COVID-19 for the Cardiologist: Basic Virology, Epidemiology, Cardiac Manifestations, and Potential Therapeutic Strategies

Deepak Atri, Hasan K Siddiqi, Joshua P Lang, Victor Nauffal, David A Morrow, Erin A Bohula, Deepak Atri, Hasan K Siddiqi, Joshua P Lang, Victor Nauffal, David A Morrow, Erin A Bohula

Abstract

Coronavirus disease-2019 (COVID-19), a contagious disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has reached pandemic status. As it spreads across the world, it has overwhelmed health care systems, strangled the global economy, and led to a devastating loss of life. Widespread efforts from regulators, clinicians, and scientists are driving a rapid expansion of knowledge of the SARS-CoV-2 virus and COVID-19. The authors review the most current data, with a focus on the basic understanding of the mechanism(s) of disease and translation to the clinical syndrome and potential therapeutics. The authors discuss the basic virology, epidemiology, clinical manifestation, multiorgan consequences, and outcomes. With a focus on cardiovascular complications, they propose several mechanisms of injury. The virology and potential mechanism of injury form the basis for a discussion of potential disease-modifying therapies.

Keywords: ACE2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; CFR, case fatality rate; COVID-19; COVID-19, coronavirus disease-2019; CoV, coronavirus; DIC, disseminated intravascular coagulation; ER, endoplasmic reticulum; ICU, intensive care unit; SARS-CoV, severe acute respiratory syndrome-coronavirus; SARS-CoV-2; SOFA, sequential organ failure assessment; TMPRSS2, transmembrane serine protease 2; cardiovascular; hsCRP, high-sensitivity C-reactive protein; treatments; virology.

© 2020 Published by Elsevier on behalf of the American College of Cardiology Foundation.

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
Putative SARS-CoV-2 Life Cycle and Therapeutic Targets Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) binds to the angiotensin-converting enzyme 2 (ACE2) receptor on the host cell membrane. Endocytosis is believed to be mediated, in part, by JAK-2. Membrane fusion occurs between the mature endosome and virion with facilitation by the transmembrane serine protease 2 (TMPRSS2) resulting in release of the SARS-CoV-2 RNA into the intracellular space. The RNA is translated by host machinery to produce the replicase and structural proteins. Host and SARS-CoV-2 proteases cleave the replicase into nonstructural proteins, including the RNA-dependent RNA polymerase (RdRp). RdRp mediates SARS-CoV-2 RNA replication and amplification. SARS-CoV-2 transmembrane proteins (spike [S], envelope [E], and membrane [M]) are shuttled via the endoplasmic reticulum and Golgi apparatus to the forming viral capsids. Viral assembly occurs with addition of the viral RNA and nucleocapsid (N) protein through association with the transmembrane viral proteins. Exocytosis results in release of the newly synthesized viral particle. Ab = antibody.
Central Illustration
Central Illustration
Potential Mechanisms of Myocardial Injury in COVID-19 ASCVD = atherosclerotic cardiovascular disease; COVID-19 = coronavirus disease-2019; DIC = disseminated intravascular coagulation; MI = myocardial infarction.

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Source: PubMed

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