The Renin-Angiotensin Aldosterone is an elegant cascade of vasoactive peptides that orchestrate key processes in human physiology. Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and SARS-CoV-2, which have been responsible for the SARS epidemic in 2002 to 2004 and for the more recent coronavirus disease 2019 (Covid-19) pandemic, respectively, interface with the RAAS through angiotensin-converting enzyme 2 (ACE2), an enzyme that physiologically counters RAAS activation but also functions as a receptor for both SARS viruses. The interaction between the SARS viruses and ACE2 has been proposed as a potential factor in their infectivity, and there are concerns about the use of RAAS inhibitors that may alter ACE2 and whether variation in ACE2 expression may be in part responsible for disease virulence in the ongoing Covid-19 pandemic. Indeed, some media sources and health systems have recently called for the discontinuation of ACE inhibitors and angiotensin-receptor blockers (ARBs), both prophylactically and in the context of suspected Covid-19.

Given the common use of ACE inhibitors and ARBs worldwide, guidance on the use of these drugs in patients with Covid-19 is urgently needed. Here, it is highlighted that the data in humans are too limited to support or refute these hypotheses and concerns. Specifically, the authors discuss the uncertain effects of RAAS blockers on ACE2 levels and activity in humans, and they propose an alternative hypothesis that ACE2 may be beneficial rather than harmful in patients with lung injury. We also explicitly raise the concern that withdrawal of RAAS inhibitors may be harmful in certain high-risk patients with known or suspected Covid-19.

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