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托珠单抗治疗新型冠状病毒肺炎严重或危重型肺受累患者的疗效:一项回顾性研究

Effectiveness of Tocilizumab in Patients with Severe or Critical Lung Involvement in COVID-19: A Retrospective Study.

作者信息

Chober Daniel, Aksak-Wąs Bogusz, Bobrek-Lesiakowska Katarzyna, Budny-Finster Anna, Hołda Ewa, Mieżyńska-Kurtycz Joanna, Jamro Grzegorz, Parczewski Miłosz

机构信息

Department of Infectious, Tropical Diseases and Immune Deficiency, Pomeranian Medical University in Szczecin, 71-455 Szczecin, Poland.

出版信息

J Clin Med. 2022 Apr 20;11(9):2286. doi: 10.3390/jcm11092286.

Abstract

Introduction: Acute lung injury is associated with dysfunctional immune response to SARS-CoV-2. This leads to CRS, which require immunomodulatory treatments aiming to limit the excessive production of cytokines. The literature so far indicates the effectiveness of tocilizumab in patients with COVID-19-associated pneumonia, but there is no clear evidence of its effectiveness in patients with at least 50% lung involvement; therefore, we aimed to bridge this gap in knowledge. Materials and methods: Longitudinal data for 4287 patients with confirmed COVID-19 infection were collected between 1st March 2020 and 16th of January 2022. In total, 182 cases with lung involvement >50% and biochemical indicators of cytokine release storm (Il-6 >100 pg/mL) were selected and analyzed using non-parametric statistics and multivariate Cox models. Results: Among the 182 included patients, 100 (55%) were treated with TCZ, while 82 (45%) did not receive TCZ. The groups were balanced regarding demographics, lung involvement and biochemical markers. Overall mortality in the group was 63.1%. Mortality in the TCZ group was 58.0% compared to 69.5% (n = 57) in the non-TCZ group (p = 0.023). In multivariate Cox proportional hazards models, intravenous administration of tocilizumab was associated with lower probability of ICU admission (HR: 0333 (CI: 0.159−0.700, p = 0.004)) and lower mortality (HR: 0.57306 (CI: 0.354−0.927, p = 0.023)). Conclusions: Tocilizumab is effective as a treatment in the most severely ill patients, in whom the level of lung involvement by the inflammatory process can exceed 50% with coexisting biochemical indices of cytokine storm (Il-6 > 100 pg/mL).

摘要

引言

急性肺损伤与对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的免疫反应功能失调有关。这会导致细胞因子释放综合征(CRS),需要进行免疫调节治疗以限制细胞因子的过度产生。迄今为止的文献表明托珠单抗对新型冠状病毒肺炎(COVID-19)相关肺炎患者有效,但尚无明确证据表明其对肺部受累至少50%的患者有效;因此,我们旨在填补这一知识空白。材料与方法:收集了2020年3月1日至2022年1月16日期间4287例确诊COVID-19感染患者的纵向数据。总共选择了182例肺部受累>50%且有细胞因子释放风暴生化指标(白细胞介素-6(Il-6)>100 pg/mL)的病例,并使用非参数统计和多变量Cox模型进行分析。结果:在纳入的182例患者中,100例(55%)接受了托珠单抗(TCZ)治疗,而82例(45%)未接受TCZ治疗。两组在人口统计学、肺部受累情况和生化指标方面均衡。该组的总体死亡率为63.1%。TCZ组的死亡率为58.0%,而非TCZ组为69.5%(n = 57)(p = 0.023)。在多变量Cox比例风险模型中,静脉注射托珠单抗与入住重症监护病房(ICU)的概率较低(风险比(HR):0.333(置信区间(CI):0.159 - 0.700,p = 0.004))和死亡率较低(HR:0.57306(CI:0.354 - 0.927,p = 0.023))相关。结论:托珠单抗对病情最严重的患者有效,这些患者炎症过程导致的肺部受累程度可超过50%,同时存在细胞因子风暴的生化指标(Il-6>100 pg/mL)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37fd/9101084/586080e2e8f3/jcm-11-02286-g001.jpg

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