Haslam Alyson, Prasad Vinay
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
Open Forum Infect Dis. 2024 Sep 7;11(9):ofae497. doi: 10.1093/ofid/ofae497. eCollection 2024 Sep.
To address the need for treatments for patients with coronavirus disease 2019 (COVID-19), 3 therapies have been given either full approval or Emergency Use Authorization. These were based on randomized data showing a reduction in deaths/hospitalization, but since then, circulating viral strains and population immunity have changed.
We searched PubMed, Web of Science, Embase, and ClinicalTrials.gov for clinical trials testing nirmatrelvir/ritonavir and molnupiravir for COVID-19. We identified all trials testing nirmatrelvir/ritonavir and molnupiravir in patients with COVID-19 and assessed the pooled efficacy in a meta-analysis. We calculated pooled estimates of hospitalization and death in patients with COVID-19 and the number of studies with published/reported data.
Of the 23 studies found, 11 tested nirmatrelvir/ritonavir, 10 tested molnupiravir, and 2 tested both agents. The pooled estimate in reducing deaths and hospitalization for molnupiravir was 0.62 (95% confidence interval [CI], 0.15-2.53), and the pooled estimate for nirmatrelvir/ritonavir was 0.33 (95% CI, 0.03-3.35). The 1 nirmatrelvir/ritonavir trial that reported significant improvements tested people who were predominantly infected with earlier COVID-19 variants, whereas the 2 null trials were tested in people infected with more recent variants. The 2 positive molnupiravir trials included participants primarily with the Delta variant, whereas the null trials were tested later, against more recent variants.
While early trial data show effectiveness of these therapies, the overall pooled effects are nonsignificant, suggesting that recommendations and use of approved oral COVID-19 treatment therapies need to be reevaluated in the context of current viral strains and population immunity.
为满足2019冠状病毒病（COVID-19）患者的治疗需求，3种疗法已获得完全批准或紧急使用授权。这些批准基于随机数据显示死亡/住院人数减少，但自那时以来，传播的病毒株和人群免疫力已经发生了变化。
我们在PubMed、科学网、Embase和ClinicalTrials.gov上搜索了测试奈玛特韦/利托那韦和莫努匹拉韦治疗COVID-19的临床试验。我们确定了所有在COVID-19患者中测试奈玛特韦/利托那韦和莫努匹拉韦的试验，并在荟萃分析中评估了汇总疗效。我们计算了COVID-19患者住院和死亡的汇总估计值以及有发表/报告数据的研究数量。
在找到的23项研究中，11项测试了奈玛特韦/利托那韦，10项测试了莫努匹拉韦，2项同时测试了这两种药物。莫努匹拉韦降低死亡和住院的汇总估计值为0.62（95%置信区间[CI]，0.15 - 2.53），奈玛特韦/利托那韦的汇总估计值为0.33（95%CI，0.03 - 3.35）。报告有显著改善的1项奈玛特韦/利托那韦试验测试的主要是感染早期COVID-19变体的人群，而2项无效试验测试的是感染较新变体的人群。2项莫努匹拉韦阳性试验的参与者主要感染的是德尔塔变体，而无效试验是后来针对更新的变体进行测试的。
虽然早期试验数据显示了这些疗法的有效性，但总体汇总效果不显著，这表明在当前病毒株和人群免疫力的背景下，需要重新评估批准的口服COVID-19治疗疗法的推荐和使用情况。
