Renin-angiotensin-aldosterone system activation in plasma as marker for prognosis in critically ill patients with COVID-19: a prospective exploratory study.

Summary

In 94 patients with COVID-19, early plasma RAS signatures predicted outcomes: AA2R predicted 60-day survival (AUROC 0.73), higher Ang II and active ACE2 were inversely associated with survival, while Ang 1-7 predicted favorable outcomes. RAS metabolites tracked severity (SOFA) and ventilatory mechanics over time.

Key Findings

• AA2R at inclusion predicted 60-day survival in ICU patients (AUROC 0.73).
• Ang II and active ACE2 were inversely associated with survival, while Ang 1-7 predicted favorable outcome (OR 6.8; 95% CI 1.5–39.9).
• ICU patients had higher angiotensin metabolites, PRA-S, ALT-S, and active ACE2, but lower ACE-S and AA2R than ward patients at inclusion.
• Over 7 days, Ang I–IV decreased while ACE and ACE2 increased; Ang I, PRA-S, Ang 1-7, and Ang 1-5 correlated with SOFA and with driving pressure at day 7.

Clinical Implications

Early measurement of AA2R and Ang 1-7 could refine risk stratification in ICU COVID-19 and inform monitoring; results motivate evaluation of RAS-modulating therapies but do not yet support treatment changes.

Limitations

• Exploratory single-center study with modest sample size.
• COVID-19-only cohort; generalizability to non-COVID ARDS remains to be tested.

Future Directions

External validation and integration into multivariable prognostic models; interventional studies to test whether modifying RAS axes alters outcomes.