Up-to-date information on hearth health, respiratory & COVID-19.

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:

  1. People with COVID-19 and heart disease are at the highest risk of death and complications.
  2. The heart might be adversely affected by the coronavirus, even in people who do not have any pre-existing heart condition.
  3. 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.


Statin use prior to hospital admission benefits COVID-19 patients

Cardiovascular Business, September 17, 2020

Hospitalized COVID-19 patients are less likely to experience severe symptoms if they were taking statins prior to being admitted, according to a new observational study published in the American Journal of Cardiology. Statin use prior to admission was also associated with a faster time to recovery. Individuals with underlying cardiovascular disease (CVD), hypertension, and diabetes have been identified as groups at particularly high risk for developing severe COVID-19,” wrote lead author Lori B. Daniels, MD, UC San Diego Health in La Jolla, California, and colleagues. “Because a large proportion of patients with these conditions are on statins and either angiotensin-converting enzyme (ACE) inhibitors or angiotensinogen II receptor blockers (ARBs), there has been speculation about whether these cardiovascular medications may influence COVID-19 risk.” The authors tracked data from more than 5,000 patients hospitalized at a single healthcare facility from Feb. 10 to June 17, 2020. The cohort included 170 patients hospitalized for COVID-19, with all other patients serving as COVID-negative controls. Among the patients hospitalized for COVID-19, 56% were obese, 44% had a history of hypertension, 21% had CVD, 20% had diabetes, 18% had chronic kidney disease and 14% had cancer. Also, 27% of hospitalized COVID-19 patients were actively taking statins when first admitted, 21% were taking an ACE inhibitor and 12% were taking an ARB.


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.


Relationship between the history of cerebrovascular disease and mortality in COVID-19 patients: A systematic review and meta-analysis

Clinical Neurology and Neurosurgery, September 12, 2020

Past history of stroke has been associated with an increased risk of a new ischemic stroke. Several studies have indicated increased prevalence of strokes among coronavirus patients. However, the role of past history of stroke in COVID19 patients is still unclear. The purpose of this systematic review is to evaluate and summarize the level of evidence on past history of stroke in COVID19 patients. A systematic review was performed according to the PRISMA guidelines was performed in PubMed, Embase, EBSCO Host, Scopus, Science Direct, Medline, and LILACS. Eligibility criteria: We evaluated studies including patients with diagnosis of COVID 19 and a past history of stroke. Risk of bias: was evaluated with the Newcastle- Ottawa Scale (NOS) and experimental studies were evaluated using the ROBINS-I scale. Seven articles out of the total 213 articles were evaluated and included, involving 3244 patients with SARS VOC 2 Disease (COVID19) of which 198 had a history of cerebrovascular disease. Meta-analysis of the data was performed, observing an increase in mortality in patients with a history of cerebrovascular disease compared to those with different comorbidities or those without underlying pathology (OR 2.78 95% CI [1.42- 5.46] p = 0.007; I 2 = 49%) showing adequate heterogeneity.


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, 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.


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.


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.


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.


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.


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

Gemoji image for :clapper: 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

Gemoji image for :clapper 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

Gemoji image for :clapper:  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%).

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 contact