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

Abstract

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 SpO 2 /F I O 2 (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 SpO 2 /F I O 2 upon hospital admission may effectively identify COVID-19 patients at high risk of requiring MV and prolonged oxygen support.