Circulating biomarkers of bronchoalveolar injury help predict the need for mechanical ventilation in patients with moderate to severe COVID-19 pneumonia: A prospective cohort study

BACKGROUND: Severe respiratory failure is a major complication of SARS-CoV-2 infection, and the need for mechanical ventilation (MV) is associated with a worse outcome. Whether some soluble biomarkers of lung injury can help predict MV requirement remains unclear. METHODS: This prospective, observational, monocentric cohort study consecutively enrolled patients with laboratory-confirmed COVID-19 pneumonia within 48 h of hospital admission. The serum concentrations of five key bronchoalveolar epithelial and endothelial biomarkers were determined at Day 0, 7 and 14: 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). The respiratory severity of COVID-19 pneumonia was defined by the maximal level of respiratory support received during hospitalization: oxygen (by mask or nasal prong); high flow oxygen therapy (HFOT); and MV. End-points were the need for MV during hospitalization and the time to liberation from oxygen. RESULTS: Fifty-four COVID-19 patients were enrolled; 23 (43%) required MV, 13 (24%) HFOT, and 18 (33%) oxygen. At inclusion, levels of KL-6, sRAGE, and CC16 were significantly higher in MV compared with non-MV patients (p < 0.05), with sRAGE showing the greatest difference (2.4-fold increase). In multivariate logistic regression, sRAGE (OR per 1000 pg/mL increase 1.316; 95% CI [1.040-1.667]; p = 0.022) and SpO2/FIO2 (OR 0.984; 95% CI [0.970-0.998]; p = 0.008) were identified as independent risk factors for MV. Furthermore, patients with an sRAGE ≥ 5449 pg/mL at inclusion had a lower probability of weaning from oxygen at Day 60 (HR 0.36; 95% CI [0.19-0.67]; p = 0.001). From Day 7 to Day 14, CC16 levels increased while sCD146 levels decreased in MV patients. CONCLUSION: Among five circulating biomarkers of bronchoalveolar injury, sRAGE showed the most favorable kinetic profile, rapidly increasing in MV patients. The early measurement of sRAGE and SpO2/FIO2 upon hospital admission may effectively identify COVID-19 patients at high risk of requiring MV and prolonged oxygen support.