细胞因子及炎症指标在新型冠状病毒肺炎患者预后评估中的价值

Prognostic value of cytokines and inflammation markers on COVID-19 patients

目的探讨细胞因子及炎症指标在新型冠状病毒肺炎(COVID-19)患者预后评估中的临床价值。方法采用回顾性分析方法。选取2020年1月19日至2020年2月26日序贯入住华中科技大学同济医学院附属同济医院的317例COVID-19患者为研究对象,记录入院24 h内首次细胞因子白细胞介素1受体(IL-1β)、白细胞介素2(IL-2R)、白细胞介素6(IL-6)、白细胞介素8(IL-8)、白细胞介素10(IL-10)、肿瘤坏死因子α(TNF-α)及炎症指标C反应蛋白(CRP)、降钙素原(PCT)、血沉(ESR)、铁蛋白(FRT)、白细胞绝对值(WBC)、中性粒细胞绝对值(NEUT#)、淋巴细胞绝对值(LYM#)、中性粒细胞绝对值与淋巴细胞绝对值比值(NLR)、临床分型、基础疾病等资料,并观察28 d生存或死亡事件。根据28 d生存或死亡事件分为生存组与死亡组,根据入院时临床分型分为普通型组、重型组与危重型组,比较分析各组细胞因子及炎症指标的差异;用ROC曲线分析以上细胞因子及炎症指标对COVID-19患者28 d死亡事件的预测价值。结果死亡组较生存组相比,IL-2R、IL-6、IL-8、IL-10、TNF-α、PCT、CRP、WBC、NEUT#、NLR显著升高,LYM#显著降低,差异均有统计学意义(P<0.001);随入院时临床分型(普通型组、重型组、危重型组)严重程度增加,IL-6、IL-8、IL-10、PCT、CRP、WBC、NEUT#、NLR亦随之显著升高,LYM#显著降低,两两比较差异均有统计学意义(P<0.05);ROC曲线分析显示,IL-6、IL-8、PCT、CRP、FRT、WBC、NEUT#、LYM#、NLR有较好的预测价值,曲线下面积(AUC)>0.7,而IL-1β、IL-2R、IL-10、TNF-α及ESR则有一般或较低的预测价值(AUC<0.7)。结论细胞因子IL-6、IL-8及炎症指标PCT、CRP、FRT、WBC、NEUT#、LYM#、NLR在COVID-19患者临床分型及28 d死亡事件中均具有良好的预测价值,以上细胞因子及炎症指标的异常往往预示不良预后。

Objective To investigate the prognostic value of cytokines and inflammation markers on corona virus disease 2019(COVID-19)patients.Method Retrospectively analysis for 317 patients with COVID-19 who were admitted to Tongji Hospital of Tongji Medical College,Huazhong University of Science and Technology from January 19,2020 to February 26,2020.The cytokines:IL-1β,IL-2R,IL-6,IL-8,IL-10 and TNF-α,inflammatory markers:CRP,PCT,ESR,ferritin(FRT),WBC,NEU count,LYM count,and neutrophil lymphocyte ratio(NLR),clinical severity grade and underlying diseases were obtained within 24 hours after admission.The events of survival or death events were monitored in 28 days.All the patients were divided into survival group and death group.The differences of cytokines and inflammation markers between survival and death groups were analyzed.According to the clinical classification on admission,the patients were also divided into moderate group,severe group and critical group,and the differences of cytokines and inflammation markers were simultaneously analyzed.ROC curve analysis was applied to explore the predictive efficiency of the cytokines and inflammation markers for motality event in 28 days.Results Compared with the survival group,the levels of IL-2R,IL-6,IL-8,IL-10,TNF-α,PCT,CRP,WBC,NEUT#and NLR were significantly increased in death group,while LYM#was significantly decreased(P<0.001).The levels of IL-6,IL-8,IL-10,PCT,CRP,WBC,NEUT#and NLR significantly increased and LYM#significantly decreased with increased severe status of the clinical classification(moderate,severe and critical group)of the patients on admission(P<0.05).ROC curve analysis indicated that IL-6,IL-8,PCT,CRP,FRT,WBC,NEUT count,LYM count and NLR showed fine predictive value(AUC>0.7).However,IL-1β,IL-2R,IL-10,TNF-αand ESR only presented poor predictive value(AUC<0.7).Conclusion The cytokines IL-6 and IL-8,and inflammation markers PCT,CRP,FRT,WBC,NEUT#,LYM#and NLR may have good predictive values in clinical severity grade as well as 28 day motality event.The abnormality of the above cytokines and inflammatory markers may indicate poor prognosis of COVID-19 patients.