应用托珠单抗的重症新型冠状病毒感染患者炎性标志物变化及与临床结局的关系

Inflammatory marker variations in critical COVID-19 patients treated with Tocilizumab and their correlation with clinical outcomes

目的探究重症新冠感染患者应用托珠单抗前后炎性标志物的变化及其与临床预后的关系。方法采用回顾性队列方法,纳入2022年12月至2023年2月于北京大学第一医院集中收治的诊断为重症新型冠状病毒感染、应用托珠单抗免疫治疗且动态监测炎性标志物的患者。收集临床资料,并根据第14日的临床结局分为临床恶化组及非临床恶化组。通过广义线性混合模型描述托珠单抗给药前后白细胞介素-6(interleukin-6,IL-6)及超敏C反应蛋白(hypersensitive C-reactive protein,hsCRP)的变化,并比较其在不同临床结局组的差异。结果共46例患者纳入分析,14 d后出现临床恶化22例,未出现临床恶化24例。广义线性混合模型显示,IL-6在应用托珠单抗后第1日呈升高趋势,第3日、第5日呈下降趋势,hsCRP在应用托珠单抗后呈持续下降趋势;临床恶化组的IL-6水平持续高于非临床恶化组,第5日两组的变化有出现分化的趋势,即临床恶化组IL-6水平较前升高,非临床恶化组IL-6较前继续下降。结论应用托珠单抗后IL-6水平偏高且在第5日出现升高趋势的患者临床预后可能不佳。

ObjectiveTo analyze the changes of inflammatory markers in critical COVID-19 patients during the administration of Tocilizumab and their relationships with clinical prognosis.MethodsThe retrospective cohort study method was used.The study enrolled patients who were diagnosed as critical COVID-19 cases,treated with Tocilizumab and dynamic monitored inflammatory markers in Peking University First Hospital from December 2022 to February 2023.The clinical data were collected and the patients were divided into clinical deterioration group and non-clinical deterioration group according to the clinical outcomes on the 14 th day.A generalized linear mixed model was used to describe the overall changes of interleukin-6(IL-6)and hypersensitive C-reactive protein(hsCRP)before and after the administration of Tocilizumab,and compare the changes of IL-6 and hsCRP in groups with different clinical outcomes.ResultsA total of 46 patients were enrolled in the study.After 14 days,22 cases showed clinical deterioration and 24 cases had no clinical deterioration.Generalized linear mixed model showed that IL-6 increased on the 1 st day after the administration of Tocilizumab and decreased on the 3 rd and 5 th day.The level of hsCRP decreased continuously.The clinical deterioration group maintained higher level of IL-6 than that in the non-clinical deterioration group.On the 5 th day,the changes in both groups varied,i.e.the levels of IL-6 increased in the clinical deterioration group and decreased in the non-clinical deterioration group.ConclusionsThe clinical prognosis of patients were poor if IL-6 level was high after admission of Tocilizumab and maintain increasing from the 5 th day.