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

Authors: Davide Eleuteri, Filippo Del Tedesco, Federico Silvia, Caterina Tucciariello, Ersilia Ruggiero, Jacopo Gervasoni, Lavinia Santucci, Aniello Primiano, Martina Petrucci, Enrico Torelli, Rossella Cianci, Diana Giannarelli, Salvatore Lucio Cutuli, Gennaro De Pascale, Giuseppe Bello, Calabrese Maria, Matteo Masullo, Andrea Urbani, Riccardo Di Santo, Massimo Antonelli, Luca Montini & the Gemelli-ICU Study Group

In this single-centre prospective observational study, the authors explored the relationship between renin–angiotensin system (RAS) activation, oxidative stress and respiratory deterioration in 155 hospitalised COVID-19 patients. Plasma levels of renin, angiotensin peptides (Ang I, Ang II, Ang 1–7), and the Ang II/Ang I ratio were measured at admission and day 3, together with the endothelial dysfunction marker asymmetric dimethylarginine (ADMA) and the Endothelial Activation and Stress Index (EASIX).

Patients with worsening respiratory status (57% of the cohort) showed progressive RAS activation, characterised by higher renin and Ang I levels, a reduced Ang II/Ang I ratio, and increased Ang 1–7 concentrations. Endothelial dysfunction markers increased in parallel, with higher ADMA levels predicting worse 28-day outcomes. These findings highlight the interplay between RAS dysregulation, oxidative stress, and endothelial injury in COVID-19 progression, suggesting that serial biomarker monitoring may help identify high-risk patients.