key: cord-0877439-hihublhw authors: Shete, Ashwini title: Urgent need for evaluating agonists of Angiotensin-(1-7)/ Mas receptor axis for treatment of patients with COVID-19 date: 2020-05-07 journal: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases DOI: 10.1016/j.ijid.2020.05.002 sha: 6bc8a14545739ea72d0a898c770f394259392359 doc_id: 877439 cord_uid: hihublhw Abstract ACE2 being a receptor of entry of SARS-CoV-2 into the host cells, its upregulation has been implicated in increasing susceptibility of individuals to the infections. Clinical picture of COVID-19 suggests a role 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 severity of SARS-CoV-2 infections indicates 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 urgent evaluation in seriously ill COVID-19 patients is urgently warranted to reduce mortality due to the infections. 1. Severity of COVID-19 is likely to be due to blockade of ACE2 actions 8 2. It results in higher angiotensin II and lower angiotensin-(1-7) activities 9 3. Angiotensin-(1-7)/MasR axis is implicated in countering effects of angiotensin II. [8, 9] . However, convincing benefits of using these agents are lacking. ACE2 is a key regulatory enzyme in the system responsible for degradation of bioactive 60 angiotensin II to angiotensin-(1-7). Angiotensin II has been shown to be the culprit in hypertension, CVD, diabetes, etc. Angiotensin II increases blood pressure through its action 62 on AT1 receptor (AT1R) expressed in renal and cardiovascular system. Activation of the 63 receptors expressed in human lung tissues has been reported to induce pulmonary fibrosis 64 [12] . It was shown to be involved in promoting tissue remodeling through formation of (1-7)/MasR axis by reducing of pro-inflammatory cytokines [40] . were also reported in males with different co-morbidities [46, 47] . Males had been shown to 154 have a higher vascular and renal sensitivity to angiotensin II compared to females possibly 155 explaining their higher frequency of severe SARS-Cov-2 infections in them [48] . Functionality of RAS has been shown to be influenced by gender and sex hormones [49] . 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