Therapeutic Advances in Respiratory Disease (Sep 2022)

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

  • Luis M Amezcua-Guerra,
  • Leonardo del Valle,
  • 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 Paez-Arenas,
  • Mauricio Castillo-Salazar,
  • Sergio Cásares-Alvarado,
  • Adrián Hernández-Diazcouder,
  • José L Sánchez-Gloria,
  • Claudia Tavera-Alonso,
  • Rodrigo Gopar-Nieto,
  • Julio Sandoval

DOI
https://doi.org/10.1177/17534666221122544
Journal volume & issue
Vol. 16

Abstract

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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.