key: cord-1042842-2rjt47j9
authors: nan
title: Letter in response to the article: Comorbidities in COVID-19: outcomes in hypertensive cohort and controversies with renin angiotensin system blockers (Singh et al.)
date: 2020-05-23
journal: Diabetes Metab Syndr
DOI: 10.1016/j.dsx.2020.05.029
sha: 649239723d758a4e3f86aa35333fde2c2d6b489d
doc_id: 1042842
cord_uid: 2rjt47j9

nan

Letter in response to the article: Comorbidities in COVID-19: outcomes in hypertensive cohort and controversies with renin angiotensin system blockers (Singh et This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. . We agree with one of the proposed mechanism that involves an increase in the soluble form of ACE-2 (Angiotensinconverting enzyme-2), which acts as an interceptor by binding to SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) and does not allow the virus to bind to the membrane bound ACE-2 receptor, thereby inhibiting viral entry inside the cell. 1,2,3 However, we do not agree with the other proposed mechanism whereby authors have suggested that "RAS blockers increase angiotensin II, which is a substrate for ACE-2. The interaction of ACE-2 with angiotensin II could induce a conformational change in the receptor binding domain of ACE-2, limiting its ability to bind with SARS CoV2." We do not agree with the above explanation since ACE-I (Angiotensin-converting enzyme inhibitors) and ARB (Angiotensin II receptor blockers) have differential effects on the levels of angiotensin II. 3, 4 While ACE-Is inhibit the conversion of angiotensin I to angiotensin II, thereby decreasing its levels, ARBs block the angiotensin II receptor and usually cause no change in levels of angiotensin II with short term use. However, the chronic long-term use of ARB does cause elevation in the levels of angiotensin II. 3, 4 Therefore, if we believe in the proposed mechanism that increased angiotensin II brings conformational change in ACE-2, and limits its binding ability to SARSCoV-2, this would mean a lower infection risk with ARBs and a higher infection risk with ACE-I. This hypothesis looks unrealistic and will need further validation. Unfortunately, the authors have not highlighted an important proposed mechanism of protection by RASB against SARS-CoV-2 associated lung injury. Based on the in-vitro studies done with other coronaviruses, it is believed that after the SARS-CoV-2 enters the alveolar cells using membrane bound ACE-2, it further downregulates the expression of ACE-2 receptors on the membrane and causes their internalization 2,3,5 ( Figure   1 ). As a result, the ACE-2 dependent conversion of angiotensin II to angiotensin (1-7) decreases, leading to an increased level of angiotensin II and a decreased level of angiotensin (1-7).

Angiotensin II then acts unopposed through its receptor AT1R (angiotensin II type 1 receptor) to induce cellular inflammation, proliferation, oxidative stress, vasoconstriction, fibrosis, and aldosterone activation, subsequently resulting in lung injury. 3 Angiotensin ( by ACE-2 and activation of the MAS receptor, which attenuates harmful effects of angiotensin II and therefore attenuates lung injury.

Comorbidities in COVID-19: outcomes in hypertensive cohort and controversies with renin angiotensin system blockers

Online ahead of print

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