Ul Haq Muhammad Zain, Ashraf Saad, Shah Muhammad Shahmeer Ullah, Sulaiman Samia Aziz, Shaukat Ayesha, Ansari Muhammad Ahsan, Basaria Areeba Aamir Ali, Fatima Laveeza, Saeed Humza, Goyal Aman, Daoud Mohamed
Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan.
School of Medicine, University of Jordan, Amman, Jordan.
Infection. 2025 Jul 31. doi: 10.1007/s15010-025-02582-0.
Since late 2019, COVID-19 has had a catastrophic impact on public health. Ensitrelvir, a new antiviral targeting the SARS-CoV-2 main protease, has reduced viral replication and disease severity. This meta-analysis and systematic review assessed Ensitrelvir's efficacy and safety in patients with mild-to-moderate COVID-19 symptoms.
A comprehensive search was conducted in PubMed (Medline), Scopus, Embase, and CENTRAL up to July 2024 to retrieve randomized controlled trials (RCTs) comparing Ensitrelvir to placebo in adults with mild to moderate, RT-PCR-confirmed COVID-19. Outcomes were assessed at standardized time points, with viral RNA measured at day 4. Mean differences (MD) for continuous outcomes and risk ratios (RR) for binary outcomes, both with 95% confidence intervals (CIs), were calculated using the Mantel-Haenszel random-effects model. Efficacy outcomes included SARS-CoV-2 viral RNA, while safety outcomes included HDL, triglycerides, bilirubin, AST, headache, diarrhea, TEAEs, TRAEs, serious TEAEs, and treatment discontinuation. The quality of the included RCTs was assessed with the Cochrane Risk of Bias 2 (ROB2) tool.
The analysis included six RCTs with 2,793 participants: 1,860 received Ensitrelvir and 933 were given a placebo. Ensitrelvir gave significant results for reduced viral RNA levels of SARS-CoV-2 [MD: - 1.35; 95% CI - 1.58 to - 1.13; p < 0.01] and the incidence of lower cholesterol levels [RR: 8.83; 95% CI 4.05 to 19.27; p < 0.01] compared to the placebo group. However, it was associated with increased risks of decreased HDL levels, elevated triglycerides, increased bilirubin, more headaches, and a higher overall occurrence of treatment-emergent adverse events.
Ensitrelvir effectively reduces viral load in COVID-19 patients, but its safety profile raises concerns due to significant adverse effects. The benefits must be carefully weighed against the risks, and further research is needed to confirm its role in treatment and to find ways to mitigate these adverse effects.
自2019年末以来，新冠病毒病（COVID-19）对公众健康造成了灾难性影响。恩昔瑞韦是一种针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）主要蛋白酶的新型抗病毒药物，可减少病毒复制并降低疾病严重程度。本荟萃分析和系统评价评估了恩昔瑞韦在轻度至中度COVID-19症状患者中的疗效和安全性。
截至2024年7月，在PubMed（医学期刊数据库）、Scopus、Embase和Cochrane系统评价数据库中进行了全面检索，以检索将恩昔瑞韦与安慰剂比较的随机对照试验（RCT），这些试验针对的是经逆转录聚合酶链反应（RT-PCR）确诊为轻度至中度COVID-19的成年人。在标准化时间点评估结局，在第4天测量病毒核糖核酸（RNA）。使用Mantel-Haenszel随机效应模型计算连续结局的平均差（MD）和二分类结局的风险比（RR），两者均具有95%置信区间（CI）。疗效结局包括SARS-CoV-2病毒RNA，而安全性结局包括高密度脂蛋白（HDL）、甘油三酯、胆红素、天冬氨酸转氨酶（AST）、头痛、腹泻、治疗中出现的不良事件（TEAE）、治疗相关不良事件（TRAE）、严重TEAE以及治疗中断。使用Cochrane偏倚风险2（ROB2）工具评估纳入的RCT的质量。
该分析纳入了6项RCT，共2793名参与者：1860人接受恩昔瑞韦治疗，933人接受安慰剂治疗。与安慰剂组相比，恩昔瑞韦在降低SARS-CoV-2病毒RNA水平[MD：-1.35；95%CI -1.58至-1.13；p<0.01]和降低胆固醇水平的发生率[RR：8.83；95%CI 4.05至19.27；p<0.01]方面取得了显著效果。然而，它与高密度脂蛋白水平降低、甘油三酯升高、胆红素增加、更多头痛以及治疗中出现的不良事件总体发生率较高的风险增加有关。
恩昔瑞韦可有效降低COVID-19患者的病毒载量，但其安全性因显著的不良反应而令人担忧。必须仔细权衡其益处与风险，需要进一步研究以确认其在治疗中的作用并找到减轻这些不良反应的方法。
