The prognostic importance of the angiotensin II/angiotensin-(1–7) ratio in patients with SARS-CoV-2 infection
Luís M. Amezcua‐Guerra, Leonardo del Valle‐Mondragón, Héctor González‐Pacheco, Rashidi Springall, Ricardo Márquez-Velasco, Felipe Massó, Malinalli Brianza-Padilla, Daniel Manzur‐Sandoval, Julieta González-Flores, Carlos García-Ávila, Yaneli Juárez-Vicuña, Fausto Sánchez‐Muñoz, Martha A. Ballinas‐Verdugo, Edna Basilio‐Gálvez, Araceli Páez, Mauricio Castillo-Salazar, Sergio Cásares-Alvarado, Adrián Hernández-Díazcouder, José L. Sánchez-Gloria, Claudia Tavera-Alonso, Rodrigo Gopar‐Nieto, Julio Sandoval
Abstract
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.