Serum hyaluronic acid as an independent predictor of disease severity in hospitalized patients with viral pneumonia Authors

Background: Viral pneumonia remains a major cause of hospitalization and critical illness worldwide, and infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to occur annually despite the transition from pandemic to endemic phases. In this prospective observational study of hospitalized patients with coronavirus disease 2019 (COVID-19), we evaluated the clinical relevance of serum hyaluronic acid (HA), an extracellular matrix component involved in inflammation and immune regulation, as a potential biomarker of disease severity. Methods: A total of 262 adult patients with laboratory-confirmed COVID-19 admitted between January 2023 and July 2024 were enrolled. Serum HA levels at admission were measured, and patients were stratified by HA tertiles. Clinical characteristics and laboratory parameters were analyzed. Logistic regression and receiver operating characteristic (ROC) analyses were performed to identify independent predictors of severe disease. Results: Elevated serum HA levels were associated with advanced age, male sex, prolonged hospitalization, and increased disease severity. Serum HA was negatively correlated with lymphocyte count and positively correlated with inflammatory and coagulation markers, including C-reactive protein and D-dimer. After adjustment for confounders, serum HA remained an independent predictor of progression to severe viral pneumonia. A combined model incorporating HA, C-reactive protein, and D-dimer demonstrated improved predictive performance compared with individual biomarkers. Conclusions: Serum hyaluronic acid is independently associated with disease severity in hospitalized patients with viral pneumonia and reflects key pathological processes related to inflammation, immune dysregulation, and coagulation abnormalities. Combined assessment of HA, C-reactive protein, and D-dimer may facilitate early risk stratification and prognostic evaluation in COVID-19–associated viral pneumonia. Keywords: Viral pneumonia, COVID-19, Hyaluronic acid, Biomarker, Disease severity