呼吸道合胞病毒黏附糖蛋白基因新变异形式的发现及其感染患儿临床特征分析

A new variant of respiratory syncytial virus glycoprotein gene and clinical features of infected children

目的分析北京地区呼吸道合胞病毒(respiratory syncytial virus,RSV)流行特征,监测黏附糖蛋白(G)基因序列变异及感染患儿临床特征。方法收集2023年1月1日—2023年12月31日首都儿科研究所附属儿童医院急性呼吸道感染患儿呼吸道标本,对经呼吸道病原体多重核酸检测确定为RSV阳性的样本,进一步通过PCR方法扩增得到RSV G蛋白基因全长,测序后建立系统发育进化树确定RSV分型及G蛋白序列变异,通过电子病历系统获得临床资料,分析北京地区RSV感染患儿临床特征。结果共收集5489份急性呼吸道感染患儿呼吸道标本,其中男3046例,女2443例,平均年龄4.36岁。核酸检测确定为RSV阳性的589例(10.7%,589/5489),其中男349例,女240例,平均年龄(2.51±2.78)岁,中位年龄0.48岁。2023年3月开始RSV呈现持续流行趋势,存在两个流行高峰,分别为5月(24.6%,122/496)和12月(18.2%,126/693)。2023年7月前以A亚型为优势亚型,8—10月为两个亚型博弈阶段,11月转变为B亚型。通过序列分析发现一种长度为954 bp的RSV B亚型新序列(RSV-B-BA9-954bp),在进化树中独立成一簇。存在新变异的RSV B亚型感染患儿收入重症监护病房(ICU)的比例(44.1%,15/34)高于未变异的RSV B亚型感染患儿(25.2%,31/123)(χ^(2)=4.600,P=0.032),但白细胞计数和C-反应蛋白低于未变异的RSV B亚型感染患儿(P<0.05)。结论2023年北京地区儿童中RSV自3月份开始持续流行,出现两个流行高峰,优势流行亚型由A转换为B,监测到一种新的RSV B亚型G蛋白基因变异(RSV-B-BA9-954bp)。

Objective To analyze the epidemiological features of respiratory syncytial virus(RSV)infection in Beijing,and monitor the sequence variations in RSV glycoprotein(G)gene and clinical features of infected children.Methods Respiratory tract specimens were collected from children with acute respiratory infection in the Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 1,2023 to December 31,2023.RSV-positive specimens screened by multiple nucleic acid testing were subjected to PCR to amplify the full-length RSV G gene.A phylogenetic tree was constructed after gene sequencing to analyze RSV subtypes and trace G gene variants.Clinical data were retrieved from the medical record system to analyze the clinical features of children with RSV infection in Beijing.Results A total of 5489 respiratory specimens were collected from 3046 male patients and 2443 female patients.The average age of the patients was 4.36 years.A total of 589 RSV-positive specimens(10.7%,589/5489)were detected with 349 from male patients and 240 from female patients.The average age of children with RSV infection was(2.51±2.78)years and the median age was 0.48 years.RSV had been circulating among children in Beijing since March 2023 with two epidemic peaks in May(24.6%,122/496)and December(18.2%,126/693).The predominant subtype of RSV in the first half of 2023 was subtype A,but it was replaced by subtype B from November 2023.Phylogenetic analysis revealed a novel G gene of RSV subtype B(RSV-B-BA9-954bp)with a length of 954 bp,which belonged to a new cluster in the phylogenetic tree.The percentage of patients admitted to the Intensive Care Unit(ICU)was higher in children with new variant of RSV subtype B infection than in those with common RSV subtype B infection[44.1%(15/34)vs 25.2%(31/123),χ^(2)=4.600,P=0.032],while the counts of white blood cells and the levels of C-reactive protein were lower in the children with new variant infection(P<0.05).Conclusions RSV has been prevalent among children in Beijing since March 2023 with two epidemic peaks.The predominant A subtype is gradually replaced by to B subtype.A new variant of RSV B G gene(RSV-B-BA9-954bp)is detected among the children.