMO. Patient selection criteria were similar to those of the ECMO to Rescue Lung Injury in Severe ARDS (EOLIA) trial group. The primary outcome was survival following safe discontinuation of ventilatory and ECMO supports.
Extracorporeal Membrane Oxygenation for Patients With COVID-19 in Severe Respiratory Failure
JAMA Surgery, August 11, 2020
Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS), necessitating prolonged mechanical ventilation. In some cases, even ventilatory support fails. Venovenous extracorporeal membrane oxygenation (ECMO) has been used in severe cases of respiratory failure. However, the need for prolonged ventilation, sedation, and immobility may limit its long-term benefits. The application of ECMO in patients with COVID-19 whose condition has rendered mechanical ventilatory support insufficient is not fully established. We present our experience in using single-access, dual-stage venovenous ECMO, with an emphasis on early extubation of patients while they received ECMO support. Data were collected retrospectively from 40 consecutive patients with COVID-19 who were in severe respiratory failure and supported with ECMO. Each diagnosis of COVID-19 was confirmed using polymerase chain reaction–based assays. A single-access, dual-stage right atrium–to-pulmonary artery cannula was implanted, following which ventilation was discontinued while the patient continued to receive ECMO. Patient selection criteria were similar to those of the ECMO to Rescue Lung Injury in Severe ARDS (EOLIA) trial group. The primary outcome was survival following safe discontinuation of ventilatory and ECMO supports. Excel for Office 365 2020 (Microsoft) was used for data analysis.
Regulatory T Cells Tested in Patients With COVID-19 ARDS
Journal of the American Medical Association, August 11, 2020
Two men with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) survived after treatment with off-the-shelf regulatory T cells, also known as Tregs, Johns Hopkins physicians recently reported. The investigational allogenic Tregs with lung-homing markers were derived from cord blood. The critically ill patients, aged 69 years and 47 years, had multiorgan failure and had been treated with therapies including tocilizumab, hydroxychloroquine, broad-spectrum antibiotics, vasopressors, and inhaled nitric oxide. The men were intubated in prone positions and the 47-year-old received extracorporeal membrane oxygenation (ECMO) support. The men eventually were extubated and needed tracheostomies. When the study was written, the patient who had undergone ECMO was discharged home and the other was at a ventilator weaning facility.
Exclusive: Over 900 health workers have died of COVID-19. And the toll is rising
News Medical, August 11, 2020
More than 900 front-line health care workers have died of COVID-19, according to an interactive database unveiled Wednesday by The Guardian and KHN. Lost on the Frontline is a partnership between the two newsrooms that aims to count, verify and memorialize every U.S. health care worker who dies during the pandemic. KHN and The Guardian are tracking health care workers who died from COVID-19 and writing about their lives and what happened in their final days. It is the most comprehensive accounting of U.S. health care workers’ deaths in the country. As coronavirus cases surge — and dire shortages of lifesaving protective gear like N95 masks, gowns and gloves persist — the nation’s health care workers are again facing life-threatening conditions in Southern and Western states. Through crowdsourcing and reports from colleagues, social media, online obituaries, workers unions and local media, Lost on the Frontline reporters have identified 922 health care workers who reportedly died of COVID-19 and its complications. A team of more than 50 journalists from the Guardian, KHN and journalism schools have spent months investigating individual deaths to make certain that they died of COVID-19, and that they were indeed working on the front lines in contact with COVID patients or working in places where they were being treated. Thus far, we have independently confirmed 167 deaths and published their names, data and stories about their lives and how they will be remembered. The tally includes doctors, nurses and paramedics, as well as crucial support staff such as hospital custodians, administrators and nursing home workers, who put their own lives at risk during the pandemic to care for others.
Diagnostic Performance of Chest CT for SARS-CoV-2 Infection in Individuals with or without COVID-19 Symptoms
Radiology, August 10, 2020
The use of chest CT for COVID-19 diagnosis or triage in healthcare settings with limited SARS-CoV-2 PCR capacity is controversial. CO-RADS categorization of the level of COVID-19 suspicion might improve diagnostic performance. Our purpose was to investigate the value of chest CT with CO-RADS classification to screen for asymptomatic SARS-CoV-2 infections and to determine its diagnostic performance in individuals with COVID-19 symptoms during the exponential phase of viral spread. In this secondary analysis of a prospective trial (Clinical Trial Number: IRB B1172020000008), from March 2020 to April 2020, we performed parallel SARS-CoV-2 PCR and CT with categorization of COVID-19 suspicion by CO-RADS, for individuals with COVID-19 symptoms and controls without COVID-19 symptoms admitted to the hospital for medical urgencies unrelated to COVID-19. CT-CORADS was categorized on a 5-point scale from 1 (very low suspicion) to 5 (very high suspicion). AUC were calculated in symptomatic versus asymptomatic individuals to predict positive SARS-CoV-2 positive PCR and likelihood ratios for each CO-RADS score were used for rational selection of diagnostic thresholds.
A Great Unknown: When Flu Season and COVID Collide
WebMD, August 10, 2020
For months scientists have urged the public to wear masks, wash their hands and socially distance. And as the flu season approaches, those practices have never been more crucial. Depending on whether people heed this advice, the U.S. could either see a record drop in flu cases or a dangerous viral storm, doctors say. “We just have no idea what’s going to happen. Are we going to get a second surge [of coronavirus]?” says Peter Chai, MD, an emergency physician at the Brigham and Women’s Hospital in Boston. . “Hopefully, knock on wood, that won’t happen.” To get an idea of how the flu season might go, public health officials in the U.S. often look to Australia and other countries in the southern hemisphere, where they are in the winter flu season. This season so far in Australia, COVID-19 precautions have served to curb the pandemic while also protecting residents against the flu. Canberra had only one case for the week ending July 26, the most recent report available. It’s had 190 total cases so far this flu season – which runs March through August – compared to 2,000 last year. Activity is low in the country overall, with just 36 deaths reported so far. And that’s not just true in Australia. The World Health organization reports few cases worldwide. But only time will tell whether the U.S. will follow suit. If not, the consequences could be dire, leaving people even more vulnerable to COVID-19 and potentially overwhelming hospitals, says Aubree Gordon, associate professor of epidemiology at the University of Michigan School of Public Health.
Ventilator Triaging Policies During the COVID-19 Pandemic
American College of Cardiology, August 10, 2020
The authors surveyed the Association of Bioethics Program Directors, advisors to hospital governing leadership in over 70 institutions throughout North America, asking:
o Whether a ventilator triage policy had been implemented in the wake of the COVID-19 pandemic,
o What criteria would be used in such a policy, and
o Which individuals are or would be involved in creating or activating the policy, or in adjudicating individual decisions.
A majority of institutions did not have a ventilator triage policy in place at the time of the survey. With 92% response rate, over half (54%) of the respondents reported no ventilator triage policy in their institution, and 10% reported inability to publicly share their policy. Findings from the 26 unique available policies were thus reported.
IV High-Dose Vitamin C Success Story in COVID-19
MedPage Today, August 10, 2020
A 74-year-old white woman presents to an emergency department in Flint, Michigan, after suffering with low-grade fever, dry cough, and shortness of breath for the previous 2 days. Her medical history for the week before includes elective surgery at an¬other hospital for total replacement of the right knee. She notes that she was healthy on admission and at discharge. She stayed in a private room, and had no contact with individuals who were ill or who had traveled recently. Lung auscultation reveals bilateral rhonchi with rales, and chest radiography shows patchy air space opacity in the right upper lobe suspicious for pneumonia. Concerns about community transmission of COVID-19 prompt a nasopharyngeal swab for detection of SARS-CoV-2. The patient is admitted to the airborne-isolation unit, maintaining compliance to the CDC recommendations for contact, droplet, and airborne precautions. Results of the nasopharyngeal swab are positive for SARS-CoV-2. Clinicians start treatment with oral hydroxychloroquine 400 mg once and then 200 mg twice a day, along with intravenous azithromycin 500 mg once a day, zinc sulfate 220 mg three times a day, and oral vitamin C 1 g twice a day. When blood and sputum cultures are negative for any organisms, broad-spectrum antibiotics are discontinued. The patient’s dyspnea rapidly worsens, and oxygen requirements increase to 15 liters. She is drowsy, in moderate distress, and her airways remain unprotected. On day 7, the second day of mechanical ventilation, at the request of the family when the patient develops ARDS, she is started on a continuous intravenous infusion of high-dose vita¬min C (11 g /24 hours). Two days later, her clinical condition gradually begins to improve, and the clinicians discontinue supportive treatment with norepinephrine. On day 10, the fifth day of mechanical ventilation, another chest x-ray shows that both the pneumonia and interstitial edema have improved considerably. The patient responds well to a spontaneous breathing trial with continuous positive airway pressure/pressure support, with the settings of positive end-expiratory pressure (PEEP) of 7 mm Hg, pressure support above PEEP of 10 mm Hg, and a fraction of inspired oxygen of 40%.
No End in Sight as U.S. Cases Pass 5 Million
WebMD, August 9, 2020
The U.S. logged 5 million confirmed COVID-19 cases, hitting another grim milestone in the nearly 6-month long pandemic that has devastated the country. The U.S. tally is substantially larger than the next closest country, Brazil, which has logged roughly 3 million cases. It is roughly 2.5 times the size of the outbreak in India, though the total population in that country is more than 4 times as large. Experts say the number of cases underscores the failure of our national response. In July, newly reported cases in the U.S. topped 70,000 a day. “Seventy thousand was the number of cases that they had in Wuhan, China where this started, in total. So we were having a Wuhan a day in this country,” says Carlos Del Rio, MD, an infectious disease specialist and a professor of Global Health and Epidemiology at Emory University in Atlanta. “We’re doing a crappy job.” While cases have slowed slightly in recent days, they have been rapidly accelerating in the U.S. Since the introduction of the virus, it took the U.S. more than 12 weeks to reach its first 1 million cases, 7 weeks to amass 2 million cases, 3.5 weeks to reach 3 million, and 2.5 weeks to hit 4 million, and another 2.5 weeks to reach 5 million.
Clinical Outcomes Associated with Methylprednisolone in Mechanically Ventilated Patients with COVID-19
Clinical Infectious Diseases, August 9, 2020
The efficacy and safety of methylprednisolone in mechanically ventilated patients with acute respiratory distress syndrome due to coronavirus disease 2019 (COVID-19) are unclear. In this study, we evaluated the association between use of methylprednisolone and key clinical outcomes. Clinical outcomes associated with the use of methylprednisolone were assessed in an unmatched, case-control study; a subset of patients also underwent propensity-score matching. The primary outcome was ventilator-free days by 28 days after admission. Secondary outcomes included extubation, mortality, discharge, positive cultures, and hyperglycemia. A total of 117 patients met inclusion criteria. Propensity matching yielded a cohort of 42 well-matched pairs. Groups were similar except for hydroxychloroquine and azithromycin use, which were more common in patients who did not receive methylprednisolone. Mean ventilator free-days were significantly higher in patients treated with methylprednisolone (6.21±7.45 versus 3.14±6.22; P = 0.044). The probability of extubation was also increased in patients receiving methylprednisolone (45% versus 21%; P = 0.021), and there were no significant differences in mortality (19% versus 36%; P = 0.087). In a multivariable linear regression analysis, only methylprednisolone use was associated with higher number of ventilator-free days (P = 0.045). The incidence of positive cultures and hyperglycemia were similar between groups.
Coronavirus in Context: The Impact of COVID on Digital Health
WebMD, August 7, 2020
[Video] Dr. John Whyte, Chief Medical Officer at Web MD, discusses the future of healthcare right now during COVID and post-COVID? Dr. Whyte interviews Dr. Bertalan Mesko, a self-described “geek physician” with a PhD in genomics and a medical futurist.
What can we learn from a COVID-19 lung biopsy?
International Journal of Infectious Diseases, August 6, 2020
The newly emerging COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has swept nearly all over the world with stunning mortality. Even lots of researches have been investigated, few pathologies in living lung tissue has been reported due to barely accessible biopsy. Here, we investigated the pathological characteristics of an alive patient who suffered from severe infection with SARS-CoV-2. This study is in accordance with regulations issued by the National Health Commission of China. Our findings will facilitate understanding of the histopathology and the treatment of COVID-19, and improve clinical strategies against the disease. The patient’s lung morphological, ultrastructure, and some important inflammatory biological markers changes are presented to help better understand the disease and make a clue for all the multidisciplinary team to save more people.
Asthma Among Hospitalized Patients with COVID-19 and Related Outcomes
Journal of Allergy and Clinical Immunology, August 6, 2020
Several underlying conditions have been associated with severe SARS-CoV2 illness, it remains unclear if underlying asthma is associated with worse COVID-19 outcomes. Given the high prevalence of asthma in the New York City area, the objective was to determine if underlying asthma was associated with poor outcomes among hospitalized patients with severe COVID-19 disease compared to patients without asthma. Electronic heath records were reviewed for 1,298 sequential patients age <65 years without chronic obstructive pulmonary disease (COPD) who were admitted to our hospital system with a confirmed positive SARS-CoV-2 test. The overall prevalence of asthma among all hospitalized patients with COVID-19 was 12.6%, yet a higher prevalence (23.6%) was observed in the subset 55 patients <21 years of age. There was no significant difference in hospital length of stay, need for intubation, length of intubation, tracheostomy tube placement, hospital readmission or mortality between asthmatic vs. non-asthmatic patients.
Early Identification of COVID-19 Cytokine Storm and Treatment with Anakinra or Tocilizumab
International Journal of Infectious Diseases, August 6, 2020
The objective of the study was to examine outcomes among patients who were treated with the targeted anti-cytokine agents, anakinra or tocilizumab, for COVID-19 -related cytokine storm (COVID19-CS). We conducted a retrospective cohort study of all SARS-coV2-RNA-positive patients treated with tocilizumab or anakinra in Kaiser Permanente Southern California. Local experts developed and implemented criteria to define COVID19-CS. All variables were extracted from the electronic health record. At tocilizumab initiation (n = 52), 50 (96.2%) were intubated, and only 7 (13.5%) received concomitant corticosteroids. At anakinra initiation (n = 41), 23 (56.1%) were intubated, and all received concomitant corticosteroids. Fewer anakinra-treated patients died (n = 9, 22%) and more were extubated/never intubated (n = 26, 63.4%) compared to tocilizumab-treated patients (n = 24, 46.2% dead, n = 22, 42.3% extubated/never intubated).
COVID-19 Breakthrough: Scientists Identify Possible “Achilles’ Heel” of SARS-CoV-2 Virus
SciTechDaily, August 6, 2020
In the case of an infection, the SARS-CoV-2 virus must overcome various defense mechanisms of the human body, including its non-specific or innate immune defense. During this process, infected body cells release messenger substances known as type 1 interferons. These attract natural killer cells, which kill the infected cells. One of the reasons the SARS-CoV-2 virus is so successful — and thus dangerous — is that it can suppress the non-specific immune response. In addition, it lets the human cell produce the viral protein PLpro (papain-like protease). PLpro has two functions: It plays a role in the maturation and release of new viral particles, and it suppresses the development of type 1 interferons. The German and Dutch researchers have now been able to monitor these processes in cell culture experiments. Moreover, if they blocked PLpro, virus production was inhibited and the innate immune response of the human cells was strengthened at the same time. Professor Ivan Dikic, Director of the Institute of Biochemistry II at University Hospital Frankfurt and last author of the paper, explains: “We used the compound GRL-0617, a non-covalent inhibitor of PLpro, and examined its mode of action very closely in terms of biochemistry, structure and function. We concluded that inhibiting PLpro is a very promising double-hit therapeutic strategy against COVID-19. The further development of PLpro-inhibiting substance classes for use in clinical trials is now a key challenge for this therapeutic approach.”
Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients With SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea
JAMA Internal Medicine, August 6, 2020
Are there viral load differences between asymptomatic and symptomatic patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection? There is limited information about the clinical course and viral load in asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this study was to quantitatively describe SARS-CoV-2 molecular viral shedding in asymptomatic and symptomatic patients. In this cohort study that included 303 patients with SARS-CoV-2 infection isolated in a community treatment center in the Republic of Korea, 110 (36.3%) were asymptomatic at the time of isolation and 21 of these (19.1%) developed symptoms during isolation. The cycle threshold values of reverse transcription–polymerase chain reaction for SARS-CoV-2 in asymptomatic patients were similar to those in symptomatic patients. Many individuals with SARS-CoV-2 infection remained asymptomatic for a prolonged period, and viral load was similar to that in symptomatic patients; therefore, isolation of infected persons should be performed.
Healthcare workers of color nearly twice as likely as whites to get COVID-19
Modern Healthcare, August 6, 2020
Healthcare workers of color were more likely to care for patients with suspected or confirmed COVID-19, more likely to report using inadequate or reused protective gear, and nearly twice as likely as white colleagues to test positive for the coronavirus, a new study found. The study from Harvard Medical School researchers also showed that healthcare workers are at least three times more likely than the general public to report a positive COVID test, with risks rising for workers treating COVID patients. Dr. Andrew Chan, a senior author and an epidemiologist at Massachusetts General Hospital, said the study further highlights the problem of structural racism, this time reflected in the front-line roles and personal protective equipment provided to people of color. “If you think to yourself, ‘healthcare workers should be on equal footing in the workplace,’ our study really showed that’s definitely not the case,” said Chan, who is also a professor at Harvard Medical School. The study was based on data from more than 2 million COVID Symptom Study app users in the U.S. and the United Kingdom from March 24 through April 23. The study, done with researchers from King’s College London, was published in the journal The Lancet Public Health.
How a Zoom forum is changing the way ICU doctors treat desperately ill Covid-19 patients\
STAT, August 6, 2020
It was late April, near the height of the Covid-19 pandemic in the big cities in the northeastern U.S., and anesthesiologist Joseph Savino was puzzled. In two months, an unexpectedly high number of coronavirus patients had died in his intensive care unit at the Hospital of the University of Pennsylvania after a stroke caused by bleeding in the brain. All were among 15 Covid-19 patients at the Philadelphia hospital who had been on a life-support technology called ECMO that is a last resort for patients when mechanical ventilators fail to help their virus-ravaged lungs. ECMO, for extracorporeal membrane oxygenation — essentially an artificial lung — is high-risk, but still, the number of fatal brain bleeds seemed unusual, said Savino, a critical-care specialist. It was too low, however, “to draw any substantive conclusions” about cutting back the blood-thinning drugs they were giving other Covid-19 patients on ECMO, because blood clots, not bleeds, were seen as the major risk to survival. Swamped by overflowing ICUs and the myriad not-seen-before ways the novel coronavirus attacks the body, doctors caring for the pandemic’s sickest patients are scrambling to share their experiences with each other in real time, hoping to find ways to stanch Covid-19’s devastating toll. Some 200 physicians from several countries and dozens of states have participated in the Friday Zoom sessions.
The effects of COVID-19 on the office visit
MJH Life Sciences, August 6, 2020
[Infographic] In this State of Physician Survey, COVID-19’s effect on the office visit was the subject. With over 1,000 responses from a variety of specialties, physicians were candid about navigating a new normal with COVID-19 and the office visit. Accommodating safe distancing in the waiting room to patient compliance and education are top areas of concern highlighted on the infographic.
Are patients with chronic rhinosinusitis with nasal polyps at a decreased risk of COVID-19 infection?
International Forum of Allergy & Rhinology, August 5, 2020
SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry to the cell and the serine protease TMPRSS2 for S protein prim. Higher ACE2 expression was recently reported in nasal compared to throat tissue. In fact, higher SARS-CoV-2 viral load was detected in nasal compared to throat swabs obtained from COVID-19 infected patients, and that was attributed to the difference in ACE2 expression between both tissues. In fact, higher SARS-CoV-2 viral load was detected in nasal compared to throat swabs obtained from COVID-19 infected patients. This was attributed to the difference in ACE2 expression between both tissues [4]. Recently, we have also shown that the upper airway expresses more SARS-CoV-2 entry genes, ACE2 and TMPRSS2 compared to the lower airway. Moreover, Hou et al, have recently established that multiciliated cells are the main cell types expressing ACE2 in nasal tissue and infected with SARS-CoV-2. Moreover, Sungnak et al by analyzing data of single-cell RNA-sequencing from healthy human nasal epithelial cells showed that ACE2 and TMPRSS2 are co-expressed in nasal epithelium with genes involved in host innate immunity, referring to the potential role of these cells in initiating SARS-CoV-2 infection. Therefore, the level of SARS-CoV-2 receptors in nasal tissue may determine the level of viral infectivity given the fact that these receptors are not upregulated following infection [1]. With that in mind, we decided to investigate potential factors that may affect the expression of SARS-CoV-2 receptors and hence the risk of infectivity with COVID-19 in various phenotypes of sinonasal inflammation.
Efforts Needed to Get Minorities Into Clinical Trials, Experts Say
MedPage, August 4, 2020
More work needs to be done to enroll people of color in clinical trials, Freda Lewis-Hall, MD, chief patient officer and executive vice president at Pfizer, said Sunday at the annual meeting of the National Medical Association. “One of the really interesting things the data tell us about participation in clinical trials of Black and brown people is they are much less likely to be asked,” Lewis-Hall said during the plenary session of the meeting, which was held remotely. Lewis-Hall said investigator bias against Black and brown patients is reflected in statements such as “I don’t know if they can get here; adherence might be a problem; it may take too long,” and this needs to improve. One thing that would help is having more Black and brown physicians, she added. “The numbers are woefully lagging. We need to increase our pipeline of physicians and physician-investigators, because over and over we heard that the trust issue is critical,” and that “we need to educate patients around clinical trials and their relative safety.”
Assessing Prone and Lateral Positioning in COVID-19 With Hypoxemic Respiratory Failure
Pulmonary Advisor, August 3, 2020
Patients with hypoxemic acute respiratory failure as a result of coronavirus disease 2019 (COVID-19) who received continuous positive airway pressure (CPAP) therapy had a high failure rate during prone/lateral positioning tests, according study results published in CHEST. Patients with COVID-19 at the high dependency unit of a hospital in Milan, Italy who were spontaneously breathing and not intubated but undergoing helmet CPAP treatment were assessed for lung function and blood oxygenation after a number of positioning tests. Patients who had monolateral lung impairment were placed laterally, while patients with bilateral impairment were placed prone. Alveolar-arterial gradient (A-aO2) was recorded at 3 time points: at baseline in a semi-seated position, after 1 hour with the patient in prone/lateral position, and 45 minutes with the patient returned to a semi-seated position. A decrease of ≥20% from baseline was considered clinically significant. Of the 26 patients with COVID-19, the mean age was 62 years and 67% were men. Systemic hypertension, diabetes, obesity, COPD, and asthma were common comorbidities. A total of 39 tests consisting of 12 prone and 27 lateral positioning were conducted. For the primary study end point, 15.4% of positioning trials were successful with a decrease of A-aO2 of ≥20% in comparison to baseline, 7.7% showed a A-aO2 decrease of ≥30% in comparison with baseline, 46.1% trials showed a decrease of <20% of A-aO2 compared with baseline, and a total of 38.5% trials failed.
Coronavirus Q&A With Anthony Fauci
JAMA Live, August 3, 2020
[Video] Anthony Fauci, MD, White House Coronavirus Task Force member and Director of the National Institutes of Allergy and Infectious Diseases, discusses latest developments in the COVID-19 pandemic with Howard Bauchner, MD, Editor in Chief, JAMA.
Covid-19: Obesity Ups Risk of Intubation, Death in Adults 65 or Younger
Physician’s Weekly, August 3, 2020
Obesity is associated with an increased risk of death or intubation in patients younger than age 65 who contract Covid-19, according to a retrospective cohort study published in the Annals of Internal Medicine. This association was independent of age, sex, race/ethnicity, and comorbid conditions, Michaela R. Anderson, MD, MS, of Columbia University Irving Medical Center, in New York, and colleagues reported. They did note that the associations varied by age. “Obesity was strongly associated with intubation or death among adults younger than 65 years, but not among those aged 65 years or older,” Anderson and colleagues noted. “Our findings provide evidence to support recommendations from the Centers for Disease Control and Prevention in the United States and the National Health Service in the United Kingdom, which state that patients with a BMI of 40 kg/m2 or greater are at high risk for poor outcomes from Covid-19 and should therefore consider prolonged social distancing. As the United States and other countries begin to lift stay-at-home orders, these findings might inform discussions between health care providers and patients regarding advanced care planning and benefits of prolonged social distancing, particularly for younger adults with class 2 or 3 obesity.”
The effect of sample site, illness duration and the presence of pneumonia on the detection of SARS-CoV-2 by real-time reverse-transcription PCR
Open Forum Infectious Diseases, August 3, 2020
The performance of rRT-PCR for SARS-CoV-2 varies with sampling site(s), illness stage and infection site were evaluated. Unilateral nasopharyngeal, nasal mid-turbinate, throat swabs, and saliva were simultaneously sampled for SARS-CoV-2 rRT-PCR from suspect or confirmed cases of COVID-19.True positives were defined as patients with at least one SARS-CoV-2 detected by rRT-PCR from any site on the evaluation day or at any time point thereafter, till discharge. Diagnostic performance was assessed and extrapolated for site combinations. We evaluated 105 patients; 73 had active SARS-CoV-2 infection. Overall, nasopharyngeal specimens had the highest clinical sensitivity at 85%, followed by throat, 80%, mid-turbinate, 62%, and saliva, 38-52%. Clinical sensitivity for nasopharyngeal, throat, mid-turbinate and saliva was 95%, 88%, 72%, and 44-56% if taken ≤7 days from onset of illness, and 70%, 67%, 47%, 28-44% if >7 days of illness. Comparing patients with URTI vs. pneumonia, clinical sensitivity for nasopharyngeal, throat, mid-turbinate and saliva was 92% vs 70%, 88% vs 61%, 70% vs 44%, 43-54% vs 26-45%. A combination of nasopharyngeal plus throat or mid-turbinate plus throat specimen afforded overall clinical sensitivities of 89-92%, this rose to 96% for persons with URTI and 98% for persons <7 days from illness onset.
No Benefit With Tocilizumab in COVID-19 Pneumonia Trial
Pulmonary Advisor, August 3, 2020
Genentech announced that a phase 3 study investigating tocilizumab (Actemra®) for the treatment of hospitalized patients with severe coronavirus disease 2019 (COVID-19) associated pneumonia did not meet its primary and key secondary end points. The multicenter, randomized, double-blind COVACTA study compared the efficacy and safety of tocilizumab, an interleukin-6 receptor antagonist, to placebo in hospitalized adult patients with severe COVID-19 pneumonia. Patients were randomized to receive 1 intravenous infusion of either tocilizumab or placebo, in addition to standard of care. The primary end point was clinical status as measured by a 7-category ordinal scale; key secondary end points included mortality, as well as mechanical ventilation and intensive care unit (ICU) variables. Results showed that the difference in clinical status between patients treated with tocilizumab and those who received placebo was not statistically significant (odds ratio 1.19; 95% CI, 0.81-1.76; P =.36). Additionally, no statistically significant differences were observed between the 2 groups with regard to mortality rate (19.7% with tocilizumab vs 19.4% with placebo; P =.9410) or ventilator-free days (22 days with tocilizumab vs 16.5 days with placebo; P =.3202).
Longitudinal dynamics of the neutralizing antibody response to SARS-CoV-2 infection
Clinical Infectious Diseases, August 3, 2020
Coronavirus disease 2019 (COVID-19) is a global pandemic with no licensed vaccine or specific antiviral agents for therapy. Little is known about the longitudinal dynamics of SARS-CoV-2-specific neutralizing antibodies (NAbs) in COVID-19 patients. In this study, blood samples (n=173) were collected from 30 COVID-19 patients over a 3-month period after symptom onset and analyzed for SARS-CoV-2-specific NAbs, using the lentiviral pseudotype assay, coincident with the levels of IgG and proinflammatory cytokines. SARS-CoV-2-specific NAb titers were low for the first 7–10 d after symptom onset and increased after 2–3 weeks. The median peak time for NAbs was 33 d (IQR 24–59 d) after symptom onset. NAb titers in 93·3% (28/30) of the patients declined gradually over the 3-month study period, with a median decrease of 34·8% (IQR 19·6–42·4%). NAb titers increased over time in parallel with the rise in IgG antibody levels, correlating well at week 3 (r = 0·41, p & 0·05). The NAb titers also demonstrated a significant positive correlation with levels of plasma proinflammatory cytokines, including SCF, TRAIL, and M-CSF.
Presidential order signed expanding use of virtual doctors
The Hill, August 3, 2020
On Monday, the President signed an executive order seeking to expand the use of virtual doctors visits, as his administration looks to highlight achievements in health care. The administration waived certain regulatory barriers to video and phone calls with doctors, known as telehealth, when the coronavirus pandemic struck and many people were stuck at home. Now, the administration is looking to make some of those changes permanent, arguing the moves will provide another option for patients to talk to their doctors. The order calls on the secretary of Health and Human Services to issue rules within 60 days making some of the changes permanent.
RLF-100 (aviptadil) clinical trial showed rapid recovery from respiratory failure and inhibition of coronavirus replication in human lung cells
Cision, August 2, 2020
NeuroRx, Inc. and Relief Therapeutics Holdings AG (SIX:RLF, OTC:RLFTF) “Relief” today announced that RLF-100 (aviptadil) showed rapid recovery from respiratory failure in the most critically ill patients with COVID-19. At the same time, independent researchers have reported that aviptadil blocked replication of the SARS coronavirus in human lung cells and monocytes. RLF-100 has been granted Fast Track designation by FDA and is being developed as a Material Threat Medical Countermeasure in cooperation with the National Institutes of Health and other federal agencies. Further research will be conducted. The first report of rapid clinical recovery under emergency use IND was posted by doctors from Houston Methodist Hospital. The report describes a 54-year-old man who developed COVID-19 while being treated for rejection of a double lung transplant and who came off a ventilator within four days. Similar results were subsequently seen in more than 15 patients treated under emergency use IND and an FDA expanded access protocol which is open to patients too ill to be admitted to the ongoing Phase 2/3 FDA trial. Patients with Critical COVID-19 were seen to have a rapid clearing of classic pneumonitis findings on x-ray, accompanied by an improvement in blood oxygen and a 50% or greater average decrease in laboratory markers associated with COVID-19 inflammation.
U.S. records over 25,000 coronavirus deaths in July
Reuters, July 31, 2020
U.S. coronavirus deaths rose by over 25,000 in July and cases doubled in 19 states during the month, according to a Reuters tally, dealing a crushing blow to hopes of quickly reopening the economy. The United States recorded 1.87 million new cases in July, bringing total infections to 4.5 million, for an increase of 69%. Deaths in July rose 20% to nearly 154,000 total. The biggest increases in July were in Florida, with over 310,000 new cases, followed by California and Texas with about 260,000 each. All three states saw cases double in June. Cases also more than doubled in Alabama, Alaska, Arizona, Arkansas, Georgia, Hawaii, Idaho, Mississippi, Missouri, Montana, Nevada, Oklahoma, Oregon, South Carolina, Tennessee and West Virginia, according to the tally. Connecticut, Massachusetts, New Jersey and New York had the lowest increases, with cases rising 8% or less.
Women Physicians and the COVID-19 Pandemic
Journal of the American Medical Association, July 31, 2020
Before the magnifying glass of the COVID-19 pandemic caused physicians to look more closely at many aspects of their profession, there was awareness of the general culture of overwork that affect all physicians and the expectation by some that women physicians would make adjustments in their professional roles to accommodate their personal roles. These professional adjustments were made, including part-time status, despite the known limitations on professional progression, career advancement, and economic potential. These adjustments further propagate gender inequities and the persistent compensation gap women physicians’ experience. Women physicians have diverse personal characteristics. There is no appropriate stereotype for a woman physician. Some are just starting their professional careers. Some are older, nearing retirement. Some are partnered, others are solo. Some are childless, others are parents. Family care responsibilities vary with some caring for their children, their aging parents, or both. Practice parameters and settings vary, including business owners, health care executives, academic physicians, and employees of hospitals and group practices. For partnered women physicians, a small number are the principal source of income with a partner assuming the primary role for home and family care. The increasing number of women physicians is accompanied by a rise in the number of dual physician households. This diversity of personal situations highlights the reason to avoid broad assumptions when considering the life-work preferences or professional work adjustments related to the COVID-19 epidemic for individuals or groups of physicians, by gender.
2nd US virus surge hits plateau, but few experts celebrate
Associated Press, July 31, 2020
While deaths from the coronavirus in the U.S. are mounting rapidly, public health experts are seeing a flicker of good news: The second surge of confirmed cases appears to be leveling off. The virus has claimed over 150,000 lives in the U.S., by far the highest death toll in the world, plus more than a half-million others around the globe. Over the past week, the average number of COVID-19 deaths per day in the U.S. has climbed more than 25%, from 843 to 1,057. Florida on Thursday reported 253 more deaths, setting its third straight single-day record, while Texas had 322 new fatalities and California had 391. The number of confirmed infections nationwide has topped 4.4 million, which could be higher because of limits on testing and because some people are infected without feeling sick.
Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network — United States, March–June 2020
CDC Morbidity and Mortality Weekly Report, July 31, 2020
Prolonged symptom duration and disability are common in adults hospitalized with severe coronavirus disease 2019 (COVID-19). Characterizing return to baseline health among outpatients with milder COVID-19 illness is important for understanding the full spectrum of COVID-19–associated illness and tailoring public health messaging, interventions, and policy. During April 15–June 25, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had a first positive reverse transcription–polymerase chain reaction (RT-PCR) test for SARS-CoV-2, the virus that causes COVID-19, at an outpatient visit at one of 14 U.S. academic health care systems in 13 states. Interviews were conducted 14–21 days after the test date. Respondents were asked about demographic characteristics, baseline chronic medical conditions, symptoms present at the time of testing, whether those symptoms had resolved by the interview date, and whether they had returned to their usual state of health at the time of interview. Among 292 respondents, 94% (274) reported experiencing one or more symptoms at the time of testing; 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the interview (median = 16 days from testing date), including 26% among those aged 18–34 years, 32% among those aged 35–49 years, and 47% among those aged ≥50 years. Among respondents reporting cough, fatigue, or shortness of breath at the time of testing, 43%, 35%, and 29%, respectively, continued to experience these symptoms at the time of the interview.
Lung Compliance in a Case Series of Four COVID-19 Patients at a Rural Institution
Cureus, July 30, 2020
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic has generated a plethora of scientific articles. One interesting aspect of the virus is the binary phenotypic presentation in patients. While patients might meet the Berlin criteria for acute respiratory distress syndrome (ARDS), not all patients experience the same decrease in lung compliance as typically seen with ARDS. We have observed patients meeting ARDS criteria with higher lung compliance as measured through peak pressures at our institution. This phenotype difference is important with regard to how the patients are managed. Lower positive end-expiratory pressure (PEEP) and higher tidal volumes can be used in this phenotype. Read this case series of four patients with confirmed COVIID-19 admitted to our hospital, with a focus on lung compliance. Three of the four patients required intubation, while the fourth passed away before intubation.
Scientists develop human lung organoids to study SARS-CoV-2 infection
News Medical, July 30, 2020
The current COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to target primarily the distal lung, including the terminal bronchioles and alveoli, which are the sites of essential gas exchange in the human body. In a significant minority of patients, this results in critical pneumonia and acute respiratory distress syndrome (ARDS). However, the mechanism by which this occurs is far from clear, and one major contributing factor to this knowledge gap is the absence of a reliable and robust human lung cell culture system that will serve as a substrate for disease of the terminal lungs. Now, a new study reports the development of a human distal lung culture system that can be functionally tested. This will help not only to understand how this infection produces disease but also to test the proliferative capacity of the stem cells in this part of the body. As of now, mouse studies provide most of our knowledge about these stem cells, which are functionally part of the lung as well as providing a source of new cells during healing of the lung. These studies have shown that these bifunctional stem cells of the distal lung comprise the secretory club cells found in the distal bronchioles and the type 2 pneumonocytes or alveolar cells (AT2) that produce surfactant in the lung alveoli.
Treatment Options for COVID-19
Helio | Infectious Disease News, July 30, 2020
[Podcast] Research and data on potential treatment modalities continue to emerge at a rapid pace. This episode explores the IDSA and NIH guidelines for the treatment and management of COVID-19, as well as available evidence on antivirals, glucocorticoids and antibodies. Gitanjali Pai, MD, is an infectious disease physician at Memorial Hospital and Physicians’ Clinic in Stilwell, Oklahoma. She is a member of the Infectious Disease News Editorial Board and host of Healio’s podcast Unmasking COVID-19.
Comparative study of lung ultrasound and chest computed tomography scan in the assessment of severity of confirmed COVID-19 pneumonia
Intensive Care Medicine, July 29, 2020
This multicentre observational study was performed between 15 March and 20 April 2020. Patients in the Emergency Department (ED) or Intensive Care Unit (ICU) with acute dyspnoea who were PCR positive for SARS-CoV-2, and who had LUS and chest CT performed within a 24-h period, were included. One hundred patients were included. LUS score was significantly associated with pneumonia severity assessed by chest CT and clinical features. The AUC of the ROC curve of the relationship of LUS versus chest CT for the assessment of severe SARS-CoV-2 pneumonia was 0.78 (CI 95% 0.68–0.87; p < 0.0001). A high LUS score was associated with the use of mechanical ventilation, and with a SpO2/FiO2 ratio below 357. In known SARS-CoV-2 pneumonia patients, the LUS score was predictive of pneumonia severity as assessed by a chest CT scan and clinical features. Within the limitations inherent to our study design, LUS can be used to assess SARS-CoV-2 pneumonia severity.
Researchers launch randomized, placebo-controlled clinical trial of pulmozyme in COVID-19 patients
NewsMedical, July 29, 2020
Researchers at Boston Children’s Hospital and Brigham and Women’s Hospital have launched a randomized, placebo-controlled clinical trial of dornase alfa (Pulmozyme) in patients with severe COVID-19 pneumonia and respiratory failure requiring mechanical ventilation. The study aims to enroll 60 adults and children (over age 3) admitted to intensive care units. Dornase alfa, also called DNase 1, is FDA-approved for patients with cystic fibrosis, to break up thick mucus secretions and prevent lung infections. The trial is supported by the Massachusetts Consortium on Pathogen Readiness, and the drug is being provided by Genentech, a member of the Roche Group, which is also providing supplementary financial support. The 18-month study will randomize patients to twice-daily nebulized dornase alfa or placebo (a saline solution) within 48 hours after intubation and placement on a ventilator.
Association between cytokine profiles and lung injury in COVID-19 pneumonia
Respiratory Research, July 29, 2020
The purpose of the present study was to investigate the association between cytokine profiles and lung injury in COVID-19 pneumonia. The retrospective study was conducted in COVID-19 patients. Demographic characteristics, symptoms, signs, underlying diseases, and laboratory data were collected. The patients were divided into COVID-19 with pneumonia and without pneumonia. CT severity score and PaO2/FiO2 ratio were used to assess lung injury. One hundred and six patients with 12 COVID-19 without pneumonia and 94 COVID-19 with pneumonia were included. Compared with COVID-19 without pneumonia, COVID-19 with pneumonia had significantly higher serum interleukin (IL)-2R, IL-6, and tumor necrosis factor (TNF)-α. Correlation analysis showed that CT severity score and PaO2/FiO2 were significantly correlated with age, presence of any coexisting disorder, lymphocyte count, procalcitonin, IL-2R, and IL-6. In multivariate analysis, log IL6 was the only independent explanatory variables for CT severity score (β = 0.397, p < 0.001) and PaO2/FiO2 (β = − 0.434, p = 0.003).
Phase 3 Trial of COVID-19 Vaccine Candidate mRNA-1273 Begins
Pulmonology Advisor, July 29, 2020
Moderna and the National Institutes of Allergy and Infectious Diseases have initiated a phase 3 trial evaluating the vaccine candidate mRNA-1273 against coronavirus disease 2019 (COVID-19). The trial, which is the first to be implemented under Operation Warp Speed, is expected to enroll around 30,000 adults and will be conducted at multiple clinical research sites across the US. In addition, the National Institutes of Health (NIH) Coronavirus Prevention Network will participate in conducting the trial. Testing sites in areas with emerging cases or high incidence rates will be prioritized for enrollment. Participants will be randomized to receive 2 intramuscular injections of either mRNA-1273 or saline placebo approximately 28 days apart. The study’s primary aim will be to assess whether the vaccine is able to prevent symptomatic COVID-19 after the administration of 2 doses; prevention after 1 dose will also be investigated as a secondary goal. Moreover, researchers will look at whether vaccination with mRNA-1273 prevents severe COVID-19 or laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with or without disease symptoms, as well as death.
U.S. records a coronavirus death every minute as total surpasses 150,000
Reuters, July 29, 2020
One person in the United States died about every minute from COVID-19 on Wednesday as the national death toll surpassed 150,000, the highest in the world. The United States recorded 1,461 new deaths on Wednesday, the highest one-day increase since 1,484 on May 27, according to a Reuters tally. U.S. coronavirus deaths are rising at their fastest rate in two months and have increased by 10,000 in the past 11 days. Nationally, COVID-19 deaths have risen for three weeks in a row while the number of new cases week-over-week recently fell for the first time since June. A spike in infections in Arizona, California, Florida and Texas this month has overwhelmed hospitals. The rise has forced states to make a U-turn on reopening economies that were restricted by lockdowns in March and April to slow the spread of the virus. Texas leads the nation with nearly 4,300 deaths so far this month, followed by Florida with 2,900 and California, the most populous state, with 2,700. The Texas figure includes a backlog of hundreds of deaths after the state changed the way it counted COVID-19 fatalities.
As pandemic rages, PPE supply remains a problem
Center for Infectious Disease Research and Policy, July 29, 2020
On top of being overwhelmed with severely ill people, healthcare workers are dealing with shortages of the personal protective equipment (PPE) that they need to keep from getting infected themselves. N95 respirators, surgical masks, gowns, and gloves were all were in short supply, forcing hospitals to ration them. At the root of the issue were several problems: a global surge in demand for protective gear that was outstripping supply, a lack of adequate supplies in the Strategic National Stockpile, which is intended to supplement state and local supplies during public health emergencies, and a response that lacked any federal coordination. A nationwide scrum for available PPE ensued, pitting state governments, healthcare systems, and individual hospitals against each other as they fought to outbid each other for adequate supplies for the pandemic response. Four months later, many hospitals have a better supply of PPE than they did in March and April. But with the dramatic nationwide rise in coronavirus cases that began in mid-June and shows no signs of slowing, concerns about PPE supplies remain. And demand is now coming not only from the hospitals that are treating COVID-19 patients, but also from nursing homes, primary care doctors who want to ensure a safe environment as they begin welcoming back patients for routine primary care, and other frontline healthcare workers.
Lung fibrosis: an undervalued finding in COVID-19 pathological series
The Lancet | Infectious Diseases, July 28, 2020
With the COVID-19 pandemic having reached tremendous proportions, post-mortem series are under the limelight to explain many of the peculiar clinical findings. Pathological descriptions of disease are fundamental for understanding pathogenetic features and might inform new treatments. Indeed, the widely discussed identification of thrombosis in patients with COVID-19 has garnered much interest, and has resulted in new treatment strategies, with anticoagulants now part of patient management. In their Article, Luca Carsana and colleagues describe the lung findings of 38 patients who died with COVID-19 and show that early-phase or intermediate-phase diffuse alveolar damage is the main pathological finding, as well as fibrin thrombi in small arterial vessels. Other autoptic series, composed of fewer cases, also show thrombotic events to be findings specifically related to COVID-19. The fibrotic changes seen in patients who died with COVID-19 who had severe disease of long duration have been, however, only briefly touched upon in published studies, and no complete pathological description of these cases is available.
SARS-CoV-2 Infection Does Not Necessarily Increase Asthma Exacerbation Risk
Pulmonary Advisor, July 28, 2020
Asthma is not a risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), and SARS-CoV-2 pneumonia may not induce severe asthma exacerbation, according to the results of a retrospective cohort study published in The Journal of Allergy and Clinical Immunology: In Practice. Viral infections are known to exacerbate asthma in adults, however these patients are rare in epidemiologic studies of SARS-CoV-2 pneumonia. Thus, it is unknown whether there is an association between SARS-CoV-2 infection and severe asthma exacerbation. Researchers at Strasbourg University Hospital in France assessed the frequency of asthma exacerbation in 106 patients hospitalized for SARS-CoV-2 pneumonia between March 4 and April 6, 2020. Of these patients, 23 had asthma, with 63.6% considered well-controlled and 23.4% considered partially controlled. A total of 11 patients had ≥1 severe exacerbation in the previous year and 68.2% were considered to have allergic asthma because of their clinical history.
Case characteristics, resource use, and outcomes of 10 021 patients with COVID-19 admitted to 920 German hospitals: an observational study
The Lancet | Respiratory Medicine, July 28, 2020
In this observational study, adult patients with a confirmed COVID-19 diagnosis, who were admitted to hospital in Germany between Feb 26 and April 19, 2020, and for whom a complete hospital course was available (ie, the patient was discharged or died in hospital) were included in the study cohort. Claims data from the German Local Health Care Funds were analysed. The data set included detailed information on patient characteristics, duration of hospital stay, type and duration of ventilation, and survival status. Patients with adjacent completed hospital stays were grouped into one case. Patients were grouped according to whether or not they had received any form of mechanical ventilation. Of 10,021 hospitalised patients being treated in 920 different hospitals, 1727 (17%) received mechanical ventilation (of whom 422 [24%] were aged 18–59 years, 382 [22%] were aged 60–69 years, 535 [31%] were aged 70–79 years, and 388 [23%] were aged ≥80 years). The median age was 72 years (IQR 57–82). Men and women were equally represented in the non-ventilated group, whereas twice as many men than women were in the ventilated group. The likelihood of being ventilated was 12% for women (580 of 4822) and 22% for men (1147 of 5199).
Effect of COVID-19 on Pulmonary Fibrosis Clinical Trials: Expert Interview
Pulmonary Advisor, July 27, 2020
For patients with chronic diseases such as pulmonary fibrosis, coronavirus disease 2019 (COVID-19) represents a threat beyond the immediate risk of infection. These individuals have a greater likelihood of developing serious complications as a result of the virus, and those awaiting organ transplantation and other surgical interventions may face delays because of the risk of viral exposure and strained resources in the current healthcare environment. In addition, clinical trials investigating potential therapies for various diseases including pulmonary fibrosis have been disrupted considerably since the pandemic emerged. According to data from the WIRB-Copernicus Group (WCG), the number of clinical research sites open to enrollment for non-COVID-19 trials decreased from 62% on March 24, 2020, to 11% on May 1, 2020. Although enrollment has begun to resume since that period, these developments have prompted experts to consider ways to address such issues in the context of ongoing and future trials.
The Color of COVID: Will Vaccine Trials Reflect America’s Diversity?
Kaiser Health News, July 27, 2020
Black and Latino people have been three times as likely as white people to become infected with COVID-19 and twice as likely to die, according to federal data obtained via a lawsuit by The New York Times. Asian Americans appear to account for fewer cases but have higher rates of death. Eight out of 10 COVID deaths reported in the U.S. have been of people ages 65 and older. And the Centers for Disease Control and Prevention warns that chronic kidney disease is among the top risk factors for serious infection. Historically, however, those groups have been less likely to be included in clinical trials for disease treatment, despite federal rules requiring minority and elder participation and the ongoing efforts of patient advocates to diversify these crucial medical studies. In a summer dominated by COVID-19 and protests against racial injustice, there are growing demands that drugmakers and investigators ensure that vaccine trials reflect the entire community.
Appropriate use of Tocilizumab in COVID-19 Infection
International Journal of Infectious Diseases, July 26, 2020
This study aimed to describe the effectiveness and optimum use of tocilizumab (TCZ) treatment by the support of clinical, laboratory, and radiologic observations. All the patients were followed up in the hospital with daily interleukin-6 (IL-6), C-reactive protein (CRP), ferritin, D-dimer, complete blood count, and procalcitonin. Computerized thoracic tomography was obtained on admission, when oxygen support was necessary, and seven days after TCZ start. Disease course of the patients was grouped as severe or critical according to their clinical, laboratory, and radiologic evaluations. In total, 43 patients were included; 70% of the patients was male; the median age was 64 (min-max: 27-94), 6 (14%) patients were fatal. The median duration of oxygen support before the onset of TCZ was shorter among the severe patient group than the critical patient group (1 vs 4 days, p < 0.001). Only 3 cases out of 21 (14%) who received TCZ in the ward were transferred to ICU, and none of them died. The levels of IL-6, CRP, ferritin, D-dimer, and procalcitonin were significantly lower in severe cases group than the critical cases group (p = 0.025, p = 0.002, p = 0.008, p = 0.002, and p = 0.001, respectively). Radiological improvement was observed in severe cases on the seventh day of TCZ. Secondary bacterial infection was detected in 41% of critical cases, but none of the severe ones.
Florida records 9,300 new coronavirus cases, blows past New York
Reuters, July 26, 2020
Florida on Sunday became the second state after California to overtake New York, the worst-hit state at the start of the U.S. novel coronavirus outbreak, according to a Reuters tally. Total COVID-19 cases in the Sunshine State rose by 9,300 to 423,855 on Sunday, just one place behind California, which now leads the country with 448,497 cases. New York is in third place with 415,827 cases. Still, New York has recorded the most deaths of any U.S. state at more than 32,000 with Florida in eighth place with nearly 6,000 deaths. On average, Florida has added more than 10,000 cases a day in July while California has been adding 8,300 cases a day and New York has been adding 700 cases.
U.S .agency vows steps to address COVID-19 inequalities
Modern Healthcare, July 25, 2020
If Black, Hispanic and Native Americans are hospitalized and killed by the coronavirus at far higher rates than others, shouldn’t the government count them as high risk for serious illness? That seemingly simple question has been mulled by federal health officials for months. And so far the answer is no. But federal public health officials have released a new strategy that vows to improve data collection and take steps to address stark inequalities in how the disease is affecting Americans. Officials at the Centers for Disease Control and Prevention stress that the disproportionately high impact on certain minority groups is not driven by genetics. Rather, it’s social conditions that make people of color more likely to be exposed to the virus and — if they catch it — more likely to get seriously ill. “To just name racial and ethnic groups without contextualizing what contributes to the risk has the potential to be stigmatizing and victimizing,” said the CDC’s Leandris Liburd, who two months ago was named chief health equity officer in the agency’s coronavirus response. Outside experts agreed that there’s a lot of potential downside to labeling certain racial and ethnic groups as high risk.
Early administration of Interleukin-6 inhibitors for patients with severe Covid-19 disease is associated with decreased intubation, reduced mortality, and increased discharge
International Journal of Infectious Diseases, July 25, 2020
This observational study aimed to determine optimal timing of interleukin-6 receptor inhibitors (IL6ri) administration for Coronavirus disease 2019 (Covid-19). Patients with Covid-19 were given an IL6ri (sarilumab or tocilizumab) based on iteratively reviewed guidelines. IL6ri were initially reserved for critically ill patients, but after review, treatment was liberalized to patients with lower oxygen requirements. Patients were divided into 2 groups: those requiring ≤ 45% fraction of inspired oxygen (FiO2) (termed stage IIB) and those requiring >45% FiO2 (termed stage III) at the time of IL6ri administration. Main outcomes were all-cause mortality, discharge alive from hospital, and extubation. Two hundred fifty-five Covid-19 patients were treated with IL6ri (149 stage IIB and 106 stage III). Patients treated in stage IIB had lower mortality than the stage III group (adjusted hazard ratio [aHR]: 0.24; 95% confidence interval [CI] 0.08-0.74). Overall, 218 (85.5%) patients were discharged alive. Patients treated in stage IIB were more likely to be discharged (aHR: 1.43; 95% CI 1.06 – 1.93) and were less likely to be intubated (HR: 0.43; 95% CI: 0.24-0.79).
US surpasses 1,000 COVID-19 deaths for fourth straight day
The Hill, July 25, 2020
The U.S. tallied over 1,000 coronavirus-related deaths Friday for the fourth straight day this week, yet another sign of the alarming spike in COVID-19 cases across the country. There were 1,178 new deaths Friday alone, according to the COVID Tracking project, compared with 1,038 Tuesday, 1,117 Wednesday, and 1,039 Thursday. Over 137,000 people have died in the U.S. and over 4 million people have contracted the virus in the country since the outbreak began. The alarming figures are largely driven by a surge in cases across the South and West, particularly in Arizona, California, Florida and Texas. The spikes have led to urgent calls from public health officials for Americans, particularly young people, to heed health guidance such as wearing masks and socially distancing.
Particle sizes of infectious aerosols: implications for infection control
The Lancet | Respiratory Medicine, July 24, 2020
The global pandemic of COVID-19 has been associated with infections and deaths among health-care workers. This Viewpoint of infectious aerosols is intended to inform appropriate infection control measures to protect health-care workers. Studies of cough aerosols and of exhaled breath from patients with various respiratory infections have shown striking similarities in aerosol size distributions, with a predominance of pathogens in small particles (<5 μm). These are immediately respirable, suggesting the need for personal respiratory protection (respirators) for individuals in close proximity to patients with potentially virulent pathogens. There is no evidence that some pathogens are carried only in large droplets. Surgical masks might offer some respiratory protection from inhalation of infectious aerosols, but not as much as respirators. However, surgical masks worn by patients reduce exposures to infectious aerosols to health-care workers and other individuals. The variability of infectious aerosol production, with some so-called super-emitters producing much higher amounts of infectious aerosol than most, might help to explain the epidemiology of super-spreading. Airborne infection control measures are indicated for potentially lethal respiratory pathogens such as severe acute respiratory syndrome coronavirus 2.
Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19
The New England Journal of Medicine, July 23, 2020
Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. This multicenter, randomized, open-label, three-group, controlled trial involved hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis.
Time to Address Race-Ethnic COVID Disparities in Seniors, Senate Panel Told
MedPage Today, July 23, 2020
Enhancing data collection, investing in research, and building trust can help mitigate the disparate impacts of the COVID-19 pandemic on Black and Latinx seniors, witnesses told members of the Senate Special Committee on Aging during a hearing on Tuesday. The pandemic’s impact on minority and ethnic groups appears most acute in young people and seems to taper off among community-dwelling older adults, Mercedes Carnethon, PhD, an epidemiologist and preventive medicine specialist at Northwestern University in Chicago, told the committee. Nevertheless, disparities persist for seniors living in congregate care settings such as nursing homes. In fact, nursing homes with a higher proportion of Black and Latinx residents have double the rates of COVID-19 infections than facilities with a greater share of non-Hispanic whites, Carnethon said. Current policies don’t require universal reporting of race or ethnicities of individuals affected by COVID-19, she said.
Dexamethasone Lowers Mortality in Patients With COVID-19 Receiving Mechanical Ventilation
Pulmonology Advisor, July 23, 2020
Treatment with dexamethasone resulted in lower rates of 28-day mortality in patients hospitalized with coronavirus disease 2019 (COVID-19) who received invasive mechanical ventilation but not in those who received no respiratory support, according to findings published in the New England Journal of Medicine. Researchers conducted a controlled, open-label clinical trial (RECOVERY; ClinicalTrials.gov Identifier: NCT04381936) to evaluate the effects of potential treatments in patients hospitalized with COVID-19 in the United Kingdom. The primary outcome was 28-day mortality, with secondary outcomes being the time until hospital discharge and subsequent receipt of invasive ventilation or death in patients who did not receive mechanical ventilation at the beginning of the study. A total of 6425 patients were randomly assigned to receive oral or intravenous dexamethasone (n=2104) at 6 mg once daily for up to 10 days or usual care alone (n=4321). Mean patient age was 66.1 years and 36% were women. More than half of the patients had ≥1 major coexisting medical condition, including heart disease, chronic lung disease, and diabetes.
Effect of Systemic Glucocorticoids on Mortality or Mechanical Ventilation in Patients With COVID-19
Journal of Hospital Medicine, July 22, 2020
The efficacy of glucocorticoids in COVID-19 is unclear. This study was designed to determine whether systemic glucocorticoid treatment in COVID-19 patients is associated with reduced mortality or mechanical ventilation. This observational study included 1,806 hospitalized COVID-19 patients; 140 were treated with glucocorticoids within 48 hours of admission. Early use of glucocorticoids was not associated with mortality or mechanical ventilation. However, glucocorticoid treatment of patients with initial C-reactive protein (CRP) ≥20 mg/dL was associated with significantly reduced risk of mortality or mechanical ventilation (odds ratio, 0.23; 95% CI, 0.08-0.70), while glucocorticoid treatment of patients with CRP <10 mg/dL was associated with significantly increased risk of mortality or mechanical ventilation (OR, 2.64; 95% CI, 1.39-5.03). Whether glucocorticoid treatment is associated with changes in mortality or mechanical ventilation in patients with high or low CRP needs study in prospective, randomized clinical trials.
Research Needed to Establish Diagnostic Chest CT Criteria for COVID-19
Pulmonary Advisor, July 22, 2020
More high-quality research is necessary to establish diagnostic chest computed tomography (CT) criteria for coronavirus disease 2019 (COVID-19), according to the results of a systematic review and meta-analysis published in Chest. Currently, real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swab specimens is considered the gold standard for the diagnosis of COVID-19. Real-time RT-PCR testing, however, is time-consuming and suboptimal for the rapid triaging of patients. In consideration of the potential benefit of chest CT for the diagnosis of COVID-19, in concert with clinical examination and RT-PCR, a team of researchers performed a systematic review to assess the methodologic quality of studies on the use of chest CT imaging in patients with COVID-19 and to determine the frequency of different chest CT findings. Studies that reported the prevalence of chest CT findings in patients with a diagnosis of COVID-19 confirmed by RT-PCR or gene sequencing were eligible for inclusion. In addition, only studies that provided a detailed description of chest CT findings according to the glossary of terms for thoracic imaging of the Fleischner Society were included.
Association of Interleukin 7 Immunotherapy With Lymphocyte Counts Among Patients With Severe Coronavirus Disease 2019 (COVID-19)
JAMA Network Open, July 22, 2020
[Research Letter] Cytokine storm–mediated organ injury continues to dominate current thinking as the primary mechanism for coronavirus disease 2019 (COVID-19). Although there is an initial hyper-inflammatory phase, mounting evidence suggests that virus-induced defective host immunity may be the real cause of death in many patients. COVID-19 has been called a serial lymphocyte killer because profound and protracted lymphopenia is a near uniform finding among patients with severe COVID-19 and correlates with morbidity and mortality. Autopsies demonstrate a devastating depletion of lymphocytes in the spleen and other organs. CD4, CD8, and natural killer cells, which play important antiviral roles, are depleted and have reduced function, leading to immune collapse. Clinical and pathological findings in patients with COVID-19 indicate that immunosuppression is a critical determinant of outcomes.
Financial Impact of COVID-19 on physicians and their practices
MJH Life Sciences, July 22, 2020
With over 1,600 responses from a variety of specialties, physicians weighed in on the financial impact of COVID-19 and how they are navigating the decrease in patient volume, telehealth reimbursements and financial relief. These results convey the challenges and concerns of physicians as they transition to the new normal with COVID-19. From anticipated loss in revenue to influence on headcount, the Financial Impact survey reveals the lasting repercussions COVID-19 will have practices for the remainder of 2020 and beyond.
HHS Rolls Out New COVID-19 Data Dashboard
MedPage Today, July 21, 2020
The Department of Health and Human Services (HHS) debuted its new COVID-19 dashboard on Monday, and the department’s data chief said it will provide even more data than the CDC’s old one did. Called the Coronavirus Data Hub, the HHS dashboard replaces the CDC’s National Healthcare Safety Network (NHSN), to which states and hospitals had previously been submitting COVID-19 data such as intensive care unit capacity, ventilator use, personal protective equipment (PPE) levels, and staffing shortages. But in guidance to hospitals, updated July 10 and published with little fanfare, HHS ordered hospitals to stop submitting such data to the NHSN and instead submit it either to HHS or to their state health department, which would then submit it to HHS. The data would then be put on the dashboard via the department’s new HHS Protect data system. The dashboard’s public-facing side allows users to see the overall number of confirmed coronavirus cases in the U.S. as well as the overall number of reported deaths. It also includes data on inpatient and ICU bed utilization.
Seroprevalence of Antibodies to SARS-CoV-2 in 10 Sites in the United States, March 23-May 12, 2020
JAMA Internal Medicine, July 21, 2020
In this cross-sectional study of 16 025 residual clinical specimens, estimates of the proportion of persons with detectable SARS-CoV-2 antibodies ranged from 1.0% in the San Francisco Bay area (collected April 23-27) to 6.9% of persons in New York City (collected March 23-April 1). Six to 24 times more infections were estimated per site with seroprevalence than with coronavirus disease 2019 (COVID-19) case report data. For most sites, it is likely that greater than 10 times more SARS-CoV-2 infections occurred than the number of reported COVID-19 cases; most persons in each site, however, likely had no detectable SARS-CoV-2 antibodies.
Asymptomatic carriers of COVID-19 still risk lung damage
Digital Journal, July 14, 2020
It’s established that many people infected with coronavirus are ‘asymptomatic’. While these people can spread the virus, the virus isn’t actually harming them, right? Not so says a new study published in Nature. Someone who is infected with the SARS-CoV-2 virus and remains asymptomatic, that is free of coughing, fever, fatigue and other common signs of infection, can still be adversely affected by the infection. A new study reveals that virus will still be causing some harm to their lungs. This may be mild and it may be reversible, but the effects will vary between different individuals. The study, published in Nature Medicine, reveals a high rate of minor lung inflammation in many individuals who exhibit no outward symptoms of coronavirus.
COVID-19-related gene expression higher in specific asthma subgroup
Helio | Pulmonology, July 14, 2020
Angiotensin-converting enzyme 2 and transmembrane protease serine 2 mediate SARS-COV-2 entry into host cells. Higher expression of ACE2 and TMPRSS2 in sputum cells of patients with asthma identified subgroups at risk of COVID-19 morbidity. “We found that among patients with asthma, gene expression of ACE2 and TMPRSS2 was higher in patients of male sex, Black race and patients with a history of diabetes mellitus,” Michael C. Peters, MD, assistant professor of medicine in the division of pulmonary and critical care medicine at the University of California, San Francisco, told Healio. Researchers analyzed gene expression for ACE2, TMPRSS2 and intercellular adhesion molecule 1 (ICAM-1), the major intercellular protein that mediates entry of human rhinoviruses, in sputum cells of 330 participants (mean age, 48.5 years; 69% female; 66% white) in the Severe Asthma Research Program-3 and in 79 healthy control participants (mean age, 40.6 years; 66% female; 57% white).
FDA grants emergency use of Gammacore for asthma in COVID-19 patient
BioWorld, July 13, 2020
Electrocore Inc. has snagged an emergency use authorization (EUA) from the U.S. FDA for use of its Gammacore Sapphire CV noninvasive vagus nerve stimulation (nVNS) to acutely treat asthma exacerbations in known or suspected COVID-19 patients. The hand-held therapy can be used at home and in a health care setting. The EUA indication covers adults who are experiencing exacerbation of asthma-related dyspnea and reduced airfow, for whom drug therapies either aren’t tolerated or provide insufficient relief. Gammacore is applied at to either side of the neck and delivers mild electrical impulses to the vagus nerve through the skin, stimulating the nerve receptors to reduce pain or distress. Patients can administer the treatment themselves, reducing reliance on medications with their potential side effects.
Tocilizumab for treatment of mechanically ventilated patients with COVID-1
Clinical Infectious Disease, July 11, 2020
Severe COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is approved treatment. Assessed, was the effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability post-intubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared to tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability weighting (IPTW). 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean 55 vs. 60 years), less likely to have chronic pulmonary disease (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death [hazard ratio 0.55 (95% CI 0.33, 0.90)] and improved status on the ordinal outcome scale [odds ratio per 1-level increase: 0.58 (0.36, 0.94)].
Extrapulmonary manifestations of COVID-19
Nature Medicine, July 10, 2020
Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here, the extrapulmonary organ-specific pathophysiology are reviewed, along with presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
Postmortem Lung Findings in a Patient With Asthma and Coronavirus Disease
Chest Journal, July 10, 2020
Asthma is increasingly recognized as an underlying risk factor for severe respiratory disease in patients with coronavirus disease 2019 (COVID-19), particularly in the United States. Here, we report the postmortem lung findings from a 37-year-old man with asthma, who met the clinical criteria for severe acute respiratory distress syndrome and died of COVID-19 less than 2 weeks after presentation to the hospital. His lungs showed mucus plugging and other histologic changes attributable to asthma, as well as early diffuse alveolar damage and a fibrinous pneumonia. The presence of diffuse alveolar damage is similar to descriptions of autopsy lung findings from patients with severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, and the absence of a neutrophil-rich acute bronchopneumonia differs from the histologic changes typical of influenza.
U.S. sets one-day record with more than 60,500 COVID cases; Americans divided
Reuters, July 9, 2020
More than 60,500 new COVID-19 infections were reported across the United States on Thursday, according to a Reuters tally, setting a one-day record as weary Americans were told to take new precautions and the pandemic becomes increasingly politicized. The total represents a slight rise from Wednesday, when there were 60,000 new cases, and marks the largest one-day increase by any country since the pandemic emerged in China last year. As infections rose in 41 of the 50 states over the last two weeks, Americans have become increasingly divided on issues such as the reopening of schools and businesses. Orders by governors and local leaders mandating face masks have become particularly divisive. “It’s just disheartening because the selfishness of (not wearing a mask) versus the selflessness of my staff and the people in this hospital who are putting themselves at risk, and I got COVID from this,” said Dr. Andrew Pastewski, ICU medical director at Jackson South Medical Center in Miami.
Cardiac Arrhythmias Seen in Critically Ill Patients With COVID-19
Pulmonary Advisor, July 8, 2020
Critically ill patients with COVID-19 are more likely to develop heart rhythm disorders than other hospitalized patients, according to a study published online June 22 in Heart Rhythm. Anjali Bhatla, from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues reviewed the incidence of cardiac arrests, arrhythmias, and inpatient mortality among 700 COVID-19 patients (mean age 50 years; 45 percent male) admitted to one center over a nine-week period. The researchers found that 11 percent of patients received care in the intensive care unit (ICU), and there were nine cardiac arrests (all occurring in ICU patients), 25 incident atrial fibrillation (AF) events, nine clinically significant bradyarrhythmias, and 10 nonsustained ventricular tachycardias (NSVTs). Admission to the ICU was associated with incident AF (odds ratio, 4.68) and NSVT (odds ratio, 8.92) in adjusted analysis. There were also independent associations seen between age and incident AF (odds ratio, 1.05) and between prevalent heart failure and bradyarrhythmias (odds ratio, 9.75). In-hospital mortality was only associated with cardiac arrest.
Asthma inhalers being trialed for treatment of COVID-19
News Medical, July 7, 2020
Researchers from Queensland University of Technology and Oxford University are working in collaboration to begin human clinical trials of inhaled corticosteroids, commonly used for asthma patients, on patients with COVID-19. The researchers believe that this could be useful for patients with the novel coronavirus infection. COVID-19 is known to cause severe respiratory illness in some individuals. Studies have shown that some corticosteroids, such as dexamethasone, could reduce the inflammation of the respiratory tract in these patients and benefit them by alleviating the symptoms of severe disease. Researchers in this new trial are studying if the steroid inhalers used for reducing the exacerbations of asthma could be useful for patients with early COVID-19 and reduce their risk of severe disease. The clinical trial has been registered under the name of STOIC (STerOids In COVID-19). It has begun recruiting patients at the Churchill Hospital in Oxford, England. The study is being led by Associate Professor Nicolau, who is also a mathematician, physician, and Australian Research Council Future Fellow. As per the trial details, the researchers have plans to recruit a total of 478 participants in the study. Some of the patients would be administered the corticosteroid (Budesonide) containing inhaler while others would be prescribed a placebo inhaler.
Asthma does not appear to increase the risk of contracting COVID-19, shows study
News Medical, July 6, 2020
Asthma does not appear to increase the risk for a person contracting COVID-19 or influence its severity, according to a team of Rutgers researchers. Panettieri’s paper was published in the Journal of Allergy and Clinical Immunology. “However, people with asthma–even those with diminished lung function who are being treated to manage asthmatic inflammation–seem to be no worse affected by SARS-CoV-2 than a non-asthmatic person. There is limited data as to why this is the case–if it is physiological or a result of the treatment to manage the inflammation.” Panettieri discusses what we know about asthma and inflammation and the important questions that still need to be answered. Since the news has focused our attention on the effects of COVID-19 on people in vulnerable populations, those with asthma may become hyper-vigilant about personal hygiene and social distancing.
In Fight Against COVID-19, CSL Behring Begins Trial to Evaluate Monoclonal Antibody (CSL312) for Respiratory Distress
PR Newswire, July 6, 2020
Global biotherapeutics leader CSL Behring today announced that the first patient has been enrolled in its Phase 2 study to assess the safety and efficacy of CSL312 (garadacimab, Factor XIIa antagonist monoclonal antibody) to treat patients suffering from severe respiratory distress, a leading cause of death in patients with COVID-19 related pneumonia. In this multicenter, double-blind, placebo-controlled study, approximately 124 adult patients testing positive for the SARS CoV-2 infection will be randomized to receive either CSL312 or placebo, in addition to standard of care (SOC) treatment. The primary endpoint being the incidence of tracheal intubation or death.
Pulmonary alveolar regeneration in adult COVID-19 patients
Cell Research, July 6, 2020
[Letter to the Editor] Alveolar regeneration after an acute lung injury has been observed in many mammals. Results in animal models have shown that alveolar type II (AT2) cells function as resident alveolar stem cells that can proliferate and differentiate into alveolar type I (AT1) cells to build new alveoli after lung injury. However, alveolar regeneration after acute lung injury in adult humans is still poorly characterized, mainly due to the lack of lung samples and regeneration-specific molecular markers. In patients with COVID-19 pneumonia, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly attack alveolar epithelial cells and cause massive AT2 cell death. It is unknown whether alveolar regeneration occurs upon SARS-CoV-2 infection-induced lung injury. This knowledge will substantially improve our basic understanding of the COVID-19 disease and our ability to prognosticate patient outcomes.
Guidelines for Family Presence Policies During the COVID-19 Pandemic
JAMA Health Forum, July 6, 2020
Active engagement of patients and their families in decisions about their own care is a foundation of a high-quality, person-centered health care system. Expanding the acceptance and participation of family care partners at the bedside has been an ongoing effort by patient advocacy communities over the past several decades. In this context, family refers to any support person defined by the patient or resident as family, including friends, neighbors, relatives, and/or professional support persons. Great progress has been made to invite partners into the labor and delivery room, to welcome parents to stay at their child’s side throughout a hospitalization, and to honor the wishes of terminally ill individuals to have family with them during end-of-life care. Significant clinical, psychological, and emotional benefits of these practices have been well documented for patients, family, and health care professionals. The National Academy of Medicine has asserted the importance that “family and/or care partners are not kept an arm’s length away as spectators but participate as integral members of their loved one’s care team.”
Q&A: With or without COVID-19, we will transform the care delivery system
Modern Healthcare, July 6, 2020
Dr. Sanjay Doddamani is chief operating officer and chief physician executive at Southwestern Health Resources, a clinically integrated network comprising independent community practices together with Texas Health Resources and the University of Texas Southwestern Medical Center in the Dallas-Fort Worth area. He started in his role in mid-March, just weeks before a national emergency was declared due to the COVID-19 outbreak. He previously served as senior physician adviser at the Center for Medicare and Medicaid Innovation and was chief medical officer for the accountable care organization and the home-based program at Geisinger Health. Read this Q&A session with Dr. Doddamani about Southwestern’s experience and the network’s approach to dealing with the pandemic and the organization’s emphasis on value-based care.
Hundreds of scientists say coronavirus is airborne, ask WHO to revise recommendations: NYT
Reuters, July 5, 2020
Hundreds of scientists say there is evidence that the novel coronavirus in smaller particles in the air can infect people and are calling for the World Health Organization to revise recommendations, the New York Times reported on Saturday. The WHO has said the coronavirus disease spreads primarily from person to person through small droplets from the nose or mouth, which are expelled when a person with COVID-19 coughs, sneezes or speaks. In an open letter to the agency, which the researchers plan to publish in a scientific journal next week, 239 scientists in 32 countries outlined the evidence showing smaller particles can infect people, the NYT said.
Coronavirus Update With Anthony Fauci
JAMA Network, July 2, 2020
[Video] Editor in Chief of JAMA, Howard Bauchner, MD, interviews Anthony Fauci, MD, White House Coronavirus Task Force member and Director of the National Institutes of Allergy and Infectious Diseases. The two discuss latest developments in the COVID-19 pandemic, including latest developments, protecting the elderly, genetic shift and mutations, vaccine durability and more.
Moving From The Five Whys To Five Hows: Addressing Racial Inequities In COVID-19 Infection And Death
Health Affairs, July 2, 2020
In recent months, states and municipalities have begun releasing data on COVID-19 infections and death that reveal profound racial disparities. In Louisiana, Black patients account for 57 percent of COVID-19 deaths, while making up only 33 percent of the total population. In Wisconsin, Hispanic patients constitute 12 percent of confirmed COVID-19 cases, but only 7 percent of the total population. In New York City, the epicenter of the pandemic in the US, age-adjusted mortality rates are more than double for Black and Hispanic patients (243.6 and 237.7 per 100,000) compared to white and Asian patients (121.5 and 109.4 per 100,000). Studies of patients hospitalized across New York have found that hypertension, diabetes, and obesity are associated with an elevated risk for COVID-19 morbidity and mortality. But why are there higher rates of hypertension, diabetes, and obesity in communities of color? The answer does not lie in biology. Here again, structural and environmental factors such as resource deprivation, poor access to health care, discrimination, and racism have driven a higher burden of these diseases in communities of color.
US posts largest single-day jump in new COVID-19 cases
Center for Infectious Disease and Research Policy (CIDRAP) News, July 2, 2020
The Centers for Disease Control and Prevention (CDC) today reported a record of 54,357 new coronavirus cases over yesterday—a record single-day jump that presses the United States further than what some thought was the peak this spring. For reference, as CNN reported, it took the United States a little more than 2 months to report its first 50,000 cases. Total US cases were at 2,679,230, including 128,024 deaths, according to the CDC. The infection curve is rising in 40 of 50 states, and 36 states are seeing an increase in the percentage of positive coronavirus tests, AP reported today. Some public health officials and governors are blaming bars for the increase in cases, the New York Times reported today, while others are pointing to hasty business reopenings, according to Politico.
Homeless More Likely to Need Ventilators for Respiratory Illness
Physician’s Briefing, July 2, 2020
Homeless people in New York state are more likely to be hospitalized and treated with mechanical ventilators for respiratory infections than people who are not homeless, according to a study published online June 4 in the Journal of General Internal Medicine. Atsushi Miyawaki, M.D., Ph.D., from the University of Tokyo, and colleagues used the 2007 to 2012 New York State Inpatient Database to identify all hospitalizations with primary or secondary diagnosis of influenza in 214 hospitals (total 20,078 patients; median age 40 years). Hospitals directly reported homeless patients. The researchers found that 6.4 percent of hospitalized influenza patients were homeless, with the majority of these hospitalizations (99.9 percent) concentrated in 10 hospitals. During the study period, homeless patients experienced a higher rate of hospitalization for influenza versus nonhomeless persons.
Rates of coinfection with other respiratory pathogens in patients positive for coronavirus disease 2019 (COVID‐19)
Journal of the American College of Emergency Physicians Open, July 2, 2020
The purpose of this study was to assess coinfection rates of coronavirus disease 2019 (COVID‐19) with other respiratory infections on presentation. This is a retrospective analysis of data from a 2 hospital academic medical centers and 2 urgent care centers during the initial 2 weeks of testing for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) , March 10, 2020 to March 23, 2020. Complete laboratory results from the first 2 weeks of testing were available for 471 emergency department patients and 117 urgent care center patients who were tested for SARS‐CoV.
Mechanical Ventilation in COVID-19: Interpreting the Current Epidemiology
American Journal of Respiratory and Critical Care Medicine, July 1, 2020
[Editorial] The world is scrutinizing every cohort and every outcome for patients with coronavirus disease (COVID-19), particularly the most critically ill who are receiving mechanical ventilation. The numbers that have been published are all over the place, and some of them—such as very high mortality—are causing panic. Two major issues are at play in these epidemiological studies. The first is when to intubate and assessment of the rates of intubation and mechanical ventilation for hospitalized patients in cohorts from across the world. The second is the reported mortality for patients who receive mechanical ventilation. Presentation and interpretation of the data for both of these issues is not straightforward and never has been. However, there are ways we can improve assessment of these cohort studies.
Blood type may contribute to likelihood of acquiring COVID-19
Helio | Primary Care, July 1, 2020
A patient’s blood type plays a role in the likelihood of developing COVID-19, data from two genetic studies show. An infectious disease expert unaffiliated with the studies told Healio Primary Care that the results are possible, but with some important caveats. In the first study, which appeared in The New England Journal of Medicine, David Ellinghaus, a scientist at the Institute of Clinical Molecular Biology in Germany, and colleagues analyzed nearly 8.6 million single nucleotide polymorphisms from 1,610 Spanish and Italian patients with COVID-19 and respiratory failure. Another 2,205 uninfected participants served as controls. Participants’ age, ethnicity and sex were also part of the analysis.
COVID-19 Severity Correlates with Weaker T Cell Immunity, Hypercytokinemia and Lung Epithelium Injury
American Journal of Respiratory and Critical Care Medicine, July 1, 2020
SARS-CoV-2 has caused a global pandemic which continues to wreak havoc on people’s lives and livelihoods. As of June 16th, 2020, the COVID-19 cases surpassed 8 million and the death toll stood at more than 400,000. Although the majority of the patients developed mild symptoms and eventually recovered from this disease, a significant proportion suffered from serious pneumonia and developed acute respiratory distress syndrome (ARDS), septic shock, and/or multi-organ failure. The degree of the disease severity should result from direct viral damages on epithelial surface layer (ESL) and the host immune response. SARS-CoV-2 infection may trigger a dysfunctional response leading to an overproduction of cytokines (cytokine storm) and the recruitment of more immune cells into the lungs, resulting in greater damages. However, the immune effectors that determine or influence the severity of the disease and the reason why immune response mediates recovery in some individuals, but not in others, are far from clear. In this study, we addressed these issues by analyzing the blood samples of COVID-19 patients with varying degrees of disease severity and by collecting their clinical data over a period of more than three months. Our findings highlight the importance of T cell immunity in COVID-19 recovery.
Respiratory failure and non-invasive respiratory support during the covid-19 pandemic: an update for re-deployed hospital doctors and primary care physicians
British Medical Journal, June 30, 2020
In response to the covid-19 pandemic, many health systems attempted to rapidly reorganise their healthcare workforce in the first half of 2020, including redeployment of doctors from primary care and non-frontline specialties to acute care wards. Preparedness for potential future redeployment remains essential given the risk of further waves of covid-19 as society negotiates repeated cycles of lockdown and reopening. Most people who become seriously unwell with covid-19 have an acute respiratory illness, and about 14% will require non-invasive respiratory support. In addition to shifting into acute care settings in the short term, primary care clinicians will also be caring for patients (or their loved ones) recovering from potentially traumatic experiences of respiratory illness. This article updates primary care and non-respiratory or intensivist specialist doctors on the recognition and non-invasive management of acute respiratory failure and will aid general practitioners in the subsequent outpatient support of patients during their recovery.
Coronavirus (COVID-19) Update: FDA Takes Action to Help Facilitate Timely Development of Safe, Effective COVID-19 Vaccines
FDA.gov, June 30, 2020
Today, the U.S. Food and Drug Administration took important action to help facilitate the timely development of safe and effective vaccines to prevent COVID-19 by providing guidance with recommendations for those developing COVID-19 vaccines for the ultimate purpose of licensure. The guidance, which reflects advice the FDA has been providing over the past several months to companies, researchers, and others, describes the agency’s current recommendations regarding the data needed to facilitate the manufacturing, clinical development, and approval of a COVID-19 vaccine. The guidance also discusses the importance of ensuring that the sizes of clinical trials are large enough to demonstrate the safety and effectiveness of a vaccine. It conveys that the FDA would expect that a COVID-19 vaccine would prevent disease or decrease its severity in at least 50% of people who are vaccinated.
Idiopathic Nonhistaminergic Acquired Angioedema in a Patient with COVID-19
Annals of Allergy, Asthma & Immunology, June 30, 2020
Idiopathic nonhistaminergic acquired angioedema (InH-AAE) is a rare disease characterized by submucosal swelling without concomitant urticaria and poor response to antihistamines and corticosteroids. Compared with other forms of hereditary and acquired angioedema, InH-AAE seems to have a predilection for facial and tongue swelling, and is often difficult to diagnose as patients have normal laboratory values and no family history. To our knowledge, there have been no publications to date describing idiopathic nonhistaminergic angioedema as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, although nonhistaminergic angioedema has been seen in the setting of other viral infections. We describe a case of suspected InH-AAE in an intubated patient with coronavirus disease 2019 (COVID-19). We review post-intubation macroglossia as a potential differential diagnosis and why this etiology is unlikely in our patient. Finally, we briefly discuss the hyperinflammatory response to SARS-CoV-2 and its potential role in the development of InH-AAE.
How to maintain momentum on telehealth after COVID-19 crisis ends
American Medical Association, June 30, 2020
The use of telehealth has exploded as many regulatory barriers to its use have been temporarily lowered during the COVID-19 pandemic. The AMA is advocating for making many of these emergency policy changes permanent. “The expansion of telehealth and the offering of new telehealth services that were not previously covered really enabled physicians to care for their patients in the midst of this crisis,” Todd Askew, the AMA’s senior vice president of advocacy, said during a recent “AMA COVID-19 Update” video. “We have moved forward a decade in the use of telemedicine in this country and it’s going to become, and will remain, an increasingly important part of physician practices going forward.”
U.S. coronavirus cases rise by 47,000, biggest one-day spike of pandemic
Reuters, June 30, 2020
New U.S. COVID-19 cases rose by more than 47,000 on Tuesday according to a Reuters tally, the biggest one-day spike since the start of the pandemic, as the government’s top infectious disease expert warned that number could soon double. California, Texas and Arizona have emerged as new U.S. epicenters of the pandemic, reporting record increases in COVID-19 cases. “Clearly we are not in total control right now,” Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, told a U.S. Senate committee. “I am very concerned because it could get very bad.”
HHS will renew public health emergency
Modern Healthcare, June 29, 2020
HHS spokesman Michael Caputo on Monday tweeted that HHS intends to extend the COVID-19 public health emergency that is set to expire July 25. The extension would prolong the emergency designation by 90 days. Several payment policies and regulatory adjustments are attached to the public health emergency, so the extension is welcome news for healthcare providers. HHS “expects to renew the Public Health Emergency due to COVID-19 before it expires. We have already renewed this PHE once,” Caputo said. Provider groups including the American Hospital Association have urged HHS to renew the distinction.
Global coronavirus deaths top half a million
Reuters, June 28, 2020
The death toll from COVID-19 surpassed half a million people on Sunday, according to a Reuters tally, a grim milestone for the global pandemic that seems to be resurgent in some countries even as other regions are still grappling with the first wave. The respiratory illness caused by the new coronavirus has been particularly dangerous for the elderly, although other adults and children are also among the 501,000 fatalities and 10.1 million reported cases. While the overall rate of death has flattened in recent weeks, health experts have expressed concerns about record numbers of new cases in countries like the United States, India and Brazil, as well as new outbreaks in parts of Asia.
Who Is Most At-Risk for Severe COVID-19?
MedPage Today, June 27, 2020
[Quiz] New information is posted daily, but keeping up can be a challenge. As an aid for readers and for a little amusement, here is a 10-question quiz based on the news of the week. Topics include COVID-19 risk factors, future pandemic preparation, and effects on kids from parents’ mental illness. After taking the quiz, scroll down in your browser window to find the correct answers and explanations, as well as links to the original articles.
COVID-19 Practice Financial Assistance
American College of Physicians, Updated June 26, 2020
The ACP provides resources to help guide practices in plans for re-opening. Resources include guides, checklists, staffing and workflow modifications, and materials for communicating with patients. The ACP also offers clinical and public policy guidance on how to resume some economic, social and medical care activities to mitigate COVID-19 and allow expansion of healthcare capacity. For more information, the CDC offers a framework for providing non-COVID-19 care during the pandemic.
Identification of pathophysiological patterns for triage and respiratory support in COVID-19
The Lancet | Respiratory Medicine, June 26, 2020
In the UK, more than 279 392 cases of COVID-19 had been documented by June 3, 2020, and more than 39 500 patients had died with the disease, according to the COVID-19 web-based dashboard at Johns Hopkins University. Data derived from the UK Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme Database show that, for the first 8062 patients admitted to the ICU across the UK with documented outcomes, by May 29, 2020, about 72% received advanced mechanical ventilation and the mortality rate was around 53%. This mortality far exceeds that of typical severe acute respiratory distress syndrome (ARDS). The significant surge in the number of patients requiring ventilatory support has presented the UK National Health Service with unprecedented challenges, including pressures on critical care capacity, resources, and supplies, concerns about staff protection, as well as ethical issues associated with triage and resource allocation.
CMS Announces Additional QPP, MIPS Flexibilities for 2020
American College of Cardiology, Jun 25, 2020
The Centers for Medicare and Medicaid Services (CMS) continues to provide flexibilities to clinicians participating in the Quality Payment Program (QPP) Merit-based Incentive Payment System (MIPS) in 2020 as a result of the COVID-19 pandemic. Clinicians significantly impacted by the public health emergency may submit an Extreme & Uncontrollable Circumstances Application to reweight any or all of the MIPS performance categories for performance year 2020. Clinicians requesting relief will need to provide a justification of the impacts to their practice as a result of the public health emergency.
Comorbid Asthma May Not Increase Risk for Severe COVID-19
Pulmonary Advisor, June 23, 2020
Individuals with coronavirus disease 2019 (COVID-19) with comorbid asthma may not have an increased risk for more severe disease, compared with those without asthma, according to a literature analysis published in The Journal of Allergy and Clinical Immunology. The impairment of antiviral responses in patients with asthma, which can, in turn, aggravate type 2 inflammation, suggests that these individuals may be at a high risk for morbidity and mortality from COVID-19.
Targeting the Immune System for Pulmonary Inflammation and Cardiovascular Complications in COVID-19 Patients
Frontiers in Immunology, June 23, 2020
In December 2019, following a cluster of pneumonia cases in China caused by a novel coronavirus (CoV), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infection disseminated worldwide and, on March 11th, 2020, the World Health Organization officially declared the pandemic of the relevant disease named coronavirus disease 2019 (COVID-19). In Europe, Italy was the first country facing a true health policy emergency, and, as at 6.00 p.m. on May 2nd, 2020, there have been more than 209,300 confirmed cases of COVID-19. Due to the increasing number of patients experiencing a severe outcome, global scientific efforts are ongoing to find the most appropriate treatment. The usefulness of specific anti-rheumatic drugs came out as a promising treatment option together with antiviral drugs, anticoagulants, and symptomatic and respiratory support. For this reason, the authors share their experience and knowledge on the use of these drugs in the immune-rheumatologic field, providing in this review the rationale for their use in the COVID-19 pandemic.
WHO reports record amount of COVID-19 cases in a single day
Helio | Infectious Disease News, June 22, 2020
As COVID-19 case counts reach 8.8 million worldwide, including 465,000 deaths, more than 183,000 new cases were reported to WHO on Sunday — the most in a single day since the beginning of the pandemic. “It seems that almost every day we reach a new and grim record,” WHO Director-General Tedros Adhanom Ghebreyesus, PhD, MSc, said in a press briefing. According to WHO, demand for dexamethasone, which was previously shown to reduce mortality by one-third in ventilated patients with COVID-19, has surged worldwide. Tedros noted that the drug should be used only in patients with severe disease.
Lifelong Lung Damage: The Serious COVID-19 Complication That Can Hit People in Their 20s
Healthline, June 22, 2020
More than 3.8 million people worldwide have recovered from COVID-19. However, recent cases are showing that even those who recover may still be at risk for long-term health issues. Despite the fact that the earliest coronavirus reports indicated that younger people were at a lower risk of serious complications from COVID-19, recent findings are contradicting that belief. Most recently, a 20-year-old COVID-19 survivor in Chicago was the recipient of a new set of lungs, due to a lung transplant that was necessary to treat a condition now being called post-COVID fibrosis. There have been two other lung transplants performed on COVID-19 survivors with post-COVID fibrosis: one was in China and the other in Vienna.
Surging U.S. virus cases raise fear that progress is slipping
Modern Healthcare, June 22, 2020
Coronavirus cases in Florida surpassed 100,000 on Monday, part of an alarming surge across the South and West as states reopen for business and many Americans resist wearing masks or keeping their distance from others. The disturbing signs in the Sunshine State as well as places like Arizona, Alabama, Louisiana, Texas and South Carolina — along with countries such as Brazil, India and Pakistan — are raising fears that the progress won after months of lockdowns is slipping away.
Guidance for tracheostomy use during COVID-19 pandemic
Helio | Pulmonology, June 22, 2020
Three medical societies released an expert panel report on the use of tracheostomy during the COVID-19 pandemic while minimizing the risk for infection to health care workers. Critically ill patients with COVID-19 account for 5% of all cases and one-quarter of all hospitalizations. Many of these patients require prolonged mechanical ventilation. Performing tracheostomies on these patients may allow for faster removal from ventilation, shorter hospitalization and thus greater ICU resource availability, but there are currently unanswered questions regarding preparation, timing, technique and protection for health care workers.
Will COVID-19 become seasonal?
The Journal of Infectious Diseases, June 21, 2020
This manuscript explores the question of the seasonality of SARS-CoV-2 by reviewing four lines of evidence related to viral viability, transmission, ecological patterns and observed epidemiology of COVID-19 in the Southern Hemispheres’ summer and early fall. There are four lines of evidence: (1) seasonality of other human coronaviruses and influenza A, (2) in vivo experiments with influenza transmission, (3) ecological data and (4) the observed epidemiology of COVID-19 in the Southern Hemispheres’ summer and early fall.
The role of peripheral blood eosinophil counts in COVID‐19 patients
European Journal of Allergy and Clinical Immunology, June 20, 2020
Coronavirus disease 2019 (COVID‐19) emerged in Wuhan city and rapidly spread globally outside China. We aimed to investigate the role of peripheral blood eosinophil (EOS) as a marker in the course of the virus infection to improve the efficiency of diagnosis and evaluation of COVID‐19 patients. This article looks at 227 pneumonia patients who visited the fever clinics in Shanghai General Hospital and 97 hospitalized COVID‐19 patients admitted to Shanghai Public Health Clinical Center were involved in a retrospective research study. Clinical, laboratory, and radiologic data were collected. The trend of EOS level in COVID‐19 patients and comparison among patients with different severity are summarized.
Variation in Ventilator Allocation Guidelines by US State During the Coronavirus Disease 2019 Pandemic: A Systematic Review
Journal of the American Medical Association, June 19, 2020
Since the advent of worldwide mechanical ventilator use for patients with polio in the 1950s, ventilators have provided life-saving support to millions of people.1 In the US, ventilators have been widely available for the past 50 years. There have been concerns during the coronavirus disease 2019 (COVID-19) pandemic that the need for ventilators could exceed their availability, thus causing a widespread shortage of ventilators. In these circumstances, tragic choices would need to be made to determine who receives mechanical ventilatory support and who does not. Individual physicians, ethicists, medical societies, and US states have published multiple recommendations regarding how to allocate ventilators in a public health emergency and are largely in consensus that ventilators should be allocated to do the greatest good for the greatest number of people.
Coronavirus and Health Inequities
JAMA Medical News, June 19, 2020
Recorded today, Linda Rae Murray, MD, MPH discusses topics in health equity with JAMA Medical News Associate Managing Editor Jennifer Abbasi.
Steroid treatment for COVID-19 has NYC doctors cautiously optimistic
Modern Healthcare, June 19, 2020
Local physicians said a U.K. study of the use of the steroid dexamethasone in treating severe COVID-19 patients showed promising results, but they’re reserving judgment until more data from the study is published. Initial results were announced Tuesday in a press release. The randomized trial, supported by the University of Oxford, tested dexamethasone in about 2,100 patients with an additional 4,300 receiving only usual care. The study found that the drug reduced the number of deaths by one-third in patients using mechanical ventilators and one-fifth in patients receiving only oxygen. There was no benefit among patients who didn’t require respiratory support.
Lifting COVID-19 “Lockdown” Restrictions May Cause Infection Resurgence
Pulmonary Advisor, June 18, 2020
Data from multiple countries demonstrate that lifting restrictions imposed to reduce the spread of coronavirus disease 2019 (COVID-19) would result in a resurgence of infections, according to provisional analyses published in the European Respiratory Journal. Most countries with significant COVID-19 outbreaks have introduced social distancing or “lockdown” measures to reduce viral transmission, however, the question of when, how, and to what extent these measures can be lifted remains.
Accelerated COVID-19 vaccine effort should not mean compromises, experts say
Helio | Infectious Disease, June 18, 2020
Public-private partnerships, collaboration among researchers and knowledge of existing coronaviruses have all contributed to the accelerated development of COVID-19 vaccine candidates, according to Infectious Disease News Editorial Board Member Kathleen M. Neuzil, MD, MPH, FIDSA. Neuzil, a professor of vaccinology and director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine, said vaccine development overall is a “continuum” from the discovery phase to “delivery and impact.” Neuzil and other presenters opened the National Foundation for Infectious Diseases’ Annual Conference on Vaccinology Research with a discussion on the current state of vaccine development for COVID-19.
Chicago has a unique COVID strain: research
Modern Healthcare, June 18, 2020
Chicagoans are being infected with a unique strain of COVID-19 that’s linked to the early coronavirus outbreak in China, according to new research. Northwestern Medicine scientists have determined that the Chicago area “is a melting pot for different versions of the virus because it is such a transportation hub,” Dr. Egon Ozer, an assistant professor at Northwestern University’s Feinberg School of Medicine and a Northwestern Medicine physician, said in a statement today. Ozer’s team is learning how variations of the severe acute respiratory syndrome that causes COVID-19 infects people differently. It’s a finding they say could help shape a potential vaccine.
R-107 Shows Promise in Early Study for PAH Linked to COVID-19
Pulmonary Hypertension News, June 17, 2020
Kalytera Therapeutics has announced positive early results for R-107, a liquid form of nitric oxide designed to treat pulmonary arterial hypertension (PAH) associated with COVID-19. Nitric oxide, known as NO, is a gas naturally present in the lungs. It facilitates oxygenation by relaxing, or dilating, the blood vessels, allowing blood to flow smoothly. R-107 is a liquid prodrug of nitric oxide, meaning that the compound is a precursor to its pharmacologically active form. Once injected into the body, R-107 is converted into its active form, called R-100, which steadily releases NO into lung tissues over the course of several days.
Fossil Fuel Decrease in COVID-19 Quarantine May Positively Affect Allergic Diseases
Pulmonary Advisor, June 17, 2020
Global quarantine as a result of the coronavirus disease 2019 (COVID-19) pandemic has decreased fossil fuel use which may affect allergic and respiratory diseases, according to an editorial published in The Journal of Allergy and Clinical Immunology. Air pollution is a causative factor of symptoms such as bronchospasm, rhinorrhea, and eye redness and irritation, as well as allergic diseases such as asthma, chronic rhinitis, nasal polyps, atopic dermatitis, seasonal or perennial allergic conjunctivitis, and vernal or atopic keraconjunctivitis. Through climate change, worldwide emission of greenhouse gasses (ie, nitrogen dioxide and carbon dioxide) has caused an increase in air humidity, mold exposure, and modified pollen patterns, which in turn, increased sensitization rates and allergic disease prevalence.
US taking ‘wrong approach’ to COVID-19 testing, expert warns
Helio | Infectious Diseases, June 16, 2020
The American Lung Association recently held a virtual Town Hall meeting to debunk widespread misperceptions in the United States about which populations should be prioritized for COVID-19 testing and how to interpret the results. “Far too many people have misinterpreted testing,” Michael T. Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota, said during the meeting. “While we need to greatly expand our SARS-CoV-2 testing as a critical component of our response to COVID-19, the pandemic messaging to date needs to move beyond the ‘Test, test, test!’ mantras. That is the wrong approach.”
China’s COVID-19 vaccine candidate shows promise in human trials, CNBG says
Reuters, June 16, 2020
China National Biotec Group (CNBG) said on Tuesday its experimental coronavirus vaccine has triggered antibodies in clinical trials and the company plans late-stage human trials in foreign countries. No vaccines have been solidly proven to be able to effectively protect people from the virus that has killed more than 400,000 people, while multiple candidates are in various stages of development globally. The vaccine, developed by a Wuhan-based research institute affiliated to CNBG’s parent company Sinopharm, was found to have induced high-level antibodies in all inoculated people without serious adverse reaction, according to the preliminary data from a clinical trial initiated in April involving 1,120 healthy participants aged between 18 and 59.
Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19
Oxford University, June 16, 2020
In March 2020, the RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial was established as a randomised clinical trial to test a range of potential treatments for COVID-19, including low-dose dexamethasone (a steroid treatment). Over 11,500 patients have been enrolled from over 175 NHS hospitals in the UK. On 8 June, recruitment to the dexamethasone arm was halted since, in the view of the trial Steering Committee, sufficient patients had been enrolled to establish whether or not the drug had a meaningful benefit. A total of 2104 patients were randomised to receive dexamethasone 6 mg once per day (either by mouth or by intravenous injection) for ten days and were compared with 4321 patients randomised to usual care alone. Among the patients who received usual care alone, 28-day mortality was highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%).
Prevalence and characterization of asthma in hospitalized and non-hospitalized patients with COVID-19
Journal of Allergy and Clinical Immunology (via Science Direct), June 15, 2020
The primary objective of this study was to determine the prevalence of asthma among COVID-19 patients in a major U.S. health system. We assessed the clinical characteristics and comorbidities in asthmatic and non-asthmatic COVID-19 patients. We also determined the risk of hospitalization associated with asthma and/or inhaled corticosteroid use. Medical records of patients with COVID-19 were searched by a computer algorithm (March 1–April 15, 2020), and chart review was used to validate the diagnosis of asthma and medications prescribed for asthma. All patients were PCR-confirmed COVID-19. Demographics and clinical features were characterized. Regression models were used to assess the associations between asthma and corticosteroid use and the risk of COVID-19-related hospitalization.
COVID-19 associated with dramatic decline in ED use by pediatric asthma patients
Medical Express, June 15, 2020
The number of patients visiting the emergency department (ED) for asthma treatment dropped by 76% in the first month of the COVID-19 pandemic, according to a new study by researchers at Children’s Hospital of Philadelphia (CHOP). The proportion of ED visits that led to a patient being hospitalized also decreased over this period, suggesting the decrease in overall visits was not solely due to patients avoiding the hospital due to the pandemic or delays in care for less serious asthma events. “We were surprised by the magnitude and extent of the reduced utilization of emergency services for asthma during the emergence of the COVID-19 pandemic,” said Chén C. Kenyon, MD, MSHP, a pediatrician in CHOP’s Division of General Pediatrics and first author of the study, which was published in JACI in Practice.
Coronavirus death rate is higher for those with chronic ills
Associated Press, June 15, 2020
Death rates are 12 times higher for coronavirus patients with chronic illnesses than for others who become infected, a new U.S. government report says. The Centers for Disease Control and Prevention report released Monday highlights the dangers posed by heart disease, diabetes and lung ailments. These are the top three health problems found in COVID-19 patients, the report suggests. The report is based on 1.3 million laboratory-confirmed coronavirus cases reported to the agency from January 22 through the end of May. Information on health conditions was available for just 22% of the patients. It shows that 32% had heart-related disease, 30% had diabetes and 18% had chronic lung disease, which includes asthma and emphysema.
Anti-contagion interventions prevented up to 62 million confirmed
Helio | Infectious Disease News, June 12, 2020
Anti-contagion policies have prevented or delayed as many as 62 million confirmed COVID-19 infections, which corresponded with the prevention of an estimated 530 million cases in six countries, according to a study published in Nature. “We found that in the absence of policy intervention, the number of COVID-19 infections doubled approximately every 2 days,” Esther Rolf, a PhD candidate in the computer science department at University of California, Berkeley, told Healio. “In all six countries we studied, we found that the anti-contagion policies put in place significantly slowed the spread of the disease, resulting in an estimated 500 million infections prevented or delayed, across the six countries in the time frame that we studied.”
Northwestern Memorial performs lung transplant on COVID survivor
Modern Healthcare, June 11, 2020
Northwestern Memorial Hospital is believed to be the first U.S. facility to perform a life-saving double-lung transplant on a former COVID-19 patient. The Chicago hospital today announced that the patient, a woman in her 20s, had the procedure this month after suffering irreversible damage to her lungs while recovering from the coronavirus. The patient had spent six weeks in Northwestern’s COVID intensive care unit on a ventilator and a machine that supports the heart and lungs, Northwestern Medicine said in a statement. She needed to test negative for the virus before doctors could put her on the waiting list for a transplant.
Early Data Show Potential Benefit of Acalabrutinib in Severe COVID-19
Pulmonary Advisor, June 11, 2020
Acalabrutinib, a Bruton tyrosine kinase (BTK) inhibitor, appears to reduce respiratory distress as well as the hyperinflammatory immune response associated with coronavirus disease 2019 (COVID-19), according to a study led by researchers at the Center for Cancer Research at the National Cancer Institute and the National Institute of Allergy and Infectious Diseases, both part of the National Institutes of Health (NIH). The prospective study included 19 patients with confirmed COVID-19 who required hospitalization for hypoxemia and had evidence of inflammation. Patients received acalabrutinib 100mg twice daily for 10 days (supplemental oxygen cohort n=11) or 14 days (mechanical ventilation cohort n=8) plus best supportive care. A subset of patients in both cohorts received concomitant treatment with steroids and/or hydroxychloroquine.
U.S. Coronavirus Cases Hit 2 Million as New Hotspots Surface
HealthDay News, June 11, 2020
The number of confirmed U.S. coronavirus cases passed 2 million on Thursday, as public health experts warned of the emergence of new COVID-19 hotspots across the country. Just three weeks after Arizona Gov. Doug Ducey lifted the state’s stay-at-home order, there has been a significant spike in coronavirus cases, with lawmakers and medical professionals warning that hospitals might not be able to handle a big influx of new cases. Already, hospitals in the state are at 83 percent capacity, the Associated Press reported. But Arizona is not alone in seeing increases in hospitalizations: new U.S. data shows at least eight other states with spikes since Memorial Day. In Texas, North and South Carolina, California, Oregon, Arkansas, Mississippi and Utah, increasing numbers of COVID-19 patients are showing up at hospitals.
Lack of Health Literacy a Barrier to Grasping COVID-19
MedPage Today, June 10, 2020
A lack of health literacy is preventing people from having a good understanding of the novel coronavirus, two speakers said Wednesday at an online briefing sponsored by the National Academies of Sciences, Engineering, and Medicine. “So many people are confused about the symptoms” of COVID-19, said Lisa Fitzpatrick, MD, MPH, founder of Grapevine Health, a nonprofit organization in Washington that helps design culturally appropriate health information campaigns targeted at underserved populations. When Grapevine Health sent workers out to talk to people about the pandemic, “So many told us they didn’t know the symptoms,” said Fitzpatrick.
Avoiding COVID-19 in Children With Asthma and Allergies
Pulmonary Advisor, June 9, 2020
Social distancing of families with children who have asthma is the best method for preventing coronavirus diseases 2019 (COVID-19), according to a letter to the editor published in Allergy. COVID-19 affects all ages, and the US Centers for Disease Control and Prevention initially stated that people with chronic lung disease, including moderate severe asthma, and allergy may be at higher risk of developing a more severe course of COVID-19 than healthy people. Very few reports are available on pediatric patients with COVID-19; therefore, researchers analyzed data on pediatric patients referred for COVID-19 at 2 hub hospitals located in Italy.
Out of the lab and into people’s arms: A list of COVID-19 vaccines that are being studied in clinical trials
ABC News, June 9, 2020
The world’s leading drug companies, universities and governments are racing to develop a vaccine for COVID-19, the disease that has taken more than 400,000 lives globally. Of the 133 candidates being explored, ten have been approved for human trials, according to the World Health Organization. Companies and research groups in China, the early epicenter of the coronavirus outbreak, are testing five of those vaccines in human trials. Meanwhile, U.S.-based companies are involved in the development of four additional vaccines, including one that has NIAID Director Anthony Fauci “cautiously optimistic.”
When the Dust Settles: Preventing a Mental Health Crisis in COVID-19 Clinicians
Annals of Internal Medicine, June 9, 2020
On 26 April, after spending weeks caring for patients with coronavirus disease 2019 (COVID-19) in New York City, emergency room physician Lorna Breen took her own life. Her grieving family recounts days of helplessness leading up to this as Dr. Breen described how COVID-19 upended her emergency department and left her feeling inadequate despite years of training and expertise. The clinical experience of Dr. Breen during this pandemic has not been unique. During the past 5 months, COVID-19 has caused an upheaval of medical systems around the world, with more than 4 million cases and 300 000 deaths worldwide so far. Unfortunately, we’ve also seen that the experience in caring for patients with the virus may have profound effects on clinicians’ mental health. A recent study conducted at the center of the outbreak in China reported that more than 70% of frontline health workers had psychological distress after caring for patients with COVID-19.
Coronavirus: What We Know Now
WebMD, June 8, 2020
The first confirmed cases of coronavirus in the U.S. appeared in January. At the time, the world knew almost nothing about how the virus spreads or how to treat it. Six months later, our knowledge has grown, but researchers continue to make discoveries almost daily. At first, health experts believed COVID-19, the disease caused by the new coronavirus, primarily affected patients’ lungs. While it’s still primarily a lung disease, other symptoms have appeared often, and they’ve been added to the list of signs of COVID.
Relief Therapeutics and NeuroRx Expand Clinical Trial of RLF-100 to All Patients with Critical COVID-19 and Respiratory Failure
BioSpace, June 8, 2020
RELIEF THERAPEUTICS Holding AG (SIX:RLF) “Relief” and its U.S. partner, NeuroRx, Inc. announced that the Phase 2/3 clinical trial evaluating RLF-100 as a treatment for critical COVID-19 with respiratory failure has been expanded to include patients receiving high flow oxygen and noninvasive ventilation (CPAP), in addition to those on ventilators. RLF-100 (Aviptadil) is a patented formulation of synthetic human Vasoactive Intestinal Peptide (VIP), which has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) in Acute Respiratory Distress Syndrome and chronic lung diseases.
First Study Investigating Antibody Treatment for COVID-19 Begins
Pulmonology Advisor, June 8, 2020
The first patients have been dosed in a phase 1 trial evaluating a potential antibody therapy designed to treat coronavirus disease 2019 (COVID-19). These patients received treatment at major medical centers in the US, including NYU Grossman School of Medicine and Cedars-Sinai in Los Angeles. The investigational agent, LY-CoV555, is a potent, neutralizing lgG1 monoclonal antibody directed against the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The randomized, double-blind, placebo-controlled study is investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of 1 dose of LY-CoV555 in patients hospitalized with COVID-19; those requiring mechanical ventilation or who have received convalescent COVID-19 plasma treatment prior to enrollment were excluded from the study.
COVID-19 Critical Care Update
🎬 Journal of the American Medical Association, June 8, 2020
Get this COVID-19 Critical Care Update when Howard Bauchner, MD, Editor in Chief, JAMA, speaks with Maurizio Cecconi, MD of Humanitas University in Milan and Derek C. Angus, MD, MPH of the University of Pittsburgh.
Coronavirus Cases in the U.S.
Center for Disease Control and Prevention, June 8, 2020
The U.S. Centers for Disease Control and Prevention (CDC) on Sunday reported 1,920,904 cases of new coronavirus, an increase of 29,214 cases from its previous count, and said COVID-19 deaths in the United States had risen by 709 to 109,901. The CDC reported its tally of cases of COVID-19, the respiratory illness caused by the new coronavirus, as of 4 p.m. EDT on June 6. Its previous tally was released on Friday.
Blood Test May Predict Clot Risk in Severe COVID-19
MedPage Today, June 7, 2020
Hypercoagulability on thromboelastography (TEG) was a good predictor of thrombotic events among COVID-19 patients entering the ICU, according to a single-center study. The clinically significant thrombosis that developed in 13 of 21 PCR-test-positive patients (62%) seen at Baylor St. Luke’s Medical Center ICU from March 15 to April 9 was associated with hypercoagulable TEG parameters in all cases. Maximum amplitude on that test was elevated in all 10 patients with two or more thrombotic complications compared with 45% of those with no more than one such event (nearly all arterial, central venous, or dialysis catheter or filter thromboses).
COVID-19 vaccine development pipeline gears up
The Lancet, June 6, 2020
Vaccine makers are racing to develop COVID-19 vaccines, and have advanced ten candidates into clinical trials. But challenges remain. Vaccine development is typically a long game. The US Food and Drug Administration only approved a first vaccine against Ebola virus last year, 43 years after the deadly virus was discovered. Vaccinologists have made little headway with HIV or respiratory syncytial virus, despite huge investments. On average, it takes 10 years to develop a vaccine. With the COVID-19 crisis looming, everyone is hoping that this time will be different. Already, ten vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) are in clinical trials, and researchers at the University of Oxford and AstraZeneca hope to have the first phase 3 data in hand this summer.
Don’t Skip Opiates for ‘Air Hunger’ From COVID-19 Ventilation
MedPage Today, June 5, 2020
Easing the traumatic “air hunger” created by mechanical ventilation settings for COVID-19 acute respiratory distress syndrome (ARDS) may take more than just sedation or paralytics, one group argued. Lung protective ventilation, with low tidal volumes and permissive hypercapnia, is a recipe for “the most uncomfortable form of dyspnea,” Richard Schwartzstein, MD, of Beth Israel Deaconess Medical Center and Harvard in Boston, wrote in the Annals of the American Thoracic Society.
Flu vaccine reduces influenza risk with no effect on coronaviruses
Healio | Infectious Disease, June 5, 2020
Influenza vaccination reduced the risk for influenza by more than 40%, with no effect on coronaviruses or other non-influenza respiratory viruses, according to a study assessing seasonal influenza and coronaviruses over seven seasons. “Vaccines induce specific antibody protection, targeting the viral or bacterial antigens that are included as vaccine components. On that basis, influenza vaccines are expected to reduce the risk for illness due to influenza viruses and have no effect on other non-influenza respiratory viruses (NIRV),” Danuta M. Skowronski, MD, FRCPC, of the British Columbia Centre for Disease Control and the University of British Columbia in Vancouver, told Healio.
Coronavirus: Nasal High Flow Therapy Alternative to Ventilator Care
HealthLeaders, June 5, 2020
Compared to ventilator care, nasal high flow therapy for seriously ill coronavirus patients has several benefits, including the ability to mobilize patients. Nasal high flow (NHF) therapy is a less invasive alternative to ventilator care for many seriously ill coronavirus patients, UnityPoint Health experts say. During the coronavirus disease 2019 (COVID-19) pandemic, ventilator care has been used commonly for coronavirus patients experiencing acute respiratory distress. However, ventilator care has posed several challenges, including shortages ventilators and the staff needed to manage patients on mechanical ventilation.
Are Symptoms From COVID-19 or Seasonal Allergies?
WebMD, June 4, 2020
In the thick of the coronavirus pandemic, it might be hard to tell if you’ve come down with COVID-19, spring allergies or a cold, which all have some similar symptoms. Fever and dry cough are common symptoms of COVID-19, along with shortness of breath and difficulty breathing, sore throat, diarrhea, fatigue, chills, muscle pain, loss of taste and smell, and body aches. But it’s rare for fever or diarrhea to occur with a cold or seasonal allergies, according to Dr. Michael Benninger, chairman of the Head and Neck Institute at the Cleveland Clinic. “It’s a matter of taking a logical approach to symptoms,” he said in a clinic news release.
Alternatives to Invasive Ventilation in the COVID-19 Pandemic
Journal of the American Medical Association, June 4, 2020
Since its invention in the 1940s, the positive pressure ventilator has always been known to have both risks and benefits. Although mechanical ventilation is unquestionably lifesaving, there are numerous associated drawbacks. Beyond the obvious and immediate limitations that patients require translaryngeal intubation and are physically attached to a ventilator, delivery of gas by positive pressure also creates mechanical stress and causes strain on lung tissue. This stress can lead to ventilator-induced lung injury, compounding the underlying lung condition that precipitated the initial respiratory failure.1 Despite advances in knowledge about protective ventilation strategies to limit ventilator-induced lung injury (most notably use of low tidal volumes), concern remains for this iatrogenic injury in all patients undergoing intubation and mechanical ventilation.
Future COVID-19 Pandemic Burden Could Be Mitigated Via Respiratory Muscle Training
Pulmonology Advisor, June 3, 2020
In cases of coronavirus disease 2019 (COVID-19), patients with poor baseline health have an elevated risk of severe respiratory complications and worse outcomes following hospital admission and mechanical ventilation. In addition, these patients are generally more likely to demonstrate impaired respiratory muscle performance. In a recent review published in the American Journal of Medicine, Rich Severin PT, DPT, PhD(c), CCS, a PhD candidate in the department of physical therapy at the University of Illinois-Chicago, and colleagues proposed that “impaired respiratory muscle performance is an underappreciated factor contributing to poor outcomes unfolding during the coronavirus pandemic.”
The Collision of COVID-19 and the U.S. Health System
Annals of Internal Medicine, June 2, 2020
The coronavirus disease 2019 (COVID-19) pandemic is wreaking havoc and causing fear, illness, suffering, and death across the world. This outbreak lays bare the fault lines in our society and highlights that the United States could have been better prepared for the pandemic had we a more equitable and just health care system. As leaders in the American College of Physicians (ACP), we have helped develop ACP’s wide-ranging policies on health care in the United States. The College has adopted a “health in all policies” approach, integrating health considerations into policymaking across sectors to improve the health and health care of all communities and people, which we believe, if enacted, would have enabled the United States to more effectively respond to the COVID-19 pandemic.
ATS/IDSA Guideline Authors Offer Insight Into COVID-19–Related Pneumonia Management
Pulmonary Advisor, June 2, 2020
The cochairs of the American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA) Guideline for Treatment of Adults With Community-Acquired Pneumonia (CAP) have published their perspectives of the guideline as it relates to the management of patients with pneumonia associated with coronavirus disease 2019 (COVID-19). The authors’ comments were published in an Ideas and Opinions paper in the Annals of Internal Medicine. The guideline cochairs wrote that empirical coverage for bacterial pathogens in patients with CAP is not required for all patients with confirmed pneumonia related to COVID-19.
Frailty Score Joins the COVID-19 Battle
MedPage Today, June 2, 2020
A clinical frailty scale (CFS) developed at Nova Scotia’s Dalhousie University is helping doctors predict outcomes of older COVID-19 patients in urgent care settings and decide who gets more aggressive treatments. Because the CFS quickly offers a quantitative number, it avoids age bias when it comes to treatment decisions, said Kenneth Rockwood, MD, of the Division of Geriatric Medicine, Department of Community Health and Epidemiology, School of Health Administration, whose team developed the scale.
Mass gatherings, erosion of trust upend coronavirus control
Associated Press, June 1, 2020
Protests erupting across the nation over the past week — and law enforcement’s response to them — are threatening to upend efforts by health officials to track and contain the spread of coronavirus just as those efforts were finally getting underway. Health experts need newly infected people to remember and recount everyone they’ve interacted with over several days in order to alert others who may have been exposed, and prevent them from spreading the disease further. But that process, known as contact tracing, relies on people knowing who they’ve been in contact with — a daunting task if they’ve been to a mass gathering.
Did Volunteers Tolerate This Coronavirus Vax?
MedPage Today, May 30, 2020
The 24-hour news cycle is just as important to medicine as it is to politics, finance, or sports. New information is posted daily, but keeping up can be a challenge. As an aid for readers and for a little amusement, here is a 10-question quiz based on the news of the week. Topics include coronavirus vaccine research, LGBTQ deaths by suicide, and hypertension. After taking the quiz, scroll down in your browser window to find the correct answers and explanations, as well as links to the original articles.
Case Study: Typical Progression of COVID-19 in Metastatic Lung Adenocarcinoma
Pulmonology Advisor, May 29, 2020
Unlike other comorbidities, metastatic lung adenocarcinoma did not escalate the progression of COVID-19 according to results from a case report published in the American Society of Clinical Oncology. A 76-year-old man with metastatic lung adenocarcinoma and a history of chronic obstructive pulmonary disease tested positive for SARS-CoV-2 infection in Spain. He presented with fever, shortness of breath, and bibasal crackles 1 week after his 6th maintenance cycle of cisplatin-pemetrexed and pembrolizumab treatment for his cancer. A blood test showed lymphocytes 120/mL, neutrophils 430/mL, platelets 84,000/mL, C-reactive protein 24.4 mg/dL, and high D-dimer. A chest radiograph revealed diffuse infiltrate in his lungs. Read more.
Coronavirus May Be a Blood Vessel Disease, Which Explains Everything
Elemental, May 29, 2020
In April, blood clots emerged as one of the many mysterious symptoms attributed to Covid-19, a disease that had initially been thought to largely affect the lungs in the form of pneumonia. Quickly after came reports of young people dying due to coronavirus-related strokes. Next it was Covid toes — painful red or purple digits. What do all of these symptoms have in common? An impairment in blood circulation. Add in the fact that 40% of deaths from Covid-19 are related to cardiovascular complications, and the disease starts to look like a vascular infection instead of a purely respiratory one.
Lung function testing in the COVID-19 endemic
The Lancet, May 29, 2020
The COVID-19 pandemic has presented considerable challenges to global health services and dictates almost every aspect of medical practice and policy. Across Europe, a surge phase in acute caseload, led to a sudden curtailment of non-COVID-19 medical care, with immediate implications for routine diagnostic and surveillance investigations. As COVID-19-related hospital admissions subside, many lung function services have started to reconsider how best to operate, within the constraints dictated by a COVID-19 endemic scenario. Central to planning in this phase are the precautions needed to protect lung function staff, and to minimise cross-infection risk, given an ongoing need to test vulnerable patient groups—eg, immunocompromised or individuals with long-term conditions.
Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study
The Lancet, May 29, 2020
The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. This international, observational, cohort study provides cross-specialty, patient-level outcomes data for patients who had surgery and acquired perioperative SARS-CoV-2 infection. 1128 patients were included across 24 countries.
The COVID-19 Rehabilitation Pandemic
Age and Aging, May 29, 2020
The COVID-19 pandemic and the response to the pandemic are combining to produce a tidal wave of need for rehabilitation. Rehabilitation will be needed for survivors of COVID-19, many of whom are older, with underlying health problems. In addition, rehabilitation will be needed for those who have become deconditioned as a result of movement restrictions, social isolation, and inability to access healthcare for pre-existing or new non-COVID-19 illnesses. Delivering rehabilitation in the same way as before the pandemic will not be practical, nor will this approach meet the likely scale of need for rehabilitation. This commentary reviews the likely rehabilitation needs of older people both with and without COVID-19 and discusses how strategies to deliver effective rehabilitation at scale can be designed and implemented in a world living with COVID-19.
COVID-19: An ACP Physician’s Guide
American College of Physicians, Updated May 28, 2020
This ACP Physician’s Guide and its collected national resources support physicians as they respond to the Covid-19 pandemic. The ACP-produced resource can be easily accessed on handheld devices and other computers to provide a clinical overview of infection control and patient care guidance. CME credit and MOC points available.
Metatranscriptomic Characterization of COVID-19 Identified A Host Transcriptional Classifier Associated With Immune Signaling
Clinical Infectious Diseases, May 28, 2020
The recent identification of a novel coronavirus, also known as SARS-CoV-2, has caused a global outbreak of respiratory illnesses. The rapidly developing pandemic has posed great challenges to diagnosis of this novel infection. However, little is known about the metatranscriptomic characteristics of patients with Coronavirus Disease 2019 (COVID-19). Metatranscriptomics in 187 patients (62 cases with COVID-19 and 125 with non-COVID-19 pneumonia) were analyzed, and transcriptional aspects of three core elements – pathogens, the microbiome, and host responses – were interrogated.
Researchers scramble to meet ‘urgent need’ for COVID-19 vaccine
Helio | Infectious Disease News, May 28, 2020
As deaths from COVID-19 increase to more than 100,000 in the United States, institutions around the world are working to develop an effective vaccine. Kaiser Permanente Washington Health Research Institute in Seattle is conducting a phase 1 clinical trial to assess an investigational vaccine, while Johnson & Johnson plans to initiate human clinical studies for its potential candidate by September. According to WHO, there are 10 COVID-19 vaccine candidates under clinical evaluation and an additional 115 candidates in preclinical evaluation. In a remote hearing of the U.S. Senate Committee on Health, Education, Labor & Pensions earlier this month, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said an NIH-directed trial is expected to enter phase 2/3 in late spring or early summer.
Asymptomatic transmission during the COVID-19 pandemic and implications for public health strategies
Clinical Infectious Diseases, May 28, 2020
SARS-CoV-2 spread rapidly within months despite global public health strategies to curb transmission by testing symptomatic patients and encouraging social distancing. Here, we summarize rapidly emerging evidence highlighting transmission by asymptomatic and pre-symptomatic individuals. Viral load of asymptomatic carriers is comparable to symptomatic patients, viral shedding is highest before symptom onset suggesting high transmissibility before symptoms. Within universally tested subgroups, surprisingly high percentages of COVID-19 positive asymptomatic individuals were found. Asymptomatic transmission was reported in several clusters.
Pulmonary pathobiology may differ in COVID-19 vs. H1N1 respiratory failure
Helio | Pulmonology, May 27, 2020
Patients who died from COVID-19-associated respiratory failure had more intussusceptive angiogenesis in their lungs than those who died from influenza, according to an autopsy study. For the study, which was published in The New England Journal of Medicine, researchers used seven-color immunohistochemical analysis, micro-CT imaging, scanning electron microscopy, corrosion casting and direct multiplexed measurement of gene expression to evaluate and compare lungs from patients who died from COVID-19 with those who died from influenza A (H1N1)-associated acute respiratory distress syndrome in 2009 and those from age-matched uninfected controls.
Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review
Annals of Internal Medicine, May 27, 2020
Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). This article summarizes evidence (from Four randomized controlled trials, 10 cohort studies, and 9 case series) about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19).
Odds of Pulmonary Embolism Higher in COVID-19 With Obesity
Pulmonary Advisor | My 26, 2020
Patients with COVID-19 with a body mass index (BMI) >30 kg/m² have increased odds of developing pulmonary embolism (PE), according to a research letter published online May 14 in Radiology. Neo Poyiadi, M.D., from the Henry Ford Health System in Detroit, and colleagues assessed the clinical characteristics of COVID-19 patients who developed PE in a retrospective analysis involving 328 COVID-19 patients who underwent pulmonary computed tomography (CT) angiography. The researchers found that 22 percent of the patients had PE.
Could the D614 G substitution in the SARS-CoV-2 spike (S) protein be associated with higher COVID-19 mortality?
International Journal of Infectious Diseases | May 26, 2020
Increasing number of deaths due to COVID-19 pandemic has raised serious global concerns. Higher testing capacity and ample intensive care availability could explain lower mortality in some countries compared to others. Nevertheless, it is also plausible that the SARS-CoV-2 mutations giving rise to different phylogenetic clades are responsible for the obvious death disparities around the world. Current research literature linking the genetic make-up of SARS-CoV-2 with fatality is lacking. Here, we suggest that this disparity in fatality rates may be attributed to SARS-CoV-2 evolving mutations and urge the international community to begin addressing the phylogenetic clade classification of SARS-CoV-2 in relation to clinical outcomes.
Treating Allergic Asthma During the Emergence of COVID-19
HCP Live, May 26 | 2020
[Video] Experts in the field of pulmonology share concerns over managing patients with allergic asthma during the current COVID-19 pandemic. Thomas Casale, MD, speaks with Geoffrey L. Chupp, MD, Stanley Goldstein, MD, Syed Shahzad Mustafa, MD and Michael E. Wechsler, MD, MMSc about challenges for physicians.
Distinguishing ILD From COVID-19 in Patients Treated With EGFR-TKIs
Pulmonary Advisor, May 25 | 2020
A list of clinical and imaging findings that may help distinguish interstitial lung disease (ILD) associated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy used in the treatment of lung cancer from lung-associated manifestations of COVID-19 infection was published in the Journal of Thoracic Oncology. While EGFR-TKI–associated ILD is relatively rare, with a reported incidence in the range of 0.3% to 4.3% depending on patient population and specific EGFR-TKI used, it is considered to be the most serious adverse effect of EGFR-TKI treatment.
Has the curve flattened?
Johns Hopkins University & Medicine | May 25, 2020
Countries around the world are working to “flatten the curve” of the coronavirus pandemic. Flattening the curve involves reducing the number of new COVID-19 cases from one day to the next. This helps prevent healthcare systems from becoming overwhelmed. When a country has fewer new COVID-19 cases emerging today than it did on a previous day, that’s a sign that the country is flattening the curve. On a trend line of total cases, a flattened curve looks how it sounds: flat. On the charts on this page, which show new cases per day, a flattened curve will show a downward trend in the number of daily new cases. This analysis uses a 5-day moving average to visualize the number of new COVID-19 cases and calculate the rate of change.
ED Chest X-Ray Score Predicts COVID-19 Outcomes in Adults <50
Physician’s Weekly | May 24, 2020
A chest X-ray (CXR) severity score can predict outcomes among young and middle-aged adults with COVID-19 on presentation to the emergency department, according to a study published online May 14 in Radiology. Danielle Toussie, M.D., from the Icahn School of Medicine at Mount Sinai in New York City, and colleagues analyzed the prognostic value of a CXR severity scoring system for 338 younger patients with COVID-19 on presentation to the emergency department. Data were included for patients aged 21 to 50 years who presented to emergency departments from March 10 to 26, 2020, with confirmed COVID-19. Each CXR was divided into six zones and was examined for opacities, with scores collated into a total lung zone severity score.
Co-infections among patients with COVID-19: the need for combination therapy with non-anti-SARS-CoV-2 agents?
Journal of Microbiology, Immunology and Infection | May 23, 2020
Co-infection has been reported in patients with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, but there is limited knowledge on co-infection among patients with coronavirus disease 2019 (COVID-19). The prevalence of co-infection was variable among COVID-19 patients in different studies, however, it could be up to 50% among non-survivors. Co-pathogens included bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumonia, Legionella pneumophila and Acinetobacter baumannii; Candida species and Aspergillus flavus; and viruses such as influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus.
Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis
The Lancet | May 22, 2020
In this large multinational real-world analysis, we did not observe any benefit of hydroxychloroquine or chloroquine (when used alone or in combination with a macrolide) on in-hospital outcomes, when initiated early after diagnosis of COVID-19. Each of the drug regimens of chloroquine or hydroxychloroquine alone or in combination with a macrolide was associated with an increased hazard for clinically significant occurrence of ventricular arrhythmias and increased risk of in-hospital death with COVID-19. The use of hydroxychloroquine or chloroquine in COVID-19 is based on widespread publicity of small, uncontrolled studies, which suggested that the combination of hydroxychloroquine with the macrolide azithromycin was successful in clearing viral replication.
Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19
New England Journal of Medicine | May 21, 2020
In patients who died from Covid-19–associated or influenza-associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001). In lungs from patients with Covid-19, the amount of new vessel growth — predominantly through a mechanism of intussusceptive angiogenesis — was 2.7 times as high as that in the lungs from patients with influenza (P<0.001).
An Update on COVID-19 for the Practicing Allergist/immunologist
American Academy of Allergy, Asthma & Immunology | May 19, 2020
This year’s spring allergy season has been greatly overshadowed by the arrival of the coronavirus disease 2019 (COVID-19) pandemic. The presence of COVID-19 is affecting everyone and many allergists’ practices have slowed to a crawl because of state-wide limitations in non-essential medical visits and testing, and because of the risk to providers and their staff as well as to patients from COVID-19 infection and transmission. The CDC has issued many guidelines for healthcare providers, which include the use of appropriate PPE and the evaluation and testing of patients suspected of being infected with COVID-19. It has become more important than ever to recognize the differences between allergies and infection with COVID-19. Educating staff and patients to recognize the differences is paramount in appropriately screening those who may otherwise need isolation or referral based on rapidly evolving state and federal guidelines.
Clinician Wellness, Burnout, and Finding the Right Work-Life Balance
🎧 American Academy of Allergy, Asthma & Immunology | May 19, 2020
[Podcast] In this CME episode, Giselle S. Mosnaim, MD, MS, FAAAAI, discusses the factors associated with high rates of burnout for medical professionals. Listen in to learn great information and helpful tips to maintain wellness, which is especially pertinent during COVID-19.
COVID-19 and the impact of social determinants of health
The Lancet | Respiratory Medicine | May 18, 2020
The novel coronavirus disease 2019 (COVID-19), caused by the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), originated in Wuhan, China, and has now spread internationally with over 4·3 million individuals infected and over 297 000 deaths as of May 14, 2020, according to the Johns Hopkins Coronavirus Resource Center. While COVID-19 has been termed a great equaliser, necessitating physical distancing measures across the globe, it is increasingly demonstrable that social inequalities in health are profoundly, and unevenly, impacting COVID-19 morbidity and mortality. Many social determinants of health—including poverty, physical environment (eg, smoke exposure, homelessness), and race or ethnicity—can have a considerable effect on COVID-19 outcomes.
Elevated levels of interleukin-6 and CRP predict the need for mechanical ventilation in COVID-19
Journal of Allergy and Clinical Immunology | May 18, 2020
COVID-19 can manifest as a viral induced hyperinflammation with multi-organ involvement. Such patients often experience rapid deterioration and need for mechanical ventilation. Currently, no prospectively validated biomarker of impending respiratory failure is available. Maximal levels of IL-6 followed by CRP were highly predictive of the need for mechanical ventilation. This suggests the possibility of using IL-6 or CRP levels to guide escalation of treatment in patients with COVID-19 related hyperinflammatory syndrome.
Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome: Results From a Prospective, Single-Center, Clinicopathologic Case Series
Annals of Internal Medicine | May 14, 2020
Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality. COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency. Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation. Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory, and imaging studies and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism.
COVID-19 Important Resources
American College of Allergy, Asthma & Immunology | Updated regularly
Review a collection of allergy and immunology clinician resources, from webinars to contingency planning and billing & coding information to Federal response updates. This comprehensive collection of links and downloads can assist you in navigating your practice during the pandemic.
COVID-19: unanswered questions on immune response and pathogenesis
Journal of Allergy and Clinical Immunology | May 7, 2020
The novel coronavirus disease 2019 (COVID-19) has rapidly increased in pandemic scale since it first appeared in Wuhan, China, in December 2019. In these troubled days the scientific community is asking rapid replies to prevent and combat the emergency. It is generally accepted that only achieving a better understanding of the interactions between the virus and host immune response and of the pathogenesis of infection is crucial to identify valid therapeutic tools to control virus entry, replication and spread as well as to impair its lethal effects. Based on the recent research progress of SARS-CoV-2 and the results on previous coronaviruses, in this contribution we underscore some of the main unsolved problems, mostly focusing on pathogenetic aspects and host immunity to the virus. On this basis, we also touch important aspects regarding the immune response in asymptomatic subjects, the immune-evasion of SARS-CoV-2 in severe patients and differences in disease severity by age and gender.
Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures
The Lancet | Respiratory Medicine | May 7, 2020
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis.
Asthma and COVID-19 Risk: Good, Bad, or Indifferent?
MedPage Today | May 5, 2020
People with asthma are classified as being at increased risk for severe COVID-19 outcomes, although evidence is emerging that may point in the opposite direction. Under normal circumstances, viral infections are a big driver of flares in asthma patients. But research indicates asthma patients with COVID-19 do not appear to have a higher rate of hospitalization or mortality compared with other COVID-19 patients, Linda Rogers, MD, of Icahn School of Medicine at Mount Sinai in New York City, told MedPage Today.
COVID-19 and Asthma
American Academy of Allergy, Asthma & Immunology | Updated Regularly
[Infographic] Download and print this infographic to share with your patients and/or hang in your offices.
A Physician’s Guide to COVID-19
American Medical Association | April 30, 2020
This quick-start COVID-19 physician guide, curated from comprehensive CDC, JAMA and WHO resources, will help prepare your practice, address patient concerns and answer your most pressing questions.
Immunotherapies for COVID-19: lessons learned from sepsis
The Lancet | Respiratory Medicine | April 28, 2020
herapeutic approaches to mitigate the severe acute lung injury associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have rapidly entered clinical trials primarily on anecdotal observations and few clinical studies. Along with the clinical symptoms related to viral invasion, the reported molecular response known as the cytokine storm has attracted the greatest attention, in both the scientific and the lay press, as a cause of organ injury. The hypothesis that quelling this storm with anti-inflammatory therapies directed at reducing interleukin-6 (IL-6), IL-1, or even tumour necrosis factor α (TNFα) might be beneficial has led to several ongoing trials. Anecdotal evidence from non-controlled clinical trials has suggested a possible beneficial effect, and anti-IL-6 has been shown to be effective in chimeric antigen receptor T (CAR-T) and cytokine response syndrome (CRS).
What You Need to Know About COVID-19
Allergy & Asthma Network | April 20, 2020
COVID-19, a disease caused by coronavirus, is spreading worldwide and the World Health Organization (WHO) has declared it a pandemic. Here is a map of reported cases, deaths and reported recoveries around the world. In the United States, different parts of the country are seeing different levels of COVID-19 activity. Cases of COVID-19 and instances of community spread are being reported in all states. People in places where there is ongoing community spread of COVID-19 are at higher risk of exposure, with the risk level dependent on your location, according to the U.S. Centers for Disease Control and Prevention (CDC). Check out their COVID-19 Information Center.
What’s the Difference Between COVID-19 and Other Viruses?
American College of Allergy, Asthma & Immunology | April 20, 2020
Allergist Jonathan Bayuk, MD, ACAAI member, explains how COVID-19 is different from other viruses, and how to avoid catching it.
Albuterol Inhaler Shortage Due to COVID-19 Could Impact People With Asthma
Asthma and Allergy Foundation of America | April 16, 2020
Certain areas of the country are experiencing shortages of albuterol inhalers. The shortage will probably spread throughout the U.S., although it is not a production problem. The shortage is occurring because of the increased use of albuterol inhalers in hospitals for COVID-19 and suspected COVID-19 patients to help with respiratory issues. There is a concern that nebulizers used on patients with COVID-19 in the hospital could spread the virus in the air. But the possible risk is to hospitalized patients with COVID-19 – not to patients using their nebulizer at home as directed.
A Closer Look at COVID-19, Allergies and the Flu
🖼 Allergy & Asthma Network
Check out this downloadable/printable infographic that helps distinguish the difference in COVID-19 versus allergies.
Using Telemedicine to Provide Care for Allergic Conditions
🎧 American Academy of Allergy Asthma & Immunology | April 16, 2020
Telemedicine expert Jennifer Shih, MD, discusses practical elements of performing virtual visits. This conversation is filled with amazing tips for both patients and clinicians – a must listen for telemedicine novices or experienced users.
Coronavirus (COVID-19): What People With Asthma Need to Know
Asthma and Allergy Foundation of America [Blog] | April 16, 2020
There are some symptoms that are similar between these respiratory illnesses. This chart can help you figure out if you may be feeling symptoms of allergies or a respiratory illness like COVID-19. If you have a fever and a cough, call your doctor. If you have seasonal allergies, there are things you can do to treat at home.
Psychosocial Impact & Interventions for Patients & Providers During the COVID-19 Crisis
Allergy and Asthma Network | April 14, 2020
Scroll down the page for this webinar hosted by Tonya Winders, President & CEO of the Allergy & Asthma Network. Listen as she interviews Dr. Gia Rosenblum, Clinical Psychologist and Dr. Jackie Eghrari, Clinical Assistant Professor of Medicine, George Washington School of Medicine & Health Sciences.
Early Treatment With Sotrovimab Decreases Risk for Progression to Severe COVID-19
We have updated the protocol of our living systematic review (PROSPERO registration: CRD42020178187). This most recent search update, which was done on 11 July 2020, identified 2756 citations. Of these, we included 3 observational cohort studies of patients with coronavirus disease 2019 (COVID-19) in the updated quantitative synthesis. One of the new studies compared bilevel positive airway pressure (BiPAP) with continuous positive airway pressure (CPAP), 1 compared high-flow oxygen by nasal cannula (HFNC) with invasive mechanical ventilation (IMV), and the last compared noninvasive ventilation (NIV) with IMV. In summary, the results suggest no change in the findings of the original systematic review. Noninvasive ventilation may have similar effects to IMV on mortality, but the evidence is uncertain.
The coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to public health. SARS-CoV-2 belongs to the Betacoronavirus of the family Coronaviridae, and commonly induces respiratory symptoms, such as fever, unproductive cough, myalgia, and fatigue. To better understand the virus, numerous studies have been performed, and strategies have been established with the aim to prevent further spread of COVID-19, and to develop efficient and safe drugs and vaccines. For example, the structures of viral proteins, such as the spike protein (S protein), main protease (Mpro), and RNA-dependent RNA polymerase (RdRp), have been uncovered, providing information for the design of drugs against SARS-CoV-2. In addition, elucidating the immune responses induced by SARS-CoV-2 is accelerating the development of therapeutic approaches. In essence, diverse small molecule drugs and vaccines are being developed to treat COVID-19. According to the World Health Organization (WHO), as of September 17, 2020, 36 vaccine candidates were under clinical evaluation to treat COVID-19, and 146 candidate vaccines were in preclinical evaluation. Given that vaccines can be applied for prophylaxis and the treatment for SARS-CoV-2 infection, in this review, we introduce the recent progress of therapeutic vaccines candidates against SARS-CoV-2. Furthermore, we summarize the safety issues that researchers may be confronted with during the development of vaccines. We also describe some effective strategies to improve the vaccine safety and efficacy that were employed in the development of vaccines against other pathogenic agents, with the hope that this review will aid in the development of therapeutic methods against COVID-19.
Spontaneous pneumothorax has been reported as a possible complication of novel coronavirus associated pneumonia (COVID-19). We report two cases of COVID-19 patients who developed spontaneous and recurrent pneumothorax as a presenting symptom, treated with surgical procedure. An insight on pathological finding is given. Two patients presented to our hospital with spontaneous pneumothorax associated with Sars-Cov2 infection onset. After initial conservative treatment with chest drain, both patients had a recurrence of pneumothorax during COVI-19 disease, contralateral (patient 1) or ipsilateral (patient 2) and therefore underwent lung surgery with thoracoscopy and bullectomy. Intraoperative findings of COVID-19 pneumonia were parenchymal atelectasis and vascular congestion. Lung tissue was very frail and prone to bleeding. Histological examination showed interstitial infiltration of lymphocytes and plasma cells, as seen in non specific interstitial pneumonia, together with myo-intimal thickening of vessels with blood extravasation and microthrombi.
Patients with Chronic Obstructive Pulmonary Disease (COPD) have a higher prevalence of coronary ischemia and other factors that put them at risk for COVID-19-related complications. We aimed to explore the impact of COVID-19 in a large population-based sample of patients with COPD in Castilla-La Mancha, Spain. We analyzed clinical data in electronic health records from 1 January to 10 May 2020 by using Natural Language Processing through the SAVANA Manager® clinical platform. Out of 31,633 COPD patients, 793 had a diagnosis of COVID-19. The proportion of patients with COVID-19 in the COPD population (2.51%; 95% CI 2.33–2.68) was significantly higher than in the general population aged >40 years (1.16%; 95% CI 1.14–1.18); p < 0.001. Compared with COPD-free individuals, COPD patients with COVID-19 showed significantly poorer disease prognosis, as evaluated by hospitalizations (31.1% vs. 39.8%: OR 1.57; 95% CI 1.14–1.18) and mortality (3.4% vs. 9.3%: OR 2.93; 95% CI 2.27–3.79). Patients with COPD and COVID-19 were significantly older (75 vs. 66 years), predominantly male (83% vs. 17%), smoked more frequently, and had more comorbidities than their non-COPD counterparts. Pneumonia was the most common diagnosis among COPD patients hospitalized due to COVID-19 (59%); 19% of patients showed pulmonary infiltrates suggestive of pneumonia and heart failure. Mortality in COPD patients with COVID-19 was associated with older age and prevalence of heart failure (p < 0.05). COPD patients with COVID-19 showed higher rates of hospitalization and mortality, mainly associated with pneumonia. This clinical profile is different from exacerbations caused by other respiratory viruses in the winter season.
Previous studies of excess deaths (the gap between observed and expected deaths) during the coronavirus disease 2019 (COVID-19) pandemic found that publicly reported COVID-19 deaths underestimated the full death toll, which includes documented and undocumented deaths from the virus and non–COVID-19 deaths caused by disruptions from the pandemic. A previous analysis found that COVID-19 was cited in only 65% of excess deaths in the first weeks of the pandemic (March-April 2020); deaths from non–COVID-19 causes increased sharply in 5 states with the most COVID-19 deaths. This study updates through August 1, 2020, the estimate of excess deaths and explores temporal relationships with state reopenings (lifting of coronavirus restrictions). Although total US death counts are remarkably consistent from year to year, US deaths increased by 20% during March-July 2020. COVID-19 was a documented cause of only 67% of these excess deaths. Some states had greater difficulty than others in containing community spread, causing protracted elevations in excess deaths that extended into the summer. US deaths attributed to some noninfectious causes increased during COVID-19 surges. Excess deaths attributed to causes other than COVID-19 could reflect deaths from unrecognized or undocumented infection with severe acute respiratory syndrome coronavirus 2 or deaths among uninfected patients resulting from disruptions produced by the pandemic.
Ivermectin was shown to inhibit SARS-CoV-2 replication in-vitro, which has led to off-label use, but clinical efficacy has not been previously described. The objective of the study was to determine if ivermectin benefits hospitalized COVID-19 patients. Charts of consecutive patients hospitalized at four Broward Health hospitals in Florida with confirmed COVID-19 between March 15 through May 11, 2020 treated with or without ivermectin were reviewed. The primary outcome was all-cause in-hospital mortality. Secondary outcomes included mortality in patients with severe pulmonary involvement, extubation rates for mechanically ventilated patients, and length of stay. Severe pulmonary involvement was defined as need for FiO2 ≥50%, noninvasive ventilation, or invasive ventilation at study entry. Logistic regression and propensity score matching were used to adjust for confounders. 280 patients, 173 treated with ivermectin and 107 without ivermectin, were reviewed. Most patients in both groups also received hydroxychloroquine and/or azithromycin. Univariate analysis showed lower mortality in the ivermectin group (15.0% versus 25.2%, OR 0.52, CI 0.29-0.96, P=0.03). Mortality was also lower among ivermectin-treated patients with severe pulmonary involvement (38.8% vs 80.7%, OR 0.15, CI 0.05-0.47, p=0.001). There were no significant differences in extubation rates (36.1% vs 15.4%, OR 3.11 (0.88-11.00), p=0.07) or length of stay. After multivariate adjustment for confounders and mortality risks, the mortality difference remained significant (OR 0.27, CI 0.09-0.80, p=0.03). 196 patients were included in the propensity-matched cohort. Mortality was significantly lower in the ivermectin group (13.3% vs 24.5%, OR 0.47, CI 0.22-0.99, p<0.05); an 11.2% (CI 0.38%-22.1%) absolute risk reduction, with a number needed to treat of 8.9 (CI 4.5-263).
Factors determining the progression of frequently mild or asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection into life-threatening pneumonia remain poorly understood. Viral and host factors involved in the development of diffuse alveolar damage have been extensively studied in influenza virus infection. Influenza is a self-limited upper respiratory tract infection that causes acute and severe systemic symptoms and its spread to the lungs is limited by CD4+ T-cell responses. A vicious cycle of CCL2- and CXCL2-mediated inflammatory monocyte and neutrophil infiltration and activation and resultant massive production of effector molecules including tumor necrosis factor (TNF)-α, nitric oxide, and TNF-related apoptosis-inducing ligand are involved in the pathogenesis of progressive tissue injury. SARS-CoV-2 directly infects alveolar epithelial cells and macrophages and induces foci of pulmonary lesions even in asymptomatic individuals. Mechanisms of tissue injury in SARS-CoV-2-induced pneumonia share some aspects with influenza virus infection, but IL-1β seems to play more important roles along with CCL2 and impaired type I interferon signaling might be associated with delayed virus clearance and disease severity. Further, data indicate that preexisting memory CD8+ T cells may play important roles in limiting viral spread in the lungs and prevent progression from mild to severe or critical pneumonia. However, it is also possible that T-cell responses are involved in alveolar interstitial inflammation and perhaps endothelial cell injury, the latter of which is characteristic of SARS-CoV-2-induced pathology.
The Healio editors have compiled a list of the most-read pulmonology news from the recent virtual European Respiratory Society International Congress. Highlights from the virtual meeting including the later-life impact of childhood bronchitis, gefapixant for refractory or unexplained chronic cough and the benefit of inhaled molgramostim in autoimmune pulmonary alveolar proteinosis. Other presentations focused on persisting pulmonary impairment in COVID-19 survivors, short-course oral dexamethasone in patients with community-acquired pneumonia and asthma prescribing based on genetic differences.
The degree of protective immunity conferred by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently unknown. As such, the possibility of reinfection with SARS-CoV-2 is not well understood. We describe an investigation of two instances of SARS-CoV-2 infection in the same individual. A 25-year-old man who was a resident of Washoe County in the US state of Nevada presented to health authorities on two occasions with symptoms of viral infection, once at a community testing event in April, 2020, and a second time to primary care then hospital at the end of May and beginning of June, 2020. Nasopharyngeal swabs were obtained from the patient at each presentation and twice during follow-up. Nucleic acid amplification testing was done to confirm SARS-CoV-2 infection. We did next-generation sequencing of SARS-CoV-2 extracted from nasopharyngeal swabs. Sequence data were assessed by two different bioinformatic methodologies. A short tandem repeat marker was used for fragment analysis to confirm that samples from both infections came from the same individual. The patient had two positive tests for SARS-CoV-2, the first on April 18, 2020, and the second on June 5, 2020, separated by two negative tests done during follow-up in May, 2020. Genomic analysis of SARS-CoV-2 showed genetically significant differences between each variant associated with each instance of infection. The second infection was symptomatically more severe than the first.
COVID-19 is caused by SARS-CoV-2 infection and characterized by diverse clinical symptoms. Type I interferon (IFN-I) production is impaired and severe cases lead to ARDS and widespread coagulopathy. We propose that COVID-19 pathophysiology is initiated by SARS-CoV-2 gene products, the NSP1 and ORF6 proteins, leading to a catastrophic cascade of failures. These viral components induce signal transducer and activator of transcription 1 (STAT1) dysfunction and compensatory hyperactivation of STAT3. In SARS-CoV-2-infected cells, a positive feedback loop established between STAT3 and plasminogen activator inhibitor-1 (PAI-1) may lead to an escalating cycle of activation in common with the interdependent signaling networks affected in COVID-19. Specifically, PAI-1 upregulation leads to coagulopathy characterized by intravascular thrombi. Overproduced PAI-1 binds to TLR4 on macrophages, inducing the secretion of proinflammatory cytokines and chemokines. The recruitment and subsequent activation of innate immune cells within an infected lung drives the destruction of lung architecture, which leads to the infection of regional endothelial cells and produces a hypoxic environment that further stimulates PAI-1 production. Acute lung injury also activates EGFR and leads to the phosphorylation of STAT3. COVID-19 patients’ autopsies frequently exhibit diffuse alveolar damage (DAD) and increased hyaluronan (HA) production which also leads to higher levels of PAI-1. COVID-19 risk factors are consistent with this scenario, as PAI-1 levels are increased in hypertension, obesity, diabetes, cardiovascular diseases, and old age. We discuss the possibility of using various approved drugs, or drugs currently in clinical development, to treat COVID-19. This perspective suggests to enhance STAT1 activity and/or inhibit STAT3 functions for COVID-19 treatment. This might derail the escalating STAT3/PAI-1 cycle central to COVID-19.
Early detection of COVID-19 based on chest CT enables timely treatment of patients and helps control the spread of the disease. We proposed an artificial intelligence (AI) system for rapid COVID-19 detection and performed extensive statistical analysis of CTs of COVID-19 based on the AI system. We developed and evaluated our system on a large dataset with more than 10 thousand CT volumes from COVID-19, influenza-A/B, non-viral community acquired pneumonia (CAP) and non-pneumonia subjects. In such a difficult multi-class diagnosis task, our deep convolutional neural network-based system is able to achieve an area under the receiver operating characteristic curve (AUC) of 97.81% for multi-way classification on test cohort of 3,199 scans, AUC of 92.99% and 93.25% on two publicly available datasets, CC-CCII and MosMedData respectively. In a reader study involving five radiologists, the AI system outperforms all of radiologists in more challenging tasks at a speed of two orders of magnitude above them. Diagnosis performance of chest x-ray (CXR) is compared to that of CT. Detailed interpretation of deep network is also performed to relate system outputs with CT presentations.
Older adults with interstitial lung disease and COVID-19 have increased risk for severe disease, hospitalization and death, researchers reported in the American Journal of Respiratory and Critical Care Medicine. “In this case-control study, patients with ILD who contracted COVID-19 had a greater than fourfold increased adjusted odds of death, were more likely to be hospitalized and require ICU level of care, and were less likely to be discharged, particularly to home, compared to a matched cohort of COVID-19 patients without ILD,” Anthony J. Esposito, MD, research fellow in the department of medicine in the division of pulmonary and critical care medicine at Brigham and Women’s Hospital, and colleagues wrote. “Accordingly, this study suggests that comorbid ILD is a risk factor for poor outcomes from COVID-19.” The multicenter, case-control study included 46 adults with pre-existing ILD and a COVID-19 diagnosis from March to June at six Mass General Brigham hospitals. For comparison, the researchers also analyzed a control cohort of 92 patients with COVID-19 without ILD. Patients with ILD and COVID-19 were more likely to be admitted to the hospital and require ICU care than those without COVID-19, and were less likely to be discharged from the hospital.
Prone positioning reduces mortality in patients with severe acute respiratory distress syndrome (ARDS), a feature of severe COVID-19. Despite this, most patients with ARDS do not receive this life-saving therapy. The objective of the study was to identify determinants of prone positioning utilization, to develop specific implementation strategies, and to incorporate strategies into an overarching response to the COVID-19 crisis. We used an implementation mapping approach guided by implementation science frameworks. We conducted semi-structured interviews with 30 ICU clinicians who staffed 12 ICUs within the Penn Medicine health system and the University of Michigan Medical Center. We performed thematic analysis utilizing the Consolidated Framework for Implementation Research (CFIR). We then conducted three focus groups with a task force of ICU leaders to develop an implementation menu, using the Expert Recommendations for Implementing Change (ERIC) framework. The task force developed five specific implementation strategies: educational outreach, learning collaborative, clinical protocol, prone positioning team, and automated alerting, elements of which were rapidly implemented at Penn Medicine.
Coronavirus disease 2019 (COVID-19) can progress to severe respiratory failure requiring intubation and mechanical ventilation, with a grim prognosis in this subset of patients. Despite the perceived increased risk from aerosol-generating procedures, data from prior severe acute respiratory syndrome suggests no increased transmission from bronchoscopy. There is a paucity of data regarding the actual risk and benefit of bronchoscopy for patients with COVID-19, leading to uncertainty regarding recommendations. The hypothesis of this report is that bronchoscopy with intermittent apnea is safe for both patients and healthcare providers. This study reports our experience with therapeutic bronchoscopy in patients with severe COVID-19. This is a retrospective analysis of all patients admitted to the New York University Langone Health (NYULH) Manhattan campus between March 13th-April 24th, 2020 with COVID19 and respiratory failure requiring mechanical ventilation that underwent bronchoscopy. COVID-19 was diagnosed by nasal pharyngeal swab for reverse transcriptase polymerase chain reaction (rtPCR) assays. Indications were concern for superimposed pneumonia, thick secretions with decreasing tidal volumes, evidence of endotracheal tube obstruction not resolved by suctioning, or significant bloody secretions. The NYULH institutional review board approved this human subjects study.
Adult patients with current or previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can develop a hyperinflammatory syndrome, which resembles multisystem inflammatory syndrome in children (MIS-C), according to a case series published in the Oct. 2 early-release issue of the U.S. Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report. Sapna Bamrah Morris, M.D., from the CDC COVID-19 Response Team, and colleagues present reports of 27 patients with cardiovascular, gastrointestinal, dermatologic, and neurologic symptoms without severe respiratory illness who concurrently received positive test results for SARS-CoV-2. The researchers highlight recognition of multisystem inflammatory syndrome in adults (MIS-A), which resembles MIS-C. The patients described had minimal respiratory symptoms, hypoxemia, or radiographic abnormalities. In case reports describing MIS-A, only eight of 16 patients had any documented respiratory symptoms before onset of MIS-A. All 16 patients had evidence of cardiac effects, 13 had gastrointestinal symptoms on admission, and five had dermatologic manifestations. Ten of the patients had pulmonary ground-glass opacities, and six had pleural effusions on chest imaging, despite minimal respiratory symptoms.
Intubation and extubation didn’t generate as much risky aerosol as expected, a real-world operating room study showed. A second study suggested that bedside tracheotomy was pretty safe, too. Aerosol recordings performed under the operating theater “clean zone” canopy at the typical distance between practitioner and patient’s mouth during the intubation sequence turned up an average of 7 and maximum 77 particles per liter of air over a 5-min period during anesthesia induction and intubation. That was higher than the background of 2 particles/L per 5 minutes in the empty operating theater but far lower than the average 732 particles by the same measure created by a voluntary cough (P<0.0001), reported Anthony Pickering, MBChB, PhD, of the University of Bristol in England, and colleagues. The results were virtually the same with the ultraclean ventilation system flow turned off as when it was on, they wrote in Anaesthesia. None of the patients had COVID-19, and the particle concentration was only a “plausible but unproven surrogate” for infection risk, the researchers cautioned. “When considering the risk of transmission of SARS-CoV-2, it is helpful to reflect on the definition of an aerosol-generating procedure that has been expressly stated as ‘aerosol generating procedures are considered to have a greater likelihood of producing aerosols compared to coughing,'” the group wrote.
Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. Immune mediated damage has been proposed as a pathogenic factor, but immune responses in lungs of COVID-19 patients remain poorly characterized. Here we show transcriptomic, histologic and cellular profiles of post mortem COVID-19 (n = 34 tissues from 16 patients) and normal lung tissues (n = 9 tissues from 6 patients). Two distinct immunopathological reaction patterns of lethal COVID-19 are identified. One pattern shows high local expression of interferon stimulated genes (ISGhigh) and cytokines, high viral loads and limited pulmonary damage, the other pattern shows severely damaged lungs, low ISGs (ISGlow), low viral loads and abundant infiltrating activated CD8+ T cells and macrophages. ISGhigh patients die significantly earlier after hospitalization than ISGlow patients. Our study may point to distinct stages of progression of COVID-19 lung disease and highlights the need for peripheral blood biomarkers that inform about patient lung status and guide treatment.
The Food and Drug Administration (FDA) has revised the Emergency Use Authorization (EUA) for remdesivir (Veklury; Gilead Sciences) removing the US government’s role in directing the allocation of the investigational coronavirus disease 2019 (COVID-19) treatment. Remdesivir is a nucleotide analogue with broad-spectrum antiviral activity. It is currently available in the US under an EUA for hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19, regardless of disease severity. Since the COVID-19 pandemic began, the US Department of Health and Human Services (HHS) was responsible for the allocation and distribution of remdesivir to COVID-19 patients. By increasing manufacturing capacity, Gilead has been able to expand the supply of remdesivir, which now exceeds market demand based on recent allocation numbers from HHS’ Office of the Assistant Secretary for Preparedness and Response. Under the revised EUA, Gilead Sciences will resume control of the distribution of remdesivir in the US. To ensure stable management of drug supply, AmerisourceBergen will remain the sole US distributor of the product through the end of this year and will sell directly to hospitals. The Company is now able to meet real-time demand for remdesivir and potential future surges of COVID-19.
Consider providing this patient education information series, which explains that SARS-CoV-2 is the virus that causes the COVID-19 infection. It further identifies for patients that they can be ill with more than one virus at the same time. As the SARS-CoV-2 virus pandemic continues, influenza and other respiratory infections will also emerge in the community. Respiratory infections may present with similar symptoms and all can spread from person to person. It is hard to tell which virus or bacteria is causing a person’s illness based on symptoms alone. At times testing is needed to see which virus(es) or bacteria are present. These tests usually involve getting a nose and/or throat swab sample, as most of these viruses are present in large amounts in the back of the nose and throat. There is still a lot to learn about the COVID-19 infection and research is ongoing.
Patients with severe Coronavirus Disease 2019 (COVID-19) have respiratory failure with hypoxemia and acute bilateral pulmonary infiltrates, consistent with acute respiratory distress syndrome (ARDS). It has been suggested that respiratory failure in COVID-19 represents a novel pathologic entity. So, how does the lung histopathology described in COVID-19 compare to the lung histopathology described in SARS and H1N1 influenza? We conducted a systematic review to characterize the lung histopathologic features of COVID-19 and compare them against findings of other recent viral pandemics, H1N1 influenza and SARS. We systematically searched MEDLINE and PubMed for studies published up to June 24, 2020 using search terms for COVID-19, H1N1 influenza and SARS with keywords for pathology, biopsy, and autopsy. Using PRISMA-IPD guidelines, our systematic review analysis included 26 articles representing 171 COVID-19 patients; 20 articles representing 287 H1N1 patients; and eight articles representing 64 SARS patients. In COVID-19, acute phase diffuse alveolar damage (DAD) was reported in 88% of patients, which was similar to the proportion of cases with DAD in both H1N1 (90%) and SARS (98%). Pulmonary microthrombi were reported in 57% of COVID-19 and 58% of SARS patients, as compared to 24% of H1N1 influenza patients.
Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 shares similarities with influenza to the extent that both cause respiratory disease which can vary markedly in its severity and present with a similar constellation of symptoms, including fever, cough, myalgia, malaise, fatigue and dyspnoea. Early reports do, however, indicate that the proportion of severe infections and mortality rate is higher for COVID-19. Older age and a range of underlying health conditions, such as immune deficiency, cardiovascular disease, chronic lung disease, neuromuscular disease, neurological disease, chronic renal disease and metabolic diseases, have been associated with an increased risk of severe influenza and associated mortality. Here we first aimed to describe the characteristics of patients hospitalised with COVID-19. In particular, we set out to summarise individuals’ demographics, medical conditions, and medication use.
Systemic complement activation is associated with respiratory failure in patients with coronavirus disease 2019 (COVID-19), according to the results of a recent study published in the journal PNAS. According to the researchers, the complement system plays a key role in the innate immune response, and has been previously associated with respiratory failure, acute respiratory distress syndrome development, and severity in bacterial and viral pneumonia. Therefore, the investigators sought to identify the degree and specific time point of systemic complement activation in COVID-19, particularly as the activation relates to the clinical course of disease. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data from were abstracted from electronic medical records from patients hospitalized with COVID-19. Blood samples were obtained at hospital admission (within 48 hours), at days 3 to 5, and days 7 to 10. Patients were divided according to the presence of respiratory failure, and associations for outcomes were examined between the 2 groups. Of the 39 patients who were positive for SARS-CoV-2 included in the study, respiratory failure was either prominent at admission or developed while hospitalized in 23 patients. Baseline characteristics revealed significant differences in myalgia, fatigue, arterial oxygen partial pressure /fractional inspired oxygen ratio, need for oxygen therapy, and Sequential Organ Failure Assessment (SOFA) score between patients with and without respiratory failure.
In August, Vir Biotechnology and Alnylam Pharmaceuticals announced that lung-targeted small interfering RNA (siRNA) conjugates against SARS-CoV-2 and other coronaviruses delivered to the lung are scheduled for preclinical studies by the end of the year. The collaboration inked in March involves Alnylam, the RNA interference (RNAi) pioneer, providing Vir with over 350 siRNAs targeting all available SARS-CoV-1 and SARS-CoV-2 genomes. Vir has been screening these molecules in vitro for potent lead siRNA candidates; if any are taken forward, Alnylam retains a 50–50 option for participation. Around the same time, Translate Bio closed a licensing deal with French pharmaceutical giant Sanofi Pasteur for use of its mRNA platform to develop vaccines for infectious diseases. Under the partnership, the mRNA vaccines will be delivered by intramuscular injection and are not targeted to specific organs or tissues. But the multibillion-dollar deal highlights the potential of Translate Bio’s expertise in mRNA delivery. That includes a tissue-specific mRNA delivery platform that the company is using to target the lung in cystic fibrosis and idiopathic pulmonary fibrosis. RNA delivery into the lungs, if successful, would be a boon for drug and vaccine makers. Other advances in lipid nanoparticle (LNP) formulations, inhalation devices, carrier particles and customized chemical modifications are making strides toward the goal of delivering RNA candidates — including mRNA, antisense RNA and siRNA — into the lung. Success could open treatment doors for lung disorders in COVID-19 and beyond.
With more than 30 million documented infections and 1 million deaths worldwide, the coronavirus disease 2019 (COVID-19) pandemic continues unabated. The clinical spectrum of severe acute respiratory syndrome coronavirus (SARS-CoV) 2 infection ranges from asymptomatic infection to life-threatening and fatal disease. Current estimates are that approximately 20 million people globally have “recovered”; however, clinicians are observing and reading reports of patients with persistent severe symptoms and even substantial end-organ dysfunction after SARS-CoV-2 infection. Because COVID-19 is a new disease, much about the clinical course remains uncertain—in particular, the possible long-term health consequences, if any. Currently, there is no consensus definition of postacute COVID-19. Based on the COVID Symptom Study, in which more than 4 million people in the US, UK and Sweden have entered their symptoms after a COVID-19 diagnosis, postacute COVID-19 is defined as the presence of symptoms extending beyond 3 weeks from the initial onset of symptoms and chronic COVID-19 as extending beyond 12 weeks. It is possible that individuals with symptoms were more likely to participate in this study than those without them. In a study of 55 patients with COVID-19, at 3 months after discharge, 35 (64%) had persistent symptoms and 39 (71%) had radiologic abnormalities consistent with pulmonary dysfunction such as interstitial thickening and evidence of fibrosis. Three months after discharge, 25% of patients had decreased diffusion capacity for carbon monoxide. In another study of 57 patients, abnormalities in pulmonary function test results obtained 30 days after discharge, including decreased diffusion capacity for carbon monoxide and diminished respiratory muscle strength, were common and occurred in 30 patients (53%) and 28 patients (49%), respectively.
If a definite diagnosis of COVID-19 infection requires real-time reverse transcription polymerase chain reaction (RT-PCR) of viral nucleic acids, chest CT scan has proved to be of clinical importance and the main tool for screening. The Fleischner Society recently validated the use of imaging in patients suspected of having COVID-19 presenting with mild clinical features and at risk for disease progression, and as a help for medical triage of patients suspected of having COVID-19 in a resource-constrained environment, in case of moderate-to-severe clinical features and high pre-test probability of disease. A recent meta-analysis by Kim et al showed that the diagnostic value of chest CT depends on the prevalence of COVID-19 infection in the studied population. In areas where the prevalence is low, chest CT screening of patients with suspected disease has a low positive predictive value. On the other hand, in the case of epidemic surge of patients at the emergency department, the clinicians will face a difficult challenge of rapid triage depending on disease presentation and severity. Patients with typical clinical symptoms and bilateral radiographic opacities may be hospitalized without a diagnostic CT scan. The patients for whom the diagnosis is unclear represent the group with intermediate probability and may benefit from a chest CT scan, looking for evidence of COVID versus other pathologies. The objective of this study was to evaluate the inter-observer agreement and diagnostic accuracy including positive and negative predictive values of chest CT to identify COVID-19 pneumonia in patients with intermediate clinical probability during an acute disease outbreak in a European country.
The impact of COVID-19 on patients with Interstitial Lung Disease (ILD) has not been established. The objective was to assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age, sex and comorbidity matched population. An international multicenter audit of patients with a prior diagnosis of ILD admitted to hospital with COVID-19 between 1 March and 1 May 2020 was undertaken and compared with patients, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished IPF from non-IPF ILD and used lung function to determine the greatest risks of death. Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity-score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching ILD patients with COVID-19 had higher mortality (HR 1.60, Confidence Intervals 1.17-2.18 p=0.003) compared with age, sex and co-morbidity matched controls without ILD. Patients with a FVC of <80% had an increased risk of death versus patients with FVC ≥80% (HR 1.72, 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR 2.27, 1.39−3.71). Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD.
In patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU) with a high acuity of illness and a prolonged period of mechanical ventilation, the time to commencement of rehabilitation was often delayed because of the severity of an individual’s condition. Researchers conducted a single-center, prospective, noninterventional, observational study in patients with a COVID-19 diagnosis admitted to the ICU at the Queen Elizabeth Hospital Birmingham (QEHB) in Birmingham, United Kingdom. Results of the analysis were published in the Annals of the American Thoracic Society. Investigators sought to describe the clinical status, demographics, level of rehabilitation, and mobility status at ICU discharge in individuals with COVID-19. Adult patients were enrolled who had been admitted to the ICU at QEHB from March through April 2020 with a confirmed diagnosis of COVID-19 and had received mechanical ventilation for more than 24 hours. The rehabilitation status of all participants was measured daily with use of the Manchester Mobility Score (MMS) to identify the time taken to first mobilize (defined as an MMS of ≥2, ie, sitting on the edge of the bed or higher) and the location of hospital discharge, as 1 of the following categories: home with no rehabilitation; home with rehabilitation; or inpatient rehabilitation facility. A total of 177 patients were identified, with 110 of them surviving to ICU discharge and thus included in the analysis. The mean participant age of those who survived to ICU discharge was 53±12 years. Overall, 75% of the participants were men; the majority of the patients were of White (48%) or Asian (35%) ethnicity. In the patient cohort, 87% were classified as overweight or obese (body mass index [BMI], 25).
As of Sept. 16, there have been 1,718 deaths from COVID-19 and related complications among health care workers in the U.S., significantly more than the 690 deaths reported by the CDC, according to a report released by National Nurses United. “Nurses and health care workers were forced to work without personal protective equipment they needed to do their job safely,” Zenei Cortez, RN, a president of National Nurses United, said in a press release. “It is immoral and unconscionable that they lost their lives.” The report follows survey results released by the American Nurses Association last month, which found that many nurses across the United States were still facing PPE shortages, with many reusing essential N-95 masks for 5 days or longer. Researchers collected information on registered nurses and other health care workers using media reports, obituaries, union memorial pages, GoFundMe and social media platforms, including Facebook, Twitter and Reddit. They assessed deaths from COVID-19 and related complications among health care workers, which they defined as all workers in care settings, including nursing homes, hospitals, medical practices, congregate-living and home health care settings. They found that among the 1,718 health care worker deaths attributed to COVID-19-related illness, 213 deaths occurred among registered nurses.
The global COVID-19 pandemic reached a grim new milestone on Tuesday: 1 million dead. Americans made up more than 200,000 of those deaths, or one in every five, according to a running tally compiled by Johns Hopkins University. “It’s not just a number. It’s human beings. It’s people we love,” Howard Markel, M.D., a professor of medical history at the University of Michigan, told the Associated Press. He is an adviser to government officials on how best to handle the pandemic – and he lost his 84-year-old mother to COVID-19 in February. “It’s people we know,” Markel said. “And if you don’t have that human factor right in your face, it’s very easy to make it abstract.” It has taken the newly emerged severe acute respiratory syndrome coronavirus 2 virus just eight months to reach a worldwide death toll that has meant personal and economic tragedy for billions. Right now, more than 33 million people worldwide are known to have been infected with the new coronavirus, the Hopkins tally showed.
Current evidence, from observational studies to systematic reviews and epidemiologic modeling, supports the use of masks by the public, especially surgical masks, on mitigating COVID-19 transmission and deaths. However, public mask use has been heavily politicized with inconsistent recommendations by authorities leading to divided public opinion. Despite evidence to the contrary, an online UK/US survey found that only 29.7-37.8% of participants thought that wearing a surgical mask was “highly effective” in protecting them from acquiring COVID-19. To evaluate whether gas exchange abnormalities occur with the use of surgical masks in subjects with and without lung function impairment. Methods and Findings In order to demonstrate the changes in end-tidal CO2 (ETCO2) and oxygen saturation (SpO2) before and after wearing a surgical mask, we used a convenience sample of 15 housestaff physicians without lung conditions (aged 31.1 1.9 years, 60% male) and 15 veterans with severe COPD (aged 71.6 8.7 years, FEV1 44.0 22.2%, 100% male). The patients needed to have a post-bronchodilator FEV1 <50% and FEV1/FVC <0.7 and were enrolled from the pulmonary function laboratory during a scheduled 6-minute walk test ordered to assess the need for supplemental oxygen. Due to the COVID-19 pandemic, the 6-minute walk tests are done with subjects using a surgical mask. Baseline measures on room air without a mask were performed non-invasively using a Life Sense monitor, followed by continuous monitoring using a surgical mask. At 5 and 30 minutes, no major changes in ETCO2 or SpO2 of clinical significance were noted at any time point in either group at rest. With the 6-minute walk, subjects with severe COPD decreased oxygenation as expected (with 2 qualifying for supplemental oxygen).
The objective of the study was to develop and validate a nomogram for early identification of severe coronavirus disease 2019 (COVID-19) based on initial clinical and CT characteristics. The initial clinical and CT imaging data of 217 patients with COVID-19 were analyzed retrospectively from January to March 2020. Two hundred seventeen patients with 146 mild cases and 71 severe cases were randomly divided into training and validation cohorts. Independent risk factors were selected to construct the nomogram for predicting severe COVID-19. Nomogram performance in terms of discrimination and calibration ability was evaluated using the AUC, calibration curve, decision curve, clinical impact curve and risk chart. In the training cohort, the severity score of lung in the severe group (7, interquartile range [IQR]:5–9) was significantly higher than that of the mild group (4, IQR, 2–5) (P < 0.001). Age, density, mosaic perfusion sign and severity score of lung were independent risk factors for severe COVID-19. The nomogram had a AUC of 0.929 (95% CI, 0.889–0.969), sensitivity of 84.0% and specificity of 86.3%, in the training cohort, and a AUC of 0.936 (95% CI, 0.867–1.000), sensitivity of 90.5% and specificity of 88.6% in the validation cohort. The calibration curve, decision curve, clinical impact curve and risk chart showed that nomogram had high accuracy and superior net benefit in predicting severe COVID-19.
The COVID-19 outbreak is becoming a public health emergency. Data are limited on the clinical characteristics and causes of death. A retrospective analysis of COVID-19 deaths were performed for patients’ clinical characteristics, laboratory results, and causes of death. In total, 56 patients (72.7%) of the decedents (male–female ratio 51:26, mean age 71 ± 13, mean survival time 17.4 ± 8.4 days) had comorbidities. Acute respiratory failure (ARF) and sepsis were the main causes of death. Increases in C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer and lactic acid and decreases in lymphocytes were common laboratory results. Intergroup analysis showed that (1) most female decedents had cough and diabetes. (2) The proportion of young- and middle-aged deaths was higher than elderly deaths for males, while elderly decedents were more prone to myocardial injury and elevated CRP. (3) CRP and LDH increased and cluster of differentiation (CD) 4+ and CD8+ cells decreased significantly in patients with hypertension. The majority of COVID-19 decedents are male, especially elderly people with comorbidities. The main causes of death are ARF and sepsis. Most female decedents have cough and diabetes. Myocardial injury is common in elderly decedents. Patients with hypertension are prone to an increased inflammatory index, tissue hypoxia and cellular immune injury.
The global pandemic of coronavirus disease 2019 (COVID-19) infection is ongoing and associated with high mortality. The aim of this study was to investigate the efficacy and safety of subcutaneous injection of interferon alpha-2b (IFN alpha-2b) combined with lopinavir/ritonavir (LPV/r) in the treatment of COVID-19 infection, compared with that of using LPV/r alone. The study included patients diagnosed with laboratory-confirmed COVID-19 infection in Wuhan Red Cross hospital during the period from January 23, 2020 to March 19, 2020. The length of stay, the time to viral clearance and adverse reactions during hospitalization were compared between patients using oral LPV/r and combined therapy of LPV/r and subcutaneous injection of IFN alpha-2b. A total of 22 patients were treated with LPV/r alone and 19 with combined therapy with subcutaneous injection of IFN alpha-2b. The average length of hospitalization in the combination group was shorter than that of LPV/r group (16 ± 9.7 vs 23 ± 10.5 days; P = 0.028). Moreover, the days of hospitalization in early intervention group decreased from 25 ± 8.5 days to 10 ± 2.9 days compared with delayed intervention group (P = 0.001). Combined therapy with IFN alpha-2b also significantly reduced the duration of detectable virus in the upper respiratory tract.
In the dark of night, in a tweet retweeted over 600,000 times in the first three hours in which it posted, Trump announced both he and first lady Melania Trump have tested positive for COVID-19, the disease he has publicly downplayed since the start of the pandemic and which has now killed over 207,000 people in the U.S. “@FLOTUS and I tested positive for COVID-19. We will begin our quarantine and recovery process immediately. We will get through this TOGETHER!” he tweeted. The potential ramifications to this are many: At the very least, Trump will be required to temporarily halt his campaign while he quarantines, and will miss the next presidential debate, planned for October 15. Longer term, should the President exhibit symptoms, under the 25th Amendment he would have the option to transfer power to Vice President Mike Pence while he recovers.
The coronavirus disease (COVID-19) pandemic has crippled the United States, halting normal social and economic activities and overstretching the health system. As of June 12, 2020, the United States had over 2 million cases and 113,900 deaths. For historically disadvantaged populations, who experience fractured access to health care under standard conditions and who are more dependent on low-wage or hourly paid employment, the pandemic has had a disproportionate impact. Reports from state and city health departments have illuminated what many already knew: Black, Latinx, and Native Americans test positive for and die of COVID-19 at higher proportion than other racial and ethnic groups. In part as a consequence of the increased prevalence of COVID-19 in minority populations, the mortality rates among Black, Latinx, and Native Americans far exceeds the proportion of the population that these groups represent. As health-disparity researchers and educators and critical care and pulmonary providers on the front line caring for these patients, we believe it is imperative to report on the root causes that have led to these sobering statistics. Applying the World Health Organization Conceptual Framework for Action on Social Determinants of Health, we also identify potential avenues for policy action. This framework differentiates how the socioeconomic and political contexts manifest broadly as structural determinants, which shape exposure to intermediary social determinants, including healthcare access, that ultimately create an individual’s unique social circumstances that shape behavior and risk for disease. For this Perspective, we focus on action steps that we, as members of the American Thoracic Society (ATS), should take to actively change the status quo and influence policies that address root causes.
Currently, no clinical studies have compared the inspiratory and expiratory volumes of unilateral lung or of each lobe among supine, standing, and sitting positions. In this prospective study, 100 asymptomatic volunteers underwent both low-radiation-dose conventional (supine position, with arms raised) and upright computed tomography (CT) (standing and sitting positions, with arms down) during inspiration and expiration breath-holds and pulmonary function test (PFT) on the same day. We compared the inspiratory/expiratory lung/lobe volumes on CT in the three positions. The inspiratory and expiratory bilateral upper and lower lobe and lung volumes were significantly higher in the standing/sitting positions than in the supine position (5.3–14.7% increases, all P < 0.001). However, the inspiratory right middle lobe volume remained similar in the three positions (all P > 0.15); the expiratory right middle lobe volume was significantly lower in the standing/sitting positions (16.3/14.1% decrease) than in the supine position (both P < 0.0001). The Pearson’s correlation coefficients (r) used to compare the total lung volumes on inspiratory CT in the supine/standing/sitting positions and the total lung capacity on PFT were 0.83/0.93/0.95, respectively. The r values comparing the total lung volumes on expiratory CT in the supine/standing/sitting positions and the functional residual capacity on PFT were 0.83/0.85/0.82, respectively. The r values comparing the total lung volume changes from expiration to inspiration on CT in the supine/standing/sitting positions and the inspiratory capacity on PFT were 0.53/0.62/0.65, respectively.
The pandemic COVID-19 abruptly exploded, taking most health professionals around the world unprepared. Italy, the first European country to be hit violently, was forced to activate the lockdown in mid-February 2020. At the time of the spread, a high number of victims were quickly registered, especially in the regions of Northern Italy which have a high rate of highly-polluting production activities. The need to hospitalize the large number of patients with severe forms of COVID-19 led the National Health System to move a large number of specialists from their disciplines to the emergency hospital departments for the treatment of COVID-19. Furthermore, the lockdown itself has limited the possibility for general practitioners and pediatricians to be able to make outpatient visits and/or home care for patients with chronic diseases. Among them, the patient with atopic diseases, such as asthma, rhinitis and atopic dermatitis, is worthy of particular attention as she/he is immersed in a studded negative scenario with the onset of spring, a factor that should not be underestimated for those who suffer from pollen allergy. The Italian Society of Asthma Allergology and Clinical Immunology, to quickly deal with the lack of references and specialist medical procedures, has produced a series of indications for immunologic patient care that are reported in this paper, and can be used as guidelines by specialists of our discipline.
We read with interest the recent article by Reynolds et al(1) describing the transcranial doppler bubble study findings in COVID-19 patients with ARDS. The authors conclude that pulmonary vascular dilatation may be present in COVID-19, analogous to the microvascular changes that occur in hepatopulmonary syndrome (HPS), as a contributory mechanism of hypoxemia in COVID-19 ARDS. Though the findings on bubble study are indisputable, we share several concerns with the conclusions in the article. The positive shunt study in severe COVID-19 indicates that abnormal arteriovenous communications open up in response to extensive small vessel occlusion, as the disease progresses. The findings fail to explain the initial severe hypoxemia in COVID-19 with preserved lung mechanics, as the degree of transpulmonary microbubble transit directly correlates with worsening lung compliance. The comparison with HPS is not appropriate due to the evidence against microcirculatory dilatation in COVID-19. To conclude, anatomical pulmonary shunts do not contribute significantly to hypoxemia in early atypical COVID-19 respiratory failure and the distinct clinical features are best explained by progressive pulmonary vascular occlusion and subsequent diffuse lung injury due to various natural (infarction and oxidative damage) and iatrogenic sequelae.
Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our knowledge, there is no effective pharmacologic prophylaxis for individuals at risk. The objective of the study was to evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy. This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants.
A study from the University of Pittsburgh School of Medicine and Cedars-Sinai addresses a mystery first raised in March: Why do some people with COVID-19 develop severe inflammation? The research shows how the molecular structure and sequence of the SARS-CoV-2 spike protein–part of the virus that causes COVID-19–could be behind the inflammatory syndrome cropping up in infected patients. The study, published this week in the Proceedings of the National Academy of Sciences, uses computational modeling to zero in on a part of the SARS-CoV-2 spike protein that may act as a “superantigen,” kicking the immune system into overdrive as in toxic shock syndrome–a rare, life-threatening complication of bacterial infections. Symptoms of a newly identified condition in pediatric COVID-19 patients, known as Multisystem Inflammatory Syndrome in Children (MIS-C), include persistent fever and severe inflammation that can affect a host of bodily systems. While rare, the syndrome can be serious or even fatal. The first reports of this condition coming out of Europe caught the attention of study co-senior author Moshe Arditi, M.D., director of the Pediatric Infectious Diseases and Immunology Division at Cedars-Sinai and an expert on another pediatric inflammatory disease–Kawasaki disease. The investigator’s labs are now using the ideas generated by this study to search for and test antibodies specific to the SARS-CoV-2 superantigen, with the goal of developing therapies that specifically address MIS-C and cytokine storm in COVID-19 patients.
In patients hospitalized with coronavirus disease 2019 (COVID-19), thrombi in segmental pulmonary arteries are common and are located in opacitated lung segments, which may suggest local clot formation, according to the results of a retrospective study published in Respiratory Medicine. Respiratory failure is a common complication in hospitalized patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is frequently complicated by pulmonary embolism in segmental pulmonary arteries. The distribution of pulmonary embolism with regard to lung parenchymal opacifications has not been investigated; therefore, researchers in Germany investigated whether pulmonary embolism manifestations are limited to lung segments affected by COVID-19-pneumonia. Of 22 patients with severe COVID-19 treated between March 8 and April 15, 2020 in the hospital intensive care unit (ICU), 16 (age, 60.4±10.2 years) underwent computed tomography (CT) and a total of 288 lung segments were analyzed. Thrombi were detectable in 56.3% (9 of 16) patients with 4.4±2.9 segments occluded per patient, and 13.9% (40 of 288) segments were affected in the whole cohort. The researchers noted that patients with thrombi had significantly worse segmental opacifications on CT (P <.05) and that all thrombi were located in opacitated segments. There was no correlation between D-dimer level and number of occluded segmental arteries.
Severe COVID-19 is characterized by excessive inflammation of the lower airways. The balance of protective versus pathological immune responses in COVID-19 is incompletely understood. Mucosa-associated invariant T (MAIT) cells are antimicrobial T cells that recognize bacterial metabolites, and can also function as innate-like sensors and mediators of antiviral responses. Here, we investigated the MAIT cell compartment in COVID-19 patients with moderate and severe disease, as well as in convalescence. We show profound and preferential decline in MAIT cells in the circulation of patients with active disease paired with strong activation. Furthermore, transcriptomic analyses indicated significant MAIT cell enrichment and pro-inflammatory IL-17A bias in the airways. Unsupervised analysis identified MAIT cell CD69high and CXCR3low immunotypes associated with poor clinical outcome. MAIT cell levels normalized in the convalescent phase, consistent with dynamic recruitment to the tissues and later release back into the circulation when disease is resolved. These findings indicate that MAIT cells are engaged in the immune response against SARS-CoV-2 and suggest their possible involvement in COVID-19 immunopathogenesis.
Two dozen states are reporting an increase in new daily coronavirus infections, including several states that are breaking record numbers. Cases mostly trended downward throughout August and most of September after major peaks in July, and now the numbers are moving back up again. Overall, the U.S. reported more than 55,000 new cases on Friday, and the total tally pushed above 7 million this week. The national 7-day average is also increasing, according to NPR. In Wisconsin, more than 2,800 new cases were reported on Saturday, marking a new record and breaking the previous high of 2,500 cases on Sept. 18, according to Fox 11 in Madison. More than 2,000 cases were reported three days in a row. In New York, daily cases passed 1,000 on Saturday for the first time since June 5, according to Bloomberg News. South Dakota also reported its highest daily total on Saturday with more than 500 new cases. North Dakota, Utah, and Montana set records as well. New Hampshire reported its first coronavirus-related death in 11 days on Saturday, which was associated with a long-term care facility, according to WMUR. The state reported 38 new cases, and health officials say community-based transmission is happening in every county. Public health officials expect cases to increase even more throughout the fall, and state leaders are urging people to continue measures to slow the spread of the virus. “Continue to practice the basic behaviors that drive our ability to fight COVID-19 as we move into the fall and flu season,” New York Gov. Andrew Cuomo said in a Saturday update. “Wearing masks, socially distancing and washing hands make a critical difference.”
The newly described severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is responsible for a pandemic (Corona virus-induced disease -19, COVID-19). It is now well established that certain comorbidities define high risk patients. They include hypertension, diabetes, and coronary artery disease. In contrast, the context with bronchial asthma is controversial and shows marked regional differences. Since asthma is the most prevalent chronic inflammatory lung disease worldwide and SARS-CoV-2 primarily affects the upper and lower airways leading to marked inflammation, the question arises about the possible clinical and pathophysiological association between asthma and SARS-CoV-2/COVID-19. Here we analyze the global epidemiology of asthma among COVID-19 patients and propose the concept that patients suffering from different asthma endotypes (type 2 asthma versus non-type 2 asthma) present with a different risk profile in terms of SARS-CoV-2 infection, development of COVID-19 and progression to severe COVID-19 outcomes. This concept may have important implications for future COVID-19 diagnostics and immune-based therapy developments.
Early stages of the novel coronavirus disease (COVID-19) are associated with silent hypoxia and poor oxygenation despite relatively minor parenchymal involvement. Although speculated that such paradoxical findings may be explained by impaired hypoxic pulmonary vasoconstriction in infected lung regions, no studies have determined whether such extreme degrees of perfusion redistribution are physiologically plausible, and increasing attention is directed towards thrombotic microembolism as the underlying cause of hypoxemia. Herein, a mathematical model demonstrates that the large amount of pulmonary venous admixture observed in patients with early COVID-19 can be reasonably explained by a combination of pulmonary embolism, ventilation-perfusion mismatching in the noninjured lung, and normal perfusion of the relatively small fraction of injured lung. Although underlying perfusion heterogeneity exacerbates existing shunt and ventilation-perfusion mismatch in the model, the reported hypoxemia severity in early COVID-19 patients is not replicated without either extensive perfusion defects, severe ventilation-perfusion mismatch, or hyperperfusion of nonoxygenated regions.
Most patients who require extracorporeal membrane oxygenation (ECMO) for severe COVID-19 survive, according to an international registry. Estimated 90-day in-hospital mortality was 37.4%, and mortality among those who completed their hospitalization (final disposition of death or discharge) was 39%. “These data from 213 hospitals worldwide provide a generalizable estimate of ECMO mortality in the setting of COVID-19,” wrote Ryan Barbaro, MD, of the University of Michigan in Ann Arbor, and colleagues reporting the findings in The Lancet. The data were also presented at the virtual Extracorporeal Life Support Organization meeting. Early reports of ECMO use in COVID-19 suggested that mortality could be greater than 90%, leading some to recommend withholding it, the group noted. More recent reports have suggested higher success rates, albeit with small numbers. “Considering the severity of hypoxemia in patients requiring ECMO, I’m intrigued by noting that at least 40% (if probably not more) had some reasonable recovery,” commented Behnood Bikdeli, MD, of Brigham and Women’s Hospital and Harvard in Boston. The findings were “consistent with previously reported survival rates in acute hypoxaemic respiratory failure, supporting current recommendations that centres experienced in ECMO should consider its use in refractory COVID-19-related respiratory failure,” the researchers concluded.
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has been spread worldwide. Because it brought so much damage and negative effects, the World Health Organization (WHO) declared the outbreak a public health emergency of international concern on January 31, 2020. This disease has progressed rapidly, and patients who are in the severe stage could develop acute respiratory distress syndrome, sepsis, and even multiple organ dysfunction syndrome in just a short time. Severe cases had unfavorable outcomes according to the latest epidemiological statistics, which means that early identification and intervention for severe patients were very important, especially because no effective treatment has been made yet directly targeting at SARS-CoV-2. So, we collected and compared data of healthy people and laboratory-confirmed SARS-CoV-2 infected patients. The aim of this study was to know the clinical characteristics of COVID-19 and then identify the independent risk factors related to disease severity and so help clinicians distinguish severe cases by using clinical data in the early stage.
[Letter to Editor] We read great interest in the risk factors of critical or mortal COVID-19 cases, recently reported by Ye, et al in this journal. Here we paid more attention about the long-term lung sequelae among survivors of severe COVID-19. With more than 21 million people worldwide recovered from COVID-19, early analysis suggested a high rate of patients had residual abnormal lung function and fibrotic remodeling on CT, especially in survivors of severe SARS-CoV-2 associated pneumonia. These might contribute to long-term impairment of lung function or even lung transplants. The early identification of patients at higher risk of lung injury and fibrotic damage is critical. Therefore, we performed an observational cohort study that compared fibrosis and non-fibrosis group to investigate the potential indicators for post-fibrosis. The two-center retrospective study was approved by the institutional review board, and a total of 430 consecutive patients with positive RT-PCR were reviewed. Finally 81 survivors who recovered from severe COVID-19 pneumonia were enrolled. The median hospitalization was 26 days; all had at least three follow-up CT scans after discharge, and the median period between the discharge and the latest CT scan was 58 days (IQR: 25-46). Pulmonary fibrosis was diagnosed based on the extensive and persistent fibrotic changes, including parenchymal bands, irregular interfaces, reticular opacities, and traction bronchiectasis with or without honeycombing on the follow-up CT scans.
Prone positioning is one of the few interventions in acute respiratory distress syndrome (ARDS) which has a proven mortality reduction. Due to the coronavirus disease 2019 (COVID-19) pandemic, severe ARDS cases have sharply increased worldwide, increasing the need for proning. Some centers have also encouraged non-intubated patients with hypoxemia due to COVID-19 to self-prone. Although generally considered low risk, pressure-related complications can occur during proning and differ from those that occur in supine patients. We present two cases of COVID-19-associated ARDS treated with prone positioning who developed meralgia paresthetica that was diagnosed in our ICU recovery clinic. Meralgia paresthetica (MP) results from compression injury of the lateral femoral cutaneous nerve between the anterior superior iliac spine and the inguinal ligament; this mononeuropathy results in sensory abnormalities in the anterolateral thigh. To our knowledge, there is only one other reported case of MP in prone positioning for ARDS, although it has been reported after surgical prone positioning in up to 24% of cases. “Identifying otherwise unseen targets for ICU quality improvement” has been postulated as one way that ICU recovery clinics might improve care, yet there are few published examples. If these patients returned to their primary care physicians, it is less likely that the cause of the MP would be known, nor would practice change. Lessons like these show the potential value of ICU recovery clinics, not only in treating post-intensive care syndrome, but in changing its underlying causes.
Respiratory outcomes were better, but 20-person trial far from conclusive. Therapeutic-level dosing of enoxaparin (Lovenox) improved respiratory outcomes in severe COVID-19, a pilot randomized trial showed. Gas exchange measured by the PaO2/FiO2 ratio improved significantly over time in the 10-patient therapeutic group (from 163 at baseline to 209 at 7 days and 261 at 14 days, P=0.0004) but not in the 10-patient control group receiving lower prophylactic-level doses in the open-label study (184, 168, and 195, respectively, P=0.487). Compared with prophylactic dosing of the drug, therapeutic dosing also led to four-fold more patients being weaned off of mechanical ventilation (P=0.031) and more ventilator-free days (15 vs 0 days, P=0.028), Carlos Henrique Miranda, MD, PhD, of São Paulo University in Brazil, and colleagues reported in Thrombosis Research. “It’s a remarkable step forward in the sense that now for the first time we are having randomized trial data related to antithrombotic therapy for COVID-19,” commented Behnood Bikdeli, MD, of Brigham and Women’s Hospital and Harvard in Boston. While the study couldn’t address the mechanism, “hypothetically, it’s reducing the risk and/or severity of macrothrombi and microthrombi in the lung,” he told MedPage Today.
[Video] Anthony S. Fauci, MD, returns to JAMA’s Q&A series to discuss the latest developments in the COVID-19 pandemic, hosted by Howard Bauchner, MD, Editor in Chief, JAMA.
Early descriptions of patients admitted to hospital during the COVID-19 pandemic showed a lower prevalence of asthma and chronic obstructive pulmonary disease (COPD) than would be expected for an acute respiratory disease like COVID-19, leading to speculation that inhaled corticosteroids (ICSs) might protect against infection with severe acute respiratory syndrome coronavirus 2 or the development of serious sequelae. We assessed the association between ICS and COVID-19-related death among people with COPD or asthma using linked electronic health records (EHRs) in England, UK. In this observational study, we analysed patient-level data for people with COPD or asthma from primary care EHRs linked with death data from the Office of National Statistics using the OpenSAFELY platform. For the COPD cohort, individuals were eligible if they were aged 35 years or older, had COPD, were a current or former smoker, and were prescribed an ICS or long-acting β agonist plus long-acting muscarinic antagonist (LABA–LAMA) as combination therapy within the 4 months before the index date. For the asthma cohort, individuals were eligible if they were aged 18 years or older, had been diagnosed with asthma within 3 years of the index date, and were prescribed an ICS or short-acting β agonist (SABA) only within the 4 months before the index date. We compared the outcome of COVID-19-related death between people prescribed an ICS and those prescribed alternative respiratory medications.
The COVID-19 pandemic has demonstrated significantly worse outcomes for Minority (Black and Hispanic) individuals. Understanding the reasons for COVID-19-related disparities among asthma patients has important public health implications. The objective of this survey was to determine factors contributing to health disparities in those with asthma during the COVID-19 pandemic. The anonymous survey was sent through social media to adult patients with asthma, and a separate survey was sent to physicians who provide asthma care. The patient survey addressed demographic information including socioeconomic status (SES), asthma control, and attitudes/health behaviors during COVID-19. A total of 1171 patients (10.1% Minority individuals) and 225 physicians completed the survey. Minority patients were more likely to have been affected by COVID-19 (e.g., became unemployed, lived in a community with high COVID-19 cases). They had worse asthma control (increased emergency visits for asthma, lower ACT score), were more likely to live in urban areas, and had a lower household income. Initial differences in attitudes and health behaviors disappeared after controlling for baseline demographic features. Institutional racism was demonstrated by findings that Minority individuals were less likely to have a primary care physician, had more trouble affording asthma medications due to COVID-19, were more likely to have lost health insurance due to COVID-19, and that 25% of physicians found it more challenging to care for Black individuals with asthma during COVID-19.
Genentech announced that a phase 3 study assessing tocilizumab (Actemra®) plus standard of care for the treatment of hospitalized adults with coronavirus disease 2019 (COVID-19) associated pneumonia met its primary end point. The multicenter, randomized, double-blind, placebo-controlled EMPACTA study included hospitalized COVID-19 patients with oxygen saturation less than 94% while on ambient air who did not require noninvasive or invasive mechanical ventilation. Patients were randomized to receive 1 intravenous infusion of tocilizumab or placebo plus standard of care, and could be given up to 1 additional infusion. The primary end point was the cumulative proportion of patients dying or requiring mechanical ventilation by day 28. Results showed that patients treated with tocilizumab were 44% less likely to progress to mechanical ventilation or death compared with placebo (hazard ratio [HR] 0.56; 95% CI, 0.32-0.97; log-rank P =.0348). The cumulative proportion of patients who progressed to mechanical ventilation or death by day 28 was 12.2% in the tocilizumab arm compared with 19.3% in the placebo arm.
A standard test that evaluates blood cells can help identify patients hospitalized with COVID-19 who are at an elevated risk for death, according to research published in JAMA Network Open. “We were surprised to find that one standard test that quantifies the variation in size of red blood cells — called red cell distribution width, or RDW — was highly correlated with patient mortality, and the correlation persisted when controlling for other identified risk factors like patient age, some other lab tests, and some pre-existing illnesses,” Jonathan Carlson, MD, PhD, an instructor in medicine at Massachusetts General Hospital, said in a press release. In their cohort study, Carlson and colleagues retrospectively analyzed adult patients with SARS-CoV-2 infection who were admitted to one of four participating hospitals in the Boston area from March 4 through April 28. As part of standard critical care, all patients had their RDW, absolute lymphocyte count and dimerized plasmin fragment D levels collected daily. According to the researchers, RDW reflects cellular volume variation, and elevated RDW (more than 14.5%) has previously been associated with an increased risk for morbidity and mortality in a variety of diseases, including heart disease, pulmonary diseases, influenza, cancer and sepsis. A total of 1,641 patients were included in the analyses. The final discharge among these patients was June 26, and there were no COVID-19-related readmissions through July 25.
Identifying independent risk factors for adverse outcomes in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can support prognostication, resource utilization, and treatment. The objective of this study was to identify excess risk and risk factors associated with hospitalization, mechanical ventilation, and mortality in patients with SARS-CoV-2 infection. In this national cohort study of 88 747 veterans tested for SARS-CoV-2, hospitalization, mechanical ventilation, and mortality were significantly higher in patients with positive SARS-CoV-2 test results than among those with negative test results. Significant risk factors for mortality included older age, high regional coronavirus disease 2019 burden, higher Charlson Comorbidity Index score, fever, dyspnea, and abnormal results in many routine laboratory tests; however, obesity, Black race, Hispanic ethnicity, chronic obstructive pulmonary disease, hypertension, and smoking were not associated with mortality.
Just over 6 months after the World Health Organization declared COVID-19 a pandemic, the United States has reached a grim milestone: the novel coronavirus death toll has climbed to a staggering 200,000. “It’s sobering. It’s a large number, and clearly it tells us that everything we’re doing right now to contain it needs to continue,” says Erica Shenoy, MD, associate chief of the Infection Control Unit at Massachusetts General Hospital. “Especially heading into the fall, where we don’t know if there will be a second surge, or if this will be compounded by other respiratory illnesses.” Doctors and scientists say the number sends a clear message: Although people are itching to return to pre-pandemic life, Americans should continue to wear masks, practice hand-washing hygiene, and keep physical distance from others. While the high death toll is a bleak glimpse into how severe the illness is, there are two silver linings: The numbers seem to be trending in the right direction, and researchers have had time to discover more about a virus that at first baffled even the world’s leading scientists.
Pneumothorax is being reported as a complication of COVID-19, and has higher incidence among men and lower survival among older patients, according to a study published online Sept. 9 in the European Respiratory Journal. Anthony W. Martinelli, Ph.D., from Addenbrooke’s Hospital in Cambridge, England, and colleagues retrospectively collected cases from U.K. hospitals limited to patients with a diagnosis of COVID-19 and presence of pneumothorax or pneumomediastinum. Data were included for 71 patients, 60 of whom had pneumothoraces (six with pneumomediastinum) and 11 had pneumomediastinum alone. Two of the patients with pneumomediastinum alone had distinct episodes of pneumothorax, resulting in a total of 62 pneumothoraces. The researchers observed no difference in survival at 28 days following pneumothorax or isolated pneumomediastinum (63.1 ± 6.5 percent and 53.0 ± 18.7 percent, respectively). Men had higher incidence of pneumothorax. Survival at 28 days did not differ for men versus women (62.5 ± 7.7 percent versus 68.4 ± 10.7 percent). Compared with younger patients, those aged 70 years and older had significantly lower 28-day survival (41.7 ± 13.5 percent versus 70.9 ± 6.8 percent survival).
Members of the CDC’s Advisory Committee on Immunization Practices (ACIP) meeting Tuesday appeared to agree that healthcare workers should be first in line to receive a COVID-19 vaccine when one is approved, followed by some combination of essential workers, those with high-risk medical conditions, and older adults. However, with no formal vote taken — that won’t happen until one or more vaccines are authorized or approved by the FDA for clinical use — it’s not yet official policy, and not much was settled about priorities for later rounds of immunizations. ACIP chair José Romero, MD, said once data is available from phase III clinical trials, an ACIP work group will conduct an independent review of its safety and efficacy. “If and when the FDA authorizes or approves vaccines, ACIP will have an emergency meeting and then vote on recommendations and populations for use,” he said.
Low-dose hydrocortisone was not associated with a significant reduction in death or need for persistent respiratory support by day 21 of treatment compared with placebo in critically ill patients with coronavirus disease 2019 (COVID-19), according to study results published in the Journal of the American Medical Association. A total of 149 patients (mean age, 62.2 years) admitted to the intensive care unit (ICU) for COVID-19-related acute respiratory failure from March 7 to June 1, 2020, were recruited into this French multicenter, randomized double-blind trial. Last available follow-up data were for June 29, 2020. Researchers planned to enroll up to 290 patients, but recommendations from the data and safety monitoring board resulted in early termination of the study. Approximately 81.2% of patients in this cohort were mechanically ventilated. Patients were randomly assigned to either continuous infusion of low-dose hydrocortisone (n=76) or placebo (n=73). The initial dose of hydrocortisone was 200 mg/d and continued at this dose until day 7, after which the dose was decreased to 100 mg/d for 4 days and 50 mg/d for 3 days. A short treatment regimen comprising 200 mg/d for 4 days, followed by 100 mg/d for 2 days and then 50 mg/d for the next 2 days was administered if the patient’s respiratory and generally status sufficiently improved by 4 days of treatment.
A new review article from Beth Israel Deaconess Medical Center (BIDMC) shows people who are biologically male are dying from COVID-19 at a higher rate than people who are biologically female. In a review published in Frontiers in Immunology, researcher-clinicians at BIDMC explore the sex-based physiological differences that may affect risk and susceptibility to COVID-19, the course and clinical outcomes of the disease and response to vaccines. “The COVID-19 pandemic has revealed a striking gender bias with increased mortality rates in men compared with women across the lifespan,” said corresponding author Vaishali R. Moulton, MD, PhD, an assistant professor of medicine in the Division of Rheumatology and Clinical Immunology at BIDMC. “Apart from behavioral and lifestyle factors that differ between men and women, sex chromosome-linked genes, sex hormones and the microbiome control aspects of the immune responses to infection and are potentially important biological contributors to the sex-based differences we’re seeing in men and women in the context of COVID-19.”
COVID-19 is spread most often through respiratory droplets or aerosols and little evidence exists supporting transmission through surfaces. As such, social distance and proper ventilation are key determinants of transmission risk. Findings from a review of published research, articles, and reports is published in Annals of Internal Medicine. Researchers from Montefiore Medical Center, Hospital of the University of Pennsylvania, Massachusetts General Hospital, Harvard Medical School, and Brigham and Women’s Hospital studied scientific articles published between January and September 2020, as well as relevant articles and institutional or governmental reports, to determine the viral, host, and environmental factors that contribute to transmission of COVID-19. They found that although several experimental studies suggest that virus particles could live for hours after inoculation in aerosols or on surfaces, the real-world studies that detect viral RNA in the environment report very low levels on surfaces, and few have isolated viable virus. Strong evidence from case and cluster reports indicates that respiratory transmission is dominant, with proximity and ventilation being key determinants of transmission risk. In the few cases where direct contact or transmission from materials or surfaces was presumed, respiratory transmission could still not be ruled out.
In December 2019, an outbreak of severe acute respiratory syndrome associated to SARS-CoV2 was reported in Wuhan, China. To date, little is known on histopathological findings in patients infected with the new SARS-CoV2. Lung histopathology shows features of acute and organising diffuse alveolar damage. Subtle cellular inflammatory infiltrate has been found in line with the cytokine storm theory. Medium-size vessel thrombi were frequent, but capillary thrombi were not present. Despite the elevation of biochemical markers of cardiac injury, little histopathological damage could be confirmed. Viral RNA from paraffin sections was detected at least in one organ in 90% patients. Novel coronavirus-associated disease (COVID-19) was first detected in Spain on 31 January 2020, with more than 204 178 cases subsequently identified in 3 months. Severe COVID-19 is associated with high circulating levels of inflammatory cytokines akin to a cytokine release syndrome that frequently results in respiratory failure. To date, scant histopathological information of infected patients is available. Few descriptions of histopathological findings have mainly reported pneumonitis and diffuse alveolar damage (DAD). To advance in the knowledge of COVID-19-associated tissue damage is important to understand the mechanisms of damage caused by SARS-COV-2. Postmortem multiorgan biopsies in 10 patients who died with SARS COV-2 infection were performed after oral authorisation of a first-degree relative. Biopsies were obtained without ultrasound guidance with the patient‘s corpse still on the hospital bed.
Point-of-care lung ultrasound (LUS) is a promising pragmatic risk stratification tool in COVID-19. This study describes and compares LUS characteristics between patients with different clinical outcomes. This prospective observational study included PCR-confirmed COVID-19 adults with symptoms of lower respiratory tract infection presenting in the emergency department (ED) of Lausanne University Hospital. A trained physician recorded LUS images using a standardized protocol. Two experts reviewed images blinded to patient outcome. We describe and compare early LUS findings (acquired within 24hours of presentation to the ED) between patient groups based on their outcome at 7 days after inclusion: 1) outpatients, 2) hospitalised and 3) intubated/death. Normalized LUS score was used to discriminate between groups. We included 80 patients (17 outpatients, 42 hospitalized and 21 intubated/dead). 73 patients (91%) had abnormal LUS (70% outpatients, 95% hospitalised and 100% intubated/death; p=0.003). The proportion of involved zones was lower in outpatients compared with other groups (median 30% [IQR 0-40%], 44% [31-70%] and 70% [50-88%], p<0.001). Predominant abnormal patterns were bilateral and multifocal spread thickening of the pleura with pleural line irregularities (70%), confluent B lines (60%) and pathologic B lines (50%). Posterior inferior zones were more often affected. Median normalized LUS score had a good level of discrimination between outpatients and others with area under the ROC of 0.80 (95% CI 0.68-0.92).
The Health and Human Services (HHS) department on Wednesday unveiled general outlines for how the first COVID-19 vaccine doses will be shipped and administered. Developed with the Department of Defense (DOD), the four-part strategy addresses engagement with state and local partners and other stakeholders; distribution under a “phased allocation methodology” still to be developed; safe vaccine administration and availability of auxiliary supplies; and data gathering via information technology to track distribution and administration. The strategy gives January 2021 as the target to begin distribution of an FDA-approved or authorized vaccine. Also released Wednesday was a COVID-19 Vaccination Program Interim Playbook from the CDC to assist local, state, tribal and territorial partners in rolling out their COVID-19 vaccination programs. The playbook identifies healthcare personnel and other essential workers as among the “critical populations,” although final decisions remain to be made by the CDC’s Advisory Committee on Immunization Practices.
Among patients hospitalized for COVID-19 in the United States, male sex, age 60 years and older, obesity, chronic kidney disease, cardiovascular disease and living in the Northeast were associated with an increased risk for mechanical ventilation, data show. The findings, published in Clinical Infectious Diseases, also indicated that the same characteristics, except for obesity, were linked to an increased risk for mortality. “This was the first attempt to try and get a broader sense of the risk factors for adverse outcome and how they interacted with one another in a much more specific manner,” Robert S. Brown, Jr., MD, MPH, clinical chief of the division of gastroenterology and hepatology at Weill Cornell Medicine Center, told Healio Primary Care. Researchers reviewed data from 11,721 patients with COVID-19 who were admitted to 245 hospitals across 38 states between Feb. 15 and April 20. Among all patients, 48 received remdesivir (Gilead) and 4,232 received hydroxychloroquine. Researchers also identified a benefit to early mechanical ventilation vs. later mechanical ventilation, suggesting that perhaps there should be a lower threshold for initiating mechanical ventilation. However, this last point is very case specific and should be based on a physician’s observations, not the findings of a descriptive study.
With overlapping signs and symptoms, surveillance, testing more important than ever. When a patient presents with acute respiratory symptoms this fall, clinicians should consider three options: influenza, COVID-19, or co-infection, CDC experts said. And given the likelihood that influenza and SARS-CoV-2 will be co-circulating in the community, clinicians should pay special attention to local surveillance data about each virus. On a CDC Clinician Outreach and Communication Activity call, CDC officials reminded clinicians that not only do influenza and COVID-19 have overlapping signs and symptoms, but co-infection with both has been documented in both case reports and case series. Co-infection, or even distinguishing SARS-CoV-2 from influenza, is particularly important because of the implications of treatment. For example, Uyeki noted that dexamethasone is recommended for severe COVID-19 infection in hospitalized patients, but corticosteroids actually prolong viral replication in influenza. Testing then becomes key in distinguishing the viruses, and Uyeki said that, as noted by Department of Health and Human Services officials, there are several kinds of “multiplex” assays that received FDA emergency use authorization (EUA), including some that received EUAs “this week,” he added.
Interventions to prevent SARS-CoV-2 transmission have led to a global decline in influenza during the COVID-19 pandemic, researchers reported in MMWR. In addition to causing a significant drop in the percentage of respiratory specimens that tested positive for influenza in the early days of the pandemic in the United States, measures such as mask wearing, social distancing, school closures and telework have kept positive tests at “historically low interseasonal levels,” the researchers said. The Southern Hemisphere has experienced a similar effect. If the measures continue through the fall, the influenza season in the U.S. “might be blunted or delayed,” according to the report. “The global decline in influenza virus circulation appears to be real and concurrent with the COVID-19 pandemic and its associated community mitigation measures,” Sonja J. Olsen, PhD, an epidemiologist in the CDC’s Influenza Division, and colleagues wrote. Olsen and colleagues reviewed data from around 300 U.S. laboratories in all 50 states, Puerto Rico, Guam and the District of Columbia. They also analyzed influenza laboratory data from surveillance platforms in Australia, Chile and South Africa to determine viral activity in the Southern Hemisphere.
Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood. The objective here, was to define the cytokine profile ofCOVID-19 and to identify evidence of immunometabolic alterations in those with severe illness. Levels of IL-1b, IL-6, IL-8, IL-10, and sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed in plasma from healthy volunteers, hospitalized but stable patients with COVID-19 (COVID stable patients), patients with COVID-19 requiring ICU admission (COVIDICU patients), and patients with severe community acquired pneumonia requiring ICU support (CAPICU patients). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of AAT (alpha-1 antitrypsin) to COVID-19 was also evaluated. Measurements and Main Results: IL-1b, IL-6, IL-8, and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVID stable patients, and demonstrated higher levels of IL-1b, IL-6, and sTNFR1 but lower IL-10 than CAPICU patients. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, HIF-1a (hypoxia-inducible factor1a), and lactate. The production and sialylation of AAT increased in COVID-19, but this antiinflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P , 0.0001). In critically unwell patients with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6:AAT was associated with clinical resolution (P , 0.0001).
Patients who have long-term effects for weeks or months after they contract the coronavirus may see improvements in their lung function after 12 weeks, according to a new study. The study, which tracked 86 COVID-19 “long-haulers” in Austria, was presented at the European Respiratory Society International Congress last week. “The bad news is that people show lung impairment from COVID-19 weeks after discharge. The good news is that the impairment tends to ameliorate over time, which suggests the lungs have a mechanism for repairing themselves,” Sabina Sahanic, one of the study authors and a PhD student at the University Clinic in Innsbruck, said in a statement. The research team evaluated the patients between April and June at the 6-week and 12-week points after being released from a hospital. At 6 weeks, about 88% had observable lung damage on CT scans. In addition, 47% had trouble with breathing and 15% had a persistent cough. At 12 weeks, about 56% had lung damage, 39% had trouble with breathing, and the persistent cough remained about the same. CT scans also showed that lung damage severity decreased by the 12-week mark. The damage, which occurs from inflammation and fluid in the lungs, shows up on scans as white patches known as “ground glass.” At 6 weeks, the patches showed up in nearly all of the patients, and by 12 weeks, was observable in about half of the patients. Tests showed an improvement in lung function, too. At 6 weeks, about 28% of patients had less than 80% of normal functioning, but at 12 weeks, that dropped to 19%. The 24-week checkup is underway now.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new human disease with few effective treatments. Convalescent plasma, donated by persons who have recovered from COVID-19, is the acellular component of blood that contains antibodies, including those that specifically recognize SARS-CoV-2. These antibodies, when transfused into patients infected with SARS-CoV-2, are thought to exert an antiviral effect, suppressing virus replication before patients have mounted their own humoral immune responses. Virus-specific antibodies from recovered persons are often the first available therapy for an emerging infectious disease, a stopgap treatment while new antivirals and vaccines are being developed. This retrospective, propensity score–matched case–control study assessed the effectiveness of convalescent plasma therapy in 39 patients with severe or life-threatening COVID-19 at The Mount Sinai Hospital in New York City. Oxygen requirements on day 14 after transfusion worsened in 17.9% of plasma recipients versus 28.2% of propensity score–matched controls who were hospitalized with COVID-19 (adjusted odds ratio (OR), 0.86; 95% confidence interval (CI), 0.75–0.98; chi-square test P value = 0.025). Survival also improved in plasma recipients (adjusted hazard ratio (HR), 0.34; 95% CI, 0.13–0.89; chi-square test P = 0.027).
In the early months of the COVID-19 pandemic, doctors struggled to keep patients breathing, and focused mainly on treating damage to the lungs and circulatory system. But even then, evidence for neurological effects was accumulating. Some people hospitalized with COVID-19 were experiencing delirium: they were confused, disorientated and agitated. In April, a group in Japan published the first report of someone with COVID-19 who had swelling and inflammation in brain tissues. Another report described a patient with deterioration of myelin, a fatty coating that protects neurons and is irreversibly damaged in neurodegenerative diseases such as multiple sclerosis. “The neurological symptoms are only becoming more and more scary,” says Alysson Muotri, a neuroscientist at the University of California, San Diego, in La Jolla. The list now includes stroke, brain haemorrhage and memory loss. It is not unheard of for serious diseases to cause such effects, but the scale of the COVID-19 pandemic means that thousands or even tens of thousands of people could already have these symptoms, and some might be facing lifelong problems as a result. Yet researchers are struggling to answer key questions — including basic ones, such as how many people have these conditions, and who is at risk. Most importantly, they want to know why these particular symptoms are showing up.
The COVID-19 pandemic has triggered precipitous entry of multiple novel therapeutic candidates into clinical trials often without control groups, randomisation, or adequate statistical power. To this long list can be added a re-purposing of existing therapeutic strategies used for other inflammatory or viral illnesses. Our still incomplete understanding of the COVID-19 disease process, including temporal change, has driven arguably inappropriate, ill-timed or ill-judged interventions, either within trials or compassionate use. Description of the ‘cytokine storm’ epithet to COVID-19 has driven the application of immunosuppressive therapies. At the time of writing, 47 registered RCTs were evaluating inhibition of interleukin-6 (IL-6), mostly recruiting on clinical criteria alone and without incorporating measurement of circulating IL-6 levels. Although circulating IL-6 levels are higher among COVID-19 non-survivors compared to survivors, circulating IL-6 levels in COVID-19 are often 1-2 log-orders lower than other causes of ARDS or viral influenza. While there may indeed be benefit from inhibiting IL-6, timing, dosing and patient selection are key. Outcome improvements in some subsets may be diluted or counterbalanced by lack of effect or harm in others. An acceptable toxicity profile for use in other inflammatory conditions does not necessarily translate to COVID-19, especially in the critically ill subset where both the severity of the disease process and multiple iatrogenic factors magnify immunosuppression and the risk of secondary nosocomial infection. A single dose of the IL-6 inhibitor, tociluzimab, can significantly dampen any C-reactive protein and temperature response for a week.
Nature, September 14, 2020
Months after infection with SARS-CoV-2, some people are still battling crushing fatigue, lung damage and other symptoms of ‘long COVID’. People with more severe infections might experience long-term damage not just in their lungs, but in their heart, immune system, brain and elsewhere. Evidence from previous coronavirus outbreaks, especially the severe acute respiratory syndrome (SARS) epidemic, suggests that these effects can last for years. And although in some cases the most severe infections also cause the worst long-term impacts, even mild cases can have life-changing effects — notably a lingering malaise similar to chronic fatigue syndrome. Many researchers are now launching follow-up studies of people who had been infected with SARS-CoV-2, the virus that causes COVID-19. Several of these focus on damage to specific organs or systems; others plan to track a range of effects. In the United Kingdom, the Post-Hospitalisation COVID-19 Study (PHOSP-COVID) aims to follow 10,000 patients for a year, analysing clinical factors such as blood tests and scans, and collecting data on biomarkers. A similar study of hundreds of people over 2 years launched in the United States at the end of July. What they find will be crucial in treating those with lasting symptoms and trying to prevent new infections from lingering.
Telehealth has helped immensely during the COVID-19 crisis. Insurance companies, although slow to approve payments, joined in to allow us to aid and interact with our patients and their families. How long this arrangement will last and how long they will waive coinsurance payments is a moving target. The AAP continues to discuss these matters with insurers. Rules have changed, confusion over which modifiers to use have been resolved and by now we are all familiar with telephone-only CPT codes 99441-3 and our old friends 99212-5 that we used for our “sick visits.” One thing has not changed, though — our fear to use 99214 and 99215, particularly when we cannot actually physically examine our patients. However, we can still use time as the main factor in choosing the proper code — 10 minutes for 99212, 15 minutes for 99213, 25 minutes for 99214 and 40 minutes for 99215. Remember, you must write down the time: For example, either 9:00 to 9:25, or 25 minutes (99214). On the other hand, do not forget that until Jan. 1, 2021, if you fulfill two-thirds of the key factors — history, physical examination and medical decision-making — you can still use 99214 with proper documentation.
Recently, a paper published in Science by Hadjadj et al. reported that type I interferon (IFN) deficiency, could be a hallmark of severe coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe COVID-19 was also associated with a lymphocytopenia, persistent blood viral load, and an exacerbated inflammatory response. These findings provide insights into the treatment of severe COVID-19 patients with type I IFN. The immunological features and mechanisms involved in COVID-19 severity are unclear. In order to test whether the severity disease can be caused by SARS-CoV-2 viral infection and hyperinflammation, Hadjadj et al. conducted a comprehensive immune analysis of grouped 50 COVID-19 patients with different disease severity. First, to identify whether the severe disease induced lymphocytopenia, Hadjadj et al. compared the peripheral blood leukocytes density of variously severe patients by combining mass cytometry with visualization of high-dimensional single-cell data based on t-distributed stochastic neighbor embedding. There is a significantly decreased density of NK cells and CD3+ T cells in severe and critical patients, while the density of B cells and monocytes was increased. The authors determined the functional status of specific T-cell subsets (CD4+/CD8+) and NK cells based on the expression of activation (CD38, HLA-DR) and exhaustion (PD-1, Tim-3) markers. They observed that the activated NK and CD4+/CD8+ T cells were increased in all infected patients, while the exhausted CD4+/CD8+ T cells and NK cells were increased in only severity patients. This result supported lymphocytopenia correlates with disease severity.
Since mechanical ventilators potentially expose the patient’s lungs to damage, all initiatives of constructing low-cost mechanical ventilators must provide the regulation of not only the lung’s pressure but also the positive end-expiratory pressure (PEEP). This paper shows the construction of a low-cost, open-source mechanical ventilator. The motivation for constructing this kind of ventilator comes from the worldwide shortage of mechanical ventilators for treating COVID-19 patients—the COVID-19 pandemic has been striking hard in some regions, especially the deprived ones. Constructing a low-cost, open-source mechanical ventilator aims to mitigate the effects of this shortage on those regions. The equipment documented here employs commercial spare parts only. This paper also shows a numerical method for monitoring the patients’ pulmonary condition. The method considers pressure measurements from the inspiratory limb and alerts clinicians in real-time whether the patient is under a healthy or unhealthy situation. Experiments carried out in the laboratory that had emulated healthy and unhealthy patients illustrate the potential benefits of the derived mechanical ventilator.
In the last week, questions have been raised about whether cytokine storm is indeed a culprit in severe COVID-19, while a paper from a government lab has made an intriguing and much-discussed case for a new mechanism, bradykinin storm. While the concepts are not necessarily mutually exclusive, scientists trying to understand how COVID-19 wreaks its damage on the human body have been buzzing about the new possibilities. The theory connects many of the disparate symptoms of COVID-19, from a loss of sense of smell and taste, to a gel-like substance forming in the lungs, and abnormal coagulation. It posits that SARS-CoV-2 disrupts both the renin-angiotensin system (RAS) and the kinin-kallikrein pathways, sending bradykinin — a peptide that dilates blood vessels and makes them leaky — out of whack. The process impedes the transfer of oxygen from the lung to the blood and subsequently to all other tissues, a common abnormality in COVID-19 patients. They found the COVID-19 cases had extremely high levels (increased nearly 200-fold) of angiotensin-converting enzyme 2 (ACE2), the surface protein used by the coronavirus to enter the cell. When the virus interacts with ACE2, it triggers an abnormal response in the bradykinin pathway, Jacobson said. At the same time, levels of angiotensin-converting enzyme, which is involved in the breakdown of bradykinin, were lower in COVID-19 patients than in controls.
Patients with severe COVID-19 have complex organ support needs that necessitate prolonged stays in the intensive care, likely to result in a high incidence of neuromuscular weakness and loss of well being. Early and structured rehabilitation has been associated with improved outcomes for patients requiring prolonged periods of mechanical ventilation, but at present no data are available to describe similar interventions or outcomes in COVID-19 populations. The objective of this observational study was to describe the demographics, clinical status, level of rehabilitation and mobility status at ICU discharge of patients with COVID-19. Study participants were adults admitted to ICU with a confirmed diagnosis of COVID-19 and mechanically ventilated for >24 hours. Rehabilitation status was measured daily using the Manchester Mobility Score (MMS) to identify the time taken to first mobilise (defined as sitting on the edge of the bed or higher) and highest level of mobility achieved at ICU discharge.
Severe forms of coronavirus disease 2019 (COVID-19) have been associated with a cytokine storm mainly involving interleukin (IL)-6, IL-1β, and TNF. Several authors have reported features of macrophage activation, thus comparing the cytokine storm of COVID-19 to reactive hemophagocytic lymphohistiocytosis (reHLH). However, these data have been balanced by other studies primarily involving IL-6 and, therefore, a mechanism closer to the complex immune dysregulation observed in sepsis. Considering these discrepancies, serum cytokine profiling may not be the best option for assessing COVID-19 severity and prognosis. Serum ferritin, an inflammatory biomarker, is elevated in most COVID-19 patients and has been correlated with severity and mortality. The measurement of the glycosylated fraction of ferritin (GF), which could be readily implemented in routine diagnosis, is of great interest in the diagnosis of reHLH (and in Still’s disease, which is frequently associated with macrophage activation syndrome). Indeed, a GF rate < 25% has a positive predictive value of 88% and a negative predictive value of 100% for reHLH. This study assessed whether the GF rate could serve as a biomarker for COVID-19 severity and prognosis.
A presumably overly robust inflammatory response has been associated with poor clinical outcomes in patients with acute respiratory failure including patients with acute respiratory distress syndrome (ARDS) and sepsis. Likewise, both abnormal gut and respiratory microbiota patterns (termed “dysbiosis”) are also predictive of increased mortality among critically ill patients. The ambitious aim of the study by Kitsios and colleagues, here, is to better define the interplay between the host inflammatory response and the lung microbiome, and the impact of this relationship on clinical outcomes in a heterogenous population of critically ill patients with acute respiratory failure. The results of this investigation represent an important step in the process of developing a microbiome-guided or based treatment for critically ill patients with acute respiratory failure. The cohort characteristics in the study by Kitsios and colleagues were typical of an intensive care unit (ICU) population with acute respiratory failure patients requiring mechanical ventilation: extrapulmonary sepsis (18%), ARDS (24%), pneumonia (40%) were common diagnoses and 32% of the patients received antibiotics prior to admission to the ICU.
Aging is a major risk factor for many diseases, especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Disease 2019 (COVID-19). Resolving cellular and molecular mechanisms associated with aging in higher mammals is therefore urgently needed. Here, we created young and old non-human primate single-nucleus/cell transcriptomic atlases of lung, heart and artery, the top tissues targeted by SARS-CoV-2. Analysis of cell type-specific aging-associated transcriptional changes revealed increased systemic inflammation and compromised virus defense as a hallmark of cardiopulmonary aging. With age, expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) was increased in the pulmonary alveolar epithelial barrier, cardiomyocytes, and vascular endothelial cells. We found that interleukin 7 (IL7) accumulated in aged cardiopulmonary tissues and induced ACE2 expression in human vascular endothelial cells in an NF-κB-dependent manner. Furthermore, treatment with vitamin C blocked IL7-induced ACE2 expression. Altogether, our findings depict the first transcriptomic atlas of the aged primate cardiopulmonary system and provide vital insights into age-linked susceptibility to SARS-CoV-2, suggesting that geroprotective strategies may reduce COVID-19 severity in the elderly.
Pulmonologists, cardiologists, neurologists, psychiatrists, and more join to get patients on their feet for good. Zijian Chen, MD, leads Mount Sinai’s COVID-19 recovery program, which is currently treating about 400 patients. At their first visit, patients are evaluated by a primary care physician for symptoms and referred to the appropriate specialists, Chen said. “Right now, we have almost every medical specialty working with the program,” Chen told MedPage Today. “We’re looking at a broad spectrum of disease. Some may have permanent lung fibrosis … that may last for the rest of their lives. Others have reactive airway or inflammatory problems that will subside over time. It’s unpredictable. It’s the same for cardiac symptoms and neurological symptoms.” At Hackensack Meridian’s COVID Recovery Center, primary care physicians develop a customized care plan and connect patients with specialists. Pulmonologists there have been treating patients with shortness of breath and exertional fatigue; cardiologists are treating heart function and rhythm disorders, and neurologists are treating comorbidities arising from strokes and clotting disorders, as well as neuropathy and cognitive impairment, according to program chair Laurie Jacobs, MD.
Aldeyra Therapeutics has received a “study may proceed” letter from the FDA for a phase 2 clinical trial evaluating ADX-629 as a treatment for adult patients hospitalized with COVID-19, according to a press release. “What’s exciting about ADX-629 is its potential to act like a dimmer switch to modulate the aggressive immune response that is a hallmark of SARS-CoV-2, the virus that causes COVID-19,” Todd C. Brady, MD, PhD, president and CEO of Aldeyra, told Healio/OSN. “We’re still in the early innings in terms of clinical testing, but in animal models, ADX-629 has demonstrated a broad and highly statistically significant reduction in cytokine levels, which are critical mediators of inflammation in COVID-19. As a first-in-class, orally available inhibitor of RASP, ADX-629 has the potential to be clinically relevant not only for treating COVID-19 but also an array of inflammatory diseases that are not being adequately addressed by currently available therapies.” The trial will enroll about 30 patients with COVID-19. Enrollment will occur upon hospitalization, and patients will be treated for up to 28 days with orally administered ADX-629 or placebo twice daily. The trial’s key endpoints will include the National Institute of Allergy and Infectious Diseases COVID-19 scale, in addition to levels of cytokines and RASP.
Researchers observed a low prevalence of lung obstruction and restriction and either mild or no cognitive impairment in patients with coronavirus disease 2019 (COVID-19) approximately 6 weeks after discharge from the intensive care unit (ICU), according to findings from a small case series published in CHEST. A total of 102 patients who were admitted to a university medical center ICU with COVID-19 as of July 30, 2020, were included in this case series. All patients in underwent follow up at a post-COVID-19 ICU clinic around 6 weeks following discharge. Spirometry was used to assess lung function and exercise capacity. Lung volumes, diffusion capacity, and the 6-minute walking distance (6MWD) were also assessed. The Patient-Reported Outcomes Measurement Information System depression 8a-short score, Quality of Life in Neurological Disorders (Neuro-QoL™) adult cognitive function v2.0 score, the Montreal Cognitive assessment (MOCA) scores, and insomnia severity index were used to assess depression, cognitive function, and insomnia. The majority of patients (85.71%) required mechanical ventilation; the median number of days on ventilation was 11. The median ICU length of stay was 14 days and the median hospital length of stay was 22 days. Additionally, the median days to postdischarge clinic follow-up was 39.5 days.
AstraZeneca’s phase 3 trial of a COVID-19 vaccine candidate has been put on hold because of a “suspected serious adverse reaction” in a participant from the United Kingdom, according to a report by STAT. AstraZeneca began the phase 3 trial in the United States on August 17. According to information available on clinicaltrials.gov, the trial is being held at 62 sites across the U.S., although not all locations have started enrolling participants. According to STAT, the trials were halted at all locations after a participant in the U.K. trial developed a suspected serious adverse reaction during the trial. In a statement from AstraZeneca issued to STAT, representatives said this is a “routine action” that happens whenever an unexplained illness occurs during a trial. “We are working to expedite the review of the single event to minimize any potential impact on the trial timeline,” they wrote. “We are committed to the safety of our participants and the highest standards of conduct in our trials.”
Abnormal respiratory vital signs coupled with electrocardiogram (ECG) findings of atrial fibrillation (AF)/flutter, right ventricular (RV) strain, or ST-segment abnormalities were found to predict early deterioration in patients with coronavirus disease 2019 (COVID-19), according to a study published in the Mayo Clinic Proceedings. Early triage is crucial for hospitalized patients with COVID-19 who require a higher level of care. In this study, researchers examined medical record data from 3 hospitals in New York City, New York to determine whether early data at emergency department presentation could predict the composite outcome of mechanical ventilation or death within the next 48 hours. The data of 1258 adults with COVID-19 (mean age, 61.6 years) who were hospitalized in March and April 2020 were examined. Electrophysiologists systematically read each patient’s ECG recordings conducted at presentation. A model adjusted for demographics, comorbidities, and vital signs was used to assess the prognostic value of ECG abnormalities. The most common comorbidities in this cohort included hypertension (57%), diabetes (37%), obesity (34%), primary lung disease (17%), and chronic kidney disease (16%). In this cohort, 73 patients (6%) died within 48 hours of presentation, and 14% of patients (n=174) were still alive at this time but were receiving mechanical ventilation. Another 277 patients (22%) died by 30 days. A total of 53% of all intubations occurred within 48 hours of presentation.
The AAP announced that a total of 513,415 pediatric cases of COVID-19 have been reported, according to an analysis of state-level data. The report found 70,630 new pediatric cases from August 20 to September 3 — a 16% increase from the total case count of 442,785 that was reported on August 19. “These numbers are a chilling reminder of why we need to take this virus seriously,” AAP President Sally Goza, MD, FAAP, said in a statement. “While much remains unknown about COVID-19, we do know that the spread among children reflects what is happening in the broader communities. A disproportionate number of cases are reported in Black and Hispanic children and in places where there is high poverty. We must work harder to address societal inequities that contribute to these disparities.” As of September 3, the total number of pediatric COVID-19 cases represents 9.8% of all reported cases.
Persistent lung issues are common following hospital discharge for COVID-19, but recovery is more the rule than the exception, according to two studies presented at the virtual European Respiratory Society International Congress. Among 86 patients admitted for COVID-19 at three hospitals in the Tyrolean Alps from late April through early June, 39% and 15% of patients, respectively, were still experiencing shortness of breath and coughing after 12 weeks, reported Sabrina Sahanic of the University Clinic of Internal Medicine in Innsbruck. Moreover, 56% showed evidence of COVID-19-related lung damage on CT scans. “COVID-19 survivors had persistent lung impairment weeks after recovery. Yet, over time, a moderate improvement is detectable,” Sahanic said at a press briefing. That was documented in a second study led by doctoral candidate Yara Al Chikhanie of Grenoble Alps University in France — another international ski destination — examining outcomes in 19 patients who had required mechanical ventilation for COVID-19.
Coronavirus disease 2019 (COVID-19) is an international public health emergency. While the prevalence of chronic respiratory disease in patients with COVID-19 has been reportedly low (1.5%), it is associated with increased risk of severe disease and—in chronic obstructive pulmonary disease—increased mortality. Along with numerous previously reported risk factors for severe COVID-19, it has been hypothesized that patients with interstitial lung diseases (ILD) may have poorer outcomes from COVID-19. In this letter, we present the results of a multicenter retrospective case-control study examining outcomes from COVID-19 in patients with pre-existing ILD. Adult patients (>18 years) with pre-existing ILD diagnosed with COVID-19 by real-time polymerase chain reaction (RT-PCR) or with negative RT-PCR but positive immunoglobulin M (IgM) and/or G (IgG) serology between March 1 and June 8, 2020 at six Mass General Brigham hospitals (Boston, MA) were identified using the electronic health record-integrated centralized clinical data registry. ILD was defined as physician diagnosis or, if no pulmonology visit existed in our system, ILD was defined as radiologic evidence with confirmatory histopathology.
A bedside low-field MRI scanner proved its mettle in Yale New Haven Hospital’s ICU, including for COVID-19 patients, clinicians there reported. Among 50 patients scanned in their ICU, the Hyperfine’s Swoop portable MRI system identified neuroimaging abnormalities for eight of the 20 on ventilation for COVID-19 (40%) and 29 of the 30 without COVID-19 (97%) reported in JAMA Neurology. No adverse events or complications occurred with the device or in-room scanning. No ICU equipment had to be removed from the room; the MRI imaging operator and bedside nurse remained in the room for the 0.064-T scans. The Swoop MRI device, which was cleared by the FDA last month for bedside use, wheels to the patient’s bedside, plugs into a standard electrical outlet, and is controlled through a wireless tablet.
When COVID-19 spread around the globe this year, David Montefiori wondered how the deadly virus behind the pandemic might be changing as it passed from person to person. Montefiori is a virologist who has spent much of his career studying how chance mutations in HIV help it to evade the immune system. The same thing might happen with SARS-CoV-2, he thought. In March, Montefiori, who directs an AIDS-vaccine research laboratory at Duke University in Durham, North Carolina, contacted Bette Korber, an expert in HIV evolution and a long-time collaborator. Korber, a computational biologist at the Los Alamos National Laboratory (LANL) in Sante Fe, New Mexico, had already started scouring thousands of coronavirus genetic sequences for mutations that might have changed the virus’s properties as it made its way around the world. Compared with HIV, SARS-CoV-2 is changing much more slowly as it spreads. But one mutation stood out to Korber. It was in the gene encoding the spike protein, which helps virus particles to penetrate cells. Korber saw the mutation appearing again and again in samples from people with COVID-19. At the 614th amino-acid position of the spike protein, the amino acid aspartate (D, in biochemical shorthand) was regularly being replaced by glycine (G) because of a copying fault that altered a single nucleotide in the virus’s 29,903-letter RNA code. Virologists were calling it the D614G mutation.
At the COVID-19 pandemic onset, when individual-level data of COVID-19 patients were not yet available, there was already a need for risk predictors to support prevention and treatment decisions. Here, we report a hybrid strategy to create such a predictor, combining the development of a baseline severe respiratory infection risk predictor and a post-processing method to calibrate the predictions to reported COVID-19 case-fatality rates. With the accumulation of a COVID-19 patient cohort, this predictor is validated to have good discrimination (area under the receiver-operating characteristics curve of 0.943) and calibration (markedly improved compared to that of the baseline predictor). At a 5% risk threshold, 15% of patients are marked as high-risk, achieving a sensitivity of 88%. We thus demonstrate that even at the onset of a pandemic, shrouded in epidemiologic fog of war, it is possible to provide a useful risk predictor, now widely used in a large healthcare organization.
Comprehensive mapping reveals that functional CD4+ and CD8+ T cells targeting multiple regions of SARS-CoV-2 are maintained in the resolution phase of both mild and severe COVID-19, and their magnitude correlates with the antibody response. CD4+ and CD8+ T cells work with other constituents of a coordinated immune response to first resolve acute viral infections and then to provide protection against reinfection. Careful delineation of the frequency, specificity, functionality and durability of T cells during COVID-19 is vital to understanding how to use them as biomarkers and targets for immunotherapies or vaccines. In this issue of Nature Immunology, Peng et al. take a comprehensive approach to characterizing circulating SARS-CoV-2-specific CD4+ and CD8+ T cells following resolution of COVID-19. They report a robust and diverse T cell response targeting multiple structural and non-structural regions of SARS-CoV-2 in most resolved cases, irrespective of whether the individual had mild or severe infection. While the most frequent responses were against peptides spanning spike, membrane and nucleoprotein antigens, all eight regions tested were recognized by multiple individuals, with a maximum of 23 reactive pools in two individuals. Such multispecific T cell responses are well suited to providing a failsafe form of multilayered protection, mitigating against viral escape by mechanisms such as mutation or variable antigen presentation.
Even healthcare professionals may not be aware of and prepared for a condition called post-intensive care unit (ICU) syndrome (PICS) that can occur in the aftermath of COVID-19. What about those who were hospitalized for COVID-19, treated in the ICU, and are unaware of the possible long-term impact and rehabilitation phase? There is a tendency to think that once the patient is discharged from the hospital, has tested negative, and looks well, the problem is resolved. However, the struggle of COVID-19 survivors and family members or caregivers may not end there. PICS is an ongoing challenge that may potentially present a public health crisis. PICS is a term used to describe the group of impairments faced by ICU survivors. It can persist for months or years. PICS encompasses a combination of physical, neurological, social, and psychological decline. The physical impairments include intensive care-acquired weakness, classified as critical illness myopathy, neuropathy, and neuromyopathy. Cognitive and psychological impairments involve impaired memory, language, delirium, depression, anxiety, and post-traumatic stress disorder (PTSD). During the COVID-19 pandemic, critically ill clients are considered the most vulnerable to PICS. Among these, 30% suffer from depression and 70% experience anxiety and PTSD after ICU discharge. Moreover, survivors can experience additional stress as a result of isolation and limited contact with loved ones and reduced contact with staff due to precautionary measures such as personal protective equipment.
As of Sept 4, almost 190,000 people in the United States have died from COVID-19, according to the Johns Hopkins COVID-19 Dashboard, but the weekly numbers appear to be slowing. The deaths attributed to COVID-19 during the last week of August are down, but the percentage still exceeds the epidemic threshold, according to the National Center for Health Statistics (NCHS) database. Provisional data from across the United States show that based on death certificates available on Aug. 27, the percentage of deaths attributed to COVID-19, pneumonia or influenza for week 34 was 7.9%. During week 33, it was 23.3%. In addition, the statistics show that only 6% of deaths listed just COVID-19 as a cause of death. Most certificates list comorbid conditions, such as respiratory and cardiovascular conditions, as contributors to the deaths. “In 94% of deaths with COVID-19, other conditions are listed in addition to COVID-19,” the NCHS told Infectious Disease Special Edition. “These causes may include chronic conditions like diabetes or hypertension. They may also include acute conditions that occurred as a result of COVID-19, such as pneumonia or respiratory failure.”
Invasive fungal disease occurs often in critically ill patients with COVID-19 on mechanical ventilation, according to a study published in Clinical Infectious Diseases. “With the COVID-19 pandemic far from over, it is paramount that our understanding of the risk from associated invasive fungal disease is enhanced,” P. Lewis White, PhD, FECMM, FRCPath, consultant clinical scientist and head of the mycology reference laboratory for Public Health Wales, told Healio. White and colleagues screened 135 patients with COVID-19 for invasive fungal disease to evaluate an enhanced testing strategy. The patients were from a national, multicenter cohort in Wales. The incidence of invasive fungal disease was 26.7% — 14.1% aspergillosis and 12.6% yeast infections. The overall mortality rate was 38%, including 53% in patients with fungal disease and 31% in patients without it (P = .0387). The overall mortality rate declined when antifungal therapy was used. It was 38.5% in patients who received antifungal therapy vs. 90% in patients who did not (P = .008). White said they did not expect the high rate of invasive yeast infections.
Hopefully, summer won’t end the way it began. Memorial Day celebrations helped set off a wave of coronavirus infections across much of the South and West. Gatherings around the Fourth of July seemed to keep those hot spots aflame. And now Labor Day arrives as those regions are cooling off from COVID-19. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, warned Wednesday that Americans should be cautious to avoid another surge in infection rates. But travelers are also weary of staying home — and tourist destinations are starved for cash. “Just getting away for an hour up the street and staying at a hotel is like a vacation, for real,” says Kimberly Michaels, who works for NASA in Huntsville, Alabama, and traveled to Nashville, Tennessee, with her boyfriend to celebrate his birthday last weekend. In time for the tail end of summer, many local governments are lifting restrictions to resuscitate tourism activity and rescue small businesses.
The four most common NCDs are cardiovascular disease, cancer, diabetes and chronic respiratory diseases; together, they contribute to more than 40 million deaths a year, said Dr Bente Mikkelsen, Director, WHO Division of Noncommunicable Diseases. “The most recent study shows that there is a disruption in healthcare services including NCD diagnosis and treatments in 69 per cent of cases”, she said. “In cancer, there are the highest numbers, with 55 per cent of people living with cancer (having) their health services disrupted.” Dr Mikkelsen noted that those living with one or more NCDs were among the most likely to become severely ill and die from the new coronavirus. Studies from several countries had indicated this, she said, highlighting how data on indigenous communities in Mexico, showed that diabetes was the most commonly found disease among COVID-19 fatalities. Research also found that in Italy, of those who succumbed to COVID-19 in hospital, 67 per cent suffered from hypertension and 31 per cent had type 2 diabetes.
Early outcomes of a single-center study demonstrate clinical benefit of extracorporeal membrane oxygenation support in patients with severe COVID-19, according to a study published in The Annals of Thoracic Surgery. “Our experience differs from other published data which suggested that ECMO is of limited value for patients with COVID-19. Although still early in many of these patients’ clinical courses, these initial outcomes are encouraging with an overall current survival of 96%, with nearly half of the patients already weaned from ECMO support, mechanical ventilation and supplemental oxygen. Furthermore, a significant number of these patients have been discharged from the hospital,” Zachary N. Kon, MD, cardiothoracic surgeon in the department of cardiothoracic surgery at NYU Langone Health, and colleagues wrote. Researchers conducted a retrospective analysis of 321 endotracheal-intubated patients with COVID-19 from March 10 to April 24, 2020. Of those, 77 (24%) were evaluated for ECMO support. ECMO support was selected based on patients’ partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio less than 150 mm Hg or pH less than 7.25 with an arterial partial pressure of carbon dioxide greater than 60 mm Hg. Patients were cannulated and managed with protective lung ventilation, early tracheostomy, bronchoscopies and proning in NYU Langone Health’s Manhattan campus ICU.
Emergency use authorization (EUA) or approval for a COVID-19 vaccine before phase 3 clinical trials are complete could be considered by the U.S. Food and Drug Administration, according to the agency’s commissioner, Stephen Hahn, M.D. “It is up to the sponsor [vaccine developer] to apply for authorization or approval, and we make an adjudication of their application,” he told the Financial Times, CNN reported. “If they do that before the end of phase 3, we may find that appropriate. We may find that inappropriate, we will make a determination.” An EUA is not the same as full-fledged approval, Hahn noted. “Our emergency use authorization is not the same as a full approval,” he said. “The legal, medical, and scientific standard for that is that the benefit outweighs the risk in a public health emergency.” Two vaccines are currently in phase 3 trials in the United States and two more are expected to begin phase 3 trials by mid-September, CNN reported.
As the COVID-19 cases continue to rise across the globe, companies are working hard to develop innovative solutions to fight the coronavirus pandemic. Chinese companies such as Alibaba have led the way using artificial intelligence, data science, and technology. Startups are teaming up with clinicians, engineers, and government entities to reduce the spread of COVID-19. As we continue our fight in the management and eventual eradication of the virus, read about nine innovative ways companies are helping on the front lines.
In patients with coronavirus disease 2019 (COVID-19) and moderate or severe acute respiratory distress syndrome (ARDS), does intravenous dexamethasone plus standard care compared with standard care alone increase the number of days alive and free from mechanical ventilation? ARDS due to COVID-19 is associated with substantial mortality and use of health care resources. Dexamethasone use might attenuate lung injury in these patients. The objective of the clinical trial was to determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19–associated ARDS. This multicenter, randomized, open-label, clinical trial was conducted in 41 intensive care units (ICUs) in Brazil. Patients with COVID-19 and moderate to severe ARDS, according to the Berlin definition, were enrolled from April 17 to June 23, 2020. Final follow-up was completed on July 21, 2020. The trial was stopped early following publication of a related study before reaching the planned sample size of 350 patients. Twenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n =151) or standard care alone (n = 148).
Public health interventions and stay-at-home orders issued in March in the Philadelphia region to limit the transmission of COVID-19 also led to a marked decrease in health care visits for outpatient and hospitalized patients with asthma. Researchers with the Children’s Hospital of Philadelphia and the Hospital of the University of Pennsylvania reviewed electronic health records to analyze asthma-related encounters and weekly summaries of respiratory viral testing in the 60 days leading up to March 17, when Philadelphia issued a series of stay-at-home orders, compared with the 60 days following stay-at-home orders. They found a 60% decrease in total daily asthma health care visits across CHOP’s hospital and Care Network, according to data published in The Journal of Allergy and Clinical Immunology: In Practice. Further, fewer rhinovirus infections due to mask wearing, social distancing and hygiene measures may have contributed to these findings, the researchers reported. After March, in-person asthma encounters decreased by 87% in the outpatient setting and by 84% in the emergency and inpatient settings, according to the findings. During the pandemic, video telemedicine was the most-utilized modality for asthma encounters and was used in 61% of all visits, while telephone encounters increased by 19%. During the same period, the researchers observed decreases in asthma-related systemic steroid prescriptions and the frequency of rhinovirus test positivity.
Among hospitalized patients with coronavirus disease 2019 (COVID-19), those who receive anticoagulation treatment have lower adjusted risk of mortality and intubation compared with in-hospital patients who do not receive anticoagulation, according to study results published in the Journal of the American College of Cardiology. A team of investigators at Icahn School of Medicine at Mount Sinai in New York, New York, expanded on previous findings that suggested an association between in-hospital anticoagulation and reduced mortality. In the present investigation, the researchers compared the effects of therapeutic and prophylactic anticoagulation treatment with the absence of such treatment. Choice of agent, survival outcomes, intubation, and major bleeding were also analyzed. In addition, the study authors also reviewed the first consecutive autopsies performed at their institution to characterize the premortem management of this patient population as it relates to anticoagulation therapy. The primary outcome was in-hospital mortality, and secondary outcomes included intubation and major bleeding. Participants were all older than 18 years, had clinically confirmed severe acute respiratory syndrome coronavirus 2 infection between March 1, 2020, and April 30, 2020, and were admitted to 1 of 5 New York City hospitals included in the study.
Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support. The objective of this analysis was to estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality. Prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The trials were conducted in 12 countries from February 26, 2020, to June 9, 2020, and the date of final follow-up was July 6, 2020. Pooled data were aggregated from the individual trials, overall, and in predefined subgroups. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance–weighted fixed-effect meta-analysis of overall mortality, with the association between the intervention and mortality quantified using odds ratios (ORs). Random-effects meta-analyses also were conducted (with the Paule-Mandel estimate of heterogeneity and the Hartung-Knapp adjustment) and an inverse variance–weighted fixed-effect analysis using risk ratios. Patients had been randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients).
Sanofi announced that its IL-6 inhibitor Kevzara failed to meet primary and secondary endpoints in a phase 3 trial of patients outside the United States hospitalized with severe COVID-19. “Although this trial did not yield the results we hoped for, we are proud of the work that was achieved by the team to further our understanding of the potential use of Kevzara for the treatment of COVID-19,” John Reed, MD, PhD, global head of research and development at Sanofi, said in a company press release. The randomized trial included 420 patients who were severely or critically ill with COVID-19, recruited from hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia and Spain. Among the participants, 161 received 200 mg of Kevzara (sarilumab), 173 were treated with 400 mg and 86 received a placebo. According to the press release, although not statistically significant, the researchers observed numerical trends toward a decrease in hospital stay duration as well as faster time to better clinical outcomes, defined as a two-point improvement on a seven-point scale. In addition, the researchers noted a trend toward reduced mortality in the critical patient group, but not in the severe group. Lastly, the time to discharge was reduced by 2 to 3 days among patients who received sarilumab within the first 2 weeks of treatment, although, again, this was not statistically significant.
An investigational inactivated whole-virus coronavirus disease 2019 (COVID-19) vaccine has demonstrated safety and immunogenicity, according to the results of an interim analysis published in JAMA. The study authors examined safety outcomes 28 days, and immunogenicity outcomes 14 days after 3 doses in a phase 1 trial and 2 doses in a phase 2 trial of an inactivated COVID-19 vaccine candidate in healthy adults in China. The double-blind, randomized, placebo-controlled study was designed by the Wuhan Institute of Biological Products Co Ltd, and Henan Provincial Center for Disease Control and Prevention (CDC). Healthy adults aged 18 to 59 years without a history of severe acute respiratory syndrome coronavirus (SARS-CoV) or SARS-CoV-2 infection were eligible for enrollment. Currently, there are 160 COVID-19 candidate vaccines in various stages of development, with 25 in different phases of clinical trials. This is the first report of phase 1 and 2 clinical trials of a whole virus-inactivated COVID-19 vaccine in adults.
A research letter published in Annals of the American Thoracic Society has challenged US Centers for Disease Control and Prevention (CDC) assumptions that those with asthma are at higher risk for severe SARS-CoV-2 infection. Research was led by Fernando Holguin, MD, MPH, of the Pulmonary Division at University of Colorado’s Anschutz Medical Campus. People living with asthma often make up more than 20 percent of those hospitalized in the United States during the annual influenza season. For SARS-CoV-2, several noteworthy risk factors for hospitalization such as hypertension, diabetes, chronic obstructive pulmonary disease, and obesity have been demonstrated. Amid the outbreak of Middle East Respiratory Syndrome (MERS), there was sparse evidence asthma patients may be at higher risk. But the underwhelming proportion of people with asthma among patients across several international studies raises questions about asthma as a particular risk factor when it comes to being hospitalized for coronavirus disease 2019 (COVID-19). The study team examined asthma prevalence among patients hospitalized for COVID-19 reported in 15 studies with population asthma prevalence and a 4-year average of asthma prevalence in influenza hospitalizations across the United States.
[Video] What’s the role of antibodies against coronavirus infection? It’s one of the biggest questions over the past six months. WebMD’s Chief Medical Officer, Dr. John Whyte, speaks with Alexander Greninger, MD, PhD, Assistant Director of the UW Medicine Clinical Virology Laboratory, University of Washington, about the effectives of antibodies for COVID-19 immunity and transmission.
The first U.S. case of a confirmed coronavirus reinfection looks to be a patient in Nevada. The U.S. case comes a few days after the first reinfection in the world was announced in Hong Kong. The Nevada case is detailed in a new paper published in The Lancet on an online preprint server. The study has not yet been reviewed by peers. Reinfection is rare, researchers said, but people should still be cautious. “If you’ve had it, you can’t necessarily be considered invulnerable to the infection,” Mark Pandori, one of the authors and director of the Nevada State Public Health Laboratory, told NBC. According to the report, the 25-year-old man from Reno, Nevada, first tested positive for COVID-19 in mid-April after experiencing a sore throat, cough, headache, nausea, and diarrhea. He recovered but got sick again in late May, marking 48 days between two positive tests after two negative tests in between the infections. During the second round, his illness was more severe, and he was hospitalized with pneumonia. Researchers found that the genetic sequencing of the virus varied, and the patient was infected with slightly different strains of the coronavirus. They aren’t sure why he was reinfected, which could be related to the virus itself or the patient’s immune system.
Pneumothorax, a major and potential fatal complication of mechanical ventilation, can further complicate the management of COVID-19 patients, whilst chest drain insertion may increase the risk of transmission of attending staff. The rate of pneumothorax in such patients has not yet been quantified. However, previous experience from the SARS outbreak, also caused by a coronavirus, suggests a high incidence (20–34%) of pneumothorax in mechanically ventilated SARS patients. Mechanical ventilation is the most common cause of iatrogenic pneumothoraces in the ICU setting; however, it is a rare occurrence in intubated patients who have relatively normal lung parenchyma. Most pneumothoraces related to mechanical ventilation are associated with a combination of high ventilation pressures and underlying chronic lung pathology such as emphysema. Previous studies have suggested that high inspiratory airway pressures and positive end-expiratory pressure were correlated with increased incidence of barotrauma. Currently, there is limited literature on how to manage pneumothoraces in mechanically ventilated COVID-19 patients. We present a case series (nine patients) and a suggested protocol for how to manage and treat pneumothoraces in COVID-19 patients in an ICU setting.
Microorganisms, August 31, 2020
The diffusion of SARS-CoV-2, starting from China in December 2019, has led to a pandemic, reaching Italy in February 2020. Previous studies in Asia have shown that the median duration of SARS-CoV-2 viral shedding was approximately 12–20 days. We considered a cohort of patients recovered from COVID-19 showing that the median disease duration between onset and end of COVID-19 symptoms was 27.5 days (interquartile range (IQR): 17.0–33.2) and that the median duration between onset of symptoms and microbiological healing, defined by two consecutive negative nasopharyngeal swabs, was 38 days (IQR: 31.7–50.2). A longer duration of COVID-19 with delayed clinical healing (symptom-free) occurred in patients presenting at admission a lower PaO2/FiO2 ratio (p < 0.001), a more severe clinical presentation (p = 0.001) and a lower lymphocyte count (p = 0.035). Moreover, patients presenting at admission a lower PaO2/FiO2 ratio and more severe disease showed longer viral shedding (p = 0.031 and p = 0.032, respectively). In addition, patients treated with corticosteroids had delayed clinical healing (p = 0.013).
Glucocorticoids (GCs) are endogenous hormones that are crucial for the homeostasis of the organism and adaptation to the external environment. Because of their anti-inflammatory effects, synthetic GCs are also extensively used in clinical practice. However, almost all cells in the body are sensitive to GC regulation. As a result, these mediators have pleiotropic effects, which may be undesirable or detrimental to human health. This articles summarizes the recent findings that contribute to deciphering the molecular mechanisms downstream of glucocorticoid receptor activation. Also discussed, is the complex role of GCs in infectious diseases such as sepsis and COVID-19, in which the balance between pathogen elimination and protection against excessive inflammation and immunopathology needs to be tightly regulated. An understanding of the cell type- and context-specific actions of GCs from the molecular to the organismal level would help to optimize their therapeutic use. Here, we highlight the many levels of GR-mediated regulation that have been identified so far and may help to predict the effect of GCs from the molecular to the organismal level. Taking this complexity into account, we also summarize the pathways regulated by endogenous and synthetic GCs in lymphocytes and myeloid cells. Finally, we use sepsis as an example of a pathological condition for which molecular and cellular studies can improve predictions regarding the systemic response to GCs. We stress the need for cell-targeted GC therapy to prevent not only the well-known adverse effects of GCs but also those effects that may reduce treatment efficacy.
Consultations via tablets, laptops and phones linked patients and doctors when society shut down in early spring. Telehealth visits dropped with the reopening, but they’re still far more common than before and now there’s a push to make them widely available in the future. Permanently expanding access will involve striking a balance between costs and quality, dealing with privacy concerns and potential fraud, and figuring out how telehealth can reach marginalized patients, including people with mental health problems. “I don’t think it is ever going to replace in-person visits, because sometimes a doctor needs to put hands on a patient,” said CMS Administrator Seema Verma, the Trump administration’s leading advocate for telehealth. Caveats aside, “it’s almost a modern-day house call,” she added. “It’s fair to say that telemedicine was in its infancy prior to the pandemic, but it’s come of age this year,” said Murray Aitken of the data firm IQVIA, which tracks the impact. In the depths of the coronavirus shutdown, telehealth accounted for more than 40% of primary care visits for patients with traditional Medicare, up from a tiny 0.1% sliver before the public health emergency. As the government’s flagship health care program, Medicare covers more than 60 million people, including those age 65 and older, and younger disabled people.
There are 21.7 million reported cases of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and over 776,000 deaths due to the coronavirus disease 2019 (COVID-19) worldwide through August 17, 2020. Over one-fourth of cases are in the U.S., with African American and Latinos being disproportionately impacted in case counts and death rates. Prevention control messages and efforts, such as sheltering in place and quarantining, may not have been as successful among African Americans and Latinos for numerous reasons, such as needing to work outside of the home, living in large households in close quarters, and including the effects of structural racism (i.e., access to health insurance and care, limited health literacy). Little is known about individual prevention measures that were taken in response to COVID-19 or how people may engage with surveillance/reporting strategies as we enter phase two of the pandemic. We investigated individual behaviors taken by White, African American, and Latino U.S. households in response to SARS-CoV-2, and likelihood of using digital tools for symptom surveillance/reporting. We analyzed cross-sectional week one data (April 2020) of the COVID Impact Survey in a large, nationally-representative sample of U.S. adults. In general, all groups engaged in the same prevention behaviors, but Whites reported being more likely to use digital tools to report/act on symptoms and seek testing, versus African Americans and Latinos.
Monoclonal antibodies could hold promise in COVID-19 treatment and prevention if the results bear out in clinical trials for efficacy, the nation’s leading infectious diseases expert told MedPage Today. “There’s a lot of activity and it’s a highly concentrated, highly specific, direct antiviral approach to a number of diseases. The success in Ebola was very encouraging,” said National Institute of Allergy and Infectious Diseases (NIAID) Director Anthony Fauci, MD. Most recently thrust into the spotlight as effective treatments for Ebola, monoclonal antibodies are currently being researched as a potential treatment for HIV, as well as COVID-19. This month, the NIH highlighted trials of monoclonal antibodies being conducted among several different COVID-19 patient populations: outpatients with COVID-19, patients hospitalized with the disease, and even a trial in household contacts of confirmed cases, where the therapy was used as prophylaxis. Fauci explained how the mechanism of monoclonal antibodies “is really one of a direct antiviral. It’s like getting a neutralizing antibody that’s highly, highly concentrated and highly, highly specific. So, the mechanism involved is blocking of the virus from essentially entering its target cell in the body and essentially interrupting the course of infection,” he said.
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), can be associated with a severe systemic disease leading to respiratory failure and the need for mechanical ventilation. Patients with underlying medical comorbidities, such as respiratory, cardiac, and liver disease, diabetes mellitus (DM), and obesity are at higher risk for respiratory failure. Therefore, prediction factors are needed to help front line providers to identify who might be at higher risk for intensive care and ventilator support for respiratory failure. The fibrosis-4 index (FIB-4), developed to predict fibrosis in liver disease, was used to identify patients with COVID-19 who will require ventilator support as well as associated with 30-day mortality. Multivariate analysis found obesity (OR 4.5), diabetes (OR 2.55), and FIB-4 ≥ 2.67 (OR 3.09) independently associated with need for mechanical ventilation. When controlling for ventilator use, gender, and comorbid conditions, FIB-4 ≥ 2.67 was also associated with increased 30-day mortality (OR 8.4; 95% CI 2.23-31.7). While it may not be measuring hepatic fibrosis, its components suggest that increases in FIB-4 may be reflecting systemic inflammation associated with poor outcomes.
SARS-CoV-2 infection is associated with significant lung and cardiac morbidity but there is a limited understanding of the endocrine manifestations of COVID-19. We present the first case of myxedema coma in COVID-19 and we discuss how SARS-CoV-2 may have precipitated multi-organ damage and sudden cardiac arrest in our patient. A 69-year-old female with a history of small cell lung cancer presented with hypothermia, hypotension, decreased respiratory rate, and a Glasgow Coma Scale score of 5. The patient was intubated and administered vasopressors. Laboratory investigation showed elevated thyroid stimulating hormone, very low free thyroxine, elevated thyroid peroxidase antibody, and markedly elevated inflammatory markers. SARS-CoV-2 test was positive. Computed tomography showed pulmonary embolism and peripheral ground glass opacities in the lungs. The patient was diagnosed with myxedema coma with concomitant COVID-19. While treatment with intravenous hydrocortisone and levothyroxine were begun the patient developed a junctional escape rhythm. Eight minutes later, the patient became pulseless and was eventually resuscitated. Echocardiogram following the arrest showed evidence of right heart dysfunction. She died two days later from multi-organ failure. This is the first report of SARS-CoV-2 infection with myxedema coma. Sudden cardiac arrest likely resulted from the presence of viral pneumonia, cardiac arrhythmia, pulmonary emboli, and myxedema coma – all of which were associated with the patient’s SARS-CoV-2 infection.
For every 1,000 people infected with the coronavirus who are under the age of 50, almost none will die. For people in their fifties and early sixties, about five will die — more men than women. The risk then climbs steeply as the years accrue. For every 1,000 people in their mid-seventies or older who are infected, around 116 will die. These are the stark statistics obtained by some of the first detailed studies into the mortality risk for COVID-19. Trends in coronavirus deaths by age have been clear since early in the pandemic. Research teams looking at the presence of antibodies against SARS-CoV-2 in people in the general population — in Spain, England, Italy and Geneva in Switzerland — have now quantified that risk, says Marm Kilpatrick, an infectious-disease researcher at the University of California, Santa Cruz. The studies reveal that age is by far the strongest predictor of an infected person’s risk of dying — a metric known as the infection fatality ratio (IFR), which is the proportion of people infected with the virus, including those who didn’t get tested or show symptoms, who will die as a result. “COVID-19 is not just hazardous for elderly people, it is extremely dangerous for people in their mid-fifties, sixties and seventies,” says Andrew Levin, an economist at Dartmouth College in Hanover, New Hampshire, who has estimated that getting COVID-19 is more than 50 times more likely to be fatal for a 60-year-old than is driving a car. But “age cannot explain everything”, says Henrik Salje, an infectious-disease epidemiologist at the University of Cambridge, UK. Gender is also a strong risk factor, with men almost twice more likely to die from the coronavirus than women.
The COVID-19 pandemic has prompted a flurry of scientific studies of various potential treatments and vaccines for the novel coronavirus. One such study, conducted by researchers at Rensselaer Polytechnic Institute and published in Antiviral Research, showed the FDA-approved anticoagulant heparin may neutralize SARS-CoV-2, the virus that causes COVID-19. SARS-CoV-2 uses a surface spike protein to attach to human cells and infect them, according to the study background. However, because heparin binds tightly with the surface spike protein, it potentially could serve as a decoy and prevent infection from occurring. “We’ve known for quite some time that heparin possesses the ability to be antiviral; it has the ability to bind to very specific proteins on the surfaces of viruses,” Jonathan S. Dordick, PhD, the Howard P. Isermann Professor of Chemical and Biological Engineering at Rensselaer and one of the study authors, said in an interview with Healio. “So that wasn’t really a surprise. The other reason we studied heparin had nothing to do with its antiviral properties.”
A phase 1 study of AstraZeneca’s investigational monoclonal antibody AZD7442 for the prevention and treatment of coronavirus disease 2019 (COVID-19) has been initiated. AZD7442 is a combination of 2 monoclonal antibodies derived from convalescent patients who were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The monoclonal antibodies have been optimized with an extended half-life to afford at least 6 months of protection from COVID-19. According to preclinical data recently published in Nature, the monoclonal antibodies protect against infection by blocking SARS-CoV-2 virus from binding to host cells. The randomized, double-blind, placebo-controlled phase 1 study will evaluate the safety, tolerability, and pharmacokinetics of AZD7442 in up to 48 healthy participants aged 18 to 55 years. The study is funded by the Defense Advanced Research Projects Agency (DARPA) and the Biomedical Advanced Research and Development Authority (BARDA) at the US Department of Health and Human Services.
A growing body of evidence reveals that male sex is a risk factor for a more severe disease, including death. Globally, ~60% of deaths from COVID-19 are reported in men, and a cohort study of 17 million adults in England reported a strong association between male sex and risk of death from COVID-19 (hazard ratio 1.59, 95% confidence interval 1.53-1.65. .53-1.65). Past studies have demonstrated that sex has a significant impact on the outcome of infections and has been associated with underlying differences in immune response to infection. For example, prevalence of hepatitis A and tuberculosis are significantly higher in men compared with women. Viral loads are consistently higher in male patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Conversely, women mount a more robust immune response to vaccines. However, the mechanism by which SARS-CoV-2 causes more severe disease in male patients than in female patients remains unknown. To elucidate the immune responses against SARS-CoV-2 infection in men and women, we performed detailed analysis on the sex differences in immune phenotype via the assessment of viral loads, SARS-CoV-2 specific antibody levels, plasma cytokines/chemokines, and blood cell phenotypes.
[Podcast] The onset of the COVID-19 pandemic and the public health response required to minimize the catastrophic spread of the disease required an immediate change in the traditional approach to medical education and clearly amplified the need for expanding the competencies of the US physician workforce. Medical educators responded at the local and national levels to outline concerns and offer guiding principles so that academic health systems could support a robust public health response while ensuring that physician graduates are prepared to contribute to addressing current and future threats to the health of communities. While each school approached their response somewhat differently, several common themes have emerged. Join Howard Bauchner, MD, Editor in Chief of JAMA, as he interviews Catherine Lucey, MD, FACP, Department of Medicine, University of California San Francisco School of Medicine and author of The Transformational Effects of COVID-19 on Medical Education.
High flow nasal cannula oxygen (HFNC) significantly reduced intubation and subsequent invasive mechanical ventilation, but did not affect case fatality in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU) for acute respiratory failure, according to study results published in the American Journal of Respiratory and Critical Care Medicine. Symptomatic management to restore oxygenation of severe acute respiratory failure is key during the COVID-19 pandemic, according to the authors of this retrospective study. HFNC has been shown to improve oxygenation, and reduce minute ventilation and the work of breathing in severe de novo acute hypoxemic respiratory failure. Thus, researchers in Paris, France, tested the hypothesis that HFNC reduces the rates of intubation and mortality in 379 critically ill patients admitted to the ICU for acute respiratory failure between February 21 and April 24, 2020. Overall, 146 (39%) patients received HFNC (all within the first 24 hours following ICU admission) and were compared with 233 patients who did not. The percentage of patients requiring invasive mechanical ventilation at day 28 was 56% in the HFNC group vs 75% in those who did not receive HFNC (P <.0001), and mortality at day 28 was 21% vs 30%, respectively.
Subcutaneous emphysema (SE) and pneumomediastinum refer to the presence of air in the subcutaneous tissue and mediastinum, respectively. Spontaneous pneumomediastinum (SPM) results from a sudden rise in intra-alveolar pressure (such as in the setting of reactive airways disease, Valsalva maneuver, cough, emesis, and barotrauma), resulting in the rupture of alveoli and subsequent dissection of air along the bronchovascular sheath into the mediastinum (Macklin effect). Air may then enter the pleural, pericardial, and peritoneal spaces or the soft tissues of the chest wall, neck, or face causing subcutaneous cervicothoracic emphysema. On their own, these conditions are not typically life-threatening and often resolve with conservative treatment. However, they may indicate the presence of severe underlying pathology. While SE and SPM have been observed in patients with a variety of viral pneumonias as a complication of mechanical ventilation, the development of these conditions in non-intubated patients suggests an alternative etiology. A total of 11 non-intubated COVID-19 patients (8 male and 3 female, median age 61 years) developed SE and SPM. Demographics (age, gender, smoking status, comorbid conditions, and body-mass index), clinical variables (temperature, oxygen saturation, and symptoms), and laboratory values (white blood cell count, C-reactive protein, D-dimer, and peak interleukin-6) were collected. Chest radiography (CXR) and computed tomography (CT) were analyzed for SE, SPM, and pneumothorax by a board-certified cardiothoracic-fellowship trained radiologist.
Healthcare workers (HCWs) facing COVID-19 pandemic represented an at-risk population for new psychosocial COVID-19 strain and consequent mental health symptoms. The aim of the present study was to identify the possible impact of working contextual and personal variables (age, gender, working position, years of experience, proximity to infected patients) on professional quality of life, represented by compassion satisfaction (CS), burnout, and secondary traumatization (ST), in HCWs facing COVID-19 emergency. Further, two multivariable linear regression analyses were fitted to explore the association of mental health selected outcomes, anxiety and depression, with some personal and working characteristics that are COVID-19-related. A sample of 265 HCWs of a major university hospital in central Italy was consecutively recruited at the outpatient service of the Occupational Health Department during the acute phase of COVID-19 pandemic. HCWs were assessed by Professional Quality of Life-5 (ProQOL-5), the Nine-Item Patient Health Questionnaire (PHQ-9), and the Seven-Item Generalized Anxiety Disorder scale (GAD-7) to evaluate, respectively, CS, burnout, ST, and symptoms of depression and anxiety. Females showed higher ST than males, while frontline staff and healthcare assistants reported higher CS rather than second-line staff and physicians, respectively. Burnout and ST, besides some work or personal variables, were associated to depressive or anxiety scores.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus, is responsible for the coronavirus disease 2019 (COVID-19) pandemic of 2020. Experimental evidence suggests that microRNA can mediate an intracellular defence mechanism against some RNA viruses. The purpose of this study was to identify microRNA with predicted binding sites in the SARS-CoV-2 genome, compare these to their microRNA expression profiles in lung epithelial tissue and make inference towards possible roles for microRNA in mitigating coronavirus infection. We hypothesize that high expression of specific coronavirus-targeting microRNA in lung epithelia may protect against infection and viral propagation, conversely, low expression may confer susceptibility to infection. We have identified 128 human microRNA with potential to target the SARS-CoV-2 genome, most of which have very low expression in lung epithelia. Six of these 128 microRNA are differentially expressed upon in vitro infection of SARS-CoV-2. Additionally, 28 microRNA also target the SARS-CoV genome while 23 microRNA target the MERS-CoV genome. We also found that a number of microRNA are commonly identified in two other studies. Further research into identifying bona fide coronavirus targeting microRNA will be useful in understanding the importance of microRNA as a cellular defence mechanism against pathogenic coronavirus infections.
We report whole-genome and intra-host variability of SARS-Cov-2 assessed by next generation sequencing (NGS) in upper (URT) and lower respiratory tract (LRT) from COVID-19 patients. The aim was to identify possible tissue-specific patterns and signatures of variant selection for each respiratory compartment. Six patients, admitted to the Intensive Care Unit, were included in the study. Thirteen URT and LRT were analyzed by NGS amplicon-based approach on Ion Torrent Platform. Bioinformatic analysis was performed using both realized in-house and supplied by ThermoFisher programs. Phylogenesis showed clade V clustering of the first patients diagnosed in Italy, and clade G for later strains. The presence of quasispecies was observed, with variants uniformly distributed along the genome and frequency of minority variants spanning from 1% to ~30%. For each patient, the patterns of variants in URT and LRT were profoundly different, indicating compartmentalized virus replication. No clear variant signature and no significant difference in nucleotide diversity between LRT and URT were observed. SARS-CoV-2 presents genetic heterogeneity and quasispecies compartmentalization in URT and LRT. Intra-patient diversity was low. The pattern of minority variants was highly heterogeneous and no specific district signature could be identified, nevertheless, analysis of samples, longitudinally collected in patients, supported quasispecies evolution.
For most patients with severe illness requiring hospitalization, COVID-19 has been a frightening and life-changing experience. At the peak of the pandemic, the attention of health care teams was focused on saving lives and protecting health services from being overwhelmed. Those who survived were often discharged without a robust process of follow-up. The prevalence of post–COVID-19 complications is not yet fully known and may only become apparent in the months and years to come. Data from previous coronavirus (severe acute respiratory syndrome coronavirus [SARS-CoV] and Middle East respiratory syndrome coronavirus [MERS-CoV]) outbreaks indicate that between 20% and 40% of survivors experience long-term complications. In a recent report of 143 patients with COVID-19 who were evaluated a mean of 2 months after hospital discharge at a follow-up clinic in Rome, Italy, many patients reported persistent fatigue (53.1%), dyspnea (43.4%), joint pain (27.3%), and chest pain (21.7%). Drawing on these experiences, respiratory, cardiovascular, neurologic, metabolic, and psychosocial complications may be important long-term sequelae of COVID-19. It is therefore essential that systems are in place for timely and thorough identification of such sequelae followed by appropriate interventions. We discuss the challenges we have addressed in establishing a multidisciplinary COVID-19 follow-up clinic in a secondary care setting at the University Hospital of Birmingham, England.
The chronic lung condition called COPD (chronic obstructive pulmonary disease) increases the risk of severe COVID-19. Inhaled corticosteroids (ICS) are commonly prescribed to stabilize respiratory function in these patients, but the associated risk of bacterial infection has daunted some healthcare professionals from using them. Moreover, in vitro, studies show that they have an immunosuppressive effect on cells exposed to viruses. There is no evidence to reveal the effects of ICS on either susceptibility to COVID-19 or the severity of infection in patients with COPD. A new study published on the preprint server medRxiv* aims to explore the effects of treatment with ICS on the expression of specific genes related to SARS-CoV-2 infection in bronchial epithelial cells in a prospective interventional design. It is known that COPD can upregulate the expression of angiotensin-converting enzyme (ACE2) in the human lungs. However, in vitro, studies show that ICS reduces ACE2 expression. Observational studies have shown that in both asthma and COPD, the use of ICS reduces the concentration of ACE2 mRNA in sputum. In the DISARM study, the researchers randomized 68 volunteers with mild to very severe COPD to receive either ICS along with a long-acting beta-agonist (LABA) or the LABA alone. Most were male, and the degree of blockage of the airways ranged from moderate to severe. The regimens in the two groups consisted of formoterol/budesonide 12/400 μg twice daily or salmeterol/fluticasone propionate 25/250 μg twice daily), for the first group, and formoterol 12 μg twice daily for the second.
Respiratory distress is the most common cause of near-term hospital readmission for patients with COVID-19, investigators have found. Among nearly 2,900 discharged patients studied, 103 returned to the emergency department within two weeks of discharge. Fully 56 of these required hospital readmittance. Respiratory complications were the chief complaint in half of these patients. They also had higher rates of chronic obstructive pulmonary disease and hypertension than their peers who did not return to the hospital, reported Girish Nadkarni, M.D., and colleagues from the Mount Sinai COVID Informatics Center. Hospital readmittance also was tied to shorter length of initial hospital stay, lower rates of anticoagulation treatment, and lower incidence of intensive care. There were no differences in age, sex or race/ethnicity in readmitted patients compared with those who did not return, the researchers wrote. The results show that some patients have substantial lingering effects from COVID-19, corresponding author Anuradha Lala, M.D., said. “As we move into a phase where COVID-19 is no longer a novel disease, we must transition our attention to the post-acute phase to understand how to keep patients well and out of the hospital,” she concluded.
We set out to analyze the incidence and predictive factors of pulmonary embolism (PE) in hospitalized patients with Covid-19. We prospectively collected data from all consecutive patients with laboratory-confirmed Covid-19 admitted to the Hospital de la Santa Creu i Sant Pau, a university hospital in Barcelona, between March 9 and April 15, 2020. Patients with suspected PE, according to standardized guidelines, underwent CT pulmonary angiography (CTPA). A total of 1,275 patients with Covid-19 were admitted to hospital. CTPA was performed on 76 inpatients, and a diagnosis of PE was made in 32 (2.6% [95%CI 1.7–3.5%]). Patients with PE were older, and they exhibited lower PaO2:FiO2 ratios and higher levels of D-dimer and C-reactive protein (CRP). They more often required admission to ICU and mechanical ventilation, and they often had longer hospital stays, although in-hospital mortality was no greater than in patients without PE. High CRP and D-dimer levels at admission (≥150 mg/L and ≥1,000 ng/ml, respectively) and a peak D-dimer ≥6,000 ng/ml during hospital stay were independent factors associated with PE. Prophylactic low molecular weight heparin did not appear to prevent PE. Increased CRP levels correlated with increased D-dimer levels and both correlated with a lower PaO2:FiO2.
British drugmaker AstraZeneca has begun testing an antibody-based cocktail for the prevention and treatment of COVID-19, adding to recent signs of progress on possible medical solutions to the disease caused by the novel coronavirus. The London-listed firm, already among the leading players in the global race to develop a successful vaccine, said the study would evaluate if AZD7442, a combination of two monoclonal antibodies (mAbs), was safe and tolerable in up to 48 healthy participants between the ages of 18 and 55 years. If the UK-based early-stage trial, which has dosed its participants, shows AZD7442 is safe, AstraZeneca said it would proceed to test it as both a preventative treatment for COVID-19 and a medicine for patients who have it, in larger, mid-to-late-stage studies. Development of mAbs to target the virus, an approach already being tested by Regeneron, ELi Lilly, Roche and Molecular Partners, has been endorsed by leading scientists. mAbs mimic natural antibodies generated in the body to fight off infection and can be synthesised in the laboratory to treat diseases in patients. Current uses include treatment of some types of cancers.
U.S. public health responses to emerging infections have involved public health agencies, healthcare systems, community leaders, and others. This Perspective will focus on providing an overview of U.S. public health resources (as of August 2020) related to the coronavirus disease 2019 (COVID-19) pandemic that might be most relevant to allergists/immunologists. A novel coronavirus was first reported in January 2020. This virus, subsequently named SARS-CoV-2, is thought to spread mainly from person to person through respiratory droplets among people who are in close contact (within about 6 feet). SARS-CoV-2 infection can result in mild to severe symptoms, which can include but are not limited to fever, chills, cough, difficulty breathing, fatigue, body aches, headache, new loss of taste or smell, sore throat, nasal congestion, rhinorrhea, nausea, vomiting, or diarrhea. Among >1.3 million laboratory-confirmed, adult and pediatric COVID-19 cases reported in the United States during January 22–May 30, 2020, 14% of cases were hospitalized, 2% were admitted to an intensive care unit, and 5% died. Limited available data suggest that among adults with severe COVID-19, dysregulated innate and adaptive immune responses contribute to host tissue damage.
People with asthma were not overrepresented in patients with severe pneumonia because of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who required hospitalization, according to study results published in the European Respiratory Journal. Researchers evaluated patient demographics, clinical history, asthma control history, and comorbid conditions from adult patients hospitalized with a diagnosis of SARS-CoV-2 infection and reporting a history of asthma. The outcomes of interest were mortality, length of intensive care unit (ICU) stay, and total length of hospital stay, which were compared with a random control group of individuals without asthma hospitalized for COVID-19 pneumonia. Of the 768 hospitalized patients with COVID-19, 37 reported a history of asthma, and 75 were randomly assigned to the nonasthma control group. Of the 37 patients with asthma, 70% were women, the mean age was 54 years, and body mass index was 28.3 kg/m², respectively. The median time from onset of symptoms to admission in the emergency room was 6 days. Compared with the control group, all differences between groups pointed to worse COVID-19 pneumonia in individuals without asthma. None of the patients with asthma presented with an exacerbation while in the hospital.
University of Hong Kong scientists claim to have the first evidence of someone being reinfected with the virus that causes COVID-19. Genetic tests revealed that a 33-year-old man returning to Hong Kong from a trip to Spain in mid-August had a different strain of the coronavirus than the one he’d previously been infected with in March, said Dr. Kelvin Kai-Wang To, the microbiologist who led the work. The man had mild symptoms the first time and none the second time; his more recent infection was detected through screening and testing at the Hong Kong airport. “It shows that some people do not have lifelong immunity” to the virus if they’ve already had it, To said. “We don’t know how many people can get reinfected. There are probably more out there.” Whether people who have had COVID-19 are immune to new infections and for how long are key questions that have implications for vaccine development and decisions about returning to work, school and social activities.
Every influenza season brings with it uncertainty about what strain will predominate and how severe it will be. While much of the world still is focusing on COVID-19, the potential for another serious influenza season can’t be ignored, and the strain on the health care system of 2 epidemics could be severe. As the SARS–CoV-2 virus continues to spread across the country, the 2020-2021 influenza season will be particularly challenging. Recent influenza seasons have been particularly serious: 2017-2018 was one of the deadliest in decades, with an estimated 61,000 deaths, and 2018-2019 was one of the longest flu seasons, lasting 21 weeks. In March 2019, the World Health Organization (WHO) announced a Global Influenza Strategy for 2019-2030 aimed at “protecting people in all countries from the threat of influenza.” The goals include the prevention of seasonal influenza, the control of spread from animals to humans, and preparation for the next influenza pandemic.
Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1β in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death.
SGLT2 inhibitors could potentially target key mechanisms activated in COVID-19, increasing lipolysis, reducing glycolysis, inflammation and oxidative stress, and improving endothelial function to reduce organ damage, according to a speaker. “We know that favorable effects on mechanisms such as endothelial function, a key driver of adverse outcomes in COVID-19, can occur very quickly after treatment with SGLT2 inhibitors,” Mikhail Kosiborod, MD, FACC, FAHA, cardiologist at Saint Luke’s Mid America Heart Institute, professor of medicine at the University of Missouri-Kansas City School of Medicine, said during an online presentation during the virtual Heart in Diabetes conference. “If you think through these mechanisms and the fact that SGLT2 inhibitors can have a positive impact on many of them, what becomes clear is that testing SGLT2 inhibitors as potential agents for organ protection in COVID-19 may be one of the key hypotheses.” The concept is relatively simple, Kosiborod said. Viral replication and spread after COVID-19 infection trigger metabolic derangements that lead to inflammatory “overdrive,” endothelial injury and, ultimately, organ damage leading to complications and death. Data suggest antiviral treatments can work in the early phase of the disease; anti-inflammatory medications show promise during the mid-phase of the disease.
Patients hospitalized with coronavirus disease 2019 (COVID-19) who were treated with noninvasive respiratory support outside of the intensive care unit (ICU) had favorable outcomes, but a risk of staff contamination persisted, according to study results published in The European Respiratory Journal. Medication, mode, and usage of noninvasive respiratory support were evaluated from hospitalized patients with COVID-19 treated outside of the ICU. The primary study outcomes were the length of stay in hospital, rate of endotracheal intubation, deaths, and staff infection rates. Of the 670 consecutive patients with confirmed COVID-19 referred to pulmonology units in 9 hospitals, 69.3% were men and the mean age was 68 years. Nearly half of the patients (49.3%) were treated with continuous positive airway pressure. The overall 30-day mortality rate was 26.9%, with specific rates of 16%, 30%, and 30%, for high-flow nasal cannula, continuous positive airway pressure, and noninvasive ventilation, respectively. The rates of endotracheal intubation and the length of stay in hospital were not different among the groups.
The pulmonary pathobiology of patients who died from respiratory failure caused by coronavirus disease 2019 (COVID-19) vs influenza was found to be distinct, according to a study published in the New England Journal of Medicine. A total of 24 lungs were obtained during the autopsy of patients who died from COVID-19 (n=7), from acute respiratory distress syndrome (ARDS) caused by influenza A (H1N1; n=7), or from causes other than infection (n=10). The lungs from patients infected with H1N1 were collected in 2009 and the lungs from control individuals were matched for age. Lungs were examined using a 7-color immunohistochemical analysis, micro-computed tomographic imaging, scanning electron microscopy, corrosion casting, and gene expression analysis through direct multiplexed measurement. The lungs from patients who died from COVID-19 were from 2 women (mean age, 68±9.2 years) and 5 men (mean age, 80±11.5 years). The H1N1 lungs were from 2 women (mean age, 62.5±4.9 years) and 5 men (mean age, 55.4±10.9 years). The control lungs were from 5 women (mean age, 68.2±6.9 years) and 5 men (mean age, 79.2±3.3 years). The lungs from patients with COVID-19 vs H1N1 were (2404±560 g vs 1681±49 g, respectively; P =.04), and lungs from control individuals (1045±91 g) were lighter compared with those from patients with COVID-19 and H1N1 vs (P <.001 and P =.003, respectively).
The SARS-CoV-2 pandemic has introduced the medical community to a lung disease heretofore unknown to most clinicians. In much of the discourse about COVID-19 lung disease, the more familiar clinical entity of ARDS has been used as the guiding paradigm. Reflecting on studies in ARDS, particularly that due to influenza, and on data from the SARS-CoV and MERS epidemics, many authorities, including within the discipline of infectious diseases, were initially passionate in their opposition to the use of corticosteroids for lung involvement in COVID-19. The voice of the pulmonology community—the community of lung experts—has continued to be among the quietest in this conversation. Herein we offer our perspective as academic pulmonologists who encountered COVID-19 in its first United States epicenter of New York City. We encourage a conceptual separation between early COVID-19 lung involvement and ARDS. We draw on history with other immune cell-mediated lung diseases, on insights from the SARS-CoV experience, and on frontline observations in an attempt to allay the skepticism towards corticosteroids in COVID-19 lung disease that is likely to persist even as favorable study results emerge.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has rapidly spread worldwide. Several studies have reported complications of COVID-19, such as bacterial pneumonia, acute respiratory distress syndrome (ARDS) and multiple organ failure syndromes. Recent guidelines for the management of adults critically ill with COVID-19 have suggested the empiric use of antimicrobial agents in patients with respiratory failure. The accurate and timely diagnosis of bacterial pneumonia, particularly in cases of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), is particularly challenging, and this condition remains a major cause of morbidity and mortality. Molecular tests provide a rapid turnaround time (TAT), together with identifications and semi-quantitative results for many pathogens responsive to antimicrobial therapy. Multiplex testing may provide additional information concerning the presence of antibiotic resistance genes, thereby improving antibiotic management. We performed a prospective single-center study on critically ill patients with COVID-19, in which we conducted parallel tests of blind bronchoalveolar lavage (BBAL) by conventional culture and FilmArray® Pneumonia Plus (FA-PP) panel. The aim of this study was to evaluate the performance of FA-PP and to compare its TAT with that of conventional cultures.
Identifying the extent of environmental contamination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for infection control and prevention. The extent of environmental contamination has not been fully investigated in the context of severe coronavirus disease (COVID-19) patients. Our objective was to investigate environmental SARS-CoV-2 contamination in the isolation rooms of severe COVID-19 patients requiring mechanical ventilation or high-flow oxygen therapy. We collected environmental swab samples and air samples from the isolation rooms of three COVID-19 patients with severe pneumonia. Patient 1 and Patient 2 received mechanical ventilation with a closed suction system, while Patient 3 received high-flow oxygen therapy and noninvasive ventilation. Real-time reverse transcription polymerase chain reaction (rRT-PCR) was used to detect SARS-CoV-2; viral cultures were performed for samples not negative on rRT-PCR.
Two recently published studies report success with extracorporeal membrane oxygenation support in patients with acute respiratory distress syndrome associated with COVID-19. In a retrospective cohort study published in The Lancet Respiratory Medicine, researchers analyzed clinical characteristics and outcomes of 492 patients treated with ECMO for COVID-19-associated ARDS at five ICUs within the Paris-Sorbonne University Hospital Network from March 8 to May 2. The researchers reported complete day-60 follow-up for 83 patients (median age, 49 years; 73% men) who received ECMO. Before ECMO, 94% of patients were prone positioned (median driving pressure, 18 cm H2O; ratio of arterial oxygen partial pressure to fractional inspired oxygen, 60 mm Hg). Sixty days after initiation of ECMO, the researchers’ estimated probability of death was 31% and the probability of being alive and out of the ICU was 45%.
It is important to distinguish asthma from chronic pulmonary diseases to elucidate COVID-19 risk, researchers reported in The Journal of Allergy and Clinical Immunology. “U.S.-based studies report that approximately 7% to 9% of hospitalized patients with COVID-19 had chronic lung disease, with asthma more prevalent than COPD. Recent analyses of COVID-19 cohorts suggest that chronic respiratory disease may unexpectedly be less of a risk factor for COVID-19 infection and severity than nonrespiratory diseases. However, most studies to date do not distinguish asthma from COPD within chronic respiratory disease, limiting identification of asthma-specific risk factors,” Liqin Wang, PhD, postdoctoral research fellow at the division of general internal medicine and primary care at Brigham and Women’s Hospital, Boston, and colleagues wrote in a letter to the editor. The researchers reported data from a case series of patients in the Mass General Brigham health system with a positive diagnosis of COVID-19, aged at least 18 years and a previous diagnosis of asthma. Wang and colleagues analyzed data on demographics, socioeconomic markers, BMI, insurance, smoking status, asthma medications, comorbidities and course of COVID-19 care. Patients were followed for 14 days from COVID-19 diagnosis for hospitalization and/or ICU admission, or by June 8, for death.
Clinical manifestations of COVID-19 have ranged from asymptomatic/mild symptoms to severe illness and mortality. Most of the mild and moderate cases are recovered completely but a small proportion of severe cases with acute respiratory distress syndrome continued to remain hypoxemic despite adequate treatment. Chest imaging of this subset of patients revealed fibrotic changes in the form of traction bronchiectasis, architectural distortion and septal thickening similar to the changes seen in other fibrotic lung diseases. The pathogenesis of post infective pulmonary fibrosis include dysregulated release of matrix metalloproteinases during the inflammatory phase of ARDS causing epithelial and endothelial injury with unchecked fibroproliferation. There is also a vascular dysfunction which is a key component of the switch from ARDS to fibrosis, with VEGF and cytokines such as IL-6 and TNFα being implicated. Although the role of presently available antifibrotic drugs (pirfenidone and nintedanib) for fibrotic lung diseases beyond idiopathic pulmonary fibrosis have been evaluated by some authors their role in post COVID-19 pneumonia pulmonary fibrosis need further research in the present pandemic.
Former CDC director Tom Frieden, MD, MPH, recently described a hierarchy of controls — elimination, substitution, engineering, administration and personal protective equipment — that may help prevent COVID-19 among health care workers. His remarks came during the National Medical Association’s Annual Meeting, held virtually due to the pandemic. Frieden said the “most effective” step is eliminating the hazard or infection. This can be accomplished by not allowing people who are ill to enter nursing homes and other congregate facilities. It can also be accomplished by ensuring that all hospitals and nursing home staffs have paid sick leave, so that there is no economic incentive to work while ill. If patients with COVID-19 cannot be separated from other patients and staff by engineering and substitution, PPE becomes necessary, Frieden said. When PPE is necessary, supply has to be ensured.
U.S. students are returning to school in person and online in the middle of a pandemic, and the stakes for educators and families are rising in the face of emerging research that shows children could be a risk for spreading the new coronavirus. Several large studies have shown that the vast majority of children who contract COVID-19, the disease caused by the virus, have milder illness than adults. And early reports did not find strong evidence of children as major contributors to the deadly virus that has killed more than 780,000 people globally. But more recent studies are starting to show how contagious infected children, even those with no symptoms, might be. “Contrary to what we believed, based on the epidemiological data, kids are not spared from this pandemic,” said Dr. Alessio Fasano, director of the Mucosal Immunology and Biology Research Center at Massachusetts General Hospital and author of a new study.
The Physicians Foundation’s 2020 Survey of America’s Physicians finds that the majority of physicians believe COVID-19 won’t be under control until January 2021, with nearly half not seeing the virus being under control until after June 1, 2021. Furthermore, a majority of physicians believe that the virus will severely impact patient health outcomes due to delayed routine care during the pandemic. Read and download the findings. The survey, conducted in July with more than 3,500 respondents, asked physicians how the pandemic is affecting their practices and patients. Nearly three-quarters of those surveyed said COVID-19 would have serious consequences for health in their communities because many are delaying needed care. Health insurance is another problem; 76% cited changes in employment and insurance status is a primary cause of harm to patients caused by COVID-19. But 59% believed opening schools, businesses and other public places posed a greater risk to their patients than continued social isolation. “The data reveals a near-consensus among America’s physicians about COVID-19’s immediate and lasting impact on our healthcare system,” said Dr. Gary Price, president of The Physicians Foundation, in a prepared statement.
Potential accuracy issues with a widely used coronavirus test could lead to false results for patients, U.S. health officials warned. The Food and Drug Administration issued the alert Monday to doctors and laboratory technicians using Thermo Fisher’s TaqPath genetic test. Regulators said issues related to laboratory equipment and software used to run the test could lead to inaccuracies. The agency advised technicians to follow updated instructions and software developed by the company to ensure accurate results. The warning comes nearly a month after Connecticut public health officials first reported that at least 90 people had received false positive results for the coronavirus. Most of those receiving the false results were residents of nursing homes or assisted living facilities. A spokeswoman for Thermo Fisher said the company was working with FDA “to make sure that laboratory personnel understand the need for strict adherence to the instructions for use.” She added that company data shows most users “follow our workflow properly and obtain accurate results.”
Given the reported health disparities in coronavirus disease 2019 (COVID-19) infection and mortality by race/ethnicity, there is an immediate need for increased assessment of the prevalence of COVID-19 across racial/ethnic subgroups of the population in the US. We examined the racial/ethnic prevalence of cumulative COVID-19 hospitalizations in the 12 states that report such data and compared how this prevalence differs from the racial/ethnic composition of each state’s population. Using data extracted from the University of Minnesota COVID-19 Hospitalization Tracking Project, we identified the 12 states that reported the race/ethnicity of individuals hospitalized with COVID-19 between April 30 and June 24, 2020. We calculated the percentage of cumulative hospitalizations by racial/ethnic categories averaged over the study period and then calculated the difference between the percentage of cumulative hospitalizations for each subgroup and the corresponding percentage of the state’s population for each racial/ethnic subgroup as reported in the US Census. The race/ethnicity categories included were White, Black, American Indian and/or Alaskan Native, Asian, and Hispanic. Descriptive statistical analyses were conducted using Stata/MP, version 14 (Stata Corp). The University of Minnesota Institutional Review Board reviewed the study data and deemed it exempt from review and informed consent requirements because the study was not human subjects research. This analysis of COVID-19 hospitalizations in 12 US states during nearly a 2-month period represented a total of 48 788 cumulative hospitalizations among a total population of 66 796 666 individuals in 12 US states.
Patients diagnosed with coronavirus disease 2019 (COVID-19) who are not admitted to the intensive care unit (ICU) may not require antibiotic therapy due to the low frequency of community-acquired coinfection, according to the results of a single-center study published in Clinical Infectious Diseases. Current literature estimates that coinfection in COVID-19 could range from 0% to 40% of patients. As such, concerns have been raised on whether coinfection could be a significant complication in COVID-19. However, only a few studies were designed to assess co-infection and differentiate between community- and hospital-acquired coinfection, coinfection definitions are variable, and microbiologic data are inconsistently reported. As a result of these challenges, the current guidelines on antibiotic use in COVID-19 patients are not strong. This retrospective, observational study described the rates of community-acquired coinfection in patients with COVID-19. In total, 321 patients with COVID-19 (³18 years of age) were admitted to the University of Chicago Medical Center in Chicago, Illinois during the evaluation period (March 1, 2020-April 11, 2020). The date of hospital admission, ICU admission, mortality, antibiotic administration, and microbiologic test results were examined. If positive test results were collected after the fifth day of hospital admission, patients were excluded to make sure only community-acquired coinfection was captured.
The findings of a second, nationwide trend survey of NPs assessing COVID-19’s impacts on NP professional practice demonstrate both significant progress and lingering challenges as health care providers work to stem the tide of the pandemic in communities nationwide. More than 80% of the profession reports their practices are better prepared to manage COVID-19 patients than at the start of the pandemic, with 35% indicating they are ready for a surge in COVID-19 cases. Despite marked progress in practice readiness and improving supplies of PPE, the number of NPs now testing positive for COVID-19 has increased three-fold since the early days of the pandemic. While acknowledging improvements in access, NPs identify testing as the most significant barrier to combatting COVID-19 in their communities, with one-third of NPs reporting patients being turned away from centralized testing sites for failure to meet pre-determined criteria, and 78% of NPs citing significant delays in receiving patients’ viral test results. Test result delays range from a low-end range of seven to 10 business days to a high-end of up to 20 days. This is the second national survey fielded by the American Association of Nurse Practitioners® (AANP), the largest national association of NPs of all specialties, aimed at understanding how COVID-19 is affecting the clinical practice of NPs across settings, specialties, and geographic location.
People infected with COVID-19 do not necessarily have immunity to reinfection for three months, the CDC said late Friday night, trying to squelch speculation the agency had inadvertently stimulated. While people can continue to test positive for SARS-CoV-2 for up to three months after diagnosis and not be infectious to others, that does not imply that infection confers immunity for that period, the agency said. The confusion stemmed from an August 3 update to CDC’s isolation guidance, which stated: Who needs to quarantine? People who have been in close contact with someone who has COVID-19 — excluding people who have had COVID-19 within the past 3 months. People who have tested positive for COVID-19 do not need to quarantine or get tested again for up to 3 months as long as they do not develop symptoms again. People who develop symptoms again within 3 months of their first bout of COVID-19 may need to be tested again if there is no other cause identified for their symptoms. These statements could be read as suggesting that those recovering from COVID-19 will likely be safe from reinfection for three months even with close exposure to infected people. Media reports took this as a tacit acknowledgment of immunity from the agency.
Although many viral respiratory illnesses are transmitted within households, the evidence base for SARS-CoV-2 is nascent. We sought to characterize SARS-CoV-2 transmission within US households and estimate the household secondary infection rate (SIR) to inform strategies to reduce transmission. We recruited laboratory-confirmed COVID-19 patients and their household contacts in Utah and Wisconsin during March 22–April 25, 2020. We interviewed patients and all household contacts to obtain demographics and medical histories. At the initial household visit, 14 days later, and when a household contact became newly symptomatic, we collected respiratory swabs from patients and household contacts for testing by SARS-CoV-2 rRT-PCR and sera for SARS-CoV-2 antibodies testing by enzyme-linked immunosorbent assay (ELISA). We estimated SIR and odds ratios (OR) to assess risk factors for secondary infection, defined by a positive rRT-PCR or ELISA test. Thirty-two (55%) of 58 households had evidence of secondary infection among household contacts. The SIR was 29% (n = 55/188; 95% confidence interval [CI]: 23–36%) overall, 42% among children (<18 years) of the COVID-19 patient and 33% among spouses/partners. Household contacts to COVID-19 patients with immunocompromised conditions had increased odds of infection (OR: 15.9, 95% CI: 2.4–106.9). Household contacts who themselves had diabetes mellitus had increased odds of infection (OR: 7.1, 95% CI: 1.2–42.5).
Masimo announced today that it received FDA clearance for its PVi for fluid responsiveness indication in ventilated adult patients. PVi (pleth variability index) now has indication as a continuous, non-invasive, dynamic indicator of responsiveness in select populations of mechanically ventilated adult patients, as it measures dynamic changes in the perfusion index that occur during the respiratory cycle, according to a news release. Irvine, Calif.-based Masimo’s PVi is available alongside its SET pulse oximetry and Rainbow pulse co-ocimetry on a variety of sensors, using a proprietary algorithm based on the relative variability of the pleth waveform. In an 18,716-patient study in France, researchers found that using PVi alongside Masimo’s SpHb continuous hemoglobin monitoring technology led to earlier transfusion and fewer units of blood transfused, as well as a 33% lower mortality rate 30 days after surgery, which trickled down to a 29% rate 90 days after surgery.
Pulmonary edema is a prominent feature in patients with severe COVID-19. SARS-CoV-2 enters the cell via ACE2. ACE2 is involved in degrading the kinin des-Arg9-bradykinin, a potent vasoactive peptide that can cause vascular leakage. Loss of ACE2 might lead to plasma leakage and further activation of the plasma kallikrein-kinin system with more bradykinin formation that could contribute to pulmonary angioedema via stimulation of bradykinin 2 receptors. We investigated whether treatment with the bradykinin 2 receptor antagonist icatibant in patients with COVID-19 could be used as a treatment strategy. This case-control study was approved by CMO region Arnhem-Nijmegen, the local ethical committee, which granted a waiver of consent because treatment concerned a licensed drug that would be given in an off-label setting. Informed consent was obtained in all patients. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. We included 10 patients for treatment with 3 doses of 30 mg of icatibant by subcutaneous injection at 6-hour intervals. Patients were eligible for icatibant treatment if they had confirmed SARS-CoV-2 by polymerase chain reaction assay, an oxygen saturation of less than 90% without supplemental oxygen, needed 3 L/min supplemental oxygen or more, and had a computed tomography severity score of 7 or greater. Patients with acute ischemic events at time of eligibility were excluded. For 9 patients who received icatibant on the ward, 2 matched control patients admitted prior to approval of this treatment were selected. Control patients with COVID-19 were matched on the factors sex, age, body mass index, and day of illness.
COVID-19 has had a significant impact on all aspects of PH, from diagnosis and management to observing an increased risk of death in patients with PAH. In addition, because of the vulnerable nature of this population, the pandemic has impacted the very manner in which care is delivered in PH. The risks associated with COVID-19 in patients with PH are significant. In a US survey of 77 PAH Comprehensive Care Centers, the incidence of COVID-19 infection was 2.1 cases per 1,000 patients with PAH, which is similar to the incidence of COVID-19 infection in the general US population. But although COVID-19 did not seem to be more prevalent in patients with PAH, the mortality did appear to be higher at 12%. In addition, 33% of patients with PAH who were infected with COVID-19 ended up being hospitalized. With the outbreak of COVID-19, it became necessary to revisit the manner in which patients receive care to decrease risk of contracting the virus.
Venous thromboembolism (VTE) has been reported in mechanically ventilated patients with severe SARS-CoV-2 infection (COVID-19). Two of the first 31 non-mechanically ventilated patients with moderate severity COVID-19 admitted to our hospital developed VTE while receiving uninterrupted prophylactic anticoagulation. Both non-mechanically ventilated patients hospitalized with COVID-19 developed symptomatic VTE while receiving uninterrupted standard prophylactic dose unfractionated or low molecular weight heparin. Reports linking severe COVID-19 and increased risk for VTE have emerged, including a high incidence of abnormal D-dimer levels among patients with COVID-19, an association between COVID-19-associated disturbances in the coagulation pathway and increased mortality, and lower 28-day mortality among patients with COVID-19 who received prophylactic heparin if they had D-dimer >3.0 mg/L or sepsis-induced coagulopathy score >4. Experts also have published interim summaries and guidance for managing VTE risk in patients with COVID-19, although the optimal approach for inpatient VTE risk stratification and prophylaxis remains uncertain. Our observations suggest that moderate severity COVID-19 might also predispose hospitalized patients to higher VTE risk than standard RAMS would predict and might even precipitate acute VTE despite use of standard prophylactic-dose anticoagulant medications.
What are the safety and immunogenicity of an inactivated vaccine against coronavirus disease 2019 (COVID-19)? This was an interim analysis of 2 randomized placebo-controlled trials. In 96 healthy adults in a phase 1 trial of patients randomized to aluminum hydroxide (alum) only and low, medium, and high vaccine doses on days 0, 28, and 56, 7-day adverse reactions occurred in 12.5%, 20.8%, 16.7%, and 25.0%, respectively; geometric mean titers of neutralizing antibodies at day 14 after the third injection were 316, 206 and 297 in the low-, medium-, and high-dose groups, respectively. In 224 healthy adults randomized to the medium dose, 7-day adverse reactions occurred in 6.0% and 14.3% of the participants who received injections on days 0 and 14 vs alum only, and 19.0% and 17.9% who received injections on days 0 and 21 vs alum only, respectively; geometric mean titers of neutralizing antibodies in the vaccine groups at day 14 after the second injection were 121 vs 247, respectively.
The prognosis of hospitalized patients with severe coronavirus disease 2019 (COVID-19) is difficult to predict, while the capacity of intensive care units (ICUs) is a limiting factor during the peak of the pandemic and generally dependent on a country’s clinical resources. The purpose of the study was to determine the value of chest radiographic findings together with patient history and laboratory markers at admission to predict critical illness in hospitalized patients with COVID-19. In this retrospective study including patients from 7th March 2020 to 24th April 2020, a consecutive cohort of hospitalized patients with RT-PCR-confirmed COVID-19 from two large Dutch community hospitals was identified. After univariable analysis, a risk model to predict critical illness (i.e. death and/or ICU admission with invasive ventilation) was developed, using multivariable logistic regression including clinical, CXR and laboratory findings. Distribution and severity of lung involvement was visually assessed using an 8-point scale (chest radiography score). Internal validation was performed using bootstrapping. Performance is presented as an area under the receiver operating characteristic curve (AUC). Decision curve analysis was performed, and a risk calculator was derived. The cohort included 356 hospitalized patients (69 ±12 years, 237 male) of whom 168 (47%) developed critical illness.
Seldom does a vaccine researcher’s job include calling city hall, big-box stores like Walmart and Target, and the US Postal Service. But Ann Falsey, MD, had those tasks on her to-do list in June as she prepared to recruit volunteers to test potential vaccines for coronavirus disease 2019 (COVID-19). Falsey, of the University of Rochester School of Medicine, hoped large employers in her area would publicize vaccine trials to their essential workers, many of whom are Black or Hispanic. “We are thinking very hard about not only how to get a diverse population that reflects the US population but also people at high risk—postal workers, home health workers, you name it,” she said. COVID-19’s startling toll on minorities has drawn widespread attention to the need for diversity in large-scale phase 3 vaccine trials. Two 30 000-person trials, led by Moderna and a joint effort of Pfizer and BioNTech, began on July 27. AstraZeneca was expected to start US recruitment to test its vaccine, developed with Oxford University, in August, followed by Johnson & Johnson in September and Novavax later this fall.
With the limited availability of testing for the presence of the SARS-CoV-2 virus and concerns surrounding the accuracy of existing methods, other means of identifying patients are urgently needed. Previous studies showing a correlation between certain laboratory tests and diagnosis suggest an alternative method based on an ensemble of tests. Here, a machine learning model was trained to analyze the correlation between SARS-CoV-2 test results and 20 routine laboratory tests collected within a 2-day period around the SARS-CoV-2 test date. We used the model to compare SARS-CoV-2 positive and negative patients. In a cohort of 75,991 veteran inpatients and outpatients who tested for SARS-CoV-2 in the months of March through July, 2020, 7,335 of whom were positive by RT-PCR or antigen testing, and who had at least 15 of 20 lab results within the window period, our model predicted the results of the SARS-CoV-2 test with a specificity of 86.8%, a sensitivity of 82.4%, and an overall accuracy of 86.4% (with a 95% confidence interval of [86.0%, 86.9%]). While molecular-based and antibody tests remain the reference standard method for confirming a SARS-CoV-2 diagnosis, their clinical sensitivity is not well known. The model described herein may provide a complementary method of determining SARS-CoV-2 infection status, based on a fully independent set of indicators, that can help confirm results from other tests as well as identify positive cases missed by molecular testing.
The total of number of confirmed COVID-19 cases worldwide went over the 20 million mark on Tuesday, the Johns Hopkins Coronavirus Resource Center reported. The number of us cases has grown exponentially since the virus was first reported in China about 6-and-a-half months ago. Total cases hit the 1 million mark on April 2, CNN reported. Ten million cases were recorded in late June. It took less than 6 weeks to double that figure as case counts surged in the United States and Latin America. The number of cases is probably much higher because of testing limitations and a high number of infected people who show no symptoms. Deaths have also gone up. More than 737,000 have people died worldwide, Johns Hopkins said. The nations with the most cases are the United States (almost 5.1 million with more than 163,000 deaths), Brazil (3 million cases and 101,000 deaths), India (2.2 million cases and 45,000 deaths), Russia (895,000 cases and 15,000 deaths), and South Africa (563,000 cases and 10,600 deaths). Africa recorded its 1 millionth case last week. The 7-day average of new cases has been more than 250,000 for two weeks, CNN said.
Steroid use for COVID-19 is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by SARS-Co-2. This study aimed at evaluating at evaluating the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19. This parallel, double-blind, placebo-controlled, randomized, phase IIb clinical trial was performed with hospitalized patients aged ≥ 18 years with clinical, epidemiological and/or radiological suspected COVID-19, at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution), twice daily, for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality. During the study, 647 patients were screened, 416 randomized, and 393 analyzed as mITT, MP in 194 and placebo in 199 individuals. SARS-CoV-2 infection was confirmed by RT-PCR in 81.3%. Mortality at day 28 was not different between groups. A subgroup analysis showed that patients over 60 years in the MP group had a lower mortality rate at day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until day 7.
[Podcast] In this episode of Annals On Call, Dr. Centor discusses challenges to diagnosing COVID-19 with Dr. Jeanne Marrazzo. Annals On Call focuses on a clinically influential article published in Annals of Internal Medicine. Dr. Robert Centor shares his own perspective on the material and interviews topic area experts to discuss, debate, and share diverse insights about patient care and health care delivery.
Many states initially spared from the COVID-19 pandemic is March, April, and May, are now reporting increasing transmission rates in non-metropolitan counties fueled by community spread. According to the Wall Street Journal, in Ohio, Missouri, Wisconsin, and Illinois, the weekly change in COVID-19 cases has been higher in rural regions compared to metro areas, and outbreaks are linked to social events, rather than workplace exposure or congregate living situations. A summer of waning social distancing restrictions has made bars and restaurants common COVID-19 outbreak sites, on par with nursing homes and prisons states across the country. In Louisiana, the New York Times reports bars and restaurants are linked to 25% of the state’s cases, and in Maryland, that percentage was 12%. Fueling these outbreaks are the twin forces of a national “quarantine fatigue” and young adults, who are more likely than older, more at-risk Americans, to be both patrons and employees in dining and drinking establishments. Young adults are driving outbreaks in many states, and experts worry those with mild or asymptomatic cases are spreading the disease to more vulnerable household members.
We are in a war against COVID-19, and this fall could be one of the worst from a public health standpoint that the U.S. has ever faced, says CDC Director Robert Redfield, MD. The surging coronavirus pandemic, paired with the flu season, could create the “worst fall” that “we’ve ever had,” he said during an interview on “Coronavirus in Context,” a video series hosted by John Whyte, MD, WebMD’s chief medical officer. Redfield also said the agency’s efforts to understand the virus were hampered by a lack of cooperation from China. He reached out to China CDC Director George Gao on Jan. 3 to see if the agency could work with health officials in Wuhan to better understand the outbreak. But he never received an invitation, Redfield said. “I think if we had been able to get in at that time, we probably would have learned quicker than we learned here,” Redfield said.
Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS), necessitating prolonged mechanical ventilation. In some cases, even ventilatory support fails. Venovenous extracorporeal membrane oxygenation (ECMO) has been used in severe cases of respiratory failure. However, the need for prolonged ventilation, sedation, and immobility may limit its long-term benefits. The application of ECMO in patients with COVID-19 whose condition has rendered mechanical ventilatory support insufficient is not fully established. Data were collected retrospectively from 40 consecutive patients with COVID-19 who were in severe respiratory failure and supported with ECMO. Each diagnosis of COVID-19 was confirmed using polymerase chain reaction–based assays. Patients were treated at 2 tertiary medical centers in Chicago, Illinois. The research protocol was approved by the institutional review boards of the Advocate Christ Medical Center and the Rush University Medical Center with a waiver for consent because of the inability of patients to give consent. A single-access, dual-stage right atrium–to-pulmonary artery cannula was implanted, following which ventilation was discontinued while the patient continued to receive ECMO. Patient selection criteria were similar to those of the ECMO to Rescue Lung Injury in Severe ARDS (EOLIA) trial group. The primary outcome was survival following safe discontinuation of ventilatory and ECMO supports.
Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS), necessitating prolonged mechanical ventilation. In some cases, even ventilatory support fails. Venovenous extracorporeal membrane oxygenation (ECMO) has been used in severe cases of respiratory failure. However, the need for prolonged ventilation, sedation, and immobility may limit its long-term benefits. The application of ECMO in patients with COVID-19 whose condition has rendered mechanical ventilatory support insufficient is not fully established. We present our experience in using single-access, dual-stage venovenous ECMO, with an emphasis on early extubation of patients while they received ECMO support. Data were collected retrospectively from 40 consecutive patients with COVID-19 who were in severe respiratory failure and supported with ECMO. Each diagnosis of COVID-19 was confirmed using polymerase chain reaction–based assays. A single-access, dual-stage right atrium–to-pulmonary artery cannula was implanted, following which ventilation was discontinued while the patient continued to receive ECMO. Patient selection criteria were similar to those of the ECMO to Rescue Lung Injury in Severe ARDS (EOLIA) trial group. The primary outcome was survival following safe discontinuation of ventilatory and ECMO supports. Excel for Office 365 2020 (Microsoft) was used for data analysis.
Two men with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) survived after treatment with off-the-shelf regulatory T cells, also known as Tregs, Johns Hopkins physicians recently reported. The investigational allogenic Tregs with lung-homing markers were derived from cord blood. The critically ill patients, aged 69 years and 47 years, had multiorgan failure and had been treated with therapies including tocilizumab, hydroxychloroquine, broad-spectrum antibiotics, vasopressors, and inhaled nitric oxide. The men were intubated in prone positions and the 47-year-old received extracorporeal membrane oxygenation (ECMO) support. The men eventually were extubated and needed tracheostomies. When the study was written, the patient who had undergone ECMO was discharged home and the other was at a ventilator weaning facility.
More than 900 front-line health care workers have died of COVID-19, according to an interactive database unveiled Wednesday by The Guardian and KHN. Lost on the Frontline is a partnership between the two newsrooms that aims to count, verify and memorialize every U.S. health care worker who dies during the pandemic. KHN and The Guardian are tracking health care workers who died from COVID-19 and writing about their lives and what happened in their final days. It is the most comprehensive accounting of U.S. health care workers’ deaths in the country. As coronavirus cases surge — and dire shortages of lifesaving protective gear like N95 masks, gowns and gloves persist — the nation’s health care workers are again facing life-threatening conditions in Southern and Western states. Through crowdsourcing and reports from colleagues, social media, online obituaries, workers unions and local media, Lost on the Frontline reporters have identified 922 health care workers who reportedly died of COVID-19 and its complications. A team of more than 50 journalists from the Guardian, KHN and journalism schools have spent months investigating individual deaths to make certain that they died of COVID-19, and that they were indeed working on the front lines in contact with COVID patients or working in places where they were being treated. Thus far, we have independently confirmed 167 deaths and published their names, data and stories about their lives and how they will be remembered. The tally includes doctors, nurses and paramedics, as well as crucial support staff such as hospital custodians, administrators and nursing home workers, who put their own lives at risk during the pandemic to care for others.
The use of chest CT for COVID-19 diagnosis or triage in healthcare settings with limited SARS-CoV-2 PCR capacity is controversial. CO-RADS categorization of the level of COVID-19 suspicion might improve diagnostic performance. Our purpose was to investigate the value of chest CT with CO-RADS classification to screen for asymptomatic SARS-CoV-2 infections and to determine its diagnostic performance in individuals with COVID-19 symptoms during the exponential phase of viral spread. In this secondary analysis of a prospective trial (Clinical Trial Number: IRB B1172020000008), from March 2020 to April 2020, we performed parallel SARS-CoV-2 PCR and CT with categorization of COVID-19 suspicion by CO-RADS, for individuals with COVID-19 symptoms and controls without COVID-19 symptoms admitted to the hospital for medical urgencies unrelated to COVID-19. CT-CORADS was categorized on a 5-point scale from 1 (very low suspicion) to 5 (very high suspicion). AUC were calculated in symptomatic versus asymptomatic individuals to predict positive SARS-CoV-2 positive PCR and likelihood ratios for each CO-RADS score were used for rational selection of diagnostic thresholds.
For months scientists have urged the public to wear masks, wash their hands and socially distance. And as the flu season approaches, those practices have never been more crucial. Depending on whether people heed this advice, the U.S. could either see a record drop in flu cases or a dangerous viral storm, doctors say. “We just have no idea what’s going to happen. Are we going to get a second surge [of coronavirus]?” says Peter Chai, MD, an emergency physician at the Brigham and Women’s Hospital in Boston. . “Hopefully, knock on wood, that won’t happen.” To get an idea of how the flu season might go, public health officials in the U.S. often look to Australia and other countries in the southern hemisphere, where they are in the winter flu season. This season so far in Australia, COVID-19 precautions have served to curb the pandemic while also protecting residents against the flu. Canberra had only one case for the week ending July 26, the most recent report available. It’s had 190 total cases so far this flu season – which runs March through August – compared to 2,000 last year. Activity is low in the country overall, with just 36 deaths reported so far. And that’s not just true in Australia. The World Health organization reports few cases worldwide. But only time will tell whether the U.S. will follow suit. If not, the consequences could be dire, leaving people even more vulnerable to COVID-19 and potentially overwhelming hospitals, says Aubree Gordon, associate professor of epidemiology at the University of Michigan School of Public Health.
The authors surveyed the Association of Bioethics Program Directors, advisors to hospital governing leadership in over 70 institutions throughout North America, asking:
o Whether a ventilator triage policy had been implemented in the wake of the COVID-19 pandemic,
o What criteria would be used in such a policy, and
o Which individuals are or would be involved in creating or activating the policy, or in adjudicating individual decisions.
A majority of institutions did not have a ventilator triage policy in place at the time of the survey. With 92% response rate, over half (54%) of the respondents reported no ventilator triage policy in their institution, and 10% reported inability to publicly share their policy. Findings from the 26 unique available policies were thus reported.
A 74-year-old white woman presents to an emergency department in Flint, Michigan, after suffering with low-grade fever, dry cough, and shortness of breath for the previous 2 days. Her medical history for the week before includes elective surgery at an¬other hospital for total replacement of the right knee. She notes that she was healthy on admission and at discharge. She stayed in a private room, and had no contact with individuals who were ill or who had traveled recently. Lung auscultation reveals bilateral rhonchi with rales, and chest radiography shows patchy air space opacity in the right upper lobe suspicious for pneumonia. Concerns about community transmission of COVID-19 prompt a nasopharyngeal swab for detection of SARS-CoV-2. The patient is admitted to the airborne-isolation unit, maintaining compliance to the CDC recommendations for contact, droplet, and airborne precautions. Results of the nasopharyngeal swab are positive for SARS-CoV-2. Clinicians start treatment with oral hydroxychloroquine 400 mg once and then 200 mg twice a day, along with intravenous azithromycin 500 mg once a day, zinc sulfate 220 mg three times a day, and oral vitamin C 1 g twice a day. When blood and sputum cultures are negative for any organisms, broad-spectrum antibiotics are discontinued. The patient’s dyspnea rapidly worsens, and oxygen requirements increase to 15 liters. She is drowsy, in moderate distress, and her airways remain unprotected. On day 7, the second day of mechanical ventilation, at the request of the family when the patient develops ARDS, she is started on a continuous intravenous infusion of high-dose vita¬min C (11 g /24 hours). Two days later, her clinical condition gradually begins to improve, and the clinicians discontinue supportive treatment with norepinephrine. On day 10, the fifth day of mechanical ventilation, another chest x-ray shows that both the pneumonia and interstitial edema have improved considerably. The patient responds well to a spontaneous breathing trial with continuous positive airway pressure/pressure support, with the settings of positive end-expiratory pressure (PEEP) of 7 mm Hg, pressure support above PEEP of 10 mm Hg, and a fraction of inspired oxygen of 40%.
The U.S. logged 5 million confirmed COVID-19 cases, hitting another grim milestone in the nearly 6-month long pandemic that has devastated the country. The U.S. tally is substantially larger than the next closest country, Brazil, which has logged roughly 3 million cases. It is roughly 2.5 times the size of the outbreak in India, though the total population in that country is more than 4 times as large. Experts say the number of cases underscores the failure of our national response. In July, newly reported cases in the U.S. topped 70,000 a day. “Seventy thousand was the number of cases that they had in Wuhan, China where this started, in total. So we were having a Wuhan a day in this country,” says Carlos Del Rio, MD, an infectious disease specialist and a professor of Global Health and Epidemiology at Emory University in Atlanta. “We’re doing a crappy job.” While cases have slowed slightly in recent days, they have been rapidly accelerating in the U.S. Since the introduction of the virus, it took the U.S. more than 12 weeks to reach its first 1 million cases, 7 weeks to amass 2 million cases, 3.5 weeks to reach 3 million, and 2.5 weeks to hit 4 million, and another 2.5 weeks to reach 5 million.
The efficacy and safety of methylprednisolone in mechanically ventilated patients with acute respiratory distress syndrome due to coronavirus disease 2019 (COVID-19) are unclear. In this study, we evaluated the association between use of methylprednisolone and key clinical outcomes. Clinical outcomes associated with the use of methylprednisolone were assessed in an unmatched, case-control study; a subset of patients also underwent propensity-score matching. The primary outcome was ventilator-free days by 28 days after admission. Secondary outcomes included extubation, mortality, discharge, positive cultures, and hyperglycemia. A total of 117 patients met inclusion criteria. Propensity matching yielded a cohort of 42 well-matched pairs. Groups were similar except for hydroxychloroquine and azithromycin use, which were more common in patients who did not receive methylprednisolone. Mean ventilator free-days were significantly higher in patients treated with methylprednisolone (6.21±7.45 versus 3.14±6.22; P = 0.044). The probability of extubation was also increased in patients receiving methylprednisolone (45% versus 21%; P = 0.021), and there were no significant differences in mortality (19% versus 36%; P = 0.087). In a multivariable linear regression analysis, only methylprednisolone use was associated with higher number of ventilator-free days (P = 0.045). The incidence of positive cultures and hyperglycemia were similar between groups.
[Video] Dr. John Whyte, Chief Medical Officer at Web MD, discusses the future of healthcare right now during COVID and post-COVID? Dr. Whyte interviews Dr. Bertalan Mesko, a self-described “geek physician” with a PhD in genomics and a medical futurist.
The newly emerging COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has swept nearly all over the world with stunning mortality. Even lots of researches have been investigated, few pathologies in living lung tissue has been reported due to barely accessible biopsy. Here, we investigated the pathological characteristics of an alive patient who suffered from severe infection with SARS-CoV-2. This study is in accordance with regulations issued by the National Health Commission of China. Our findings will facilitate understanding of the histopathology and the treatment of COVID-19, and improve clinical strategies against the disease. The patient’s lung morphological, ultrastructure, and some important inflammatory biological markers changes are presented to help better understand the disease and make a clue for all the multidisciplinary team to save more people.
Several underlying conditions have been associated with severe SARS-CoV2 illness, it remains unclear if underlying asthma is associated with worse COVID-19 outcomes. Given the high prevalence of asthma in the New York City area, the objective was to determine if underlying asthma was associated with poor outcomes among hospitalized patients with severe COVID-19 disease compared to patients without asthma. Electronic heath records were reviewed for 1,298 sequential patients age <65 years without chronic obstructive pulmonary disease (COPD) who were admitted to our hospital system with a confirmed positive SARS-CoV-2 test. The overall prevalence of asthma among all hospitalized patients with COVID-19 was 12.6%, yet a higher prevalence (23.6%) was observed in the subset 55 patients <21 years of age. There was no significant difference in hospital length of stay, need for intubation, length of intubation, tracheostomy tube placement, hospital readmission or mortality between asthmatic vs. non-asthmatic patients.
The objective of the study was to examine outcomes among patients who were treated with the targeted anti-cytokine agents, anakinra or tocilizumab, for COVID-19 -related cytokine storm (COVID19-CS). We conducted a retrospective cohort study of all SARS-coV2-RNA-positive patients treated with tocilizumab or anakinra in Kaiser Permanente Southern California. Local experts developed and implemented criteria to define COVID19-CS. All variables were extracted from the electronic health record. At tocilizumab initiation (n = 52), 50 (96.2%) were intubated, and only 7 (13.5%) received concomitant corticosteroids. At anakinra initiation (n = 41), 23 (56.1%) were intubated, and all received concomitant corticosteroids. Fewer anakinra-treated patients died (n = 9, 22%) and more were extubated/never intubated (n = 26, 63.4%) compared to tocilizumab-treated patients (n = 24, 46.2% dead, n = 22, 42.3% extubated/never intubated).
In the case of an infection, the SARS-CoV-2 virus must overcome various defense mechanisms of the human body, including its non-specific or innate immune defense. During this process, infected body cells release messenger substances known as type 1 interferons. These attract natural killer cells, which kill the infected cells. One of the reasons the SARS-CoV-2 virus is so successful — and thus dangerous — is that it can suppress the non-specific immune response. In addition, it lets the human cell produce the viral protein PLpro (papain-like protease). PLpro has two functions: It plays a role in the maturation and release of new viral particles, and it suppresses the development of type 1 interferons. The German and Dutch researchers have now been able to monitor these processes in cell culture experiments. Moreover, if they blocked PLpro, virus production was inhibited and the innate immune response of the human cells was strengthened at the same time. Professor Ivan Dikic, Director of the Institute of Biochemistry II at University Hospital Frankfurt and last author of the paper, explains: “We used the compound GRL-0617, a non-covalent inhibitor of PLpro, and examined its mode of action very closely in terms of biochemistry, structure and function. We concluded that inhibiting PLpro is a very promising double-hit therapeutic strategy against COVID-19. The further development of PLpro-inhibiting substance classes for use in clinical trials is now a key challenge for this therapeutic approach.”
Are there viral load differences between asymptomatic and symptomatic patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection? There is limited information about the clinical course and viral load in asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this study was to quantitatively describe SARS-CoV-2 molecular viral shedding in asymptomatic and symptomatic patients. In this cohort study that included 303 patients with SARS-CoV-2 infection isolated in a community treatment center in the Republic of Korea, 110 (36.3%) were asymptomatic at the time of isolation and 21 of these (19.1%) developed symptoms during isolation. The cycle threshold values of reverse transcription–polymerase chain reaction for SARS-CoV-2 in asymptomatic patients were similar to those in symptomatic patients. Many individuals with SARS-CoV-2 infection remained asymptomatic for a prolonged period, and viral load was similar to that in symptomatic patients; therefore, isolation of infected persons should be performed.
Healthcare workers of color were more likely to care for patients with suspected or confirmed COVID-19, more likely to report using inadequate or reused protective gear, and nearly twice as likely as white colleagues to test positive for the coronavirus, a new study found. The study from Harvard Medical School researchers also showed that healthcare workers are at least three times more likely than the general public to report a positive COVID test, with risks rising for workers treating COVID patients. Dr. Andrew Chan, a senior author and an epidemiologist at Massachusetts General Hospital, said the study further highlights the problem of structural racism, this time reflected in the front-line roles and personal protective equipment provided to people of color. “If you think to yourself, ‘healthcare workers should be on equal footing in the workplace,’ our study really showed that’s definitely not the case,” said Chan, who is also a professor at Harvard Medical School. The study was based on data from more than 2 million COVID Symptom Study app users in the U.S. and the United Kingdom from March 24 through April 23. The study, done with researchers from King’s College London, was published in the journal The Lancet Public Health.
It was late April, near the height of the Covid-19 pandemic in the big cities in the northeastern U.S., and anesthesiologist Joseph Savino was puzzled. In two months, an unexpectedly high number of coronavirus patients had died in his intensive care unit at the Hospital of the University of Pennsylvania after a stroke caused by bleeding in the brain. All were among 15 Covid-19 patients at the Philadelphia hospital who had been on a life-support technology called ECMO that is a last resort for patients when mechanical ventilators fail to help their virus-ravaged lungs. ECMO, for extracorporeal membrane oxygenation — essentially an artificial lung — is high-risk, but still, the number of fatal brain bleeds seemed unusual, said Savino, a critical-care specialist. It was too low, however, “to draw any substantive conclusions” about cutting back the blood-thinning drugs they were giving other Covid-19 patients on ECMO, because blood clots, not bleeds, were seen as the major risk to survival. Swamped by overflowing ICUs and the myriad not-seen-before ways the novel coronavirus attacks the body, doctors caring for the pandemic’s sickest patients are scrambling to share their experiences with each other in real time, hoping to find ways to stanch Covid-19’s devastating toll. Some 200 physicians from several countries and dozens of states have participated in the Friday Zoom sessions.
[Infographic] In this State of Physician Survey, COVID-19’s effect on the office visit was the subject. With over 1,000 responses from a variety of specialties, physicians were candid about navigating a new normal with COVID-19 and the office visit. Accommodating safe distancing in the waiting room to patient compliance and education are top areas of concern highlighted on the infographic.
SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry to the cell and the serine protease TMPRSS2 for S protein prim. Higher ACE2 expression was recently reported in nasal compared to throat tissue. In fact, higher SARS-CoV-2 viral load was detected in nasal compared to throat swabs obtained from COVID-19 infected patients, and that was attributed to the difference in ACE2 expression between both tissues. In fact, higher SARS-CoV-2 viral load was detected in nasal compared to throat swabs obtained from COVID-19 infected patients. This was attributed to the difference in ACE2 expression between both tissues [4]. Recently, we have also shown that the upper airway expresses more SARS-CoV-2 entry genes, ACE2 and TMPRSS2 compared to the lower airway. Moreover, Hou et al, have recently established that multiciliated cells are the main cell types expressing ACE2 in nasal tissue and infected with SARS-CoV-2. Moreover, Sungnak et al by analyzing data of single-cell RNA-sequencing from healthy human nasal epithelial cells showed that ACE2 and TMPRSS2 are co-expressed in nasal epithelium with genes involved in host innate immunity, referring to the potential role of these cells in initiating SARS-CoV-2 infection. Therefore, the level of SARS-CoV-2 receptors in nasal tissue may determine the level of viral infectivity given the fact that these receptors are not upregulated following infection [1]. With that in mind, we decided to investigate potential factors that may affect the expression of SARS-CoV-2 receptors and hence the risk of infectivity with COVID-19 in various phenotypes of sinonasal inflammation.
More work needs to be done to enroll people of color in clinical trials, Freda Lewis-Hall, MD, chief patient officer and executive vice president at Pfizer, said Sunday at the annual meeting of the National Medical Association. “One of the really interesting things the data tell us about participation in clinical trials of Black and brown people is they are much less likely to be asked,” Lewis-Hall said during the plenary session of the meeting, which was held remotely. Lewis-Hall said investigator bias against Black and brown patients is reflected in statements such as “I don’t know if they can get here; adherence might be a problem; it may take too long,” and this needs to improve. One thing that would help is having more Black and brown physicians, she added. “The numbers are woefully lagging. We need to increase our pipeline of physicians and physician-investigators, because over and over we heard that the trust issue is critical,” and that “we need to educate patients around clinical trials and their relative safety.”
Patients with hypoxemic acute respiratory failure as a result of coronavirus disease 2019 (COVID-19) who received continuous positive airway pressure (CPAP) therapy had a high failure rate during prone/lateral positioning tests, according study results published in CHEST. Patients with COVID-19 at the high dependency unit of a hospital in Milan, Italy who were spontaneously breathing and not intubated but undergoing helmet CPAP treatment were assessed for lung function and blood oxygenation after a number of positioning tests. Patients who had monolateral lung impairment were placed laterally, while patients with bilateral impairment were placed prone. Alveolar-arterial gradient (A-aO2) was recorded at 3 time points: at baseline in a semi-seated position, after 1 hour with the patient in prone/lateral position, and 45 minutes with the patient returned to a semi-seated position. A decrease of ≥20% from baseline was considered clinically significant. Of the 26 patients with COVID-19, the mean age was 62 years and 67% were men. Systemic hypertension, diabetes, obesity, COPD, and asthma were common comorbidities. A total of 39 tests consisting of 12 prone and 27 lateral positioning were conducted. For the primary study end point, 15.4% of positioning trials were successful with a decrease of A-aO2 of ≥20% in comparison to baseline, 7.7% showed a A-aO2 decrease of ≥30% in comparison with baseline, 46.1% trials showed a decrease of <20% of A-aO2 compared with baseline, and a total of 38.5% trials failed.
[Video] Anthony Fauci, MD, White House Coronavirus Task Force member and Director of the National Institutes of Allergy and Infectious Diseases, discusses latest developments in the COVID-19 pandemic with Howard Bauchner, MD, Editor in Chief, JAMA.
Obesity is associated with an increased risk of death or intubation in patients younger than age 65 who contract Covid-19, according to a retrospective cohort study published in the Annals of Internal Medicine. This association was independent of age, sex, race/ethnicity, and comorbid conditions, Michaela R. Anderson, MD, MS, of Columbia University Irving Medical Center, in New York, and colleagues reported. They did note that the associations varied by age. “Obesity was strongly associated with intubation or death among adults younger than 65 years, but not among those aged 65 years or older,” Anderson and colleagues noted. “Our findings provide evidence to support recommendations from the Centers for Disease Control and Prevention in the United States and the National Health Service in the United Kingdom, which state that patients with a BMI of 40 kg/m2 or greater are at high risk for poor outcomes from Covid-19 and should therefore consider prolonged social distancing. As the United States and other countries begin to lift stay-at-home orders, these findings might inform discussions between health care providers and patients regarding advanced care planning and benefits of prolonged social distancing, particularly for younger adults with class 2 or 3 obesity.”
The performance of rRT-PCR for SARS-CoV-2 varies with sampling site(s), illness stage and infection site were evaluated. Unilateral nasopharyngeal, nasal mid-turbinate, throat swabs, and saliva were simultaneously sampled for SARS-CoV-2 rRT-PCR from suspect or confirmed cases of COVID-19.True positives were defined as patients with at least one SARS-CoV-2 detected by rRT-PCR from any site on the evaluation day or at any time point thereafter, till discharge. Diagnostic performance was assessed and extrapolated for site combinations. We evaluated 105 patients; 73 had active SARS-CoV-2 infection. Overall, nasopharyngeal specimens had the highest clinical sensitivity at 85%, followed by throat, 80%, mid-turbinate, 62%, and saliva, 38-52%. Clinical sensitivity for nasopharyngeal, throat, mid-turbinate and saliva was 95%, 88%, 72%, and 44-56% if taken ≤7 days from onset of illness, and 70%, 67%, 47%, 28-44% if >7 days of illness. Comparing patients with URTI vs. pneumonia, clinical sensitivity for nasopharyngeal, throat, mid-turbinate and saliva was 92% vs 70%, 88% vs 61%, 70% vs 44%, 43-54% vs 26-45%. A combination of nasopharyngeal plus throat or mid-turbinate plus throat specimen afforded overall clinical sensitivities of 89-92%, this rose to 96% for persons with URTI and 98% for persons <7 days from illness onset.
Genentech announced that a phase 3 study investigating tocilizumab (Actemra®) for the treatment of hospitalized patients with severe coronavirus disease 2019 (COVID-19) associated pneumonia did not meet its primary and key secondary end points. The multicenter, randomized, double-blind COVACTA study compared the efficacy and safety of tocilizumab, an interleukin-6 receptor antagonist, to placebo in hospitalized adult patients with severe COVID-19 pneumonia. Patients were randomized to receive 1 intravenous infusion of either tocilizumab or placebo, in addition to standard of care. The primary end point was clinical status as measured by a 7-category ordinal scale; key secondary end points included mortality, as well as mechanical ventilation and intensive care unit (ICU) variables. Results showed that the difference in clinical status between patients treated with tocilizumab and those who received placebo was not statistically significant (odds ratio 1.19; 95% CI, 0.81-1.76; P =.36). Additionally, no statistically significant differences were observed between the 2 groups with regard to mortality rate (19.7% with tocilizumab vs 19.4% with placebo; P =.9410) or ventilator-free days (22 days with tocilizumab vs 16.5 days with placebo; P =.3202).
Coronavirus disease 2019 (COVID-19) is a global pandemic with no licensed vaccine or specific antiviral agents for therapy. Little is known about the longitudinal dynamics of SARS-CoV-2-specific neutralizing antibodies (NAbs) in COVID-19 patients. In this study, blood samples (n=173) were collected from 30 COVID-19 patients over a 3-month period after symptom onset and analyzed for SARS-CoV-2-specific NAbs, using the lentiviral pseudotype assay, coincident with the levels of IgG and proinflammatory cytokines. SARS-CoV-2-specific NAb titers were low for the first 7–10 d after symptom onset and increased after 2–3 weeks. The median peak time for NAbs was 33 d (IQR 24–59 d) after symptom onset. NAb titers in 93·3% (28/30) of the patients declined gradually over the 3-month study period, with a median decrease of 34·8% (IQR 19·6–42·4%). NAb titers increased over time in parallel with the rise in IgG antibody levels, correlating well at week 3 (r = 0·41, p & 0·05). The NAb titers also demonstrated a significant positive correlation with levels of plasma proinflammatory cytokines, including SCF, TRAIL, and M-CSF.
On Monday, the President signed an executive order seeking to expand the use of virtual doctors visits, as his administration looks to highlight achievements in health care. The administration waived certain regulatory barriers to video and phone calls with doctors, known as telehealth, when the coronavirus pandemic struck and many people were stuck at home. Now, the administration is looking to make some of those changes permanent, arguing the moves will provide another option for patients to talk to their doctors. The order calls on the secretary of Health and Human Services to issue rules within 60 days making some of the changes permanent.
NeuroRx, Inc. and Relief Therapeutics Holdings AG (SIX:RLF, OTC:RLFTF) “Relief” today announced that RLF-100 (aviptadil) showed rapid recovery from respiratory failure in the most critically ill patients with COVID-19. At the same time, independent researchers have reported that aviptadil blocked replication of the SARS coronavirus in human lung cells and monocytes. RLF-100 has been granted Fast Track designation by FDA and is being developed as a Material Threat Medical Countermeasure in cooperation with the National Institutes of Health and other federal agencies. Further research will be conducted. The first report of rapid clinical recovery under emergency use IND was posted by doctors from Houston Methodist Hospital. The report describes a 54-year-old man who developed COVID-19 while being treated for rejection of a double lung transplant and who came off a ventilator within four days. Similar results were subsequently seen in more than 15 patients treated under emergency use IND and an FDA expanded access protocol which is open to patients too ill to be admitted to the ongoing Phase 2/3 FDA trial. Patients with Critical COVID-19 were seen to have a rapid clearing of classic pneumonitis findings on x-ray, accompanied by an improvement in blood oxygen and a 50% or greater average decrease in laboratory markers associated with COVID-19 inflammation.
U.S. coronavirus deaths rose by over 25,000 in July and cases doubled in 19 states during the month, according to a Reuters tally, dealing a crushing blow to hopes of quickly reopening the economy. The United States recorded 1.87 million new cases in July, bringing total infections to 4.5 million, for an increase of 69%. Deaths in July rose 20% to nearly 154,000 total. The biggest increases in July were in Florida, with over 310,000 new cases, followed by California and Texas with about 260,000 each. All three states saw cases double in June. Cases also more than doubled in Alabama, Alaska, Arizona, Arkansas, Georgia, Hawaii, Idaho, Mississippi, Missouri, Montana, Nevada, Oklahoma, Oregon, South Carolina, Tennessee and West Virginia, according to the tally. Connecticut, Massachusetts, New Jersey and New York had the lowest increases, with cases rising 8% or less.
Before the magnifying glass of the COVID-19 pandemic caused physicians to look more closely at many aspects of their profession, there was awareness of the general culture of overwork that affect all physicians and the expectation by some that women physicians would make adjustments in their professional roles to accommodate their personal roles. These professional adjustments were made, including part-time status, despite the known limitations on professional progression, career advancement, and economic potential. These adjustments further propagate gender inequities and the persistent compensation gap women physicians’ experience. Women physicians have diverse personal characteristics. There is no appropriate stereotype for a woman physician. Some are just starting their professional careers. Some are older, nearing retirement. Some are partnered, others are solo. Some are childless, others are parents. Family care responsibilities vary with some caring for their children, their aging parents, or both. Practice parameters and settings vary, including business owners, health care executives, academic physicians, and employees of hospitals and group practices. For partnered women physicians, a small number are the principal source of income with a partner assuming the primary role for home and family care. The increasing number of women physicians is accompanied by a rise in the number of dual physician households. This diversity of personal situations highlights the reason to avoid broad assumptions when considering the life-work preferences or professional work adjustments related to the COVID-19 epidemic for individuals or groups of physicians, by gender.
While deaths from the coronavirus in the U.S. are mounting rapidly, public health experts are seeing a flicker of good news: The second surge of confirmed cases appears to be leveling off. The virus has claimed over 150,000 lives in the U.S., by far the highest death toll in the world, plus more than a half-million others around the globe. Over the past week, the average number of COVID-19 deaths per day in the U.S. has climbed more than 25%, from 843 to 1,057. Florida on Thursday reported 253 more deaths, setting its third straight single-day record, while Texas had 322 new fatalities and California had 391. The number of confirmed infections nationwide has topped 4.4 million, which could be higher because of limits on testing and because some people are infected without feeling sick.
Prolonged symptom duration and disability are common in adults hospitalized with severe coronavirus disease 2019 (COVID-19). Characterizing return to baseline health among outpatients with milder COVID-19 illness is important for understanding the full spectrum of COVID-19–associated illness and tailoring public health messaging, interventions, and policy. During April 15–June 25, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had a first positive reverse transcription–polymerase chain reaction (RT-PCR) test for SARS-CoV-2, the virus that causes COVID-19, at an outpatient visit at one of 14 U.S. academic health care systems in 13 states. Interviews were conducted 14–21 days after the test date. Respondents were asked about demographic characteristics, baseline chronic medical conditions, symptoms present at the time of testing, whether those symptoms had resolved by the interview date, and whether they had returned to their usual state of health at the time of interview. Among 292 respondents, 94% (274) reported experiencing one or more symptoms at the time of testing; 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the interview (median = 16 days from testing date), including 26% among those aged 18–34 years, 32% among those aged 35–49 years, and 47% among those aged ≥50 years. Among respondents reporting cough, fatigue, or shortness of breath at the time of testing, 43%, 35%, and 29%, respectively, continued to experience these symptoms at the time of the interview.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic has generated a plethora of scientific articles. One interesting aspect of the virus is the binary phenotypic presentation in patients. While patients might meet the Berlin criteria for acute respiratory distress syndrome (ARDS), not all patients experience the same decrease in lung compliance as typically seen with ARDS. We have observed patients meeting ARDS criteria with higher lung compliance as measured through peak pressures at our institution. This phenotype difference is important with regard to how the patients are managed. Lower positive end-expiratory pressure (PEEP) and higher tidal volumes can be used in this phenotype. Read this case series of four patients with confirmed COVIID-19 admitted to our hospital, with a focus on lung compliance. Three of the four patients required intubation, while the fourth passed away before intubation.
The current COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to target primarily the distal lung, including the terminal bronchioles and alveoli, which are the sites of essential gas exchange in the human body. In a significant minority of patients, this results in critical pneumonia and acute respiratory distress syndrome (ARDS). However, the mechanism by which this occurs is far from clear, and one major contributing factor to this knowledge gap is the absence of a reliable and robust human lung cell culture system that will serve as a substrate for disease of the terminal lungs. Now, a new study reports the development of a human distal lung culture system that can be functionally tested. This will help not only to understand how this infection produces disease but also to test the proliferative capacity of the stem cells in this part of the body. As of now, mouse studies provide most of our knowledge about these stem cells, which are functionally part of the lung as well as providing a source of new cells during healing of the lung. These studies have shown that these bifunctional stem cells of the distal lung comprise the secretory club cells found in the distal bronchioles and the type 2 pneumonocytes or alveolar cells (AT2) that produce surfactant in the lung alveoli.
[Podcast] Research and data on potential treatment modalities continue to emerge at a rapid pace. This episode explores the IDSA and NIH guidelines for the treatment and management of COVID-19, as well as available evidence on antivirals, glucocorticoids and antibodies. Gitanjali Pai, MD, is an infectious disease physician at Memorial Hospital and Physicians’ Clinic in Stilwell, Oklahoma. She is a member of the Infectious Disease News Editorial Board and host of Healio’s podcast Unmasking COVID-19.
This multicentre observational study was performed between 15 March and 20 April 2020. Patients in the Emergency Department (ED) or Intensive Care Unit (ICU) with acute dyspnoea who were PCR positive for SARS-CoV-2, and who had LUS and chest CT performed within a 24-h period, were included. One hundred patients were included. LUS score was significantly associated with pneumonia severity assessed by chest CT and clinical features. The AUC of the ROC curve of the relationship of LUS versus chest CT for the assessment of severe SARS-CoV-2 pneumonia was 0.78 (CI 95% 0.68–0.87; p < 0.0001). A high LUS score was associated with the use of mechanical ventilation, and with a SpO2/FiO2 ratio below 357. In known SARS-CoV-2 pneumonia patients, the LUS score was predictive of pneumonia severity as assessed by a chest CT scan and clinical features. Within the limitations inherent to our study design, LUS can be used to assess SARS-CoV-2 pneumonia severity.
Researchers at Boston Children’s Hospital and Brigham and Women’s Hospital have launched a randomized, placebo-controlled clinical trial of dornase alfa (Pulmozyme) in patients with severe COVID-19 pneumonia and respiratory failure requiring mechanical ventilation. The study aims to enroll 60 adults and children (over age 3) admitted to intensive care units. Dornase alfa, also called DNase 1, is FDA-approved for patients with cystic fibrosis, to break up thick mucus secretions and prevent lung infections. The trial is supported by the Massachusetts Consortium on Pathogen Readiness, and the drug is being provided by Genentech, a member of the Roche Group, which is also providing supplementary financial support. The 18-month study will randomize patients to twice-daily nebulized dornase alfa or placebo (a saline solution) within 48 hours after intubation and placement on a ventilator.
The purpose of the present study was to investigate the association between cytokine profiles and lung injury in COVID-19 pneumonia. The retrospective study was conducted in COVID-19 patients. Demographic characteristics, symptoms, signs, underlying diseases, and laboratory data were collected. The patients were divided into COVID-19 with pneumonia and without pneumonia. CT severity score and PaO2/FiO2 ratio were used to assess lung injury. One hundred and six patients with 12 COVID-19 without pneumonia and 94 COVID-19 with pneumonia were included. Compared with COVID-19 without pneumonia, COVID-19 with pneumonia had significantly higher serum interleukin (IL)-2R, IL-6, and tumor necrosis factor (TNF)-α. Correlation analysis showed that CT severity score and PaO2/FiO2 were significantly correlated with age, presence of any coexisting disorder, lymphocyte count, procalcitonin, IL-2R, and IL-6. In multivariate analysis, log IL6 was the only independent explanatory variables for CT severity score (β = 0.397, p < 0.001) and PaO2/FiO2 (β = − 0.434, p = 0.003).
Moderna and the National Institutes of Allergy and Infectious Diseases have initiated a phase 3 trial evaluating the vaccine candidate mRNA-1273 against coronavirus disease 2019 (COVID-19). The trial, which is the first to be implemented under Operation Warp Speed, is expected to enroll around 30,000 adults and will be conducted at multiple clinical research sites across the US. In addition, the National Institutes of Health (NIH) Coronavirus Prevention Network will participate in conducting the trial. Testing sites in areas with emerging cases or high incidence rates will be prioritized for enrollment. Participants will be randomized to receive 2 intramuscular injections of either mRNA-1273 or saline placebo approximately 28 days apart. The study’s primary aim will be to assess whether the vaccine is able to prevent symptomatic COVID-19 after the administration of 2 doses; prevention after 1 dose will also be investigated as a secondary goal. Moreover, researchers will look at whether vaccination with mRNA-1273 prevents severe COVID-19 or laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with or without disease symptoms, as well as death.
One person in the United States died about every minute from COVID-19 on Wednesday as the national death toll surpassed 150,000, the highest in the world. The United States recorded 1,461 new deaths on Wednesday, the highest one-day increase since 1,484 on May 27, according to a Reuters tally. U.S. coronavirus deaths are rising at their fastest rate in two months and have increased by 10,000 in the past 11 days. Nationally, COVID-19 deaths have risen for three weeks in a row while the number of new cases week-over-week recently fell for the first time since June. A spike in infections in Arizona, California, Florida and Texas this month has overwhelmed hospitals. The rise has forced states to make a U-turn on reopening economies that were restricted by lockdowns in March and April to slow the spread of the virus. Texas leads the nation with nearly 4,300 deaths so far this month, followed by Florida with 2,900 and California, the most populous state, with 2,700. The Texas figure includes a backlog of hundreds of deaths after the state changed the way it counted COVID-19 fatalities.
On top of being overwhelmed with severely ill people, healthcare workers are dealing with shortages of the personal protective equipment (PPE) that they need to keep from getting infected themselves. N95 respirators, surgical masks, gowns, and gloves were all were in short supply, forcing hospitals to ration them. At the root of the issue were several problems: a global surge in demand for protective gear that was outstripping supply, a lack of adequate supplies in the Strategic National Stockpile, which is intended to supplement state and local supplies during public health emergencies, and a response that lacked any federal coordination. A nationwide scrum for available PPE ensued, pitting state governments, healthcare systems, and individual hospitals against each other as they fought to outbid each other for adequate supplies for the pandemic response. Four months later, many hospitals have a better supply of PPE than they did in March and April. But with the dramatic nationwide rise in coronavirus cases that began in mid-June and shows no signs of slowing, concerns about PPE supplies remain. And demand is now coming not only from the hospitals that are treating COVID-19 patients, but also from nursing homes, primary care doctors who want to ensure a safe environment as they begin welcoming back patients for routine primary care, and other frontline healthcare workers.
With the COVID-19 pandemic having reached tremendous proportions, post-mortem series are under the limelight to explain many of the peculiar clinical findings. Pathological descriptions of disease are fundamental for understanding pathogenetic features and might inform new treatments. Indeed, the widely discussed identification of thrombosis in patients with COVID-19 has garnered much interest, and has resulted in new treatment strategies, with anticoagulants now part of patient management. In their Article, Luca Carsana and colleagues describe the lung findings of 38 patients who died with COVID-19 and show that early-phase or intermediate-phase diffuse alveolar damage is the main pathological finding, as well as fibrin thrombi in small arterial vessels. Other autoptic series, composed of fewer cases, also show thrombotic events to be findings specifically related to COVID-19. The fibrotic changes seen in patients who died with COVID-19 who had severe disease of long duration have been, however, only briefly touched upon in published studies, and no complete pathological description of these cases is available.
Asthma is not a risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), and SARS-CoV-2 pneumonia may not induce severe asthma exacerbation, according to the results of a retrospective cohort study published in The Journal of Allergy and Clinical Immunology: In Practice. Viral infections are known to exacerbate asthma in adults, however these patients are rare in epidemiologic studies of SARS-CoV-2 pneumonia. Thus, it is unknown whether there is an association between SARS-CoV-2 infection and severe asthma exacerbation. Researchers at Strasbourg University Hospital in France assessed the frequency of asthma exacerbation in 106 patients hospitalized for SARS-CoV-2 pneumonia between March 4 and April 6, 2020. Of these patients, 23 had asthma, with 63.6% considered well-controlled and 23.4% considered partially controlled. A total of 11 patients had ≥1 severe exacerbation in the previous year and 68.2% were considered to have allergic asthma because of their clinical history.
In this observational study, adult patients with a confirmed COVID-19 diagnosis, who were admitted to hospital in Germany between Feb 26 and April 19, 2020, and for whom a complete hospital course was available (ie, the patient was discharged or died in hospital) were included in the study cohort. Claims data from the German Local Health Care Funds were analysed. The data set included detailed information on patient characteristics, duration of hospital stay, type and duration of ventilation, and survival status. Patients with adjacent completed hospital stays were grouped into one case. Patients were grouped according to whether or not they had received any form of mechanical ventilation. Of 10,021 hospitalised patients being treated in 920 different hospitals, 1727 (17%) received mechanical ventilation (of whom 422 [24%] were aged 18–59 years, 382 [22%] were aged 60–69 years, 535 [31%] were aged 70–79 years, and 388 [23%] were aged ≥80 years). The median age was 72 years (IQR 57–82). Men and women were equally represented in the non-ventilated group, whereas twice as many men than women were in the ventilated group. The likelihood of being ventilated was 12% for women (580 of 4822) and 22% for men (1147 of 5199).
For patients with chronic diseases such as pulmonary fibrosis, coronavirus disease 2019 (COVID-19) represents a threat beyond the immediate risk of infection. These individuals have a greater likelihood of developing serious complications as a result of the virus, and those awaiting organ transplantation and other surgical interventions may face delays because of the risk of viral exposure and strained resources in the current healthcare environment. In addition, clinical trials investigating potential therapies for various diseases including pulmonary fibrosis have been disrupted considerably since the pandemic emerged. According to data from the WIRB-Copernicus Group (WCG), the number of clinical research sites open to enrollment for non-COVID-19 trials decreased from 62% on March 24, 2020, to 11% on May 1, 2020. Although enrollment has begun to resume since that period, these developments have prompted experts to consider ways to address such issues in the context of ongoing and future trials.
Black and Latino people have been three times as likely as white people to become infected with COVID-19 and twice as likely to die, according to federal data obtained via a lawsuit by The New York Times. Asian Americans appear to account for fewer cases but have higher rates of death. Eight out of 10 COVID deaths reported in the U.S. have been of people ages 65 and older. And the Centers for Disease Control and Prevention warns that chronic kidney disease is among the top risk factors for serious infection. Historically, however, those groups have been less likely to be included in clinical trials for disease treatment, despite federal rules requiring minority and elder participation and the ongoing efforts of patient advocates to diversify these crucial medical studies. In a summer dominated by COVID-19 and protests against racial injustice, there are growing demands that drugmakers and investigators ensure that vaccine trials reflect the entire community.
This study aimed to describe the effectiveness and optimum use of tocilizumab (TCZ) treatment by the support of clinical, laboratory, and radiologic observations. All the patients were followed up in the hospital with daily interleukin-6 (IL-6), C-reactive protein (CRP), ferritin, D-dimer, complete blood count, and procalcitonin. Computerized thoracic tomography was obtained on admission, when oxygen support was necessary, and seven days after TCZ start. Disease course of the patients was grouped as severe or critical according to their clinical, laboratory, and radiologic evaluations. In total, 43 patients were included; 70% of the patients was male; the median age was 64 (min-max: 27-94), 6 (14%) patients were fatal. The median duration of oxygen support before the onset of TCZ was shorter among the severe patient group than the critical patient group (1 vs 4 days, p < 0.001). Only 3 cases out of 21 (14%) who received TCZ in the ward were transferred to ICU, and none of them died. The levels of IL-6, CRP, ferritin, D-dimer, and procalcitonin were significantly lower in severe cases group than the critical cases group (p = 0.025, p = 0.002, p = 0.008, p = 0.002, and p = 0.001, respectively). Radiological improvement was observed in severe cases on the seventh day of TCZ. Secondary bacterial infection was detected in 41% of critical cases, but none of the severe ones.
Florida on Sunday became the second state after California to overtake New York, the worst-hit state at the start of the U.S. novel coronavirus outbreak, according to a Reuters tally. Total COVID-19 cases in the Sunshine State rose by 9,300 to 423,855 on Sunday, just one place behind California, which now leads the country with 448,497 cases. New York is in third place with 415,827 cases. Still, New York has recorded the most deaths of any U.S. state at more than 32,000 with Florida in eighth place with nearly 6,000 deaths. On average, Florida has added more than 10,000 cases a day in July while California has been adding 8,300 cases a day and New York has been adding 700 cases.
If Black, Hispanic and Native Americans are hospitalized and killed by the coronavirus at far higher rates than others, shouldn’t the government count them as high risk for serious illness? That seemingly simple question has been mulled by federal health officials for months. And so far the answer is no. But federal public health officials have released a new strategy that vows to improve data collection and take steps to address stark inequalities in how the disease is affecting Americans. Officials at the Centers for Disease Control and Prevention stress that the disproportionately high impact on certain minority groups is not driven by genetics. Rather, it’s social conditions that make people of color more likely to be exposed to the virus and — if they catch it — more likely to get seriously ill. “To just name racial and ethnic groups without contextualizing what contributes to the risk has the potential to be stigmatizing and victimizing,” said the CDC’s Leandris Liburd, who two months ago was named chief health equity officer in the agency’s coronavirus response. Outside experts agreed that there’s a lot of potential downside to labeling certain racial and ethnic groups as high risk.
This observational study aimed to determine optimal timing of interleukin-6 receptor inhibitors (IL6ri) administration for Coronavirus disease 2019 (Covid-19). Patients with Covid-19 were given an IL6ri (sarilumab or tocilizumab) based on iteratively reviewed guidelines. IL6ri were initially reserved for critically ill patients, but after review, treatment was liberalized to patients with lower oxygen requirements. Patients were divided into 2 groups: those requiring ≤ 45% fraction of inspired oxygen (FiO2) (termed stage IIB) and those requiring >45% FiO2 (termed stage III) at the time of IL6ri administration. Main outcomes were all-cause mortality, discharge alive from hospital, and extubation. Two hundred fifty-five Covid-19 patients were treated with IL6ri (149 stage IIB and 106 stage III). Patients treated in stage IIB had lower mortality than the stage III group (adjusted hazard ratio [aHR]: 0.24; 95% confidence interval [CI] 0.08-0.74). Overall, 218 (85.5%) patients were discharged alive. Patients treated in stage IIB were more likely to be discharged (aHR: 1.43; 95% CI 1.06 – 1.93) and were less likely to be intubated (HR: 0.43; 95% CI: 0.24-0.79).
The U.S. tallied over 1,000 coronavirus-related deaths Friday for the fourth straight day this week, yet another sign of the alarming spike in COVID-19 cases across the country. There were 1,178 new deaths Friday alone, according to the COVID Tracking project, compared with 1,038 Tuesday, 1,117 Wednesday, and 1,039 Thursday. Over 137,000 people have died in the U.S. and over 4 million people have contracted the virus in the country since the outbreak began. The alarming figures are largely driven by a surge in cases across the South and West, particularly in Arizona, California, Florida and Texas. The spikes have led to urgent calls from public health officials for Americans, particularly young people, to heed health guidance such as wearing masks and socially distancing.
The global pandemic of COVID-19 has been associated with infections and deaths among health-care workers. This Viewpoint of infectious aerosols is intended to inform appropriate infection control measures to protect health-care workers. Studies of cough aerosols and of exhaled breath from patients with various respiratory infections have shown striking similarities in aerosol size distributions, with a predominance of pathogens in small particles (<5 μm). These are immediately respirable, suggesting the need for personal respiratory protection (respirators) for individuals in close proximity to patients with potentially virulent pathogens. There is no evidence that some pathogens are carried only in large droplets. Surgical masks might offer some respiratory protection from inhalation of infectious aerosols, but not as much as respirators. However, surgical masks worn by patients reduce exposures to infectious aerosols to health-care workers and other individuals. The variability of infectious aerosol production, with some so-called super-emitters producing much higher amounts of infectious aerosol than most, might help to explain the epidemiology of super-spreading. Airborne infection control measures are indicated for potentially lethal respiratory pathogens such as severe acute respiratory syndrome coronavirus 2.
Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. This multicenter, randomized, open-label, three-group, controlled trial involved hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis.
Enhancing data collection, investing in research, and building trust can help mitigate the disparate impacts of the COVID-19 pandemic on Black and Latinx seniors, witnesses told members of the Senate Special Committee on Aging during a hearing on Tuesday. The pandemic’s impact on minority and ethnic groups appears most acute in young people and seems to taper off among community-dwelling older adults, Mercedes Carnethon, PhD, an epidemiologist and preventive medicine specialist at Northwestern University in Chicago, told the committee. Nevertheless, disparities persist for seniors living in congregate care settings such as nursing homes. In fact, nursing homes with a higher proportion of Black and Latinx residents have double the rates of COVID-19 infections than facilities with a greater share of non-Hispanic whites, Carnethon said. Current policies don’t require universal reporting of race or ethnicities of individuals affected by COVID-19, she said.
Treatment with dexamethasone resulted in lower rates of 28-day mortality in patients hospitalized with coronavirus disease 2019 (COVID-19) who received invasive mechanical ventilation but not in those who received no respiratory support, according to findings published in the New England Journal of Medicine. Researchers conducted a controlled, open-label clinical trial (RECOVERY; ClinicalTrials.gov Identifier: NCT04381936) to evaluate the effects of potential treatments in patients hospitalized with COVID-19 in the United Kingdom. The primary outcome was 28-day mortality, with secondary outcomes being the time until hospital discharge and subsequent receipt of invasive ventilation or death in patients who did not receive mechanical ventilation at the beginning of the study. A total of 6425 patients were randomly assigned to receive oral or intravenous dexamethasone (n=2104) at 6 mg once daily for up to 10 days or usual care alone (n=4321). Mean patient age was 66.1 years and 36% were women. More than half of the patients had ≥1 major coexisting medical condition, including heart disease, chronic lung disease, and diabetes.
The efficacy of glucocorticoids in COVID-19 is unclear. This study was designed to determine whether systemic glucocorticoid treatment in COVID-19 patients is associated with reduced mortality or mechanical ventilation. This observational study included 1,806 hospitalized COVID-19 patients; 140 were treated with glucocorticoids within 48 hours of admission. Early use of glucocorticoids was not associated with mortality or mechanical ventilation. However, glucocorticoid treatment of patients with initial C-reactive protein (CRP) ≥20 mg/dL was associated with significantly reduced risk of mortality or mechanical ventilation (odds ratio, 0.23; 95% CI, 0.08-0.70), while glucocorticoid treatment of patients with CRP <10 mg/dL was associated with significantly increased risk of mortality or mechanical ventilation (OR, 2.64; 95% CI, 1.39-5.03). Whether glucocorticoid treatment is associated with changes in mortality or mechanical ventilation in patients with high or low CRP needs study in prospective, randomized clinical trials.
More high-quality research is necessary to establish diagnostic chest computed tomography (CT) criteria for coronavirus disease 2019 (COVID-19), according to the results of a systematic review and meta-analysis published in Chest. Currently, real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swab specimens is considered the gold standard for the diagnosis of COVID-19. Real-time RT-PCR testing, however, is time-consuming and suboptimal for the rapid triaging of patients. In consideration of the potential benefit of chest CT for the diagnosis of COVID-19, in concert with clinical examination and RT-PCR, a team of researchers performed a systematic review to assess the methodologic quality of studies on the use of chest CT imaging in patients with COVID-19 and to determine the frequency of different chest CT findings. Studies that reported the prevalence of chest CT findings in patients with a diagnosis of COVID-19 confirmed by RT-PCR or gene sequencing were eligible for inclusion. In addition, only studies that provided a detailed description of chest CT findings according to the glossary of terms for thoracic imaging of the Fleischner Society were included.
[Research Letter] Cytokine storm–mediated organ injury continues to dominate current thinking as the primary mechanism for coronavirus disease 2019 (COVID-19). Although there is an initial hyper-inflammatory phase, mounting evidence suggests that virus-induced defective host immunity may be the real cause of death in many patients. COVID-19 has been called a serial lymphocyte killer because profound and protracted lymphopenia is a near uniform finding among patients with severe COVID-19 and correlates with morbidity and mortality. Autopsies demonstrate a devastating depletion of lymphocytes in the spleen and other organs. CD4, CD8, and natural killer cells, which play important antiviral roles, are depleted and have reduced function, leading to immune collapse. Clinical and pathological findings in patients with COVID-19 indicate that immunosuppression is a critical determinant of outcomes.
With over 1,600 responses from a variety of specialties, physicians weighed in on the financial impact of COVID-19 and how they are navigating the decrease in patient volume, telehealth reimbursements and financial relief. These results convey the challenges and concerns of physicians as they transition to the new normal with COVID-19. From anticipated loss in revenue to influence on headcount, the Financial Impact survey reveals the lasting repercussions COVID-19 will have practices for the remainder of 2020 and beyond.
The Department of Health and Human Services (HHS) debuted its new COVID-19 dashboard on Monday, and the department’s data chief said it will provide even more data than the CDC’s old one did. Called the Coronavirus Data Hub, the HHS dashboard replaces the CDC’s National Healthcare Safety Network (NHSN), to which states and hospitals had previously been submitting COVID-19 data such as intensive care unit capacity, ventilator use, personal protective equipment (PPE) levels, and staffing shortages. But in guidance to hospitals, updated July 10 and published with little fanfare, HHS ordered hospitals to stop submitting such data to the NHSN and instead submit it either to HHS or to their state health department, which would then submit it to HHS. The data would then be put on the dashboard via the department’s new HHS Protect data system. The dashboard’s public-facing side allows users to see the overall number of confirmed coronavirus cases in the U.S. as well as the overall number of reported deaths. It also includes data on inpatient and ICU bed utilization.
In this cross-sectional study of 16 025 residual clinical specimens, estimates of the proportion of persons with detectable SARS-CoV-2 antibodies ranged from 1.0% in the San Francisco Bay area (collected April 23-27) to 6.9% of persons in New York City (collected March 23-April 1). Six to 24 times more infections were estimated per site with seroprevalence than with coronavirus disease 2019 (COVID-19) case report data. For most sites, it is likely that greater than 10 times more SARS-CoV-2 infections occurred than the number of reported COVID-19 cases; most persons in each site, however, likely had no detectable SARS-CoV-2 antibodies.
It’s established that many people infected with coronavirus are ‘asymptomatic’. While these people can spread the virus, the virus isn’t actually harming them, right? Not so says a new study published in Nature. Someone who is infected with the SARS-CoV-2 virus and remains asymptomatic, that is free of coughing, fever, fatigue and other common signs of infection, can still be adversely affected by the infection. A new study reveals that virus will still be causing some harm to their lungs. This may be mild and it may be reversible, but the effects will vary between different individuals. The study, published in Nature Medicine, reveals a high rate of minor lung inflammation in many individuals who exhibit no outward symptoms of coronavirus.
Angiotensin-converting enzyme 2 and transmembrane protease serine 2 mediate SARS-COV-2 entry into host cells. Higher expression of ACE2 and TMPRSS2 in sputum cells of patients with asthma identified subgroups at risk of COVID-19 morbidity. “We found that among patients with asthma, gene expression of ACE2 and TMPRSS2 was higher in patients of male sex, Black race and patients with a history of diabetes mellitus,” Michael C. Peters, MD, assistant professor of medicine in the division of pulmonary and critical care medicine at the University of California, San Francisco, told Healio. Researchers analyzed gene expression for ACE2, TMPRSS2 and intercellular adhesion molecule 1 (ICAM-1), the major intercellular protein that mediates entry of human rhinoviruses, in sputum cells of 330 participants (mean age, 48.5 years; 69% female; 66% white) in the Severe Asthma Research Program-3 and in 79 healthy control participants (mean age, 40.6 years; 66% female; 57% white).
Electrocore Inc. has snagged an emergency use authorization (EUA) from the U.S. FDA for use of its Gammacore Sapphire CV noninvasive vagus nerve stimulation (nVNS) to acutely treat asthma exacerbations in known or suspected COVID-19 patients. The hand-held therapy can be used at home and in a health care setting. The EUA indication covers adults who are experiencing exacerbation of asthma-related dyspnea and reduced airfow, for whom drug therapies either aren’t tolerated or provide insufficient relief. Gammacore is applied at to either side of the neck and delivers mild electrical impulses to the vagus nerve through the skin, stimulating the nerve receptors to reduce pain or distress. Patients can administer the treatment themselves, reducing reliance on medications with their potential side effects.
Severe COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is approved treatment. Assessed, was the effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability post-intubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared to tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability weighting (IPTW). 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean 55 vs. 60 years), less likely to have chronic pulmonary disease (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death [hazard ratio 0.55 (95% CI 0.33, 0.90)] and improved status on the ordinal outcome scale [odds ratio per 1-level increase: 0.58 (0.36, 0.94)].
Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here, the extrapulmonary organ-specific pathophysiology are reviewed, along with presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
Asthma is increasingly recognized as an underlying risk factor for severe respiratory disease in patients with coronavirus disease 2019 (COVID-19), particularly in the United States. Here, we report the postmortem lung findings from a 37-year-old man with asthma, who met the clinical criteria for severe acute respiratory distress syndrome and died of COVID-19 less than 2 weeks after presentation to the hospital. His lungs showed mucus plugging and other histologic changes attributable to asthma, as well as early diffuse alveolar damage and a fibrinous pneumonia. The presence of diffuse alveolar damage is similar to descriptions of autopsy lung findings from patients with severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, and the absence of a neutrophil-rich acute bronchopneumonia differs from the histologic changes typical of influenza.
More than 60,500 new COVID-19 infections were reported across the United States on Thursday, according to a Reuters tally, setting a one-day record as weary Americans were told to take new precautions and the pandemic becomes increasingly politicized. The total represents a slight rise from Wednesday, when there were 60,000 new cases, and marks the largest one-day increase by any country since the pandemic emerged in China last year. As infections rose in 41 of the 50 states over the last two weeks, Americans have become increasingly divided on issues such as the reopening of schools and businesses. Orders by governors and local leaders mandating face masks have become particularly divisive. “It’s just disheartening because the selfishness of (not wearing a mask) versus the selflessness of my staff and the people in this hospital who are putting themselves at risk, and I got COVID from this,” said Dr. Andrew Pastewski, ICU medical director at Jackson South Medical Center in Miami.
Critically ill patients with COVID-19 are more likely to develop heart rhythm disorders than other hospitalized patients, according to a study published online June 22 in Heart Rhythm. Anjali Bhatla, from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues reviewed the incidence of cardiac arrests, arrhythmias, and inpatient mortality among 700 COVID-19 patients (mean age 50 years; 45 percent male) admitted to one center over a nine-week period. The researchers found that 11 percent of patients received care in the intensive care unit (ICU), and there were nine cardiac arrests (all occurring in ICU patients), 25 incident atrial fibrillation (AF) events, nine clinically significant bradyarrhythmias, and 10 nonsustained ventricular tachycardias (NSVTs). Admission to the ICU was associated with incident AF (odds ratio, 4.68) and NSVT (odds ratio, 8.92) in adjusted analysis. There were also independent associations seen between age and incident AF (odds ratio, 1.05) and between prevalent heart failure and bradyarrhythmias (odds ratio, 9.75). In-hospital mortality was only associated with cardiac arrest.
Researchers from Queensland University of Technology and Oxford University are working in collaboration to begin human clinical trials of inhaled corticosteroids, commonly used for asthma patients, on patients with COVID-19. The researchers believe that this could be useful for patients with the novel coronavirus infection. COVID-19 is known to cause severe respiratory illness in some individuals. Studies have shown that some corticosteroids, such as dexamethasone, could reduce the inflammation of the respiratory tract in these patients and benefit them by alleviating the symptoms of severe disease. Researchers in this new trial are studying if the steroid inhalers used for reducing the exacerbations of asthma could be useful for patients with early COVID-19 and reduce their risk of severe disease. The clinical trial has been registered under the name of STOIC (STerOids In COVID-19). It has begun recruiting patients at the Churchill Hospital in Oxford, England. The study is being led by Associate Professor Nicolau, who is also a mathematician, physician, and Australian Research Council Future Fellow. As per the trial details, the researchers have plans to recruit a total of 478 participants in the study. Some of the patients would be administered the corticosteroid (Budesonide) containing inhaler while others would be prescribed a placebo inhaler.
Asthma does not appear to increase the risk for a person contracting COVID-19 or influence its severity, according to a team of Rutgers researchers. Panettieri’s paper was published in the Journal of Allergy and Clinical Immunology. “However, people with asthma–even those with diminished lung function who are being treated to manage asthmatic inflammation–seem to be no worse affected by SARS-CoV-2 than a non-asthmatic person. There is limited data as to why this is the case–if it is physiological or a result of the treatment to manage the inflammation.” Panettieri discusses what we know about asthma and inflammation and the important questions that still need to be answered. Since the news has focused our attention on the effects of COVID-19 on people in vulnerable populations, those with asthma may become hyper-vigilant about personal hygiene and social distancing.
Global biotherapeutics leader CSL Behring today announced that the first patient has been enrolled in its Phase 2 study to assess the safety and efficacy of CSL312 (garadacimab, Factor XIIa antagonist monoclonal antibody) to treat patients suffering from severe respiratory distress, a leading cause of death in patients with COVID-19 related pneumonia. In this multicenter, double-blind, placebo-controlled study, approximately 124 adult patients testing positive for the SARS CoV-2 infection will be randomized to receive either CSL312 or placebo, in addition to standard of care (SOC) treatment. The primary endpoint being the incidence of tracheal intubation or death.
[Letter to the Editor] Alveolar regeneration after an acute lung injury has been observed in many mammals. Results in animal models have shown that alveolar type II (AT2) cells function as resident alveolar stem cells that can proliferate and differentiate into alveolar type I (AT1) cells to build new alveoli after lung injury. However, alveolar regeneration after acute lung injury in adult humans is still poorly characterized, mainly due to the lack of lung samples and regeneration-specific molecular markers. In patients with COVID-19 pneumonia, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly attack alveolar epithelial cells and cause massive AT2 cell death. It is unknown whether alveolar regeneration occurs upon SARS-CoV-2 infection-induced lung injury. This knowledge will substantially improve our basic understanding of the COVID-19 disease and our ability to prognosticate patient outcomes.
Active engagement of patients and their families in decisions about their own care is a foundation of a high-quality, person-centered health care system. Expanding the acceptance and participation of family care partners at the bedside has been an ongoing effort by patient advocacy communities over the past several decades. In this context, family refers to any support person defined by the patient or resident as family, including friends, neighbors, relatives, and/or professional support persons. Great progress has been made to invite partners into the labor and delivery room, to welcome parents to stay at their child’s side throughout a hospitalization, and to honor the wishes of terminally ill individuals to have family with them during end-of-life care. Significant clinical, psychological, and emotional benefits of these practices have been well documented for patients, family, and health care professionals. The National Academy of Medicine has asserted the importance that “family and/or care partners are not kept an arm’s length away as spectators but participate as integral members of their loved one’s care team.”
Dr. Sanjay Doddamani is chief operating officer and chief physician executive at Southwestern Health Resources, a clinically integrated network comprising independent community practices together with Texas Health Resources and the University of Texas Southwestern Medical Center in the Dallas-Fort Worth area. He started in his role in mid-March, just weeks before a national emergency was declared due to the COVID-19 outbreak. He previously served as senior physician adviser at the Center for Medicare and Medicaid Innovation and was chief medical officer for the accountable care organization and the home-based program at Geisinger Health. Read this Q&A session with Dr. Doddamani about Southwestern’s experience and the network’s approach to dealing with the pandemic and the organization’s emphasis on value-based care.
Hundreds of scientists say there is evidence that the novel coronavirus in smaller particles in the air can infect people and are calling for the World Health Organization to revise recommendations, the New York Times reported on Saturday. The WHO has said the coronavirus disease spreads primarily from person to person through small droplets from the nose or mouth, which are expelled when a person with COVID-19 coughs, sneezes or speaks. In an open letter to the agency, which the researchers plan to publish in a scientific journal next week, 239 scientists in 32 countries outlined the evidence showing smaller particles can infect people, the NYT said.
[Video] Editor in Chief of JAMA, Howard Bauchner, MD, interviews Anthony Fauci, MD, White House Coronavirus Task Force member and Director of the National Institutes of Allergy and Infectious Diseases. The two discuss latest developments in the COVID-19 pandemic, including latest developments, protecting the elderly, genetic shift and mutations, vaccine durability and more.
In recent months, states and municipalities have begun releasing data on COVID-19 infections and death that reveal profound racial disparities. In Louisiana, Black patients account for 57 percent of COVID-19 deaths, while making up only 33 percent of the total population. In Wisconsin, Hispanic patients constitute 12 percent of confirmed COVID-19 cases, but only 7 percent of the total population. In New York City, the epicenter of the pandemic in the US, age-adjusted mortality rates are more than double for Black and Hispanic patients (243.6 and 237.7 per 100,000) compared to white and Asian patients (121.5 and 109.4 per 100,000). Studies of patients hospitalized across New York have found that hypertension, diabetes, and obesity are associated with an elevated risk for COVID-19 morbidity and mortality. But why are there higher rates of hypertension, diabetes, and obesity in communities of color? The answer does not lie in biology. Here again, structural and environmental factors such as resource deprivation, poor access to health care, discrimination, and racism have driven a higher burden of these diseases in communities of color.
The Centers for Disease Control and Prevention (CDC) today reported a record of 54,357 new coronavirus cases over yesterday—a record single-day jump that presses the United States further than what some thought was the peak this spring. For reference, as CNN reported, it took the United States a little more than 2 months to report its first 50,000 cases. Total US cases were at 2,679,230, including 128,024 deaths, according to the CDC. The infection curve is rising in 40 of 50 states, and 36 states are seeing an increase in the percentage of positive coronavirus tests, AP reported today. Some public health officials and governors are blaming bars for the increase in cases, the New York Times reported today, while others are pointing to hasty business reopenings, according to Politico.
Homeless people in New York state are more likely to be hospitalized and treated with mechanical ventilators for respiratory infections than people who are not homeless, according to a study published online June 4 in the Journal of General Internal Medicine. Atsushi Miyawaki, M.D., Ph.D., from the University of Tokyo, and colleagues used the 2007 to 2012 New York State Inpatient Database to identify all hospitalizations with primary or secondary diagnosis of influenza in 214 hospitals (total 20,078 patients; median age 40 years). Hospitals directly reported homeless patients. The researchers found that 6.4 percent of hospitalized influenza patients were homeless, with the majority of these hospitalizations (99.9 percent) concentrated in 10 hospitals. During the study period, homeless patients experienced a higher rate of hospitalization for influenza versus nonhomeless persons.
The purpose of this study was to assess coinfection rates of coronavirus disease 2019 (COVID‐19) with other respiratory infections on presentation. This is a retrospective analysis of data from a 2 hospital academic medical centers and 2 urgent care centers during the initial 2 weeks of testing for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) , March 10, 2020 to March 23, 2020. Complete laboratory results from the first 2 weeks of testing were available for 471 emergency department patients and 117 urgent care center patients who were tested for SARS‐CoV.
[Editorial] The world is scrutinizing every cohort and every outcome for patients with coronavirus disease (COVID-19), particularly the most critically ill who are receiving mechanical ventilation. The numbers that have been published are all over the place, and some of them—such as very high mortality—are causing panic. Two major issues are at play in these epidemiological studies. The first is when to intubate and assessment of the rates of intubation and mechanical ventilation for hospitalized patients in cohorts from across the world. The second is the reported mortality for patients who receive mechanical ventilation. Presentation and interpretation of the data for both of these issues is not straightforward and never has been. However, there are ways we can improve assessment of these cohort studies.
A patient’s blood type plays a role in the likelihood of developing COVID-19, data from two genetic studies show. An infectious disease expert unaffiliated with the studies told Healio Primary Care that the results are possible, but with some important caveats. In the first study, which appeared in The New England Journal of Medicine, David Ellinghaus, a scientist at the Institute of Clinical Molecular Biology in Germany, and colleagues analyzed nearly 8.6 million single nucleotide polymorphisms from 1,610 Spanish and Italian patients with COVID-19 and respiratory failure. Another 2,205 uninfected participants served as controls. Participants’ age, ethnicity and sex were also part of the analysis.
SARS-CoV-2 has caused a global pandemic which continues to wreak havoc on people’s lives and livelihoods. As of June 16th, 2020, the COVID-19 cases surpassed 8 million and the death toll stood at more than 400,000. Although the majority of the patients developed mild symptoms and eventually recovered from this disease, a significant proportion suffered from serious pneumonia and developed acute respiratory distress syndrome (ARDS), septic shock, and/or multi-organ failure. The degree of the disease severity should result from direct viral damages on epithelial surface layer (ESL) and the host immune response. SARS-CoV-2 infection may trigger a dysfunctional response leading to an overproduction of cytokines (cytokine storm) and the recruitment of more immune cells into the lungs, resulting in greater damages. However, the immune effectors that determine or influence the severity of the disease and the reason why immune response mediates recovery in some individuals, but not in others, are far from clear. In this study, we addressed these issues by analyzing the blood samples of COVID-19 patients with varying degrees of disease severity and by collecting their clinical data over a period of more than three months. Our findings highlight the importance of T cell immunity in COVID-19 recovery.
In response to the covid-19 pandemic, many health systems attempted to rapidly reorganise their healthcare workforce in the first half of 2020, including redeployment of doctors from primary care and non-frontline specialties to acute care wards. Preparedness for potential future redeployment remains essential given the risk of further waves of covid-19 as society negotiates repeated cycles of lockdown and reopening. Most people who become seriously unwell with covid-19 have an acute respiratory illness, and about 14% will require non-invasive respiratory support. In addition to shifting into acute care settings in the short term, primary care clinicians will also be caring for patients (or their loved ones) recovering from potentially traumatic experiences of respiratory illness. This article updates primary care and non-respiratory or intensivist specialist doctors on the recognition and non-invasive management of acute respiratory failure and will aid general practitioners in the subsequent outpatient support of patients during their recovery.
Today, the U.S. Food and Drug Administration took important action to help facilitate the timely development of safe and effective vaccines to prevent COVID-19 by providing guidance with recommendations for those developing COVID-19 vaccines for the ultimate purpose of licensure. The guidance, which reflects advice the FDA has been providing over the past several months to companies, researchers, and others, describes the agency’s current recommendations regarding the data needed to facilitate the manufacturing, clinical development, and approval of a COVID-19 vaccine. The guidance also discusses the importance of ensuring that the sizes of clinical trials are large enough to demonstrate the safety and effectiveness of a vaccine. It conveys that the FDA would expect that a COVID-19 vaccine would prevent disease or decrease its severity in at least 50% of people who are vaccinated.
Idiopathic nonhistaminergic acquired angioedema (InH-AAE) is a rare disease characterized by submucosal swelling without concomitant urticaria and poor response to antihistamines and corticosteroids. Compared with other forms of hereditary and acquired angioedema, InH-AAE seems to have a predilection for facial and tongue swelling, and is often difficult to diagnose as patients have normal laboratory values and no family history. To our knowledge, there have been no publications to date describing idiopathic nonhistaminergic angioedema as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, although nonhistaminergic angioedema has been seen in the setting of other viral infections. We describe a case of suspected InH-AAE in an intubated patient with coronavirus disease 2019 (COVID-19). We review post-intubation macroglossia as a potential differential diagnosis and why this etiology is unlikely in our patient. Finally, we briefly discuss the hyperinflammatory response to SARS-CoV-2 and its potential role in the development of InH-AAE.
The use of telehealth has exploded as many regulatory barriers to its use have been temporarily lowered during the COVID-19 pandemic. The AMA is advocating for making many of these emergency policy changes permanent. “The expansion of telehealth and the offering of new telehealth services that were not previously covered really enabled physicians to care for their patients in the midst of this crisis,” Todd Askew, the AMA’s senior vice president of advocacy, said during a recent “AMA COVID-19 Update” video. “We have moved forward a decade in the use of telemedicine in this country and it’s going to become, and will remain, an increasingly important part of physician practices going forward.”
New U.S. COVID-19 cases rose by more than 47,000 on Tuesday according to a Reuters tally, the biggest one-day spike since the start of the pandemic, as the government’s top infectious disease expert warned that number could soon double. California, Texas and Arizona have emerged as new U.S. epicenters of the pandemic, reporting record increases in COVID-19 cases. “Clearly we are not in total control right now,” Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, told a U.S. Senate committee. “I am very concerned because it could get very bad.”
HHS spokesman Michael Caputo on Monday tweeted that HHS intends to extend the COVID-19 public health emergency that is set to expire July 25. The extension would prolong the emergency designation by 90 days. Several payment policies and regulatory adjustments are attached to the public health emergency, so the extension is welcome news for healthcare providers. HHS “expects to renew the Public Health Emergency due to COVID-19 before it expires. We have already renewed this PHE once,” Caputo said. Provider groups including the American Hospital Association have urged HHS to renew the distinction.
The death toll from COVID-19 surpassed half a million people on Sunday, according to a Reuters tally, a grim milestone for the global pandemic that seems to be resurgent in some countries even as other regions are still grappling with the first wave. The respiratory illness caused by the new coronavirus has been particularly dangerous for the elderly, although other adults and children are also among the 501,000 fatalities and 10.1 million reported cases. While the overall rate of death has flattened in recent weeks, health experts have expressed concerns about record numbers of new cases in countries like the United States, India and Brazil, as well as new outbreaks in parts of Asia.
[Quiz] New information is posted daily, but keeping up can be a challenge. As an aid for readers and for a little amusement, here is a 10-question quiz based on the news of the week. Topics include COVID-19 risk factors, future pandemic preparation, and effects on kids from parents’ mental illness. After taking the quiz, scroll down in your browser window to find the correct answers and explanations, as well as links to the original articles.
The ACP provides resources to help guide practices in plans for re-opening. Resources include guides, checklists, staffing and workflow modifications, and materials for communicating with patients. The ACP also offers clinical and public policy guidance on how to resume some economic, social and medical care activities to mitigate COVID-19 and allow expansion of healthcare capacity. For more information, the CDC offers a framework for providing non-COVID-19 care during the pandemic.
In the UK, more than 279 392 cases of COVID-19 had been documented by June 3, 2020, and more than 39 500 patients had died with the disease, according to the COVID-19 web-based dashboard at Johns Hopkins University. Data derived from the UK Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme Database show that, for the first 8062 patients admitted to the ICU across the UK with documented outcomes, by May 29, 2020, about 72% received advanced mechanical ventilation and the mortality rate was around 53%. This mortality far exceeds that of typical severe acute respiratory distress syndrome (ARDS). The significant surge in the number of patients requiring ventilatory support has presented the UK National Health Service with unprecedented challenges, including pressures on critical care capacity, resources, and supplies, concerns about staff protection, as well as ethical issues associated with triage and resource allocation.
The Centers for Medicare and Medicaid Services (CMS) continues to provide flexibilities to clinicians participating in the Quality Payment Program (QPP) Merit-based Incentive Payment System (MIPS) in 2020 as a result of the COVID-19 pandemic. Clinicians significantly impacted by the public health emergency may submit an Extreme & Uncontrollable Circumstances Application to reweight any or all of the MIPS performance categories for performance year 2020. Clinicians requesting relief will need to provide a justification of the impacts to their practice as a result of the public health emergency.
Individuals with coronavirus disease 2019 (COVID-19) with comorbid asthma may not have an increased risk for more severe disease, compared with those without asthma, according to a literature analysis published in The Journal of Allergy and Clinical Immunology. The impairment of antiviral responses in patients with asthma, which can, in turn, aggravate type 2 inflammation, suggests that these individuals may be at a high risk for morbidity and mortality from COVID-19.
In December 2019, following a cluster of pneumonia cases in China caused by a novel coronavirus (CoV), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infection disseminated worldwide and, on March 11th, 2020, the World Health Organization officially declared the pandemic of the relevant disease named coronavirus disease 2019 (COVID-19). In Europe, Italy was the first country facing a true health policy emergency, and, as at 6.00 p.m. on May 2nd, 2020, there have been more than 209,300 confirmed cases of COVID-19. Due to the increasing number of patients experiencing a severe outcome, global scientific efforts are ongoing to find the most appropriate treatment. The usefulness of specific anti-rheumatic drugs came out as a promising treatment option together with antiviral drugs, anticoagulants, and symptomatic and respiratory support. For this reason, the authors share their experience and knowledge on the use of these drugs in the immune-rheumatologic field, providing in this review the rationale for their use in the COVID-19 pandemic.
As COVID-19 case counts reach 8.8 million worldwide, including 465,000 deaths, more than 183,000 new cases were reported to WHO on Sunday — the most in a single day since the beginning of the pandemic. “It seems that almost every day we reach a new and grim record,” WHO Director-General Tedros Adhanom Ghebreyesus, PhD, MSc, said in a press briefing. According to WHO, demand for dexamethasone, which was previously shown to reduce mortality by one-third in ventilated patients with COVID-19, has surged worldwide. Tedros noted that the drug should be used only in patients with severe disease.
More than 3.8 million people worldwide have recovered from COVID-19. However, recent cases are showing that even those who recover may still be at risk for long-term health issues. Despite the fact that the earliest coronavirus reports indicated that younger people were at a lower risk of serious complications from COVID-19, recent findings are contradicting that belief. Most recently, a 20-year-old COVID-19 survivor in Chicago was the recipient of a new set of lungs, due to a lung transplant that was necessary to treat a condition now being called post-COVID fibrosis. There have been two other lung transplants performed on COVID-19 survivors with post-COVID fibrosis: one was in China and the other in Vienna.
Coronavirus cases in Florida surpassed 100,000 on Monday, part of an alarming surge across the South and West as states reopen for business and many Americans resist wearing masks or keeping their distance from others. The disturbing signs in the Sunshine State as well as places like Arizona, Alabama, Louisiana, Texas and South Carolina — along with countries such as Brazil, India and Pakistan — are raising fears that the progress won after months of lockdowns is slipping away.
Three medical societies released an expert panel report on the use of tracheostomy during the COVID-19 pandemic while minimizing the risk for infection to health care workers. Critically ill patients with COVID-19 account for 5% of all cases and one-quarter of all hospitalizations. Many of these patients require prolonged mechanical ventilation. Performing tracheostomies on these patients may allow for faster removal from ventilation, shorter hospitalization and thus greater ICU resource availability, but there are currently unanswered questions regarding preparation, timing, technique and protection for health care workers.
This manuscript explores the question of the seasonality of SARS-CoV-2 by reviewing four lines of evidence related to viral viability, transmission, ecological patterns and observed epidemiology of COVID-19 in the Southern Hemispheres’ summer and early fall. There are four lines of evidence: (1) seasonality of other human coronaviruses and influenza A, (2) in vivo experiments with influenza transmission, (3) ecological data and (4) the observed epidemiology of COVID-19 in the Southern Hemispheres’ summer and early fall.
Coronavirus disease 2019 (COVID‐19) emerged in Wuhan city and rapidly spread globally outside China. We aimed to investigate the role of peripheral blood eosinophil (EOS) as a marker in the course of the virus infection to improve the efficiency of diagnosis and evaluation of COVID‐19 patients. This article looks at 227 pneumonia patients who visited the fever clinics in Shanghai General Hospital and 97 hospitalized COVID‐19 patients admitted to Shanghai Public Health Clinical Center were involved in a retrospective research study. Clinical, laboratory, and radiologic data were collected. The trend of EOS level in COVID‐19 patients and comparison among patients with different severity are summarized.
Since the advent of worldwide mechanical ventilator use for patients with polio in the 1950s, ventilators have provided life-saving support to millions of people.1 In the US, ventilators have been widely available for the past 50 years. There have been concerns during the coronavirus disease 2019 (COVID-19) pandemic that the need for ventilators could exceed their availability, thus causing a widespread shortage of ventilators. In these circumstances, tragic choices would need to be made to determine who receives mechanical ventilatory support and who does not. Individual physicians, ethicists, medical societies, and US states have published multiple recommendations regarding how to allocate ventilators in a public health emergency and are largely in consensus that ventilators should be allocated to do the greatest good for the greatest number of people.
Recorded today, Linda Rae Murray, MD, MPH discusses topics in health equity with JAMA Medical News Associate Managing Editor Jennifer Abbasi.
Local physicians said a U.K. study of the use of the steroid dexamethasone in treating severe COVID-19 patients showed promising results, but they’re reserving judgment until more data from the study is published. Initial results were announced Tuesday in a press release. The randomized trial, supported by the University of Oxford, tested dexamethasone in about 2,100 patients with an additional 4,300 receiving only usual care. The study found that the drug reduced the number of deaths by one-third in patients using mechanical ventilators and one-fifth in patients receiving only oxygen. There was no benefit among patients who didn’t require respiratory support.
Data from multiple countries demonstrate that lifting restrictions imposed to reduce the spread of coronavirus disease 2019 (COVID-19) would result in a resurgence of infections, according to provisional analyses published in the European Respiratory Journal. Most countries with significant COVID-19 outbreaks have introduced social distancing or “lockdown” measures to reduce viral transmission, however, the question of when, how, and to what extent these measures can be lifted remains.
Helio | Infectious Disease, June 18, 2020
Public-private partnerships, collaboration among researchers and knowledge of existing coronaviruses have all contributed to the accelerated development of COVID-19 vaccine candidates, according to Infectious Disease News Editorial Board Member Kathleen M. Neuzil, MD, MPH, FIDSA. Neuzil, a professor of vaccinology and director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine, said vaccine development overall is a “continuum” from the discovery phase to “delivery and impact.” Neuzil and other presenters opened the National Foundation for Infectious Diseases’ Annual Conference on Vaccinology Research with a discussion on the current state of vaccine development for COVID-19.
Chicagoans are being infected with a unique strain of COVID-19 that’s linked to the early coronavirus outbreak in China, according to new research. Northwestern Medicine scientists have determined that the Chicago area “is a melting pot for different versions of the virus because it is such a transportation hub,” Dr. Egon Ozer, an assistant professor at Northwestern University’s Feinberg School of Medicine and a Northwestern Medicine physician, said in a statement today. Ozer’s team is learning how variations of the severe acute respiratory syndrome that causes COVID-19 infects people differently. It’s a finding they say could help shape a potential vaccine.
Kalytera Therapeutics has announced positive early results for R-107, a liquid form of nitric oxide designed to treat pulmonary arterial hypertension (PAH) associated with COVID-19. Nitric oxide, known as NO, is a gas naturally present in the lungs. It facilitates oxygenation by relaxing, or dilating, the blood vessels, allowing blood to flow smoothly. R-107 is a liquid prodrug of nitric oxide, meaning that the compound is a precursor to its pharmacologically active form. Once injected into the body, R-107 is converted into its active form, called R-100, which steadily releases NO into lung tissues over the course of several days.
Global quarantine as a result of the coronavirus disease 2019 (COVID-19) pandemic has decreased fossil fuel use which may affect allergic and respiratory diseases, according to an editorial published in The Journal of Allergy and Clinical Immunology. Air pollution is a causative factor of symptoms such as bronchospasm, rhinorrhea, and eye redness and irritation, as well as allergic diseases such as asthma, chronic rhinitis, nasal polyps, atopic dermatitis, seasonal or perennial allergic conjunctivitis, and vernal or atopic keraconjunctivitis. Through climate change, worldwide emission of greenhouse gasses (ie, nitrogen dioxide and carbon dioxide) has caused an increase in air humidity, mold exposure, and modified pollen patterns, which in turn, increased sensitization rates and allergic disease prevalence.
The American Lung Association recently held a virtual Town Hall meeting to debunk widespread misperceptions in the United States about which populations should be prioritized for COVID-19 testing and how to interpret the results. “Far too many people have misinterpreted testing,” Michael T. Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota, said during the meeting. “While we need to greatly expand our SARS-CoV-2 testing as a critical component of our response to COVID-19, the pandemic messaging to date needs to move beyond the ‘Test, test, test!’ mantras. That is the wrong approach.”
China National Biotec Group (CNBG) said on Tuesday its experimental coronavirus vaccine has triggered antibodies in clinical trials and the company plans late-stage human trials in foreign countries. No vaccines have been solidly proven to be able to effectively protect people from the virus that has killed more than 400,000 people, while multiple candidates are in various stages of development globally. The vaccine, developed by a Wuhan-based research institute affiliated to CNBG’s parent company Sinopharm, was found to have induced high-level antibodies in all inoculated people without serious adverse reaction, according to the preliminary data from a clinical trial initiated in April involving 1,120 healthy participants aged between 18 and 59.
In March 2020, the RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial was established as a randomised clinical trial to test a range of potential treatments for COVID-19, including low-dose dexamethasone (a steroid treatment). Over 11,500 patients have been enrolled from over 175 NHS hospitals in the UK. On 8 June, recruitment to the dexamethasone arm was halted since, in the view of the trial Steering Committee, sufficient patients had been enrolled to establish whether or not the drug had a meaningful benefit. A total of 2104 patients were randomised to receive dexamethasone 6 mg once per day (either by mouth or by intravenous injection) for ten days and were compared with 4321 patients randomised to usual care alone. Among the patients who received usual care alone, 28-day mortality was highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%).
The primary objective of this study was to determine the prevalence of asthma among COVID-19 patients in a major U.S. health system. We assessed the clinical characteristics and comorbidities in asthmatic and non-asthmatic COVID-19 patients. We also determined the risk of hospitalization associated with asthma and/or inhaled corticosteroid use. Medical records of patients with COVID-19 were searched by a computer algorithm (March 1–April 15, 2020), and chart review was used to validate the diagnosis of asthma and medications prescribed for asthma. All patients were PCR-confirmed COVID-19. Demographics and clinical features were characterized. Regression models were used to assess the associations between asthma and corticosteroid use and the risk of COVID-19-related hospitalization.
The number of patients visiting the emergency department (ED) for asthma treatment dropped by 76% in the first month of the COVID-19 pandemic, according to a new study by researchers at Children’s Hospital of Philadelphia (CHOP). The proportion of ED visits that led to a patient being hospitalized also decreased over this period, suggesting the decrease in overall visits was not solely due to patients avoiding the hospital due to the pandemic or delays in care for less serious asthma events. “We were surprised by the magnitude and extent of the reduced utilization of emergency services for asthma during the emergence of the COVID-19 pandemic,” said Chén C. Kenyon, MD, MSHP, a pediatrician in CHOP’s Division of General Pediatrics and first author of the study, which was published in JACI in Practice.
Death rates are 12 times higher for coronavirus patients with chronic illnesses than for others who become infected, a new U.S. government report says. The Centers for Disease Control and Prevention report released Monday highlights the dangers posed by heart disease, diabetes and lung ailments. These are the top three health problems found in COVID-19 patients, the report suggests. The report is based on 1.3 million laboratory-confirmed coronavirus cases reported to the agency from January 22 through the end of May. Information on health conditions was available for just 22% of the patients. It shows that 32% had heart-related disease, 30% had diabetes and 18% had chronic lung disease, which includes asthma and emphysema.
Helio | Infectious Disease News, June 12, 2020
Anti-contagion policies have prevented or delayed as many as 62 million confirmed COVID-19 infections, which corresponded with the prevention of an estimated 530 million cases in six countries, according to a study published in Nature. “We found that in the absence of policy intervention, the number of COVID-19 infections doubled approximately every 2 days,” Esther Rolf, a PhD candidate in the computer science department at University of California, Berkeley, told Healio. “In all six countries we studied, we found that the anti-contagion policies put in place significantly slowed the spread of the disease, resulting in an estimated 500 million infections prevented or delayed, across the six countries in the time frame that we studied.”
Northwestern Memorial Hospital is believed to be the first U.S. facility to perform a life-saving double-lung transplant on a former COVID-19 patient. The Chicago hospital today announced that the patient, a woman in her 20s, had the procedure this month after suffering irreversible damage to her lungs while recovering from the coronavirus. The patient had spent six weeks in Northwestern’s COVID intensive care unit on a ventilator and a machine that supports the heart and lungs, Northwestern Medicine said in a statement. She needed to test negative for the virus before doctors could put her on the waiting list for a transplant.
Acalabrutinib, a Bruton tyrosine kinase (BTK) inhibitor, appears to reduce respiratory distress as well as the hyperinflammatory immune response associated with coronavirus disease 2019 (COVID-19), according to a study led by researchers at the Center for Cancer Research at the National Cancer Institute and the National Institute of Allergy and Infectious Diseases, both part of the National Institutes of Health (NIH). The prospective study included 19 patients with confirmed COVID-19 who required hospitalization for hypoxemia and had evidence of inflammation. Patients received acalabrutinib 100mg twice daily for 10 days (supplemental oxygen cohort n=11) or 14 days (mechanical ventilation cohort n=8) plus best supportive care. A subset of patients in both cohorts received concomitant treatment with steroids and/or hydroxychloroquine.
The number of confirmed U.S. coronavirus cases passed 2 million on Thursday, as public health experts warned of the emergence of new COVID-19 hotspots across the country. Just three weeks after Arizona Gov. Doug Ducey lifted the state’s stay-at-home order, there has been a significant spike in coronavirus cases, with lawmakers and medical professionals warning that hospitals might not be able to handle a big influx of new cases. Already, hospitals in the state are at 83 percent capacity, the Associated Press reported. But Arizona is not alone in seeing increases in hospitalizations: new U.S. data shows at least eight other states with spikes since Memorial Day. In Texas, North and South Carolina, California, Oregon, Arkansas, Mississippi and Utah, increasing numbers of COVID-19 patients are showing up at hospitals.
A lack of health literacy is preventing people from having a good understanding of the novel coronavirus, two speakers said Wednesday at an online briefing sponsored by the National Academies of Sciences, Engineering, and Medicine. “So many people are confused about the symptoms” of COVID-19, said Lisa Fitzpatrick, MD, MPH, founder of Grapevine Health, a nonprofit organization in Washington that helps design culturally appropriate health information campaigns targeted at underserved populations. When Grapevine Health sent workers out to talk to people about the pandemic, “So many told us they didn’t know the symptoms,” said Fitzpatrick.
Social distancing of families with children who have asthma is the best method for preventing coronavirus diseases 2019 (COVID-19), according to a letter to the editor published in Allergy. COVID-19 affects all ages, and the US Centers for Disease Control and Prevention initially stated that people with chronic lung disease, including moderate severe asthma, and allergy may be at higher risk of developing a more severe course of COVID-19 than healthy people. Very few reports are available on pediatric patients with COVID-19; therefore, researchers analyzed data on pediatric patients referred for COVID-19 at 2 hub hospitals located in Italy.
The world’s leading drug companies, universities and governments are racing to develop a vaccine for COVID-19, the disease that has taken more than 400,000 lives globally. Of the 133 candidates being explored, ten have been approved for human trials, according to the World Health Organization. Companies and research groups in China, the early epicenter of the coronavirus outbreak, are testing five of those vaccines in human trials. Meanwhile, U.S.-based companies are involved in the development of four additional vaccines, including one that has NIAID Director Anthony Fauci “cautiously optimistic.”
On 26 April, after spending weeks caring for patients with coronavirus disease 2019 (COVID-19) in New York City, emergency room physician Lorna Breen took her own life. Her grieving family recounts days of helplessness leading up to this as Dr. Breen described how COVID-19 upended her emergency department and left her feeling inadequate despite years of training and expertise. The clinical experience of Dr. Breen during this pandemic has not been unique. During the past 5 months, COVID-19 has caused an upheaval of medical systems around the world, with more than 4 million cases and 300 000 deaths worldwide so far. Unfortunately, we’ve also seen that the experience in caring for patients with the virus may have profound effects on clinicians’ mental health. A recent study conducted at the center of the outbreak in China reported that more than 70% of frontline health workers had psychological distress after caring for patients with COVID-19.
The first confirmed cases of coronavirus in the U.S. appeared in January. At the time, the world knew almost nothing about how the virus spreads or how to treat it. Six months later, our knowledge has grown, but researchers continue to make discoveries almost daily. At first, health experts believed COVID-19, the disease caused by the new coronavirus, primarily affected patients’ lungs. While it’s still primarily a lung disease, other symptoms have appeared often, and they’ve been added to the list of signs of COVID.
RELIEF THERAPEUTICS Holding AG (SIX:RLF) “Relief” and its U.S. partner, NeuroRx, Inc. announced that the Phase 2/3 clinical trial evaluating RLF-100 as a treatment for critical COVID-19 with respiratory failure has been expanded to include patients receiving high flow oxygen and noninvasive ventilation (CPAP), in addition to those on ventilators. RLF-100 (Aviptadil) is a patented formulation of synthetic human Vasoactive Intestinal Peptide (VIP), which has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) in Acute Respiratory Distress Syndrome and chronic lung diseases.
The first patients have been dosed in a phase 1 trial evaluating a potential antibody therapy designed to treat coronavirus disease 2019 (COVID-19). These patients received treatment at major medical centers in the US, including NYU Grossman School of Medicine and Cedars-Sinai in Los Angeles. The investigational agent, LY-CoV555, is a potent, neutralizing lgG1 monoclonal antibody directed against the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The randomized, double-blind, placebo-controlled study is investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of 1 dose of LY-CoV555 in patients hospitalized with COVID-19; those requiring mechanical ventilation or who have received convalescent COVID-19 plasma treatment prior to enrollment were excluded from the study.
Get this COVID-19 Critical Care Update when Howard Bauchner, MD, Editor in Chief, JAMA, speaks with Maurizio Cecconi, MD of Humanitas University in Milan and Derek C. Angus, MD, MPH of the University of Pittsburgh.
The U.S. Centers for Disease Control and Prevention (CDC) on Sunday reported 1,920,904 cases of new coronavirus, an increase of 29,214 cases from its previous count, and said COVID-19 deaths in the United States had risen by 709 to 109,901. The CDC reported its tally of cases of COVID-19, the respiratory illness caused by the new coronavirus, as of 4 p.m. EDT on June 6. Its previous tally was released on Friday.
Hypercoagulability on thromboelastography (TEG) was a good predictor of thrombotic events among COVID-19 patients entering the ICU, according to a single-center study. The clinically significant thrombosis that developed in 13 of 21 PCR-test-positive patients (62%) seen at Baylor St. Luke’s Medical Center ICU from March 15 to April 9 was associated with hypercoagulable TEG parameters in all cases. Maximum amplitude on that test was elevated in all 10 patients with two or more thrombotic complications compared with 45% of those with no more than one such event (nearly all arterial, central venous, or dialysis catheter or filter thromboses).
Vaccine makers are racing to develop COVID-19 vaccines, and have advanced ten candidates into clinical trials. But challenges remain. Vaccine development is typically a long game. The US Food and Drug Administration only approved a first vaccine against Ebola virus last year, 43 years after the deadly virus was discovered. Vaccinologists have made little headway with HIV or respiratory syncytial virus, despite huge investments. On average, it takes 10 years to develop a vaccine. With the COVID-19 crisis looming, everyone is hoping that this time will be different. Already, ten vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) are in clinical trials, and researchers at the University of Oxford and AstraZeneca hope to have the first phase 3 data in hand this summer.
Easing the traumatic “air hunger” created by mechanical ventilation settings for COVID-19 acute respiratory distress syndrome (ARDS) may take more than just sedation or paralytics, one group argued. Lung protective ventilation, with low tidal volumes and permissive hypercapnia, is a recipe for “the most uncomfortable form of dyspnea,” Richard Schwartzstein, MD, of Beth Israel Deaconess Medical Center and Harvard in Boston, wrote in the Annals of the American Thoracic Society.
Influenza vaccination reduced the risk for influenza by more than 40%, with no effect on coronaviruses or other non-influenza respiratory viruses, according to a study assessing seasonal influenza and coronaviruses over seven seasons. “Vaccines induce specific antibody protection, targeting the viral or bacterial antigens that are included as vaccine components. On that basis, influenza vaccines are expected to reduce the risk for illness due to influenza viruses and have no effect on other non-influenza respiratory viruses (NIRV),” Danuta M. Skowronski, MD, FRCPC, of the British Columbia Centre for Disease Control and the University of British Columbia in Vancouver, told Healio.
Compared to ventilator care, nasal high flow therapy for seriously ill coronavirus patients has several benefits, including the ability to mobilize patients. Nasal high flow (NHF) therapy is a less invasive alternative to ventilator care for many seriously ill coronavirus patients, UnityPoint Health experts say. During the coronavirus disease 2019 (COVID-19) pandemic, ventilator care has been used commonly for coronavirus patients experiencing acute respiratory distress. However, ventilator care has posed several challenges, including shortages ventilators and the staff needed to manage patients on mechanical ventilation.
In the thick of the coronavirus pandemic, it might be hard to tell if you’ve come down with COVID-19, spring allergies or a cold, which all have some similar symptoms. Fever and dry cough are common symptoms of COVID-19, along with shortness of breath and difficulty breathing, sore throat, diarrhea, fatigue, chills, muscle pain, loss of taste and smell, and body aches. But it’s rare for fever or diarrhea to occur with a cold or seasonal allergies, according to Dr. Michael Benninger, chairman of the Head and Neck Institute at the Cleveland Clinic. “It’s a matter of taking a logical approach to symptoms,” he said in a clinic news release.
Since its invention in the 1940s, the positive pressure ventilator has always been known to have both risks and benefits. Although mechanical ventilation is unquestionably lifesaving, there are numerous associated drawbacks. Beyond the obvious and immediate limitations that patients require translaryngeal intubation and are physically attached to a ventilator, delivery of gas by positive pressure also creates mechanical stress and causes strain on lung tissue. This stress can lead to ventilator-induced lung injury, compounding the underlying lung condition that precipitated the initial respiratory failure.1 Despite advances in knowledge about protective ventilation strategies to limit ventilator-induced lung injury (most notably use of low tidal volumes), concern remains for this iatrogenic injury in all patients undergoing intubation and mechanical ventilation.
In cases of coronavirus disease 2019 (COVID-19), patients with poor baseline health have an elevated risk of severe respiratory complications and worse outcomes following hospital admission and mechanical ventilation. In addition, these patients are generally more likely to demonstrate impaired respiratory muscle performance. In a recent review published in the American Journal of Medicine, Rich Severin PT, DPT, PhD(c), CCS, a PhD candidate in the department of physical therapy at the University of Illinois-Chicago, and colleagues proposed that “impaired respiratory muscle performance is an underappreciated factor contributing to poor outcomes unfolding during the coronavirus pandemic.”
The coronavirus disease 2019 (COVID-19) pandemic is wreaking havoc and causing fear, illness, suffering, and death across the world. This outbreak lays bare the fault lines in our society and highlights that the United States could have been better prepared for the pandemic had we a more equitable and just health care system. As leaders in the American College of Physicians (ACP), we have helped develop ACP’s wide-ranging policies on health care in the United States. The College has adopted a “health in all policies” approach, integrating health considerations into policymaking across sectors to improve the health and health care of all communities and people, which we believe, if enacted, would have enabled the United States to more effectively respond to the COVID-19 pandemic.
The cochairs of the American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA) Guideline for Treatment of Adults With Community-Acquired Pneumonia (CAP) have published their perspectives of the guideline as it relates to the management of patients with pneumonia associated with coronavirus disease 2019 (COVID-19). The authors’ comments were published in an Ideas and Opinions paper in the Annals of Internal Medicine. The guideline cochairs wrote that empirical coverage for bacterial pathogens in patients with CAP is not required for all patients with confirmed pneumonia related to COVID-19.
A clinical frailty scale (CFS) developed at Nova Scotia’s Dalhousie University is helping doctors predict outcomes of older COVID-19 patients in urgent care settings and decide who gets more aggressive treatments. Because the CFS quickly offers a quantitative number, it avoids age bias when it comes to treatment decisions, said Kenneth Rockwood, MD, of the Division of Geriatric Medicine, Department of Community Health and Epidemiology, School of Health Administration, whose team developed the scale.
Protests erupting across the nation over the past week — and law enforcement’s response to them — are threatening to upend efforts by health officials to track and contain the spread of coronavirus just as those efforts were finally getting underway. Health experts need newly infected people to remember and recount everyone they’ve interacted with over several days in order to alert others who may have been exposed, and prevent them from spreading the disease further. But that process, known as contact tracing, relies on people knowing who they’ve been in contact with — a daunting task if they’ve been to a mass gathering.
The 24-hour news cycle is just as important to medicine as it is to politics, finance, or sports. New information is posted daily, but keeping up can be a challenge. As an aid for readers and for a little amusement, here is a 10-question quiz based on the news of the week. Topics include coronavirus vaccine research, LGBTQ deaths by suicide, and hypertension. After taking the quiz, scroll down in your browser window to find the correct answers and explanations, as well as links to the original articles.
Unlike other comorbidities, metastatic lung adenocarcinoma did not escalate the progression of COVID-19 according to results from a case report published in the American Society of Clinical Oncology. A 76-year-old man with metastatic lung adenocarcinoma and a history of chronic obstructive pulmonary disease tested positive for SARS-CoV-2 infection in Spain. He presented with fever, shortness of breath, and bibasal crackles 1 week after his 6th maintenance cycle of cisplatin-pemetrexed and pembrolizumab treatment for his cancer. A blood test showed lymphocytes 120/mL, neutrophils 430/mL, platelets 84,000/mL, C-reactive protein 24.4 mg/dL, and high D-dimer. A chest radiograph revealed diffuse infiltrate in his lungs. Read more.
In April, blood clots emerged as one of the many mysterious symptoms attributed to Covid-19, a disease that had initially been thought to largely affect the lungs in the form of pneumonia. Quickly after came reports of young people dying due to coronavirus-related strokes. Next it was Covid toes — painful red or purple digits. What do all of these symptoms have in common? An impairment in blood circulation. Add in the fact that 40% of deaths from Covid-19 are related to cardiovascular complications, and the disease starts to look like a vascular infection instead of a purely respiratory one.
The COVID-19 pandemic has presented considerable challenges to global health services and dictates almost every aspect of medical practice and policy. Across Europe, a surge phase in acute caseload, led to a sudden curtailment of non-COVID-19 medical care, with immediate implications for routine diagnostic and surveillance investigations. As COVID-19-related hospital admissions subside, many lung function services have started to reconsider how best to operate, within the constraints dictated by a COVID-19 endemic scenario. Central to planning in this phase are the precautions needed to protect lung function staff, and to minimise cross-infection risk, given an ongoing need to test vulnerable patient groups—eg, immunocompromised or individuals with long-term conditions.
The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. This international, observational, cohort study provides cross-specialty, patient-level outcomes data for patients who had surgery and acquired perioperative SARS-CoV-2 infection. 1128 patients were included across 24 countries.
The COVID-19 pandemic and the response to the pandemic are combining to produce a tidal wave of need for rehabilitation. Rehabilitation will be needed for survivors of COVID-19, many of whom are older, with underlying health problems. In addition, rehabilitation will be needed for those who have become deconditioned as a result of movement restrictions, social isolation, and inability to access healthcare for pre-existing or new non-COVID-19 illnesses. Delivering rehabilitation in the same way as before the pandemic will not be practical, nor will this approach meet the likely scale of need for rehabilitation. This commentary reviews the likely rehabilitation needs of older people both with and without COVID-19 and discusses how strategies to deliver effective rehabilitation at scale can be designed and implemented in a world living with COVID-19.
This ACP Physician’s Guide and its collected national resources support physicians as they respond to the Covid-19 pandemic. The ACP-produced resource can be easily accessed on handheld devices and other computers to provide a clinical overview of infection control and patient care guidance. CME credit and MOC points available.
The recent identification of a novel coronavirus, also known as SARS-CoV-2, has caused a global outbreak of respiratory illnesses. The rapidly developing pandemic has posed great challenges to diagnosis of this novel infection. However, little is known about the metatranscriptomic characteristics of patients with Coronavirus Disease 2019 (COVID-19). Metatranscriptomics in 187 patients (62 cases with COVID-19 and 125 with non-COVID-19 pneumonia) were analyzed, and transcriptional aspects of three core elements – pathogens, the microbiome, and host responses – were interrogated.
As deaths from COVID-19 increase to more than 100,000 in the United States, institutions around the world are working to develop an effective vaccine. Kaiser Permanente Washington Health Research Institute in Seattle is conducting a phase 1 clinical trial to assess an investigational vaccine, while Johnson & Johnson plans to initiate human clinical studies for its potential candidate by September. According to WHO, there are 10 COVID-19 vaccine candidates under clinical evaluation and an additional 115 candidates in preclinical evaluation. In a remote hearing of the U.S. Senate Committee on Health, Education, Labor & Pensions earlier this month, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said an NIH-directed trial is expected to enter phase 2/3 in late spring or early summer.
SARS-CoV-2 spread rapidly within months despite global public health strategies to curb transmission by testing symptomatic patients and encouraging social distancing. Here, we summarize rapidly emerging evidence highlighting transmission by asymptomatic and pre-symptomatic individuals. Viral load of asymptomatic carriers is comparable to symptomatic patients, viral shedding is highest before symptom onset suggesting high transmissibility before symptoms. Within universally tested subgroups, surprisingly high percentages of COVID-19 positive asymptomatic individuals were found. Asymptomatic transmission was reported in several clusters.
Patients who died from COVID-19-associated respiratory failure had more intussusceptive angiogenesis in their lungs than those who died from influenza, according to an autopsy study. For the study, which was published in The New England Journal of Medicine, researchers used seven-color immunohistochemical analysis, micro-CT imaging, scanning electron microscopy, corrosion casting and direct multiplexed measurement of gene expression to evaluate and compare lungs from patients who died from COVID-19 with those who died from influenza A (H1N1)-associated acute respiratory distress syndrome in 2009 and those from age-matched uninfected controls.
Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). This article summarizes evidence (from Four randomized controlled trials, 10 cohort studies, and 9 case series) about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19).
Patients with COVID-19 with a body mass index (BMI) >30 kg/m² have increased odds of developing pulmonary embolism (PE), according to a research letter published online May 14 in Radiology. Neo Poyiadi, M.D., from the Henry Ford Health System in Detroit, and colleagues assessed the clinical characteristics of COVID-19 patients who developed PE in a retrospective analysis involving 328 COVID-19 patients who underwent pulmonary computed tomography (CT) angiography. The researchers found that 22 percent of the patients had PE.
Increasing number of deaths due to COVID-19 pandemic has raised serious global concerns. Higher testing capacity and ample intensive care availability could explain lower mortality in some countries compared to others. Nevertheless, it is also plausible that the SARS-CoV-2 mutations giving rise to different phylogenetic clades are responsible for the obvious death disparities around the world. Current research literature linking the genetic make-up of SARS-CoV-2 with fatality is lacking. Here, we suggest that this disparity in fatality rates may be attributed to SARS-CoV-2 evolving mutations and urge the international community to begin addressing the phylogenetic clade classification of SARS-CoV-2 in relation to clinical outcomes.
[Video] Experts in the field of pulmonology share concerns over managing patients with allergic asthma during the current COVID-19 pandemic. Thomas Casale, MD, speaks with Geoffrey L. Chupp, MD, Stanley Goldstein, MD, Syed Shahzad Mustafa, MD and Michael E. Wechsler, MD, MMSc about challenges for physicians.
A list of clinical and imaging findings that may help distinguish interstitial lung disease (ILD) associated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy used in the treatment of lung cancer from lung-associated manifestations of COVID-19 infection was published in the Journal of Thoracic Oncology. While EGFR-TKI–associated ILD is relatively rare, with a reported incidence in the range of 0.3% to 4.3% depending on patient population and specific EGFR-TKI used, it is considered to be the most serious adverse effect of EGFR-TKI treatment.
Countries around the world are working to “flatten the curve” of the coronavirus pandemic. Flattening the curve involves reducing the number of new COVID-19 cases from one day to the next. This helps prevent healthcare systems from becoming overwhelmed. When a country has fewer new COVID-19 cases emerging today than it did on a previous day, that’s a sign that the country is flattening the curve. On a trend line of total cases, a flattened curve looks how it sounds: flat. On the charts on this page, which show new cases per day, a flattened curve will show a downward trend in the number of daily new cases. This analysis uses a 5-day moving average to visualize the number of new COVID-19 cases and calculate the rate of change.
A chest X-ray (CXR) severity score can predict outcomes among young and middle-aged adults with COVID-19 on presentation to the emergency department, according to a study published online May 14 in Radiology. Danielle Toussie, M.D., from the Icahn School of Medicine at Mount Sinai in New York City, and colleagues analyzed the prognostic value of a CXR severity scoring system for 338 younger patients with COVID-19 on presentation to the emergency department. Data were included for patients aged 21 to 50 years who presented to emergency departments from March 10 to 26, 2020, with confirmed COVID-19. Each CXR was divided into six zones and was examined for opacities, with scores collated into a total lung zone severity score.
Co-infection has been reported in patients with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, but there is limited knowledge on co-infection among patients with coronavirus disease 2019 (COVID-19). The prevalence of co-infection was variable among COVID-19 patients in different studies, however, it could be up to 50% among non-survivors. Co-pathogens included bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumonia, Legionella pneumophila and Acinetobacter baumannii; Candida species and Aspergillus flavus; and viruses such as influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus.
In this large multinational real-world analysis, we did not observe any benefit of hydroxychloroquine or chloroquine (when used alone or in combination with a macrolide) on in-hospital outcomes, when initiated early after diagnosis of COVID-19. Each of the drug regimens of chloroquine or hydroxychloroquine alone or in combination with a macrolide was associated with an increased hazard for clinically significant occurrence of ventricular arrhythmias and increased risk of in-hospital death with COVID-19. The use of hydroxychloroquine or chloroquine in COVID-19 is based on widespread publicity of small, uncontrolled studies, which suggested that the combination of hydroxychloroquine with the macrolide azithromycin was successful in clearing viral replication.
In patients who died from Covid-19–associated or influenza-associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001). In lungs from patients with Covid-19, the amount of new vessel growth — predominantly through a mechanism of intussusceptive angiogenesis — was 2.7 times as high as that in the lungs from patients with influenza (P<0.001).
This year’s spring allergy season has been greatly overshadowed by the arrival of the coronavirus disease 2019 (COVID-19) pandemic. The presence of COVID-19 is affecting everyone and many allergists’ practices have slowed to a crawl because of state-wide limitations in non-essential medical visits and testing, and because of the risk to providers and their staff as well as to patients from COVID-19 infection and transmission. The CDC has issued many guidelines for healthcare providers, which include the use of appropriate PPE and the evaluation and testing of patients suspected of being infected with COVID-19. It has become more important than ever to recognize the differences between allergies and infection with COVID-19. Educating staff and patients to recognize the differences is paramount in appropriately screening those who may otherwise need isolation or referral based on rapidly evolving state and federal guidelines.
[Podcast] In this CME episode, Giselle S. Mosnaim, MD, MS, FAAAAI, discusses the factors associated with high rates of burnout for medical professionals. Listen in to learn great information and helpful tips to maintain wellness, which is especially pertinent during COVID-19.
The novel coronavirus disease 2019 (COVID-19), caused by the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), originated in Wuhan, China, and has now spread internationally with over 4·3 million individuals infected and over 297 000 deaths as of May 14, 2020, according to the Johns Hopkins Coronavirus Resource Center. While COVID-19 has been termed a great equaliser, necessitating physical distancing measures across the globe, it is increasingly demonstrable that social inequalities in health are profoundly, and unevenly, impacting COVID-19 morbidity and mortality. Many social determinants of health—including poverty, physical environment (eg, smoke exposure, homelessness), and race or ethnicity—can have a considerable effect on COVID-19 outcomes.
COVID-19 can manifest as a viral induced hyperinflammation with multi-organ involvement. Such patients often experience rapid deterioration and need for mechanical ventilation. Currently, no prospectively validated biomarker of impending respiratory failure is available. Maximal levels of IL-6 followed by CRP were highly predictive of the need for mechanical ventilation. This suggests the possibility of using IL-6 or CRP levels to guide escalation of treatment in patients with COVID-19 related hyperinflammatory syndrome.
Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality. COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency. Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation. Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory, and imaging studies and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism.
Review a collection of allergy and immunology clinician resources, from webinars to contingency planning and billing & coding information to Federal response updates. This comprehensive collection of links and downloads can assist you in navigating your practice during the pandemic.
The novel coronavirus disease 2019 (COVID-19) has rapidly increased in pandemic scale since it first appeared in Wuhan, China, in December 2019. In these troubled days the scientific community is asking rapid replies to prevent and combat the emergency. It is generally accepted that only achieving a better understanding of the interactions between the virus and host immune response and of the pathogenesis of infection is crucial to identify valid therapeutic tools to control virus entry, replication and spread as well as to impair its lethal effects. Based on the recent research progress of SARS-CoV-2 and the results on previous coronaviruses, in this contribution we underscore some of the main unsolved problems, mostly focusing on pathogenetic aspects and host immunity to the virus. On this basis, we also touch important aspects regarding the immune response in asymptomatic subjects, the immune-evasion of SARS-CoV-2 in severe patients and differences in disease severity by age and gender.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis.
People with asthma are classified as being at increased risk for severe COVID-19 outcomes, although evidence is emerging that may point in the opposite direction. Under normal circumstances, viral infections are a big driver of flares in asthma patients. But research indicates asthma patients with COVID-19 do not appear to have a higher rate of hospitalization or mortality compared with other COVID-19 patients, Linda Rogers, MD, of Icahn School of Medicine at Mount Sinai in New York City, told MedPage Today.
[Infographic] Download and print this infographic to share with your patients and/or hang in your offices.
This quick-start COVID-19 physician guide, curated from comprehensive CDC, JAMA and WHO resources, will help prepare your practice, address patient concerns and answer your most pressing questions.
herapeutic approaches to mitigate the severe acute lung injury associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have rapidly entered clinical trials primarily on anecdotal observations and few clinical studies. Along with the clinical symptoms related to viral invasion, the reported molecular response known as the cytokine storm has attracted the greatest attention, in both the scientific and the lay press, as a cause of organ injury. The hypothesis that quelling this storm with anti-inflammatory therapies directed at reducing interleukin-6 (IL-6), IL-1, or even tumour necrosis factor α (TNFα) might be beneficial has led to several ongoing trials. Anecdotal evidence from non-controlled clinical trials has suggested a possible beneficial effect, and anti-IL-6 has been shown to be effective in chimeric antigen receptor T (CAR-T) and cytokine response syndrome (CRS).
COVID-19, a disease caused by coronavirus, is spreading worldwide and the World Health Organization (WHO) has declared it a pandemic. Here is a map of reported cases, deaths and reported recoveries around the world. In the United States, different parts of the country are seeing different levels of COVID-19 activity. Cases of COVID-19 and instances of community spread are being reported in all states. People in places where there is ongoing community spread of COVID-19 are at higher risk of exposure, with the risk level dependent on your location, according to the U.S. Centers for Disease Control and Prevention (CDC). Check out their COVID-19 Information Center.
American College of Allergy, Asthma & Immunology | April 20, 2020Allergist Jonathan Bayuk, MD, ACAAI member, explains how COVID-19 is different from other viruses, and how to avoid catching it.
Certain areas of the country are experiencing shortages of albuterol inhalers. The shortage will probably spread throughout the U.S., although it is not a production problem. The shortage is occurring because of the increased use of albuterol inhalers in hospitals for COVID-19 and suspected COVID-19 patients to help with respiratory issues. There is a concern that nebulizers used on patients with COVID-19 in the hospital could spread the virus in the air. But the possible risk is to hospitalized patients with COVID-19 – not to patients using their nebulizer at home as directed.
Check out this downloadable/printable infographic that helps distinguish the difference in COVID-19 versus allergies.
Telemedicine expert Jennifer Shih, MD, discusses practical elements of performing virtual visits. This conversation is filled with amazing tips for both patients and clinicians – a must listen for telemedicine novices or experienced users.
There are some symptoms that are similar between these respiratory illnesses. This chart can help you figure out if you may be feeling symptoms of allergies or a respiratory illness like COVID-19. If you have a fever and a cough, call your doctor. If you have seasonal allergies, there are things you can do to treat at home.
Allergy and Asthma Network | April 14, 2020Scroll down the page for this webinar hosted by Tonya Winders, President & CEO of the Allergy & Asthma Network. Listen as she interviews Dr. Gia Rosenblum, Clinical Psychologist and Dr. Jackie Eghrari, Clinical Assistant Professor of Medicine, George Washington School of Medicine & Health Sciences.
Early Treatment With Sotrovimab Decreases Risk for Progression to Severe COVID-19