Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.
Department of Pulmonary, Critical Care & Sleep Medicine, All India Institute of Medical Sciences, New Delhi, India.
Eur J Clin Invest. 2020 Nov;50(11):e13383. doi: 10.1111/eci.13383. Epub 2020 Sep 13.
Several therapeutic agents have been investigated for treatment of novel coronavirus 2019 (nCOV-2019). We conducted a systematic review and meta-analysis to assess the efficacy of various treatment modalities in nCOV-2019 patients.
A literature search was conducted before 29 June 2020 in PubMed, Google Scholar and Cochrane library databases. A fixed-effect model was applied if I < 50%, else results were combined using random-effect model. Risk ratio (RR) or standardized mean difference (SMD) along with 95% confidence interval (95% CI) was used to pool the results. Between-study heterogeneity was explored using influence and sensitivity analyses, and publication bias was assessed using funnel plots. Entire statistical analysis was conducted in R version 3.6.2.
Fifty studies involving 15 in vitro and 35 clinical studies including 9170 nCOV-2019 patients were included. Lopinavir-ritonavir was significantly associated with shorter mean time to clinical recovery (SMD -0.32; 95% CI -0.57 to -0.06), remdesivir was significantly associated with better overall clinical recovery (RR 1.17; 95% CI 1.07 to 1.29), and tocilizumab was associated with less all-cause mortality (RR 0.38; 95% CI 0.16 to 0.93). Hydroxychloroquine was associated with longer time to clinical recovery and less overall clinical recovery. It additionally had higher all-cause mortality and more total adverse events.
Our meta-analysis suggests that except in vitro studies, no treatment has shown overall favourable outcomes in nCOV-2019 patients. Lopinavir-ritonavir, remdesivir and tocilizumab may have some benefits, while hydroxychloroquine administration may cause harm in nCOV-2019 patients. Results from upcoming large clinical trials may further clarify role of these drugs.
已经有几种治疗药物被用于治疗新型冠状病毒 2019（nCOV-2019）。我们进行了一项系统回顾和荟萃分析，以评估各种治疗方法在 nCOV-2019 患者中的疗效。
我们在 2020 年 6 月 29 日前在 PubMed、Google Scholar 和 Cochrane 图书馆数据库中进行了文献检索。如果 I ² < 50%，则应用固定效应模型；否则，使用随机效应模型合并结果。使用风险比（RR）或标准化均数差（SMD）及其 95%置信区间（95%CI）来汇总结果。通过影响分析和敏感性分析来探讨研究间异质性，并使用漏斗图评估发表偏倚。整个统计分析在 R 版本 3.6.2 中进行。
共有 50 项研究纳入了 15 项体外研究和 35 项临床研究，共包括 9170 例 nCOV-2019 患者。洛匹那韦-利托那韦与临床恢复的平均时间更短显著相关（SMD -0.32；95%CI -0.57 至 -0.06），瑞德西韦与总体临床恢复更好显著相关（RR 1.17；95%CI 1.07 至 1.29），托珠单抗与全因死亡率降低显著相关（RR 0.38；95%CI 0.16 至 0.93）。羟氯喹与临床恢复时间延长和总体临床恢复减少有关。此外，羟氯喹还与更高的全因死亡率和更多的总不良反应有关。
我们的荟萃分析表明，除了体外研究外，没有一种治疗方法在 nCOV-2019 患者中显示出总体有利的结果。洛匹那韦-利托那韦、瑞德西韦和托珠单抗可能有一些益处，而羟氯喹的应用可能会对 nCOV-2019 患者造成伤害。即将进行的大型临床试验的结果可能会进一步阐明这些药物的作用。
