RAS Peptide Dynamics Predict COVID-19 Respiratory Deterioration and Outcomes | Research

The takeaway

Worsening COVID-19 patients showed progressive RAS activation with rising renin and Ang I, declining ACE activity, and a shift toward the Ang 1-7 pathway, alongside increasing endothelial dysfunction markers.

57% worsened
Patients who deteriorated showed distinctive RAS peptide activation patterns detectable by day 3 of hospitalization

What the researchers found

Worsening COVID-19 patients showed rising renin and Ang I (p<0.001), declining Ang II/Ang I ratio (p<0.001), increasing Ang 1-7 (p<0.001), and rising ADMA (p<0.001), with 28-day outcomes predicted by renin, Ang I, Ang 1-7, and ADMA.

Why it matters

Understanding how RAS peptides change during COVID-19 could improve risk stratification and guide the use of RAS-targeting therapies in critically ill patients.

How the study worked

Single-center prospective observational study of 155 hospitalized COVID-19 patients with plasma RAS peptides and ADMA measured at admission (D0) and day 3 (D3), stratified by WHO respiratory trajectory.

What this study cannot tell us

Single-center. Observational design. Only two timepoints measured. Cannot determine if RAS changes drive disease or result from it.

How to read the evidence

Prospective observational study with serial biomarker measurements. Well-designed for biomarker discovery, though causal relationships remain unclear.

When this study was published

Published in 2025.

The bigger picture

RAS dysregulation is central to COVID-19 pathophysiology. This study maps how specific RAS peptides change as disease progresses, informing therapeutic strategies targeting the RAS system.

Questions still open

Could early RAS peptide profiles guide ACE inhibitor decisions in COVID-19?
Is the shift toward Ang 1-7 protective or simply a marker of severity?
Would continuous RAS monitoring improve COVID-19 patient management?

Common questions

How do RAS peptides relate to COVID-19?

The virus that causes COVID-19 enters cells through ACE2, part of the RAS system. This study shows that as COVID-19 worsens, the RAS system becomes progressively dysregulated, with specific peptide changes that predict who will deteriorate.

Could measuring these peptides help treat COVID patients?

Possibly. If doctors could identify patients whose RAS system is becoming dysregulated early, they could adjust treatment accordingly — potentially using or avoiding RAS-targeting medications based on individual peptide profiles.

Read the original research

Renin-angiotensin system activation and oxidative stress in hospitalized COVID-19 patients: a single-centre prospective observational study.

Intensive care medicine experimental, 14(1), 15

View on PubMed ↗Publisher’s paper ↗

Citation

Eleuteri, Davide; Del Tedesco, Filippo; Silvia, Federico; Tucciariello, Caterina; Ruggiero, Ersilia; Gervasoni, Jacopo; Santucci, Lavinia; Primiano, Aniello; Petrucci, Martina; Torelli, Ernico; Cianci, Rossella; Giannarelli, Diana; Cutuli, Salvatore Lucio; De Pascale, Gennaro; Bello, Giuseppe; Maria, Calabrese; Masullo, Matteo; Urbani, Andrea; Di Santo, Riccardo; Antonelli, Massimo; Montini, Luca. (2026). Renin-angiotensin system activation and oxidative stress in hospitalized COVID-19 patients: a single-centre prospective observational study.. Intensive care medicine experimental, 14(1), 15. https://doi.org/10.1186/s40635-026-00857-w