Background There is accumulating evidence for an overly activated immune response in severe COVID-19, with several studies exploring the therapeutic role of immunomodulation. Through systematic review and meta-analysis, we assess the effectiveness of specific interleukin inhibitors for the treatment of COVID-19. Methods Electronic databases were searched on 7 January 2021 to identify studies of immunomodulatory agents (anakinra, sarilumab, siltuximab and tocilizumab) for the treatment of COVID-19. The primary outcomes were severity on an Ordinal Scale measured at day 15 from intervention and days to hospital discharge. Key secondary endpoints included overall mortality. Results 71 studies totalling 22 058 patients were included, 6 were randomised trials. Most studies explored outcomes in patients who received tocilizumab (60/71). In prospective studies, tocilizumab was associated with improved unadjusted survival (risk ratio 0.83, 95% CI 0.72 to 0.96, I2=0.0%), but conclusive benefit was not demonstrated for other outcomes. In retrospective studies, tocilizumab was associated with less severe outcomes on an Ordinal Scale (generalised OR 1.34, 95% CI 1.10 to 1.64, I2=98%) and adjusted mortality risk (HR 0.52, 95% CI 0.41 to 0.66, I2=76.6%). The mean difference in duration of hospitalisation was 0.36 days (95% CI −0.07 to 0.80, I2=93.8%). There was substantial heterogeneity in retrospective studies, and estimates should be interpreted cautiously. Other immunomodulatory agents showed similar effects to tocilizumab, but insufficient data precluded meta-analysis by agent. Conclusion Tocilizumab was associated with a lower relative risk of mortality in prospective studies, but effects were inconclusive for other outcomes. Current evidence for the efficacy of anakinra, siltuximab or sarilumab in COVID-19 is insufficient, with further studies urgently needed for conclusive findings. PROSPERO registration number CRD42020176375. Data sharing not applicable as no datasets were generated and/or analysed for this study.

中文翻译：

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阿那白滞素、萨利鲁单抗、西妥昔单抗和托珠单抗治疗 COVID-19 的系统评价和荟萃分析

背景 越来越多的证据表明，严重的 COVID-19 中免疫反应过度激活，多项研究探索了免疫调节的治疗作用。通过系统评价和荟萃分析，我们评估了特定白细胞介素抑制剂治疗 COVID-19 的有效性。方法 于 2021 年 1 月 7 日检索电子数据库，以确定免疫调节剂（阿那白滞素、sarilumab、siltuximab 和 tocilizumab）用于治疗 COVID-19 的研究。主要结局是在干预第 15 天和出院前几天测量的顺序量表的严重程度。关键的次要终点包括总体死亡率。结果纳入71项研究，共计22 058例患者，其中6项为随机试验。大多数研究探讨了接受托珠单抗治疗的患者的结果 (60/71)。在前瞻性研究中，托珠单抗与改善未调整生存期相关（风险比 0.83，95% CI 0.72 至 0.96，I2=0.0%），但尚未证明其他结果具有决定性的益处。在回顾性研究中，托珠单抗与序数量表上不太严重的结局相关（广义 OR 1.34，95% CI 1.10 至 1.64，I2=98%）和调整后的死亡风险（HR 0.52，95% CI 0.41 至 0.66，I2=76.6） %）。住院时间的平均差异为 0.36 天（95% CI -0.07 至 0.80，I2=93.8%）。回顾性研究存在很大的异质性，应谨慎解释估计值。其他免疫调节剂显示出与托珠单抗相似的效果，但数据不足，无法对药物进行荟萃分析。结论 在前瞻性研究中，托珠单抗与较低的相对死亡风险相关，但对其他结局的影响尚无定论。目前阿那白滞素、西妥昔单抗或 sarilumab 对 COVID-19 疗效的证据不足，迫切需要进一步研究以获得结论性的结果。PROSPERO 注册号 CRD42020176375。数据共享不适用，因为本研究没有生成和/或分析数据集。