阿比多尔治疗新型冠状病毒肺炎的有效性和安全性——基于目前与既往抗病毒治疗的系统评价

Efficacy and safety of arbidol in the treatment of novel coronavirus pneumonia:a systematic review based on current and previous antiviral therapy

目的系统评价阿比多尔治疗新型冠状病毒肺炎(COVID-19)的有效性和安全性。方法检索国内外有关数据库及健康科学论文预印本杂志网络平台(medRxiv)截至2020年4月25日收录的文献,收集阿比多尔治疗COVID-19、流行性感冒(流感)或其他呼吸道病毒感染有效性和安全性的随机对照试验(RCT)、队列研究和病例-对照研究,分别以Cochrane协作网偏倚风险评估工具和纽卡斯尔-渥太华量表(NOS)对文献进行质量评价,采用RevMan 5.3软件对相关结局指标进行meta分析或描述性分析。结果共15篇文献(7篇队列研究均为高质量研究,8篇RCT中6篇为“低偏倚风险”,2篇为“中偏倚风险”)纳入本研究。阿比多尔治疗COVID-19的8篇文献(5项回顾性队列研究、2项前瞻性队列研究和1项RCT)涉及809例COVID-19患者,其中阿比多尔组479例,对照组330例;阿比多尔治疗流感或其他呼吸道病毒感染的7篇RCT涉及1471例患者,其中阿比多尔组745例,对照组726例。阿比多尔组均采用阿比多尔治疗(0.15~1.2 g/d,疗程5~21 d),对照组采用其他抗病毒药物或未使用抗病毒药物。阿比多尔治疗COVID-19有效性和安全性的meta分析结果显示,阿比多尔组新型冠状病毒(2019-nCoV)核酸转阴率高于对照组,差异有统计学意义[71.7%(109/152)比58.8%(94/160),相对危险度(RR)=1.30,95%置信区间(CI):1.01~1.67,P=0.04];2019-nCoV核酸转阴时间与对照组差异无统计学意义(标准化均数差=-0.17,95%CI:-0.72~0.38,P=0.55);治疗第7天阿比多尔组与对照组胸部CT成像改善率的差异无统计学意义[46.2%(30/65)比50.7%(36/71),RR=0.88,95%CI:0.39~1.98,P=0.76];阿比多尔组与对照组不良反应发生率的差异无统计学意义[16.9%(39/231)比19.2%(47/245),风险差异=-0.03,95%CI:-0.10~0.04,P=0.44]。阿比多尔用于治疗流感或及其他呼吸道病毒感染安全性的meta分析结果显示,阿比多尔组不良反应发生率低于对照组,差异有统计学意义[5.9%(44/745)比11.3%(82/726),RR=0.52,95%CI:0.37~0.74,P<0.01]。结论阿比多尔可有效提高2019-nCoV核酸转阴率,治疗COVID-19具有安全性。

Objective To systematically evaluate the efficacy and safety of arbidol in the treatment of novel coronavirus pneumonia(COVID-19).Methods Randomized controlled trials(RCTs),cohort studies,and case-control studies on the efficacy and safety of arbidol for COVID-19,influenza,and other respiratory virus infections were collected by searching related database at home and abroad and network platform for preprint of Health Science Papers(medRxiv)(up to April 25,2020).Quality of the enrolled studies was evaluated by bias risk assessment tool of Cochrane collaboration network and Newcastle-Ottawa Scale(NOS).Meta-analysis and descriptive analysis of relevant outcome indicators were performed using RevMan 5.3 software.Results A total of 15 studies were enrolled in the study,including 7 cohort studies with high-quality and 8 RCTs,6 of which were with low bias risk and the other 2 of which were with medium bias risk.Among these studies,8 were on arbidol treatment for COVID-19,including 5 retrospective cohort studies,2 prospective cohort studies,and 1 RCT,and involving 809 patients(479 patients in the arbidol group and 330 in the control group);7 were RCTs on arbidol treatment for influenza or other respiratory virus infections,involving 1471 patients(745 patients in the arbidol group and 726 in the control group).In these studies,patients were treated with arbidol(0.15-1.2 g daily for 5-21 d)in the arbidol group while with the other antiviral agents or without any antiviral drug in the control group.Meta analysis on the efficacy and safety of arbidol in treatment for COVID-19 showed that the novel coronavirus(2019-nCoV)nucleic acid negative conversion rate in the arbidol group was significantly higher than that in the control group[71.7%(109/152)vs.58.8%(94/160),relative risk(RR)=1.30,95%confidence interval(CI):1.01-1.67,P=0.04];the difference of time taken for 2019-nCoV nucleic acid negative conversion between the 2 groups was not statistically significant(standardized mean difference=-0.17,95%CI:-0.72-0.38,P=0.55);the difference of disease improvement rate shown by chest CT on day 7 after treatment between the 2 groups was not statistically significant[46.2%(30/65)vs.50.7%(36/71),RR=0.88,95%CI:0.39-1.98,P=0.76];and the difference of incidence of adverse reactions between the 2 groups was not statistically significant[16.9%(39/231)vs.19.2%(47/245),risk difference(RD)=-0.03,95%CI:-0.10-0.04,P=0.44].Meta analysis on the safety of arbidol in treatment for influenza and other respiratory virus infections showed that the incidence of adverse reactions in the arbidol group was significantly lower than that in the control group[5.9%(44/745)vs.11.3%(82/726),RR=0.52,95%CI:0.37-0.74,P<0.01].Conclusion Arbidol could effectively increase the 2019-nCoV nucleic acid negative conversion rate and it might be safe to treat COVID-19 using arbidol.