Sound Science before Quick Judgement Regarding RAS Blockade in COVID-19

Potential effect of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–induced alterations to renin-angiotensin system pathways. SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) via its spike protein and induces internalization and shedding of ACE2, leading to increased angiotensin II (Ang II) and decreased angiotensin (1–7) [Ang-(1–7)] with net increase in inflammation and fibrosis (red) relative to anti-inflammatory and antifibrotic actions (blue). In the left panel, there is no ACEi or ARB; in the right panel, ACEi and/or ARB treatment could diminish effects of Ang II and increase Ang-(1–7) effects, leading to attenuated inflammation and fibrosis. The dashed inset in the right panel represents a theoretical increase in cell membrane expression of ACE2 with ACEi and/or ARB use. AT₁R, type 1 angiotensin receptor; AT₂R, type 2 angiotensin receptor; MasR, Mas receptor.