Clinical utility of hyaluronic acid as biomarker for severity and prognosis in COVID-19

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Created On: 11/11/2025

This study investigated the association between serum hyaluronic acid (HA) levels and clinical outcomes, including disease intensity and prognosis, in patients with COVID-19.

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Key take away

Hyaluronic acid levels in serum show a strong correlation with COVID-19 severity and serve as an independent predictor of 28-day mortality, with higher levels indicating poorer survival.

Background

This study investigated the association between serum hyaluronic acid (HA) levels and clinical outcomes, including disease intensity and prognosis, in patients with COVID-19.

Method

In this retrospective cohort study, patients with confirmed COVID-19 by nucleic acid testing were enrolled. The primary outcome ascertained was 28-day mortality. Disease intensity was determined using the Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Trial Version 9). Statistical analyses included Kendall correlation for severity, logistic regression and receiver operating characteristic (ROC) analysis (with Delong test) for mortality prediction, and Kaplan–Meier survival analysis using a Youden index-based HA threshold.

Result

In total, 862 people were enrolled (median age: 72 years; 58.47% male), of whom 108 died. Non-survivors were generally older, predominantly male, had a lower body-mass index, and presented with more comorbidities. The median HA concentration was 121.65 ng/ml, with considerably higher levels in non-survivors. HA levels exhibited a significant correlation with COVID-19 severity (Kendall’s τ = 0.365) and were positively linked with D-dimer and chest computed tomography findings.

Logistic regression confirmed HA as an independent determinant of 28-day mortality. The area under the receiver operating characteristic curve (AUROC) for HA was 0.840 (95% CI: 0.806–0.974), with an optimal cut-off of 141.65 ng/ml (sensitivity 61.27%, specificity 91.67%). Kaplan–Meier analysis illustrated considerably reduced survival among patients with HA levels above this threshold.