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
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
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DOI：
10.1503/cmaj.200647
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发表时间：
2020-07-06
影响因子：
14.6
通讯作者：
Zhai, Suodi
中科院分区：
文献类型：
--
作者：
Liu, Wei;Zhou, Pengxiang;Zhai, Suodi
背景：抗病毒药物正在经验性地给予一些2019冠状病毒病（COVID-19）患者。为支持COVID-19管理指引的制定，我们进行了一项系统性审查，探讨了7种抗病毒治疗COVID-19的益处和危害。方法：我们检索了MEDLINE、Embase、科克伦对照试验中心（CENTRAL）、PubMed和3个中文数据库（CNKI、万方和SinoMed）至2020年4月19日，检索了medRxiv和Chinaxiv至2020年4月27日，检索了重庆维普至2020年4月30日。我们纳入了利巴韦林、氯喹、羟氯喹、乌非诺韦（阿比朵尔）、法维普韦、干扰素和洛匹那韦/利托那韦的研究。如果没有来自COVID-19研究的直接证据，我们纳入了来自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，用于疗效结局，并纳入了其他急性呼吸道病毒感染研究的间接证据，用于安全性结局。结果：在非严重COVID-19疾病患者中，死亡率极低，排除了对死亡率的重要影响。我们只发现了非常低质量的证据，对于大多数治疗和结果，无论是非重度还是重度COVID-19，几乎没有或根本没有益处。一个例外是洛匹那韦/利托那韦治疗，我们发现低质量的证据表明，在重症监护室的住院时间缩短（风险差异短5天，95%置信区间[CI] 0至9天）和住院时间缩短（风险差异短1天，95% CI 0至2天）。对于安全性结局，证据质量较低或非常低，但洛匹那韦/利托那韦治疗除外，中等质量的证据表明腹泻、恶心和呕吐可能会增加。释义：到目前为止，任何抗病毒治疗都不存在对COVID-19有重要益处的有说服力的证据，尽管每种治疗证据都没有排除重要益处。在有信心地实施此类治疗之前，还需要对COVID-19患者进行额外的随机对照试验。
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.