Urgent need for evaluating agonists of angiotensin-(1-7)/Mas receptor axis for treating patients with COVID-19.

ABSTRACT

ACE2 is a receptor of entry of SARS-CoV-2 into the host cells, and its upregulation has been implicated in increasing susceptibility of individuals to this infection. The clinical picture of COVID-19 suggests a role of ACE2 blockade, rather than its overexpression, in causing the pathogenesis. ACE2 blockade results in increased angiotensin II activity with simultaneous hampering of functions of angiotensin-(1-7)/MasR axis. Acute respiratory distress due to interstitial pulmonary fibrosis, cardiomyopathy and shock reported in COVID-19 patients can be explained by imbalanced angiotensin II and angiotensin-(1-7) activities. Failure of angiotensin II type 1 receptor blockers to control the severity of SARS-CoV-2 infections indicates the importance of simultaneous induction of angiotensin-(1-7)/MasR axis for correcting pathological conditions in COVID-19 through its anti-fibrotic, anti-inflammatory, vasodilatory, and cardioprotective roles. MasR agonists have also shown organ protective effects in a number of animal studies. Unfortunately, these agonists have not been tested in clinical studies. Their evaluation in seriously ill COVID-19 patients is urgently warranted to reduce mortality due to infection.