C74-01 Renin Angiotensin Aldosterone System Components in Severe Covid-19: A Cross-sectional Study

Abstract Rationale In COVID-19, SARS-CoV-2 binds angiotensin-converting enzyme 2 (ACE2) to enter cells, possibly affecting the renin-angiotensin system (RAS). High levels of angiotensin II (ANGII) are found in acute respiratory distress syndrome (ARDS), but its role in COVID-19 is unknown. We investigated if individuals with different disease severities had distinct serum RAS component levels. Methods Cross-sectional study conducted at the Ribeirão Preto Medical School Hospital, University of São Paulo. COVID-19-diagnosed individuals were enrolled between April and December, 2020. Serum levels of ACE2, Ang II, IL-6 were measured by ELISA and compared between severe (severe and critical) and non-severe (mild and moderate) cases using Student’s t-test, ANOVA, or Kruskal-Wallis tests. We used receiver operating characteristic (ROC) curves to assess the accuracies of mediators in distinguishing severe from non-severe cases. We used multivariate regression to explore associations between mediator levels and disease severity. A p-value 0.05 was considered statistically significant. Results We enrolled 176 individuals. Interleukin-6 and Ang II levels were higher in severe vs non-severe disease (129.71 ± 195.58 pg/mL vs 37.45 ± 81.93 pg/mL (p = 0.00019); 377.46 ± 445 pg/mL vs 126.85 ± 172.05 pg/mL (p 0.0001), respectively ). ACE2 levels were similar (3.052 ± 12.97 - non-severe vs 10.64 ± 61.64 - severe disease (p = 0.26)).The areas under the ROC curves (AUC) were 0.676 for IL-6 (sensitivity: 60.3%, specificity: 78.2%), 0.620 for ACE2 (sensitivity: 51.2%, specificity: 77.2%), and 0.573 for Ang II (sensitivity: 90.0%, specificity: 35.0%).Crude regression models showed associations between higher ACE2 and IL-6 levels and severe disease (prevalence ratio - PR- =1.02 (95% CI: 1.01-1.02; p 0.01) and 1.01 (95% CI: 1.01-1.02; p 0.01), respectively), but adjusted models did not. A crude model did not show association between Ang-II levels and severity (PR = 0.98; 95% CI: 0.93-1.03; p = 0.36), but did so after adjustment (PR = 0.94; 95% CI: 0.88-1.00; p = 0.04). Conclusions Our findings indicate that, although AngII and ACE2 are not as accurate as IL-6 as biomarkers of severity, RAS may play a role in severe COVID-19 disease. The findings of our regression models highlight the complex interplay between inflammation and RAS activity in COVID-19 pathophysiology. This abstract is funded by: none