• Mina K Chung, Sadashiva Karnik, Joshua Saef, Cornelia Bergmann, John Barnard, Michael M Lederman, John Tilton, Feixiong Cheng, Clifford V Harding, James B Young, Neil Mehta, Scott J Cameron, Keith R McCrae, Alvin H Schmaier, Jonathan D Smith, Ankur Kalra, Surafel K Gebreselassie, George Thomas, Edward S Hawkins, and Lars G Svensson.
• Heart, Vascular and Thoracic Institute, United States; Lerner Research Institute, Cleveland Clinic, United States; Cleveland Clinic Lerner College of Medicine, United States; Case Western Reserve University, United States. Electronic address: chungm@ccf.org.
• EBioMedicine. 2020 Aug 1; 58: 102907.

BackgroundSARS-CoV-2 enters cells by binding of its spike protein to angiotensin-converting enzyme 2 (ACE2). Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have been reported to increase ACE2 expression in animal models, and worse outcomes are reported in patients with co-morbidities commonly treated with these agents, leading to controversy during the COVID-19 pandemic over whether these drugs might be helpful or harmful.MethodsAnimal, in vitro and clinical data relevant to the biology of the renin-angiotensin system (RAS), its interaction with the kallikrein-kinin system (KKS) and SARS-CoV-2, and clinical studies were reviewed.Findings And InterpretationSARS-CoV-2 hijacks ACE2to invade and damage cells, downregulating ACE2, reducing its protective effects and exacerbating injurious Ang II effects. However, retrospective observational studies do not show higher risk of infection with ACEI or ARB use. Nevertheless, study of the RAS and KKS in the setting of coronaviral infection may yield therapeutic targets.Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

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