Hernandez Adrian V, Ingemi John, Sherman Michael, Pasupuleti Vinay, Barboza Joshuan J, Piscoya Alejandro, Roman Yuani M, White C Michael
Department of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, CT, USA.
Unidad de Revisiones Sistemáticas y Meta-análisis (URSIGET), Vicerrectorado de Investigación, Universidad San Ignacio de Loyola (USIL), Lima, Peru.
Arch Med Sci. 2021 Oct 24;18(4):939-948. doi: 10.5114/aoms/143147. eCollection 2022.
No early treatment intervention for COVID-19 has proven effective to date. We systematically reviewed the efficacy of hydroxychloroquine as early treatment for COVID-19.
Randomized controlled trials (RCTs) evaluating hydroxychloroquine for early treatment of COVID-19 were searched in five engines and preprint websites until September 14, 2021. Primary outcomes were hospitalization and all-cause mortality. Secondary outcomes included COVID-19 symptom resolution, viral clearance, and adverse events. Inverse variance random-effects meta-analyses were performed and quality of evidence (QoE) per outcome was assessed with GRADE methods.
Five RCTs ( = 1848) were included. The comparator was placebo in four RCTs and usual care in one RCT. The RCTs used hydroxychloroquine total doses between 1,600 and 4,400 mg and had follow-up times between 14 and 90 days. Compared to the controls, early treatment with hydroxychloroquine did not reduce hospitalizations (RR = 0.80, 95% CI: 0.47-1.36, = 2%, 5 RCTs, low QoE), all-cause mortality (RR = 0.77, 95% CI: 0.16-3.68, = 0%, 5 RCTs, very low QoE), symptom resolution (RR = 0.94, 95% CI: 0.77-1.16, = 71%, 3 RCTs, low QoE) or viral clearance at 14 days (RR = 1.02, 95% CI: 0.82-1.27, = 65%, 2 RCTs, low QoE). There was a larger non-significant increase of adverse events with hydroxychloroquine vs. controls (RR = 2.17, 95% CI: 0.86-5.45, = 92%, 5 RCTs, very low QoE).
Hydroxychloroquine was not efficacious as early treatment for COVID-19 infections in RCTs with low to very low quality of evidence for all outcomes. More RCTs are needed to elucidate the efficacy of hydroxychloroquine as early treatment intervention.
迄今为止，尚无针对2019冠状病毒病（COVID-19）的早期治疗干预措施被证明有效。我们系统回顾了羟氯喹作为COVID-19早期治疗的疗效。
在五个搜索引擎和预印本网站上检索评估羟氯喹用于COVID-19早期治疗的随机对照试验（RCT），检索截至2021年9月14日。主要结局为住院治疗和全因死亡率。次要结局包括COVID-19症状缓解、病毒清除及不良事件。采用逆方差随机效应荟萃分析，并使用GRADE方法评估每个结局的证据质量（QoE）。
纳入了5项RCT（n = 1848）。在4项RCT中对照为安慰剂，在1项RCT中对照为常规治疗。这些RCT使用的羟氯喹总剂量在1600至4400毫克之间，随访时间在14至90天之间。与对照组相比，羟氯喹早期治疗并未降低住院率（RR = 0.80，95%CI：0.47 - 1.36，I² = 2%，5项RCT，低QoE）、全因死亡率（RR = 0.77，95%CI：0.16 - 3.68，I² = 0%，5项RCT，极低QoE）、症状缓解（RR = 0.94，95%CI：0.77 - 1.16，I² = 71%，3项RCT，低QoE）或14天时的病毒清除率（RR = 1.02，95%CI：0.82 - 1.27，I² = 65%，2项RCT，低QoE）。与对照组相比，羟氯喹导致不良事件有更大的非显著性增加（RR = 2.17，95%CI：0.86 - 5.45，I² = 92%，5项RCT，极低QoE）。
在所有结局证据质量低至极低的RCT中，羟氯喹作为COVID-19感染的早期治疗无效。需要更多RCT来阐明羟氯喹作为早期治疗干预措施的疗效。
