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纽约市 COVID-19 患者白细胞介素-6 值、白细胞介素抑制剂与结局的相关性。

The association of interleukin-6 value, interleukin inhibitors, and outcomes of patients with COVID-19 in New York City.

机构信息

Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York City, New York.

出版信息

J Med Virol. 2021 Jan;93(1):463-471. doi: 10.1002/jmv.26365. Epub 2020 Aug 25.

Abstract

Since cytokine release syndrome with elevation of interleukin-6 (IL-6) is considered to be associated with severe cases of coronavirus disease 2019 (COVID-19); IL-6 inhibitors, such as tocilizumab, are expected to be effective for its treatment. This was a retrospective study using a consecutive cohort of 224 patients hospitalized with COVID-19 in March 2020. Patients were divided into those admitted to the intensive care unit (ICU group) and those not (no ICU group), and clinical data including usage of tocilizumab were compared. Correlation between IL-6 value at admission and at peak, and tocilizumab use, as well as clinical outcomes were also investigated. The ICU group had higher rates of pre-existing comorbidities such as hypertension, diabetes, and coronary disease, and higher IL-6 than no ICU group (all P < .05). Age, peak IL-6, and peak d-dimer were significant predictors of in-hospital mortality (1.05 [1.01-1.09], P = .012; 1.001 [1.000-1.002], P = .002; 1.10 [1.03-1.18], P = .008). Receiver operating characteristics curve showed higher predictability of in-hospital mortality with IL-6 at peak than others (area under curve; IL-6 at peak: 0.875 [0.87-0.942], IL-6 at admission: 0.794 [0.699-0.889], d-dimer at peak 0.787 [0.690-0.883], d-dimer at admission 0.726 [0.625-0.827]). Incidence of fungal infections was significantly higher in patients who were given tocilizumab than those who were not (13.0% vs 1.1%, P < .001). Notably, tocilizumab did not affect in-hospital mortality after adjustment including IL-6 (odds ratio [95% confidential interval]: 1.00 [0.27-3.72, P = .998]). Age, peak IL-6, and peak d-dimer levels were significant predictors of in-hospital mortality. Tocilizumab did not decrease in-hospital mortality in our cohort.

摘要

由于细胞因子释放综合征伴白细胞介素-6(IL-6)升高被认为与 2019 年冠状病毒病(COVID-19)的重症病例有关;因此,IL-6 抑制剂,如托珠单抗,有望成为 COVID-19 的有效治疗药物。这是一项回顾性研究,纳入了 2020 年 3 月期间因 COVID-19 住院的 224 例连续队列患者。患者分为入住重症监护病房(ICU 组)和未入住 ICU(非 ICU 组),比较了包括使用托珠单抗在内的临床数据。还研究了入院时和峰值时的 IL-6 值与托珠单抗使用以及临床结局之间的相关性。ICU 组患者更常合并高血压、糖尿病和冠心病等既往合并症,且 IL-6 水平高于非 ICU 组(均 P<0.05)。年龄、峰值 IL-6 和峰值 D-二聚体是住院死亡率的显著预测因素(1.05[1.01-1.09],P=0.012;1.001[1.000-1.002],P=0.002;1.10[1.03-1.18],P=0.008)。受试者工作特征曲线显示,峰值 IL-6 对住院死亡率的预测能力高于其他指标(曲线下面积;峰值 IL-6:0.875[0.87-0.942],入院时 IL-6:0.794[0.699-0.889],峰值 D-二聚体:0.787[0.690-0.883],入院时 D-二聚体:0.726[0.625-0.827])。与未使用托珠单抗的患者相比,使用托珠单抗的患者真菌感染发生率显著更高(13.0% vs 1.1%,P<0.001)。值得注意的是,在包括 IL-6 在内的调整后,托珠单抗并未降低住院死亡率(比值比[95%置信区间]:1.00[0.27-3.72],P=0.998)。年龄、峰值 IL-6 和峰值 D-二聚体水平是住院死亡率的显著预测因素。在本队列中,托珠单抗并未降低住院死亡率。

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