Impact of renin–angiotensin–aldosterone system inhibitors on COVID-19

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the possible roles of renin–angiotensin system (RAS) inhibitors in COVID-19 have been debated as favorable, harmful, or neutral. Angiotensin-converting enzyme 2 (ACE2) not only is the entry route of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but also triggers a major mechanism of COVID-19 aggravation by promoting tissue RAS dysregulation, which induces a hyperinflammatory state in several organs, leading to lung injury, hematological alterations, and immunological dysregulation. ACE inhibitors and angiotensin II type-1 receptor blockers (ARBs) inhibit the detrimental hyperactivation of the RAS by SARS-CoV-2 and increase the expression of ACE2, which is a counter-regulator of the RAS. Several studies have investigated the beneficial profile of RAS inhibitors in COVID-19; however, this finding remains unclear. Further prospective studies are warranted to confirm the role of RAS inhibitors in COVID-19. In this review, we summarize the potential effects of RAS inhibitors that have come to light thus far and review the impact of RAS inhibitors on COVID-19.