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

Ther Adv Respir Dis. 2022 Jan-Dec:16:17534666221122544. doi: 10.1177/17534666221122544.


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 × 103/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.

Keywords: COVID-19; SARS-CoV-2; angiotensin II; angiotensin-(1-7); angiotensin-converting enzyme 2.

MeSH terms

  • Angiotensin I* / blood
  • Angiotensin I* / chemistry
  • Angiotensin II* / blood
  • Angiotensin II* / chemistry
  • Angiotensin-Converting Enzyme 2* / metabolism
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • COVID-19* / diagnosis
  • COVID-19* / mortality
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments
  • Peptidyl-Dipeptidase A
  • Prognosis
  • SARS-CoV-2


  • Angiotensin-Converting Enzyme Inhibitors
  • Peptide Fragments
  • Angiotensin II
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)