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


Interaction between SARS-CoV-2 and the Renin–Angiotensin–Aldosterone System (Source: NEJM)

Source: Muthiah Vaduganathan et. al.| NEJM

As the number of people infected with COVID-19 grows, researchers write in a special report, so too is concern about how the virus interacts with the renin-angiotensin-aldosterone system (RAAS), which directs key processes in human physiology.

Coronavirus interfaces with the RAAS through angiotensin-converting enzyme 2 (ACE2), which physiologically counters RAAS activation. However, because it also acts as the functional receptor for coronavirus, some suspect that ACE2 could be implicated in the likelihood of or severity of the infection.

Specifically, lab studies have found that RAAS inhibitors may boost ACE2 expression and that this variation may increase COVID virulence. Despite calls to discontinue ACE inhibitors—which are used to treat medical comorbidities, including hypertension, that have shown to be more prevalent in the sickest coronavirus patients—the report authors warn there is inadequate evidence to support such a move. In the absence of clinical human data to the contrary, they caution against abruptly terminating RAAS inhibitor therapy in high-risk patients with known or suspected coronavirus—including those with heart failure or past myocardial infarction—especially if they are otherwise in stable condition.

Key Points Related to the Interplay Between COVID-19 and the Renin-Angiotensin-Aldosterone System

  • ACE2, an enzyme that physiologically counters RAAS activation, is the functional receptor to SARS-CoV-2, the virus responsible for the Covid-19 pandemic
  • Select preclinical studies have suggested that RAAS inhibitors may increase ACE2 expression, raising concerns regarding their safety in patients with Covid-19
  • Insufficient data are available to determine whether these observations readily translate to humans, and no studies have evaluated the effects of RAAS inhibitors in Covid-19
  • Clinical trials are under way to test the safety and efficacy of RAAS modulators, including recombinant human ACE2 and the ARB losartan in Covid-19
  • Abrupt withdrawal of RAAS inhibitors in high-risk patients, including those who have heart failure or have had myocardial infarction, may result in clinical instability and adverse health outcomes
  • Until further data are available, we think that RAAS inhibitors should be continued in patients in otherwise stable condition who are at risk for, being evaluated for, or with Covid-19

Reference: 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 Mar 30. doi: 10.1056/NEJMsr2005760. [Epub ahead of print] PubMed PMID: 32227760. DOI: 10.1056/NEJMsr2005760


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