Two new studies have been published that further focus attention on how the renin–angiotensin system — and specifically the ACE2 receptor — may be involved in COVID-19 infection.
Leading experts suggest that effects of the virus on the renin–angiotensin system may be the key to understanding why men and individuals with underlying cardiovascular diseases appear to have worse outcomes from COVID-19.
Noting that the SARS-CoV-2 virus that causes COVID-19 interacts with the ACE2 receptor, the authors suggest that their findings may explain why men have worse outcomes with the virus.
The study also shows that neither ACE inhibitors nor angiotensin-receptor blockers (ARBs) were associated with higher plasma ACE2 concentrations.
A second study, published as a letter to the New England Journal of Medicine, studied the relationship between ACE-inhibitor and ARB use and influenza A infection in a large United Kingdom patient database.
The authors note that influenza A has been shown to use the ACE2 receptor to mediate lung damage, similar to that seen in severe acute respiratory syndrome (SARS) with COVID-19.
Results showed that during a median 8.7 years of follow-up, individuals who had received a prescription for an ACE inhibitor had a lower risk of influenza than those who had not (adjusted hazard ratio, 0.66).
A second analysis found that the longer the duration of ACE-inhibitor use, the lower the risk of influenza infection. Similar results were found for ARBs.
“These associations regarding observed susceptibility to influenza may reflect mechanisms that are shared with coronaviruses, including SARS-CoV-2,” the researchers conclude.
Is COVID-19 Activating the Renin–Angiotensin System?
In an editorial accompanying the European Heart Journal publication, Gavin Oudit, MD, University of Alberta, Edmonton, Canada, and Mark Pfeffer, MD, Brigham and Women’s Hospital, Boston, Massachusetts, suggest that further work should measure plasma angiotensin peptides and plasma ACE2 levels and activity in COVID-19 patients to provide a direct evaluation of the state of the renin–angiotensin system, which could guide therapeutic interventions.
In comments to Medscape Medical News, Oudit, who has researched extensively on ACE2, put forward a hypothesis that the COVID-19 virus could be bringing about its harmful effects by causing an over-activation of the renin–angiotensin system.