The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.
Cardiovascular research. 2020 Apr 30 [Epub ahead of print]
Tomasz J Guzik, Saidi A Mohiddin, Anthony Dimarco, Vimal Patel, Kostas Savvatis, Federica M Marelli-Berg, Meena S Madhur, Maciej Tomaszewski, Pasquale Maffia, Fulvio D'Acquisto, Stuart A Nicklin, Ali J Marian, Ryszard Nosalski, Eleanor C Murray, Bartlomiej Guzik, Colin Berry, Rhian M Touyz, Reinhold Kreutz, Dao Wen Wang, David Bhella, Orlando Sagliocco, Filippo Crea, Emma C Thomson, Iain B McInnes
Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK., Barts Heart Center, St Bartholomew's NHS Trust, London, UK., William Harvey Institute Queen Mary University of London, London, UK., Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester, Manchester, UK., Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK., Department of Life Science, University of Roehampton, London, UK., Department of Medicine, Center for Cardiovascular Genetics, Institute of Molecular Medicine, University of Texas Health Sciences Center at Houston, Houston, TX, USA., Jagiellonian University Medical College, Institute of Cardiology, Department of Interventional Cardiology; John Paul II Hospital, Krakow, Poland., Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Klinische Pharmakologie und Toxikologie, Germany., Division of Cardiology and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China., MRC-University of Glasgow Centre for Virus Research, University of Glasgow, UK., Emergency Department, Intensive Care Unit; ASST Bergamo Est Bolognini Hospital Bergamo, Italy., Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Largo A. Gemelli, 8, 00168 Rome, Italy.