干扰素抗新型冠状病毒感染的作用及临床研究进展
Research progress in antiviral effects of interferons against COVID-19 and clinical studies
吴桂娟 1张鹏 2李传海 3张记1
作者信息
- 1. 陆军军医大学基础医学院免疫学教研室(暨全军免疫学研究所),重庆 400038
- 2. 山东省第二人民医院呼吸与危重症医学科,济南 250117
- 3. 中国人民解放军联勤保障部队第九六○医院胸外科,济南 250031
- 折叠
摘要
新型冠状病毒(2019 novel coronavirus,2019-nCoV)引起新型冠状病毒感染(Coronavirus Disease 2019,COVID-19).Ⅰ 型和 Ⅲ 型干扰素(interferon,IFN)作为重要广谱抗病毒药物,是潜在的用于COVID-19治疗和预防的药物.2020年初,陆续启动了包括世界卫生组织SOLIDARITY研究在内的40余项临床试验,探索IFN治疗COVID-19的临床效力及使用方法.同时,多个实验室利用动物模型和临床标本,从免疫机理层面探究了 IFN在COVID-19中的作用和功能.然而,虽然过去3年积累了众多数据,但其结论并不一致甚至相反,这反应了 IFN在COVID-19中作用和功能的复杂性.最近,4项高质量的大型随机对照Ⅲ期临床试验发表了结果.本文从免疫病理和临床试验两个层面,系统总结并分析了这些复杂而矛盾的数据,阐明了人类感染2019-nCoV以后不同的临床结局与IFN水平及其产生时间密切相关,IFN在COVID-19早期具有免疫保护作用,而在晚期具有加重炎症的免疫损伤作用.IFN在COVID-19中的精准作用和临床使用,需要进一步开展严格控制混杂因素的高质量前瞻性临床试验研究.
Abstract
Coronavirus Disease 2019(COVID-19)is caused by 2019 novel coronavirus(2019-nCoV).Type Ⅰ and type Ⅲ interferons,as important available clinically used broad-spectrum antiviral drugs,have been considered as promising candidate drugs for the treatment and prevention of COVID-19.In early 2020,more than 40 clinical trials,including the World Health Organization(WHO)SOLIDARITY study,have been launched in the world to explore the clinical efficacy and application method of interferons in the treatment of COVID-19.Meanwhile,animal models and human clinical specimens were used in many laboratories to explore the immunologic role and mechanistic function of interferons in COVID-19.However,the conclusion of the studies in the past three years were not consistent and even contradictory albeit numerous data were accumulated by the scientific community,which reflects the complexity of the role and function of interferons in COVID-19.Recently,the results of four large high-quality randomized controlled phase Ⅲ clinical trials were reported.In this review,we systematically summarize and analyze the complicated and contradictory data from the level of immunopathological mechanism and clinical trials.We clarify that the heterogeneous clinical outcome of 2019-nCoV infection is closely related to the level and production time of interferons and that interferons are protective in the early stage of COVID-19 but may cause immunological damages in the late stage which may exacerbate inflammation.Further high-quality prospective clinical trials that strictly control confounding factors are still warranted to finally elucidate the precise role and clinical application of interferons in COVID-19.
关键词
新型冠状病毒感染/新型冠状病毒/Ⅰ型干扰素/Ⅲ型干扰素Key words
COVID-19/2019-nCoV/Type Ⅰ interferon/Type Ⅲ interferon引用本文复制引用
基金项目
陆军军医大学红医人才支持经费()
国家自然科学基金(32270987)
国家自然科学基金(31900672)
山东省中医药科技项目(2020M215)
出版年
2024
NETL
NSTL
万方数据