key: cord-344011-w9zn7hb2
authors: Schiffrin, Ernesto L; Flack, John M; Ito, Sadayoshi; Muntner, Paul; Webb, R Clinton
title: Response to COVID-19 and ACEI/ARB: NOT ASSOCIATED?
date: 2020-05-16
journal: Am J Hypertens
DOI: 10.1093/ajh/hpaa077
sha: 
doc_id: 344011
cord_uid: w9zn7hb2

nan

. 3 Hajra and Bandyopadhyay mention ACE2, the receptor for the novel coronavirus severe acute respiratory syndrome (SARS)-CoV-2, in the lung where the virus may bind to enter cells and produce pulmonary injury. ACE2 is in fact widely distributed, and was recently demonstrated in nasal epithelial goblet/secretory cells and in nasal epithelial ciliated cells, in corneal cells in the eye, and in esophagus and intestinal epithelial cells 4 as well as in oral mucosa cells, 5 which are probably ways whereby the virus enters the body and proliferates to eventually infect the lower respiratory tract and the lung. These findings may explain the respiratory transmission as well as the potential for fecal-oral transmission.

Hajra and Bandyopadhyay have cited recent retrospective studies 6,7 that were published after our Editorial in the last month that support our conclusion that there is no evidence of harm of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with COVID-19. A population-based case-control study in the Lombardy region of Italy evaluated a total of 6272 case patients in who SARS-CoV-2 was confirmed between February 21 and March 11, 2020. 8 These were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and residence. In this large, population-based study, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19. As well, among a total of 18,472 patients tested for COVID-19 in the Cleveland Clinic Health System in Ohio and Florida between March 8 and April 12, 2020, there was no association of use of ACEIs and ARBs with testing positive A c c e p t e d M a n u s c r i p t 3 for COVID-19, 9 which suggests that taking these agents did not increase susceptibility to infection by the novel virus RAS-CoV-2.

Hajra and Bandyopadhyay mention that "COVID-19 is a new threat for all health care providers, but would like (us) to highlight the future of these widely used antihypertensives in the setting of this newly emerging infection." As we have indicated in our Editorial, use of ACEIs and ARBs should be maintained for the control of blood pressure and treatment of other cardiovascular conditions for which they are used. Randomized controlled trials of both initiation or replacement of renin-angiotensin system (RAS) inhibitors would be necessary to answer in a definitive way the question of whether these agents are harmful, beneficial or neutral in patients with COVID-19. In the meantime, these drugs should certainly not be discontinued, at least on the basis of the most current and recent retrospective evidence, in agreement with recommendations of different national and international societies and organizations. 10 As well, to the best of our knowledge, there is no reason to avoid the initiation of RAS blockers in any patient subgroup unless there are specific contraindications unrelated to COVID-19.

A c c e p t e d M a n u s c r i p t 4

COVID-19 and ACEI/ARB: NOT ASSOCIATED?

Hypertension and COVID-19

Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering

SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes

High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa

Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China

Drug Therapy, and Mortality in Covid-19

Renin-Angiotensin-Aldosterone System Blockers and the Risk of Covid-19

Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease

HFSA/ACC/AHA Statement Addresses Concerns Re: Using RAAS Antagonists in COVID-19