The predictive value of hyaluronic acid for the severity and prognosis of COVID-19: a retrospective multicenter cohort study

The aim of this study was to elucidate the relationship between HA levels and clinical outcomes, including disease severity and prognosis. A retrospective multicenter cohort analysis was conducted across three medical centers in China from September 2022 to February 2023. Patients with positive nucleic acid for the novel coronavirus were included in the study. The primary endpoint is 28-day mortality.The severity was assessed by the ‘Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Trial Version 9)’. Analyses assessed HA correlation with severity (Kendall), predictive value for mortality (logistic regression, ROC, Delong test), and survival differences (KM analysis using a Youden index-derived HA cutoff). A total of 862 patients (median age 72; 58.47% male) were included in the study, of whom 108 died. Non-survivors were older, more men, lower BMI, and more complicatinos. The overall median HA level was 121.65 ng/ml, significantly higher in non-survivors(<i>p</i> &lt; 0.001). Kendall correlation analysis revealed a significant correlation between HA level and COVID-19 severity (correlation coefficient: 0.365, <i>p</i> &lt; 0.001). Our preliminary analysis revealed positive correlations between HA and D-dimer and chest CT. In logistic regression models, HA was an independent predictor of 28-day mortality(<i>p</i> = 0.001). The AUROC for HA was 0.840 (95% CI: 0.806-0.974). The cut-off value was 141.65 ng/ml (sensitivity 61.27%, specificity 91.67%). KM survival analysis showed that patients with HA levels higher than 141.65 ng/ml had a significantly lower survival probability(<i>p</i> &lt; 0.001). HA may potentially function as a biomarker for COVID-19 and could provide a vital reference for the clinical treatment.

本研究旨在阐明透明质酸（HA）水平与临床结局（包括疾病严重程度及预后）之间的关联。本研究于2022年9月至2023年2月在中国三家医疗中心开展，为回顾性多中心队列分析。研究纳入新型冠状病毒核酸检测阳性的患者，主要终点为28天死亡率。疾病严重程度依据《新型冠状病毒肺炎诊疗方案（试行第九版）》进行评估。本研究采用多种统计方法开展分析：通过Kendall相关分析评估HA与疾病严重程度的相关性；借助logistic回归、受试者工作特征（ROC）曲线及Delong检验，评价HA对死亡率的预测价值；采用基于Youden指数推导的HA截断值进行Kaplan-Meier（KM）生存分析，以比较不同HA水平患者的生存差异。本研究共纳入862例患者，中位年龄72岁，男性占比58.47%，其中108例患者最终死亡。与存活患者相比，非存活患者年龄更大、男性比例更高、体质量指数（BMI）更低，且合并症更多。研究总体人群的中位HA水平为121.65 ng/ml，非存活患者的HA水平显著更高（p<0.001）。Kendall相关分析结果显示，HA水平与COVID-19严重程度呈显著正相关（相关系数为0.365，p<0.001）。初步分析表明，HA与D-二聚体水平、胸部CT影像结果呈正相关。在logistic回归模型中，HA是28天死亡率的独立预测因子（p=0.001）。HA的受试者工作特征曲线下面积（AUROC）为0.840（95%置信区间：0.806~0.974），最佳截断值为141.65 ng/ml（灵敏度61.27%，特异度91.67%）。KM生存分析结果显示，HA水平高于141.65 ng/ml的患者生存概率显著更低（p<0.001）。综上，HA或可作为COVID-19的潜在生物标志物，为临床诊疗提供重要参考依据。