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托珠单抗在重症 COVID-19 患者中的再利用。

Repurposed Tocilizumab in Patients with Severe COVID-19.

机构信息

Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan 430030, China.

Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China.

出版信息

J Immunol. 2021 Feb 1;206(3):599-606. doi: 10.4049/jimmunol.2000981. Epub 2020 Dec 9.

Abstract

The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable morbidity and mortality. Tocilizumab, an inhibitor of IL-6, has been widely repurposed as a treatment of severely ill patients without robust evidence supporting its use. In this study, we aimed to systematically describe the effectiveness of treatment and prevention of the cytokine storms in COVID-19 patients with tocilizumab. In this multicentered retrospective and observational cohort study, 65 patients with COVID-19 receiving tocilizumab and 130 not receiving tocilizumab were propensity score matched at a ratio of 2:1 based on age, sex, and comorbidities from January 20, 2020 to March 18, 2020 in Wuhan, China. After adjusting for confounding, the detected risk for in-hospital death was lower in the tocilizumab group versus nontocilizumab group (hazard ratio = 0.47; 95% confidence interval = 0.25-0.90; = 0.023). Moreover, use of tocilizumab was associated with a lower risk of acute respiratory distress syndrome (odds ratio = 0.23; 95% confidence interval = 0.11-0.45; < 0.0001). Furthermore, patients had heightened inflammation and more dysregulated immune cells before treatment, which might aggravate disease progression. After tocilizumab administration, abnormally elevated IL-6, C-reactive protein, fibrinogen, and activated partial thromboplastin time decreased. Tocilizumab may be of value in prolonging survival in patients with severe COVID-19, which provided a novel strategy for COVID-19-induced cytokine release syndrome. Our findings could inform bedside decisions until data from randomized, controlled clinical trials become available.

摘要

新型冠状病毒肺炎(COVID-19)已在全球范围内流行,导致大量发病和死亡。白细胞介素-6(IL-6)抑制剂托珠单抗已被广泛重新用于治疗重症患者,但缺乏支持其使用的有力证据。本研究旨在系统描述托珠单抗治疗 COVID-19 患者细胞因子风暴的疗效和预防作用。

在这项多中心回顾性观察队列研究中,2020 年 1 月 20 日至 3 月 18 日,中国武汉根据年龄、性别和合并症,将接受托珠单抗治疗的 65 例 COVID-19 患者和未接受托珠单抗治疗的 130 例患者按 2:1 的比例进行倾向性评分匹配。在调整混杂因素后,与未接受托珠单抗治疗组相比,托珠单抗组住院死亡风险降低(风险比=0.47;95%置信区间=0.25-0.90;=0.023)。此外,托珠单抗的使用与急性呼吸窘迫综合征的风险降低相关(比值比=0.23;95%置信区间=0.11-0.45;<0.0001)。

此外,患者在治疗前炎症水平升高且免疫细胞失调,这可能加重疾病进展。托珠单抗治疗后,异常升高的白细胞介素-6、C 反应蛋白、纤维蛋白原和活化部分凝血活酶时间降低。托珠单抗可能对延长重症 COVID-19 患者的生存时间有价值,为 COVID-19 诱导的细胞因子释放综合征提供了新的治疗策略。在随机对照临床试验数据公布之前,本研究结果可为临床决策提供依据。

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Efficacy of Tocilizumab in Patients Hospitalized with Covid-19.托珠单抗治疗 COVID-19 住院患者的疗效。
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Proc Natl Acad Sci U S A. 2020 May 19;117(20):10970-10975. doi: 10.1073/pnas.2005615117. Epub 2020 Apr 29.
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Cytokine release syndrome in severe COVID-19.重症新型冠状病毒肺炎中的细胞因子释放综合征
Science. 2020 May 1;368(6490):473-474. doi: 10.1126/science.abb8925. Epub 2020 Apr 17.

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