Elevated sRAGE levels predict mechanical ventilation need in moderate to severe COVID-19 pneumonia patients

Severe respiratory failure is a critical complication of SARS-CoV-2 infection, often necessitating mechanical ventilation (MV), which is associated with poorer outcomes. Identifying patients at high risk for MV early could enable proactive interventions and optimize resource allocation. Current clinical assessments alone may not fully capture the evolving lung injury. This study investigates whether specific soluble biomarkers of bronchoalveolar epithelial and endothelial injury can reliably predict MV requirement in COVID-19 pneumonia.

This prospective, observational, monocentric cohort study enrolled 54 COVID-19 patients with pneumonia within 48 h of hospital admission. Researchers measured serum concentrations of five bronchoalveolar injury biomarkers: Krebs von den Lungen-6 (KL-6), soluble receptor for advanced glycation end-products (sRAGE), club cell protein 16 (CC16), angiopoietin-2 (Ang-2), and soluble CD146 (sCD146) at Day 0, 7, and 14 using ELISA assays. The primary endpoint was the need for mechanical ventilation during hospitalization.

Of the 54 enrolled patients, 23 (43%) required mechanical ventilation (MV), 13 (24%) high flow oxygen therapy (HFOT), and 18 (33%) standard oxygen. At inclusion (Day 0), levels of KL-6, sRAGE, and CC16 were significantly higher in MV patients compared to non-MV patients (p < 0.05). sRAGE showed the most pronounced difference, with a 2.4-fold increase in MV patients. In multivariate logistic regression, sRAGE and SpO2/FIO2 were identified as independent risk factors for MV. For every 1000 pg/mL increase in sRAGE, the odds of requiring MV increased by 1.316 (95% CI [1.040-1.667]; p = 0.022).

Patients with an sRAGE level ≥ 5449 pg/mL at inclusion had a significantly lower probability of weaning from oxygen at Day 60 (HR 0.36; 95% CI [0.19-0.67]; p = 0.001). Furthermore, from Day 7 to Day 14, CC16 levels increased while sCD146 levels decreased in MV patients, indicating distinct kinetic profiles.