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

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 × 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.

Angiotensin-(1–7) ameliorates sepsis-induced cardiomyopathy by alleviating inflammatory response and mitochondrial damage through the NF-κB and MAPK pathways

“…In COVID-19 patients, lower Ang-(1–7) levels influenced the activation of multiple immunological responses and disseminated coagulation [ 54 ]. Furthermore, the COVID-19 patients, who died, had lower serum Ang-(1–7) levels and correspondingly higher Ang II/Ang-(1–7) levels [ 55 ]. Thus, the Ang II/Ang-(1–7) concentrations could be regarded as independent predictors of COVID-19 mortality [ 55 ].…”

Investigating the possible mechanisms of autonomic dysfunction post-COVID-19

“…Studies examining RAS imbalance in patients with COVID-19 exhibit conflicting results. In one study, it was shown that patients with COVID-19 had elevated levels of Ang II and low levels of Ang 1–7 despite high ACE-2 activity compared to control subjects ( Amezcua-Guerra et al, 2022 ). There was also a significant increase in Ang II/Ang 1–7 ratio that correlated with decreased ACE-2 activity ( Amezcua-Guerra et al, 2022 ).…”

“…In one study, it was shown that patients with COVID-19 had elevated levels of Ang II and low levels of Ang 1–7 despite high ACE-2 activity compared to control subjects ( Amezcua-Guerra et al, 2022 ). There was also a significant increase in Ang II/Ang 1–7 ratio that correlated with decreased ACE-2 activity ( Amezcua-Guerra et al, 2022 ). Patients who died had a significantly low Ang II/Ang 1–7 ratio ( Amezcua-Guerra et al, 2022 ).…”

“…There was also a significant increase in Ang II/Ang 1–7 ratio that correlated with decreased ACE-2 activity ( Amezcua-Guerra et al, 2022 ). Patients who died had a significantly low Ang II/Ang 1–7 ratio ( Amezcua-Guerra et al, 2022 ). Measuring ACE-2 activity in the tissues rather than in the blood may better reflect ACE-2 function and explain the contradictory results regarding ACE-2 activity in this study ( Amezcua-Guerra et al, 2022 ).…”

“…Patients who died had a significantly low Ang II/Ang 1–7 ratio ( Amezcua-Guerra et al, 2022 ). Measuring ACE-2 activity in the tissues rather than in the blood may better reflect ACE-2 function and explain the contradictory results regarding ACE-2 activity in this study ( Amezcua-Guerra et al, 2022 ). However, other studies demonstrated an increase in Ang 1–7 and a decrease in Ang II ( Reindl-Schwaighofer et al, 2021 ; Valle Martins et al, 2021 ).…”