key: cord-329363-kaw3h5xm authors: Vardeny, Orly; Madjid, Mohammad; Solomon, Scott D. title: Applying the Lessons of Influenza to COVID-19 During a Time of Uncertainty date: 2020-05-26 journal: Circulation DOI: 10.1161/circulationaha.120.046837 sha: doc_id: 329363 cord_uid: kaw3h5xm nan dysfunction and inflammation, which can attenuate innate immune function. Immune dysregulation and cytokine storm appear to be key components of progression to critical disease in COVID-19. Individuals with heart failure exhibit attenuated immune response to influenza viruses and most certainly will have similar altered immune responses to COVID-19. Even among those without underlying cardiac disease, the prior coronavirus outbreaks have been associated with adverse cardiovascular effects. Both transient cardiomegaly and decreases in left ventricular ejection fraction, observed during acute illness with improvement after recovery, were reported during the 2002 to 2003 severe acute respiratory syndrome (SARS) epidemic. SARS coronavirus 2 (SARS-CoV-2) shares 79.5% sequence identity with SARS coronavirus (SARS-CoV), and the point of entry of SARS-CoV-2 into the host cell is also analogous to SARS-CoV, through the angiotensin-converting enzyme 2 receptor, which is expressed on airway epithelial cells. Whereas the majority of severe morbidity associated with COVID-19 has been pulmonary, reports are emerging of cardiac injury, left ventricular dysfunction, and myocarditis associated with severe COVID-19, 4 and the molecular similarities of SARS-CoV-2 and SARS-CoV make cardiac effects similar to those reported with SARS likely. Whereas COVID-19 shares similarities with seasonal influenza, it appears to be more transmissible and more virulent than any influenza since the 1918 influenza pandemic. Estimates from China indicate that the COVID-19 basic reproductive number (secondary cases generated by a primary case of infection in a susceptible population) is ≈1.94, which is higher than that of influenza, estimated at 1.3 for most years and 1.8 for the 1918 influenza pandemic. Accumulating data indicate higher mortality rates for COVID-19 compared with the 2009 H1N1 pandemic. Although most individuals with COVID-19 do not experience severe symptoms, evidence of asymptomatic transmission and substantial community spread suggest that this virus will infect a larger number of people and lead to more deaths than SARS and Middle East respiratory syndrome. 5 Current strategies for COVID-19 management focus on minimizing transmission and spread of infection and providing supportive care for individuals who experience airway compromise or other adverse clinical sequelae. Because severity of illness with COVID-19 can be highly variable, with some individuals displaying no or minimal symptoms, and with restricted testing available in most places, individuals at high risk should avoid contact with people with even mild respiratory infections. Other strategies for minimizing risk of exposure include delaying routine, in-person medical appointments and elective procedures. In the absence of an effective vaccine or targeted antiviral therapies, management options are limited. Several pharmacological treatments are under investigation, and we need to be vigilant in considering how they may affect the cardiovascular system. For example, use of chloroquine and hydroxychloroquine, for which limited data exist, can cause QT prolongation. For patients with underlying cardiovascular disease, other opportunities for minimizing complications from infection include remaining up to date on other immunizations, including influenza vaccine, which is available and effective, and pneumococcal vaccine, as secondary bacterial infections often lead to hospitalizations among those with primary viral infections. Because viral illness has been shown to exacerbate underlying cardiac illness and can lead to acute events such as acute myocardial infarction or decompensated heart failure, efforts should be made to optimize guideline-directed treatment strategies that have been shown to improve clinical status in high-risk patients, and thus reduce the risk of worsening symptoms or acute events in case of infection. In patients without known or suspected COVID-19, this includes all evidence-based therapies in cardiovascular disease, such as aspirin, statins, and β-blockers for secondary prevention in patients with coronary disease, and guideline-directed medical therapy in those with heart failure. Keeping patients out of the hospital is an essential component to reducing infection. The use of guideline-directed medical therapy is also warranted in patients with known or suspected COVID-19. One area of uncertainty is the influence of angiotensin receptor enzyme inhibitors and angiotensin receptor blockers on this disease, because coronaviruses gain entrance to cells by the angiotensin-converting enzyme 2 receptor, which might be upregulated by use of these therapies. The American Heart Association, the American College of Cardiology, the Heart Failure Society of America, and the European Society of Cardiology recommend not withdrawing renin-angiotensin system inhibitors on the basis of the available data unless warranted clinically. The rapid spread of COVID-19 is testing healthcare systems around the world profoundly and likely will continue to do so before this pandemic abates. The increased vulnerability of patients with cardiovascular disease at risk for adverse cardiovascular outcomes, in conjunction with patients' reduced access to healthcare services while the healthcare system is stressed, underscores the importance of understanding COV-ID-19 and its implications for all practitioners of cardiovascular medicine. Orly Vardeny, PharmD, MS, Associate Professor of Medicine, University of Minnesota Medical School, 1 Veterans Way, Minneapolis, MN 55417. Email ovar-deny@umn.edu Acute myocardial infarction after laboratory-confirmed influenza infection Association of influenzalike illness activity with hospitalizations for heart failure: the Atherosclerosis Risk in Communities Study Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention Coronavirus disease 2019 (CO-VID-19) and cardiovascular disease Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China Dr Vardeny has received research grants from the US National Institutes of Health and AstraZeneca and has consulted for Novartis, Amgen, and Sanofi-Pasteur. Dr Madjid reports serving as a speaker and consultant for Sanofi-Pasteur. Dr Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Sanofi Pasteur, and Theracos; and has consulted for Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Bristol-Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GlaxoSmithKline, Ironwood, Merck, MyoKardia, Novartis, Roche, Sanofi-Pasteur, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, Tenaya, Dinaqor, and Tremeau.