Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics

Gurwitz, D. (2020), Angiotensin receptor blockers as tentative SARS‐CoV‐2 therapeutics. Drug Dev Res. doi:10.1002/ddr.21656

Review written by:

Eytan Palte, edited by Robert Parry

Yellow – good evidence for a pathophysiologic mechanism, but next steps include large-scale research studies that will not be immediately applicable

It is postulated, based on virologic sequence homology between SARS-CoV1 and SARS-CoV2, that the latter’s virus spike protein binds to angiotensin converting enzyme 2 (ACE2) to facilitate entry into host cells. This binding leads to downregulation of ACE2, creating an imbalance of genetic expression and subsequent compensatory overexpression of ACE. Overexpressed ACE generates higher levels of angiotensin 2 (AT2), increasing pulmonary vascular permeability, which may also increase risk for severe lung damage.

Rats given angiotensin 1 receptor blocker (ARB) drugs losartan following coronary artery ligation were shown to have upregulation of ACE2 in the myocardium and kidneys. Similarly, humans chronically treated with ARBs have increased urinary ACE2 levels. The use of these drugs and consequent upregulation of ACE2 to prevent serious COVID-19 infection seems counterintuitive, but may actually block excess activity of ACE, prevent excess AT2, and serve as a protective factor against serious lung injury. This mechanism is similar to patients with high CCR5 and CD4 expression being somewhat protected from HIV virulence.

ARBs are overall safe, but many patients with SARS developed hypotension during the course of their illness. If this is also the case with COVID-19 patients, ARB use may be limited. The recommended next steps are to first look at COVID-19 patients on ARBs prior to hospitalization and compare their outcomes to those patients not on ARBs, and second, compare the percentage of the general population on ARBs to the percentage of severely-ill hospitalized patients on ARBs. With further studies, a more evidence-based recommendation on the use of ARBs to limit COVID-19 pathology could be possible.

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