Division of Internal Medicine (Pitre), McMaster University, Hamilton, Ont.; Department of Medicine (Pitre, Van Alstine, Chick), Grand River Hospital, Kitchener, Ont.; Michael G. DeGroote School of Medicine (Pitre, Van Alstine, Chick, Khalid), McMaster University, Hamilton, Ont.; Faculty of Medicine (Leung), University of Ottawa, Ottawa, Ont.; Faculty of Health Sciences (Mikhail), McMaster University, Hamilton, Ont.; Division of Hematology and Hematological Malignancies (Cusano), Department of Medicine, University of Calgary, Alta.; Harvard Medical School (Zeraatkar), Harvard University, Boston, Mass.; Health Research Methods, Evidence and Impact, Faculty of Health Sciences (Zeraatkar), McMaster University, Hamilton, Ont.
CMAJ. 2022 Jul 25;194(28):E969-E980. doi: 10.1503/cmaj.220471.
Randomized trial evidence suggests that some antiviral drugs are effective in patients with COVID-19. However, the comparative effectiveness of antiviral drugs in nonsevere COVID-19 is unclear.
We searched the Epistemonikos COVID-19 L·OVE (Living Overview of Evidence) database for randomized trials comparing antiviral treatments, standard care or placebo in adult patients with nonsevere COVID-19 up to Apr. 25, 2022. Reviewers extracted data and assessed risk of bias. We performed a frequentist network meta-analysis and assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.
We identified 41 trials, which included 18 568 patients. Compared with standard care or placebo, molnupiravir and nirmatrelvir-ritonavir each reduced risk of death with moderate certainty (10.9 fewer deaths per 1000, 95% confidence interval [CI] 12.6 to 4.5 fewer for molnupiravir; 11.7 fewer deaths per 1000, 95% CI 13.1 fewer to 2.6 more). Compared with molnupiravir, nirmatrelvir-ritonavir probably reduced risk of hospital admission (27.8 fewer admissions per 1000, 95% CI 32.8 to 18.3 fewer; moderate certainty). Remdesivir probably has no effect on risk of death, but may reduce hospital admissions (39.1 fewer admissions per 1000, 95% CI 48.7 to 13.7 fewer; low certainty).
Molnupiravir and nirmatrelvir-ritonavir probably reduce risk of hospital admissions and death among patients with nonsevere COVID-19. Nirmatrelvir-ritonavir is probably more effective than molnupiravir for reducing risk of hospital admissions. Most trials were conducted with unvaccinated patients, before the emergence of the Omicron variant; the effectiveness of these drugs must thus be tested among vaccinated patients and against newer variants.
随机试验证据表明，一些抗病毒药物对 COVID-19 患者有效。然而，非重症 COVID-19 患者中抗病毒药物的比较疗效尚不清楚。
我们在 Epistemonikos COVID-19 L·OVE（证据综合概述）数据库中检索了截至 2022 年 4 月 25 日比较抗病毒治疗、标准治疗或安慰剂在非重症 COVID-19 成年患者中的随机试验。审查员提取数据并评估偏倚风险。我们进行了频率网络荟萃分析，并使用推荐评估、制定与评价（GRADE）方法评估证据确定性。
我们确定了 41 项试验，共纳入 18568 名患者。与标准治疗或安慰剂相比，莫努匹韦和奈玛特韦-利托那韦均可降低死亡风险，其确定性为中度（每 1000 人减少 10.9 例死亡，95%置信区间 [CI] 莫努匹韦为 12.6 至 4.5 例减少；每 1000 人减少 11.7 例死亡，95% CI 奈玛特韦-利托那韦为 13.1 例减少至 2.6 例增加）。与莫努匹韦相比，奈玛特韦-利托那韦可能降低住院风险（每 1000 人减少 27.8 例住院，95% CI 奈玛特韦-利托那韦为 32.8 至 18.3 例减少；确定性为中度）。瑞德西韦可能对死亡风险没有影响，但可能减少住院（每 1000 人减少 39.1 例住院，95% CI 瑞德西韦为 48.7 至 13.7 例减少；低确定性）。
莫努匹韦和奈玛特韦-利托那韦可能降低非重症 COVID-19 患者的住院和死亡风险。奈玛特韦-利托那韦降低住院风险的效果可能优于莫努匹韦。大多数试验都是在未接种疫苗的患者中进行的，而且是在奥密克戎变异出现之前进行的；因此，这些药物的有效性必须在接种疫苗的患者中进行测试，并针对新的变异进行测试。
