Department of Biostatistics, High Institute of Public Health, Alexandria University, Alexandria, Egypt.
IQVIA for the Human Data Science, The Fifth Settlement, Cairo, Egypt.
J Med Virol. 2021 Mar;93(3):1265-1275. doi: 10.1002/jmv.26442. Epub 2020 Sep 29.
Being a pandemic and having a high global case fatality rate directed us to assess the evidence strength of hydroxychloroquine efficacy in treating coronavirus disease-2019 (COVID-19) arising from clinical trials and to update the practice with the most reliable clinical evidence. A comprehensive search was started in June up to 18 July, 2020 in many databases, including PubMed, Embase, and others. Of 432 studies found, only six studies fulfilled the inclusion criteria, which includes: clinical trials, age more than 12 years with nonsevere COVID-19, polymerase chain reaction-confirmed COVID-19, hydroxychloroquine is the intervention beyond the usual care. Data extraction and bias risk assessment were done by two independent authors. Both fixed-effect and random-effect models were utilized for pooling data using risk difference as a summary measure. The primary outcomes are clinical and radiological COVID-19 progression, severe acute respiratory syndrome coronavirus-2 clearance in the pharyngeal swab, and mortality. The secondary outcomes are the adverse effects of hydroxychloroquine. Among 609 COVID-19 confirmed patients obtained from pooling six studies, 294 patients received hydroxychloroquine and 315 patients served as a control. Hydroxychloroquine significantly prevents early radiological progression relative to control with risk difference and 95% confidence interval of -0.2 (-0.36 to -0.03). On the other hand, hydroxychloroquine did not prevent clinical COVID-19 progression, reduce 5-day mortality, or enhance viral clearance on days 5, 6, and 7. Moreover, many adverse effects were reported with hydroxychloroquine therapy. Failure of hydroxychloroquine to show viral clearance or clinical benefits with additional adverse effects outweigh its protective effect from radiological progression in nonsevere COVID-19 patients. Benefit-risk balance should determine the hydroxychloroquine use in COVID-19.
鉴于 COVID-19 大流行且全球病死率较高，我们评估了临床试验中羟氯喹治疗 COVID-19 的疗效证据强度，并根据最可靠的临床证据更新了治疗方案。2020 年 6 月至 7 月 18 日，我们在包括 PubMed、Embase 在内的多个数据库中进行了全面检索。共检索到 432 项研究，仅有 6 项研究符合纳入标准，即：临床试验、年龄＞12 岁且为非重症 COVID-19、聚合酶链反应确诊 COVID-19、羟氯喹为常规治疗以外的干预措施。两名作者独立进行数据提取和偏倚风险评估。采用固定效应和随机效应模型，以风险差作为汇总测量指标进行数据合并。主要结局为临床和影像学 COVID-19 进展、咽拭子中 SARS-CoV-2 清除和死亡率。次要结局为羟氯喹的不良反应。对纳入的 6 项研究中 609 例 COVID-19 确诊患者进行汇总分析，其中 294 例患者接受羟氯喹治疗，315 例患者作为对照。与对照组相比，羟氯喹治疗可显著降低早期影像学进展的风险，风险差及 95%置信区间为-0.2（-0.36 至-0.03）。另一方面，羟氯喹并不能预防临床 COVID-19 进展、降低 5 日死亡率或增加第 5、6、7 日的病毒清除率。此外，羟氯喹治疗还出现了许多不良反应。在非重症 COVID-19 患者中，羟氯喹未能显示出病毒清除或临床获益，且不良反应较多，因此羟氯喹的保护作用可能被夸大。羟氯喹在 COVID-19 中的使用应权衡利弊。
