Background. The pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in an unprecedented public health challenge worldwide. Despite urgent and extensive global efforts, the existing evidence is inconclusive regarding the medications used for the treatment of COVID-19. Purpose. To generate an up-to-date evidence for the clinical safety and efficacy of hydroxychloroquine (HCQ) with or without azithromycin (AZ) among patients treated for COVID-19. Data Source. PubMed, Cochrane CENTRAL, LITCOVID, Web of Science, SCOPUS, BioRxiv, Embase, MedRxiv, and Wiley online library were searched from 2019/12/30 to 2020/05/23. Study Selection. Three investigators assessed the quality of the studies. Data Extraction. Data about study characteristics, effect estimates, and the quality of the studies were extracted by two independent reviewers and cross-checked by the third reviewer. Data Synthesis. The data of 6,782 (HCQ group, 3623; HCQ + AZ group, 1,020; control group, 2139) participants were included. HCQ was compared with standard care for virologic efficacy, disease progression, mortality, and adverse effects. HCQ was also compared with HCQ + AZ for QTc prolongation, admission to the intensive care unit, and mortality. The study found HCQ did not alter the rate of virologic cure (OR = 0.78; 95% CI: 0.39–1.56) and the risk of mortality (OR = 1.26; 95% CI: 0.66–2.39). The pooled prevalence for mortality was 5.8% (95% CI: 0.9%–10.8%). Moreover, HCQ did not impact disease progression (OR = 0.9; 95% CI: 0.36–2.29) but resulted in a higher risk of adverse effects (OR = 2.35; 95% CI: 1.15–4.8). HCQ was also compared against HCQ + AZ, and no difference was observed in QTc prolongation above 500 ms (OR = 1.11; 95% CI: 0.54–2.28), admission to the intensive care unit (OR = 0.92; 95% CI: 0.52–1.63), and mortality (OR = 0.88; 95% CI: 0.55–1.43). However, in the analysis of single-arm studies, about 11.2% (95% CI: 7.0%–15.5%) of patients have developed an absolute increase of QTc greater than 500 ms, and 4.1% (95% CI: 1.1%–7.1%) of patients discontinued their medication. Conclusion. This meta-analysis and systematic review, which included a limited number of poorly designed studies of patients with COVID-19, revealed HCQ is intolerable, unsafe, and not efficacious. Similarly, HCQ + AZ combination was not different from HCQ alone in curbing mortality and ICU admission.

中文翻译：

---

羟氯喹治疗 COVID-19 患者的结果：系统评价和荟萃分析

背景。由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 引起的 2019 年冠状病毒病 (COVID-19) 大流行给全球带来了前所未有的公共卫生挑战。尽管全球做出了紧急而广泛的努力，但关于用于治疗 COVID-19 的药物的现有证据尚无定论。目的。生成最新证据，证明羟氯喹 (HCQ) 联合或不联合阿奇霉素 (AZ) 在接受 COVID-19 治疗的患者中的临床安全性和有效性。数据源。检索时间为 2019 年 12 月 30 日至 2020 年 5 月 23 日。研究选择。三名研究人员评估了研究的质量。数据提取。有关研究特征、效果估计和研究质量的数据由两名独立评审员提取，并由第三名评审员交叉检查。数据综合。纳入 6,782 名参与者（HCQ 组，3623 名；HCQ + AZ 组，1,020 名；对照组，2139 名）参与者的数据。将 HCQ 与标准治疗的病毒学疗效、疾病进展、死亡率和不良反应进行比较。还比较了 HCQ 与 HCQ + AZ 的 QTc 延长、入住重症监护室和死亡率。研究发现，HCQ 不会改变病毒学治愈率（OR = 0.78；95% CI：0.39–1.56）和死亡风险（OR = 1.26；95% CI：0.66–2.39）。死亡率的汇总患病率为 5.8%（95% CI：0.9%–10.8%）。此外，HCQ 不会影响疾病进展（OR = 0.9；95% CI：0.36–2.29），但会导致不良反应的风险较高（OR = 2.35；95% CI：1.15–4.8）。HCQ 与 HCQ + AZ 进行了比较，在 QTc 延长超过 500 ms（OR = 1.11；95% CI：0.54–2.28）、入住重症监护室（OR = 0.92；95% CI：0.52）方面没有观察到差异。 –1.63）和死亡率（OR = 0.88；95% CI：0.55–1.43）。然而，在单组研究分析中，约 11.2%（95% CI：7.0%–15.5%）的患者 QTc 绝对增加超过 500 ms，4.1%（95% CI：1.1%– 7.1%）的患者停止服药。结论。这项荟萃分析和系统评价包括针对 COVID-19 患者进行的数量有限、设计不当的研究，结果表明 HCQ 无法耐受、不安全且无效。同样，HCQ + AZ 组合在控制死亡率和 ICU 入院方面与单独使用 HCQ 没有什么不同。