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《高剂量静脉注射免疫球蛋白治疗重症 2019 冠状病毒病:中国多中心回顾性研究》。

High-Dose Intravenous Immunoglobulin in Severe Coronavirus Disease 2019: A Multicenter Retrospective Study in China.

机构信息

Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.

出版信息

Front Immunol. 2021 Feb 19;12:627844. doi: 10.3389/fimmu.2021.627844. eCollection 2021.

Abstract

BACKGROUND

The effective treatment of coronavirus disease 2019 (COVID-19) remains unclear. We reported successful use of high-dose intravenous immunoglobulin (IVIg) in cases of severe COVID-19, but evidence from larger case series is still lacking.

METHODS

A multi-center retrospective study was conducted to evaluate the effectiveness of IVIg administered within two weeks of disease onset at a total dose of 2 g/kg body weight, in addition to standard care. The primary endpoint was 28-day mortality. Efficacy of high-dose IVIg was assessed by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) analysis, and IPTW after multiple imputation (MI) analysis.

RESULTS

Overall, 26 patients who received high-dose IVIg with standard therapy and 89 patients who received standard therapy only were enrolled in this study. The IVIg group was associated with a lower 28-day mortality rate and less time to normalization of inflammatory markers including IL-6, IL-10, and ferritin compared with the control. The adjusted HR of 28-day mortality in high-dose IVIg group was 0.24 (95% CI 0.06-0.99, p<0.001) in IPTW model, and 0.27 (95% CI 0.10-0.57, p=0.031) in IPTW-MI model. In subgroup analysis, patients with no comorbidities or treated in the first week of disease were associated with more benefit from high-dose IVIg.

CONCLUSIONS

High-dose IVIg administered in severe COVID-19 patients within 14 days of onset was linked to reduced 28-day mortality, more prominent with those having no comorbidities or treated at earlier stage.

摘要

背景

新冠肺炎(COVID-19)的有效治疗方法仍不明确。我们曾报道过在严重 COVID-19 患者中使用大剂量静脉注射免疫球蛋白(IVIg)治疗取得成功,但仍缺乏更大规模病例系列的证据。

方法

我们进行了一项多中心回顾性研究,评估了在疾病发病两周内,给予 2g/kg 体重的总剂量的 IVIg 联合标准治疗的效果。主要终点为 28 天死亡率。采用 Cox 比例风险回归模型和 Kaplan-Meier 曲线(通过逆概率治疗加权(IPTW)分析和多重插补(MI)后 IPTW 分析进行调整)评估大剂量 IVIg 的疗效。

结果

总体而言,本研究共纳入 26 例接受大剂量 IVIg 联合标准治疗和 89 例仅接受标准治疗的患者。与对照组相比,IVIg 组的 28 天死亡率较低,白细胞介素 6(IL-6)、白细胞介素 10(IL-10)和铁蛋白等炎症标志物恢复正常的时间更短。在 IPTW 模型中,大剂量 IVIg 组 28 天死亡率的调整 HR 为 0.24(95%CI 0.06-0.99,p<0.001),在 IPTW-MI 模型中为 0.27(95%CI 0.10-0.57,p=0.031)。亚组分析显示,无合并症或在发病第一周内接受治疗的患者从大剂量 IVIg 治疗中获益更多。

结论

在发病 14 天内对严重 COVID-19 患者给予大剂量 IVIg 治疗与降低 28 天死亡率相关,在无合并症或早期治疗的患者中效果更为显著。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12f1/7933558/74ea6f42db51/fimmu-12-627844-g001.jpg

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