新冠病毒感染者病毒RNA脱落时间的影响因素研究  

Influencing factors of viral RNA shedding time in patients with SARS-CoV-2 infection

作　　者：邹鑫 许可[2] 戴启刚[2] 付建光[2] 丁松宁[3] 王寅 王慎骄[2] 黄昊頔 胡建利[2] 周扬[2] 霍翔[2] 尚庆香 鲍倡俊 Zou Xin;Xu Ke;Dai Qigang;Fu Jianguang;Ding Songning;Wang Yin;Wang Shenjiao;Huang Haodi;Hu Jianli;Zhou Yang;Huo Xiang;Shang Qingxiang;Bao Changjun(School of Public Health,Nanjing Medical University,Nanjing 211166,China;Jiangsu Provincial Center for Disease Control and Prevention,Nanjing 210009,China;Nanjing Center for Disease Control and Prevention,Nanjing 210003,China;Yangzhou Center for Disease Control and Prevention,Yangzhou 225007,China)

机构地区：[1]南京医科大学公共卫生学院,南京211166 [2]江苏省疾病预防控制中心,南京210009 [3]南京市疾病预防控制中心,南京210003 [4]扬州市疾病预防控制中心,扬州225007

出　　处：《中华实验和临床病毒学杂志》2023年第3期296-302,共7页Chinese Journal of Experimental and Clinical Virology

基　　金：江苏省卫生健康委重点项目(ZD2021037);江苏省卫生健康委面上项目(M2020026)。

摘　　要：目的了解新冠病毒感染者病毒RNA脱落时间与病毒单核苷酸突变和感染者人口、基础疾病等因素的关系,为新冠病毒感染动力学的研究提供更多线索。方法收集江苏省2021年7月至9月暴发的一起新冠肺炎聚集性疫情感染者流行病学、临床表现、基础疾病等资料,采集病例鼻咽拭子样本,采用二代测序技术对样本进行病毒全基因组测序。利用在线分析平台判断病毒型别、分析突变位点,利用Cox比例风险模型分析新冠病毒RNA脱落时间与各研究因素的关系。结果本起新冠疫情最终获得病毒全基因组序列的人员350例,其中女性占60.3%,年龄中位数49岁[四分位数间距(IQR,37~65岁)],中位病毒RNA脱落时间33天(IQR,26~44天)。全基因组测序分析显示,同武汉参考株序列相比,感染者序列存在34~41个核苷酸突变位点,属于VOC/Delta变异株(B.1.617.2进化分支),C346T、C1060T、T2803C、T7513C、A29681C为本起疫情350例病例新冠病毒基因组序列主要单核苷酸变异位点(SNP)。单因素Cox回归分析显示,年龄、基础疾病、临床分型、疫苗接种情况、SNP T2803C和T7513C对新冠病毒RNA的脱落时间存在影响;调整后的多因素Cox回归结果显示,年龄[HR=0.73,95%CI(0.55,0.95)]及T7513C[HR=0.37,95%CI(0.18,0.77)]仍然是新冠病毒RNA脱落时间延长的危险因素。结论本研究从病例个体因素和病毒单核苷酸变异两个角度分析了对病毒RNA脱落时间的影响,发现年长、患有高血压、较重临床症状、未接种或未全程接种疫苗,感染病毒存在T7513C突变者,存在新冠病毒RNA脱落时间较长的风险,应给予重点关注和康复后随访。Objective To understand the relationship between the RNA shedding time of SARS-CoV-2 infected persons and the single nucleotide mutation of the virus,the population of infected persons,underlying diseases and other factors,so as to provide more clues for the study of SARS-CoV-2 infection dynamics.Methods The data of epidemiology,clinical manifestations,and underlying diseases of infected persons in a cluster epidemic of COVID-19 in Jiangsu province from July to September 2021 were collected.Nasopharyngeal swab samples of cases were collected,and the whole genome of the virus was sequenced by second-generation sequencing technology.The online analysis platform was used to judge the virus type and analyze the mutation site,and Cox proportional risk model was used to analyze the relationship between the RNA shedding time of SARS-CoV-2 and various research factors.Results There were 350 persons who finally obtained the whole genome sequence of the virus in this COVID-19 outbreak,of which 60.3%were female,the median age was 49 years old(interquartile range,IQR:37-65 years old)),and the median time of virus shedding was 33 days(IQR,26-44 days).The whole-genome sequencing analysis showed that compared with the Wuhan reference strain sequence,the infected persons’sequence had 34~41 nucleotide mutation sites,belonging to VOC/Delta variant(B.1.617.2 evolutionary branch),and C346T,C1060T,T2803C,T7513C,A29681C were the main single nucleotide polymorphisms(SNPs)of this epidemic.Cox regression analysis showed that age,underlying disease,clinical classification,vaccination,SNP T2803C and T7513C had an impact on the RNA shedding time of SARS-CoV-2.The adjusted multivariate Cox regression result showed that age[HR=0.73,95%CI(0.55,0.95)]and T7513C[HR=0.37,95%CI(0.18,0.77)]were still the risk factors for the extension of SARS-CoV-2 RNA shedding time.Conclusions This study analyzed the effects of the individual factors and viral single nucleotide variations on the time of viral RNA shedding.Those who were older,suffered from hyper

关 键 词：新型冠状病毒 病毒RNA脱落时间 危险因素 突变 

分 类 号：R373[医药卫生—病原生物学]