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
许果 1樊欢 2付建光 2余慧燕 2邓斐 2董竹涵 1张诗晗 3朱凤才 4鲍倡俊 2朱立国5
作者信息
- 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. 南京医科大学公共卫生学院,南京 211166;江苏省疾病预防控制中心急性传染病防制所,南京 210009;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
- 折叠
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2 659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1 150例(43.2％),男性1 367例(51.4％),有新冠疫苗接种史者2 044例(76.9％),初次感染新冠者1 629例(61.3％);感染者临床症状以轻型为主,共2 434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)×10-4 subs/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.
Abstract
Objective To analyze the effects of SARS-CoV-2 infection and vaccination on virus mutation.Methods The whole genome sequencing sequences of 2 659 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.Results The average age of these infected patients was 55.0(31.0,74.0)years,1 150 cases(43.2％)in the age group of ≥60 years,1 367 cases(51.4％)were males,2 044 cases(76.9％)had a history of COVID-19 vaccination,and 1 629 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.Conclusions Under 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Key words
SARS-CoV-2/S gene/Variation characteristics/Substitution rate/Selective pressure引用本文复制引用
基金项目
江苏省社会发展项目(BE2021739)
江苏省社会发展项目(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)
出版年
2024
NETL
NSTL
万方数据