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IL-6 血清水平可预测 COVID-19 的严重程度和对托珠单抗的反应:一项观察性研究。

IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study.

机构信息

Internal Medicine Service, Hospital Universitario de la Princesa, Universidad Autónoma Madrid, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.

Rheumatology Service, Hospital Universitario de la Princesa, Universidad Autónoma Madrid, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.

出版信息

J Allergy Clin Immunol. 2021 Jan;147(1):72-80.e8. doi: 10.1016/j.jaci.2020.09.018. Epub 2020 Sep 30.

Abstract

BACKGROUND

Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19.

OBJECTIVE

We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ.

METHODS

A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality.

RESULTS

One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients.

CONCLUSIONS

Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.

摘要

背景

患有 2019 年冠状病毒病(COVID-19)的患者会发生细胞因子释放综合征,最终导致需要进行有创机械通气(IMV)的急性呼吸窘迫综合征。由于白细胞介素 6(IL-6)是急性呼吸窘迫综合征中的相关细胞因子,因此使用托珠单抗(TCZ)阻断其受体可降低重症 COVID-19 患者的死亡率和/或发病率。

目的

我们旨在确定基线血清 IL-6 水平是否可以预测需要 IMV 和 TCZ 的治疗反应。

方法

对确诊为 COVID-19 的住院患者进行回顾性观察性研究。收集临床信息和实验室检查结果,包括 IL-6 水平,这些结果在入院后大约 3 天和 9 天收集,以与 TCZ 给药前和给药后进行匹配。根据结局(需要 IMV、动脉血氧分压/吸入氧浓度比值的变化或死亡率)进行多变量逻辑和线性回归以及生存分析。

结果

共研究了 146 例患者,主要为男性(66%);中位年龄为 63 岁。44 例(30%)患者需要 IMV,58 例(40%)患者接受 TCZ 治疗。IL-6 水平大于 30 pg/mL 是预测 IMV 的最佳指标(优势比,7.1;P<0.001)。早期给予 TCZ 与高 IL-6 患者的氧合改善(动脉血氧分压/吸入氧浓度比值)相关(P=0.048)。未接受 TCZ 治疗的高 IL-6 患者死亡率较高(危险比,4.6;P=0.003),而接受 TCZ 治疗的低 IL-6 患者死亡率也较高(危险比,3.6;P=0.016)。在接受 TCZ 治疗的患者中,未观察到与治疗相关的严重不良事件。

结论

基线 IL-6 大于 30 pg/mL 可预测 COVID-19 患者对 IMV 的需求,并有助于为 TCZ 给药提供适当的适应证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fec/7525244/bbb19cc03712/gr1_lrg.jpg

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