人附睾蛋白4联合炎性指标对新型冠状病毒肺炎患者重症化的预测价值

Predictive value of HE4 in conjunction with inflammatory markers for severity stratification of COVID-19 patients

目的探讨人附睾蛋白4(HE4)在新型冠状病毒肺炎患者血清中的表达变化及其在新型冠状病毒肺炎(COVID-19)患者重症化预测中的应用价值。方法选取144例COVID-19患者作为感染组,50例健康体检者作为对照组,测定所有研究对象入院时血清HE4及C-反应蛋白(CRP)、白细胞介素6(IL-6)、降钙素原(PCT)、铁蛋白(Fer)等其他炎症标志物的表达水平;将COVID-19患者分为普通型(包括轻型、中型)及重型(包括重型及危重型)患者两组,比较血清HE4及其他炎症指标水平的差异,采用多因素Logistic回归分析探讨重症发生的相关因素,绘制受试者工作特征(ROC)曲线以评价各指标对COVID-19重症的预测价值。结果入院时COVID-19患者血清HE4、CRP、IL-6、PCT、Fer、中性粒细胞与淋巴细胞计数比值(NLR)、补体C3(C3)及补体C4(C4)水平均明显高于对照组,差异有统计学意义(P﹤0.01)。其中发展为重型的患者起初血清HE4、CRP、IL-6、PCT、Fer、NLR水平均高于普通型患者,差异有统计学意义(P﹤0.05)。多因素Logistic回归模型显示,HE4、CRP、NLR为COVID-19发展为重症的独立危险因素。经ROC曲线分析,HEA、CRP、NLR单独预测COVID-19重症化的曲线下面积(AUC)分别为0.856、0.815、0.781,临界值分别为151 pmol/L、7.89 mg/dL、6.355时,约登指数最大,其中HE4敏感度为91.11%,特异度为67.37%;HE4、CRP、NLR三项指标联合检测AUC为0.890,敏感度为84.09%,特异度为79.76%。结论入院时HE4对COVID-19重症化的预测效能最高,可作为COVID-19重症化预测的潜在生物标志物,HE4与CRP、NLR联合检测对COVID-19重症化预测具有更高的准确度和临床应用价值。

Objective To investigate the level of human epididymal protein 4(HE4)and its predictive value for the progression to severe in COVID-19 patients.Methods A total of 144 COVID-19 patients were selected as the infection group,while 50 healthy individuals served as the control group.Serum levels of HE4 and other inflammatory markers,including CRP,IL-6,PCT,and Ferritin,were measured upon admission.COVID-19 patients were classified into mild(including asymptomatic and moderate)and severe groups(including severe and critical cases),comparing the differences in serum levels of HE4 and other inflammatory markers.Multivariable logistic regression analysis was employed to explore risk factors associated with severe progression,and receiver operating characteristic(ROC)curves were constructed to evaluate the predictive value of each marker for severe COVID-19.Results Upon admission,serum levels of HE4,CRP,IL-6,PCT,Ferritin,NLR,C3,and C4 in COVID-19 patients were significantly elevated compared to the control group(P<0.01).Among those who progressed to severe disease,initial serum levels of HE4,CRP,IL-6,PCT,Ferritin,and NLR were significantly higher than those in the mild group(P<0.05).The multivariable logistic regression model identified HE4,CRP,and NLR as independent risk factors for severe COVID-19.ROC curve analysis revealed that the area under the curve for the individual predictions of severe progression were 0.856,0.815,and 0.781,with critical values of 7.89 mg/dL,151 pmol/L,and 6.355,respectively,corresponding to the maximum Youden index.The sensitivity and specificity of HE4 were found to be 91.11%and 67.37%,respectively.The combined assessment of HE4,CRP,and NLR yielded an area under the curve of 0.890,with a sensitivity of 84.09%and specificity of 79.76%.Conclusion HE4 demonstrated the highest predictive efficacy for severe COVID-19 upon admission and has the potential to serve as a biomarker for predicting severe progression in COVID-19 patients.The joint assessment of HE4 with CRP and NLR provides enhanced accuracy and clinical significance in predicting severe COVID-19 outcomes.