2022 Articles

A randomized, placebo-controlled, double-blinded pilot study of angiotensin 1–7 (TXA-127) for the treatment of severe COVID-19

Wagener, Gebhard; Goldklang, Monica P.; Gerber, Adam; Elisman, Katerina; Eiseman, Katherine A.; Fonseca, Laura D.; D’Armiento, Jeanine M.

Coronavirus disease 2019 (COVID-19) is associated with acute respiratory distress syndrome and multi-organ failure. SARS-CoV-2 enters cells through angiotensin-converting enzyme 2 (ACE-2), resulting in endocytosis and translocation. During this process, ACE-2 is phagocytosed and rendered non-functional [1]. ACE-2 mediates the conversion of angiotensin II to angiotensin 1–7, a vasodilator that opposes the effect of angiotensin [2, 3]. Reduction of ACE-2 likely causes a decrease in conversion of angiotensin I and II with excess angiotensin II causing vasoconstriction, oxidative stress, inflammation, apoptosis, fibrosis and water and solute retention. The hyperinflammatory state and acute kidney injury in COVID-19 could be in part explained by a reduction of ACE-2 and angiotensin 1–7.