利巴韦林治疗冠状病毒肺炎有效性与安全性的系统评价

Systematic Review of Efficacy and Safety of Ribavirin in the Treatment of Pneumonia Caused by Coronavirus

目的:探讨利巴韦林治疗冠状病毒感染性疾病的有效性及安全性,为新型冠状病毒肺炎(COVID-19)的诊疗提供决策支持。方法:计算机检索PubMed、Embase以及Cochrane Library中评估利巴韦林治疗冠状病毒肺炎有效性及安全性的英文文献,并将符合纳入排除标准的文献进行系统综述,检索截止日期至2020年2月1日。结果:3个数据库共检索到861篇文献,通过文题/摘要和全文筛选后得到38篇符合纳入标准的文献。所纳入文献中有19篇的研究对象为中东呼吸综合征冠状病毒(MERS-CoV), 19篇的研究对象为严重急性呼吸综合征冠状病毒(SARS-CoV)。利巴韦林多与其他药物如干扰素、糖皮质激素等联合治疗MERS-CoV和SARS-CoV感染,常用日剂量为1.2~4.0 g,约75%的研究的平均或中位治疗疗程为1.0~2.0周,初发症状至利巴韦林给药的时间间期在0~23.0 d之间。各研究中报道的使用利巴韦林的中东呼吸综合征(MERS)患者和严重急性呼吸综合征(SARS)患者病死率分别为22.9%~75.0%和3.4%~55.6%,而未使用组MERS和SARS患者的病死率分别为28.6%~83.3%和6.0%~50.0%,利巴韦林组病死率未显著降低(P>0.05)。4项研究的多因素分析结果也证实利巴韦林并非患者死亡的独立保护因素。在MERS-CoV和SARS-CoV的治疗剂量下,使用利巴韦林常见的不良反应为贫血等。结论:利巴韦林的使用并未显著降低MERS和SARS患者的病死率,在症状发生后及早使用或许会获益,大剂量应用可能会带来更多的不良事件。利巴韦林用于MERS、SARS及COVID-19治疗的有效性和安全性还需要更多设计良好的临床研究来验证。

Objective:To explore the effectiveness and safety of ribavirin in the treatment of coronavirus,and provide decision support for the management of Corona Virus Disease 2019(COVID-19).Methods:PubMed,Embase,and Cochrane Library were searched for the literature on the effectiveness and safety of ribavirin for coronavirus,and reviewed the literature that met the inclusion criteria systematically.Results:A total of 861 articles were retrieved from the databases,and 38 articles meeting the inclusion criteria were included after the title/abstract and full-text screening.Nineteen of the included articles were for Middle East respiratory syndrome coronavirus(MERS-CoV),and 19 were for severe acute respiratory syndrome coronavirus(SARS-CoV).Ribavirin were often combined with other drugs such as interferon and glucocorticoid to treat MERS-CoV and SARS-CoV infections,the usual daily dose was 1.2-4.0 g,the course of treatment was generally 1 to 2 weeks,and the time interval between initial symptoms and ribavirin administration was 0 to 23 days.The case fatality rates of MERS and SARS using ribavirin were 22.9%-75.0%and 3.4%-55.6%,respectively,which were not significantly reduced compared with the overall patient population.Multivariate analysis also showed that ribavirin was not an independent risk factor for death.In the dosage of MERS-CoV and SARS-CoV treatment,the common adverse reaction was anemia.Conclusion:Ribavirin did not significantly reduce the case fatality of MERS and SARS,and early use after the onset of symptoms might benefit,while application the high-dose may bring more adverse events.The efficacy and safety of ribavirin in the treatment of MERS,SARS,and COVID-19 needs to be validated by more well-designed clinical studies.