The prognostic importance of the angiotensin II/angiotensin-(1–7) ratio in patients with SARS-CoV-2 infection

BACKGROUND: Information about angiotensin II (Ang II), angiotensin-converting enzyme 2 (ACE2), and Ang-(1–7) levels in patients with COVID-19 is scarce. OBJECTIVE: To characterize the Ang II–ACE2–Ang-(1–7) axis in patients with SARS-CoV-2 infection to understand its role in pathogenesis and prognosis. METHODS: Patients greater than 18 years diagnosed with COVID-19, based on clinical findings and positive RT-PCR test, who required hospitalization and treatment were included. We compared Ang II, aldosterone, Ang-(1–7), and Ang-(1–9) concentrations and ACE2 concentration and activity between COVID-19 patients and historic controls. We compared baseline demographics, laboratory results (enzyme, peptide, and inflammatory marker levels), and outcome (patients who survived versus those who died). RESULTS: Serum from 74 patients [age: 58 (48–67.2) years; 68% men] with moderate (20%) or severe (80%) COVID-19 were analyzed. During 13 (10–21) days of hospitalization, 25 patients died from COVID-19 and 49 patients survived. Compared with controls, Ang II concentration was higher and Ang-(1–7) concentration was lower, despite significantly higher ACE2 activity in patients. Ang II concentration was higher and Ang-(1–7) concentration was lower in patients who died. The Ang II/Ang-(1–7) ratio was significantly higher in patients who died. In multivariate analysis, Ang II/Ang-(1–7) ratio greater than 3.45 (OR = 5.87) and lymphocyte count ⩽0.65 × 10(3)/µl (OR = 8.43) were independent predictors of mortality from COVID-19. CONCLUSION: In patients with severe SARS-CoV-2 infection, imbalance in the Ang II–ACE2–Ang-(1–7) axis may reflect deleterious effects of Ang II and may indicate a worse outcome.