抗 SARS-CoV-2 和其他急性病毒感染的抗病毒治疗 COVID-19 的疗效和安全性：系统评价和荟萃分析。
Efficacy and safety of antiviral treatment for COVID-19 from evidence in studies of SARS-CoV-2 and other acute viral infections: a systematic review and meta-analysis.
机构信息
Department of Pharmacy (W. Liu, Zhou, F. Liu, Li, He, Wu, Q. Zhang, Tang, Du, Ying, Xu, Y. Zhang, Li, Zhai), Peking University Third Hospital, Beijing, China; Institute for Drug Evaluation (Zhai, F. Liu), Departments of Pharmacy Administration and Clinical Pharmacy (Wu, Du, Y. Zhang), and Respiratory and Critical Care Medicine (Shen), Peking University Health Science Center, Beijing, China; College of Pharmacy (Chen), University of Nebraska Medical Center, Omaha, Neb.; Department of Health Research Methods, Evidence and Impact (Ye, Ibrahim, Guyatt), McMaster University, Hamilton, Ont.; Department of Pharmacy (Gong, J. Liu), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; DeGroote Institute for Pain Research and Care (Couban), McMaster University, Hamilton, Ont.; Pharmacy Department (Y. Li), First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Department of Pharmacy (W. Liu, Zhou, F. Liu, Li, He, Wu, Q. Zhang, Tang, Du, Ying, Xu, Y. Zhang, Li, Zhai), Peking University Third Hospital, Beijing, China; Institute for Drug Evaluation (Zhai, F. Liu), Departments of Pharmacy Administration and Clinical Pharmacy (Wu, Du, Y. Zhang), and Respiratory and Critical Care Medicine (Shen), Peking University Health Science Center, Beijing, China; College of Pharmacy (Chen), University of Nebraska Medical Center, Omaha, Neb.; Department of Health Research Methods, Evidence and Impact (Ye, Ibrahim, Guyatt), McMaster University, Hamilton, Ont.; Department of Pharmacy (Gong, J. Liu), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; DeGroote Institute for Pain Research and Care (Couban), McMaster University, Hamilton, Ont.; Pharmacy Department (Y. Li), First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
出版信息
CMAJ. 2020 Jul 6;192(27):E734-E744. doi: 10.1503/cmaj.200647. Epub 2020 Jun 3.
BACKGROUND
Antiviral medications are being given empirically to some patients with coronavirus disease 2019 (COVID-19). To support the development of a COVID-19 management guideline, we conducted a systematic review that addressed the benefits and harms of 7 antiviral treatments for COVID-19.
METHODS
We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and 3 Chinese databases (CNKI, WANFANG and SinoMed) through Apr. 19, medRxiv and Chinaxiv through Apr. 27, and Chongqing VIP through Apr. 30, 2020. We included studies of ribavirin, chloroquine, hydroxychloroquine, umifenovir (arbidol), favipravir, interferon and lopinavir/ritonavir. If direct evidence from COVID-19 studies was not available, we included indirect evidence from studies of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for efficacy outcomes and other acute respiratory viral infections for safety outcomes.
RESULTS
In patients with nonsevere COVID-19 illness, the death rate was extremely low, precluding an important effect on mortality. We found only very low-quality evidence with little or no suggestion of benefit for most treatments and outcomes in both nonsevere and severe COVID-19. An exception was treatment with lopinavir/ritonavir, for which we found low-quality evidence for a decrease in length of stay in the intensive care unit (risk difference 5 d shorter, 95% confidence interval [CI] 0 to 9 d) and hospital stay (risk difference 1 d shorter, 95% CI 0 to 2 d). For safety outcomes, evidence was of low or very low quality, with the exception of treatment with lopinavir/ritonavir for which moderate-quality evidence suggested likely increases in diarrhea, nausea and vomiting.
INTERPRETATION
To date, persuasive evidence of important benefit in COVID-19 does not exist for any antiviral treatments, although for each treatment evidence has not excluded important benefit. Additional randomized controlled trials involving patients with COVID-19 will be needed before such treatments can be administered with confidence.
背景
目前正在对一些新型冠状病毒肺炎（COVID-19）患者使用抗病毒药物进行经验性治疗。为支持 COVID-19 管理指南的制定，我们进行了一项系统评价，以评估 7 种抗病毒治疗 COVID-19 的获益与危害。
方法
我们检索了 MEDLINE、Embase、Cochrane 中央对照试验注册库（CENTRAL）、PubMed 及 3 个中文数据库（CNKI、万方和中国生物医学文献数据库），检索时间截至 2020 年 4 月 19 日，还检索了 medRxiv 和 Chinaxiv 截至 2020 年 4 月 27 日的资料，以及 Chongqing VIP 截至 2020 年 4 月 30 日的资料。我们纳入了利巴韦林、氯喹、羟氯喹、乌苯美司（阿比多尔）、法维拉韦、干扰素和洛匹那韦/利托那韦的研究。如果 COVID-19 研究没有直接证据，我们也纳入了严重急性呼吸综合征（SARS）和中东呼吸综合征（MERS）研究的间接证据，以评估疗效结局，以及其他急性呼吸道病毒感染研究的间接证据，以评估安全性结局。
结果
在非重症 COVID-19 患者中，死亡率极低，不可能对死亡率产生重要影响。我们仅发现了非常低质量的证据，对于非重症和重症 COVID-19 的大多数治疗和结局，几乎没有或没有任何获益的提示。洛匹那韦/利托那韦治疗是一个例外，我们发现其可降低重症监护病房（ICU）入住时间（风险差 5 d，95%置信区间[CI]0 至 9 d）和住院时间（风险差 1 d，95%CI 0 至 2 d）的低质量证据。对于安全性结局，证据的质量为低或极低，只有洛匹那韦/利托那韦治疗的中度质量证据表明可能会增加腹泻、恶心和呕吐。
解释
迄今为止，没有证据表明任何抗病毒治疗对 COVID-19 有重要获益，尽管对于每种治疗，证据并未排除重要获益。在有信心使用这些治疗方法之前，还需要针对 COVID-19 患者开展更多的随机对照试验。
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