University of Connecticut Health Outcomes, Policy, and Evidence Synthesis Group and Hartford Hospital Department of Research Administration, Hartford, and School of Pharmacy, Storrs, Connecticut, and Vicerrectorado de Investigación, Universidad San Ignacio de Loyola, Lima, Peru (A.V.H.).
University of Connecticut Health Outcomes, Policy, and Evidence Synthesis Group and Hartford Hospital Department of Research Administration, Hartford, Connecticut (Y.M.R.).
Ann Intern Med. 2020 Aug 18;173(4):287-296. doi: 10.7326/M20-2496. Epub 2020 May 27.
Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19).
PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020.
Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection.
Independent, dually performed data extraction and quality assessments.
Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate, 500 mg once or twice daily, with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine.
There were few controlled studies, and control for confounding was inadequate in observational studies.
Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting.
Agency for Healthcare Research and Quality.
羟氯喹和氯喹在体外对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）具有抗病毒作用。
总结羟氯喹或氯喹治疗或预防 2019 年冠状病毒病（COVID-19）的益处和危害的证据。
PubMed（通过 MEDLINE）、EMBASE（通过 Ovid）、Scopus、Web of Science、Cochrane 图书馆、bioRxiv、预印本、ClinicalTrials.gov、世界卫生组织国际临床试验注册平台和中国临床试验注册中心，时间为 2019 年 12 月 1 日至 2020 年 5 月 8 日。
在任何语言中报告在疑似 COVID-19 或有 SARS-CoV-2 感染风险的成人或儿童中使用羟氯喹或氯喹的疗效或安全性结局的研究，无论其研究场所如何。
独立的、双人执行的数据提取和质量评估。
四项随机对照试验、十项队列研究和九项病例系列评估了药物的治疗效果，但没有研究评估预防效果。羟氯喹对全因死亡率、向严重疾病进展、临床症状以及抗原检测的上呼吸道病毒学清除率等结局的影响证据相互矛盾且不充分。一些研究发现接受羟氯喹治疗的患者出现 QTc 间期 500 ms 或更长，但在这些研究中，出现这种情况的患者比例不同。两项研究评估了氯喹的疗效；一项试验比较了高剂量（600 mg 每日两次，共 10 天）与低剂量（第 1 天 450 mg 每日两次，第 4 天每日一次）治疗，由于担心高剂量治疗会增加死亡率和 QTc 间期延长，该试验停止。一项比较接受磷酸氯喹 500 mg 每日一次或两次治疗的 COVID-19 成人与未接受氯喹治疗的患者的观察性研究发现，氯喹可轻微缓解发热并促进病毒学清除。
对照研究较少，观察性研究中混杂因素的对照不足。
关于使用羟氯喹或氯喹治疗 COVID-19 的益处和危害的证据非常薄弱且相互矛盾。
医疗保健研究和质量局。
