新冠感染次数和免疫对病毒变异的影响研究  

Influence of infection frequency and vaccination on virus mutation of SARS-CoV-2

作　　者：许果 樊欢[2] 付建光[2] 余慧燕[2] 邓斐[2] 董竹涵 张诗晗 朱凤才[4] 鲍倡俊[2] 朱立国 Xu Guo;Fan Huan;Fu Jianguang;Yu Huiyan;Deng Fei;Dong Zhuhan;Zhang Shihan;Zhu Fengcai;Bao Changjun;Zhu Liguo(School of Public Health,Nanjing Medical University,Nanjing 211166,China;Department of Acute Infectious Disease Control and Prevention,Jiangsu Provincial Center for Disease Control and Prevention,Nanjing 210009,China;School of Public Health,Southeast University,Nanjing 210009,China;National Health Commission Key Laboratory of Enteric Pathogenic Microbiology,Jiangsu Provincial Center for Disease Control and Prevention,Nanjing 210009,China;Medical Key Laboratory of Pathogenic Microbiology in Emerging Major Infectious Diseases,Jiangsu Provincial Center for Disease Control and Prevention,Nanjing 210009,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急性传染病防制所,南京210009 [3]东南大学公共卫生学院,南京210009 [4]江苏省疾病预防控制中心国家卫生健康委员会肠道病原微生物重点实验室,南京210009 [5]江苏省疾病预防控制中心新发突发重大传染病病原微生物重点实验室,南京210009

出　　处：《中华实验和临床病毒学杂志》2024年第5期481-488,共8页Chinese Journal of Experimental and Clinical Virology

基　　金：江苏省社会发展项目(BE2021739,BE2023601);江苏省第六期"333工程"重点行业领域人才项目;江苏省卫生健康委科研课题(DX202301);国家重点研发计划(2023YFC2309100)。

摘　　要：目的分析新冠病毒感染和疫苗接种在病毒变异中的影响。方法选取了江苏省2023年2659份本土新型冠状病毒标本的全基因组测序序列进行了分析,并收集人口学和临床特征等相关信息,利用单因素和多因素线性回归模型分析探讨感染及疫苗接种对病毒全基因组变异速率和S基因选择压力的影响。结果这些感染者的平均年龄为55.0(31.0,74.0)岁,60岁及以上年龄组1150例(43.2%),男性1367例(51.4%),有新冠疫苗接种史者2044例(76.9%),初次感染新冠者1629例(61.3%);感染者临床症状以轻型为主,共2434例(91.5%),重型及以上症状者29例(1.1%)。SARS-CoV-2全基因组的平均替换速率为9.69(9.38,9.98)×10-4subs/site/year,S基因的dN/dS值为6.08(5.56,8.66),显著大于1(P<0.001),表明受到了正选择作用。单因素和多因素线性回归模型分析结果显示,具有疫苗接种史且再次感染、年龄20~30岁、60岁及以上者的SARS-CoV-2替换速率更高,男性、临床症状为中型、重型及以上者的SARS-CoV-2替换速率更低;具有疫苗接种史且再次感染、50~60岁、60岁及以上者的S基因dN/dS更小。结论在新冠疫苗接种及感染施加的免疫压力下,新冠病毒全基因组变异加快,但S基因的非同义突变率减弱,引起这些现象的机制需进一步深入研究。ObjectiveTo analyze the effects of SARS-CoV-2 infection and vaccination on virus mutation.MethodsThe whole genome sequencing sequences of 2659 local SARS-CoV-2 specimens from Jiangsu Province in 2023 were selected for analysis,and relevant information such as demographic and clinical characteristics were collected,and the effects of infection and vaccination on the genome-wide mutation rate and S gene′s selective pressure of the virus were analyzed by univariate and multivariate linear regression models.ResultsThe average age of these infected patients was 55.0(31.0,74.0)years,1150 cases(43.2%)in the age group of≥60 years,1367 cases(51.4%)were males,2044 cases(76.9%)had a history of COVID-19 vaccination,and 1629 cases(61.3%)had the first-time infection.The clinical symptoms of the infected patients were mainly mild,with a total of 2434 cases(91.5%),and 29 cases(1.1%)with severe symptoms or more.The average substitution rate of SARS-CoV-2 was 9.69(9.38,9.98)×10-4 subs/site/year,and the dN/dS value of the S gene was 6.08(5.56,8.66),which was significantly greater than that of 1(P<0.001),indicating positive selection.The result of univariate and multivariate linear regression model analysis showed that the SARS-CoV-2 substitution rate was higher in those with vaccination history and reinfection,aged 20-30 years,≥60 years,and the SARS-CoV-2 substitution rate was lower in males with moderate clinical symptoms and severe disease and above.Those with a history of vaccination and reinfection,aged 50-60 years old,≥60 years old have smaller S gene dN/dS.ConclusionsUnder the immune pressure exerted by vaccination and infection,the genome-wide mutation of SARS-COV-2 accelerated,but the non-synonymous mutation rate of the S gene decreased.The mechanism causing these phenomena needs further study.

关 键 词：SARS-CoV-2 S基因 变异特征 替换速率 选择压力 

分 类 号：R511[医药卫生—内科学]