Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19

Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19. N Engl J Med. 2020;382(17):1653‐1659. doi:10.1056/NEJMsr2005760

Review written by:

Qian Ma, edited by Diogo Teles, MD, Robert Parry

Yellow - A thorough review of the physiology and rationale for Angiotensin-converting enzyme inhibitors (ACEi) use in COVID patients and published in the reputable NEJM. However, one cannot put too much stake in a clinical recommendation not based on clinical evidence

ACE2, an enzyme widely expressed in the body, counteracts activation of the renin-angiotensin-aldosterone system (RAAS) via degrading angiotensin II. ACE2 is the functional receptor of SARS-CoV-2. There are recent concerns that use of RAAS inhibitors (ACEi and Angiotensin II Receptor Blockers) can elevate the level of ACE2, therefore increasing the infectivity of SARS-CoV-2.


Preclinical animal studies as well as studies in humans have shown inconsistent findings of the impact of RAAS inhibitors on ACE2 level. These observations do not readily translate into human physiology. Further clinical data are needed to assess whether RAAS inhibitors modify the level or activity of human ACE2 in vital organs, especially the lung. On the contrary, ACE2 may be beneficial instead of harmful, given that SARS-CoV-2 downregulates ACE2 after binding, which may contribute to unopposed angiotensin II activity, RAAS activation, and acute lung injury. Based on preclinical evidence, clinical trials are now under way to test the safety and efficacy of RAAS modulations, including recombinant human ACE2 and ARB losartan, in treatment of COVID-19 patients.


Along with multiple specialty societies, the authors recommend against abrupt withdrawal of RAAS inhibitors in high-risk patients, including those who have severe cardiovascular diseases, as these patients are particularly vulnerable to blood pressure instability. Premature discontinuation of RAAS inhibitors based on incomplete evidence may result in clinical decompensation of these patients, who are at highest risk to develop severe illnesses caused by COVID-19.

Review Notes
 

This letter lacks any data of its own and any clinical data on ACEi/ARBs in patients with COVID-19.

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