Supplementary Material for: Seroprevalence of Enterovirus D68 infection among humans: A systematic review and meta-analysis

Introduction : Human enterovirus D68 (EV-D68), which belongs to enteroviruses of the small RNA family, is a type of enterovirus that can cause acute respiratory tract infection and central nervous system diseases. This study systematically analysed and summarized EV-D68 antibody studies in databases and identified the seropositivity rates of different regions, ages, and sexes. Methods: Meta-analysis was performed using STATA 16.0 software. I2 and Q tests were used to analyse the heterogeneity of the included studies. Meta-regression analysis was performed for different groups, and Egger's linear regression analysis was used to evaluate publication bias. Results: The results of multiple studies indicated that the serological prevalence range of EV-D68 antibody was 17.78%-96.69%. The results of the meta-analysis showed that the seropositivity rate of EV-D68 antibody was 76% (95% CI: 67%-84%), among which that of the Chinese population was 74% (95% CI: 61%-86%) and that of other countries was 79% (95% CI: 65%-91%). At the same time, a subgroup analysis was conducted. The seroprevalence of EV-D68 antibody was related to age but not sex or region. Conclusion: The seropositivity rate was lower in the below 5 years age group; however, it gradually increased with age. The results of this study showed that EV-D68 infection was widespread in the population, and the current clinical infection situation could not reflect the actual epidemic situation of the virus, among which children under 5 years old were vulnerable to infection, which should be given greater attention for epidemic prevention and control.

引言：人类肠道病毒D68（EV-D68）隶属于小RNA病毒科肠道病毒属，是一类可引发急性呼吸道感染及中枢神经系统疾病的肠道病毒。本研究对数据库中EV-D68抗体相关研究进行系统梳理与总结，明确了不同地域、年龄及性别群体的血清阳性率。
方法：本研究采用STATA 16.0软件开展Meta分析（Meta-analysis），通过I2检验与Q检验分析纳入研究的异质性；针对不同亚组实施Meta回归分析（Meta-regression analysis），并采用Egger线性回归分析（Egger's linear regression analysis）评估发表偏倚（publication bias）。
结果：多项研究结果显示，EV-D68抗体的血清流行率（serological prevalence）区间为17.78%~96.69%。本次Meta分析结果表明，EV-D68抗体总血清阳性率（seropositivity rate）为76%（95%置信区间：67%~84%），其中中国人群阳性率为74%（95%置信区间：61%~86%），其他国家人群为79%（95%置信区间：65%~91%）。本研究同时开展了亚组分析（subgroup analysis），结果提示EV-D68抗体血清流行率与年龄相关，而与性别及地域无显著关联。
结论：5岁以下年龄组的血清阳性率相对较低，随后随年龄增长逐渐升高。本研究结果证实，EV-D68感染在人群中广泛流行，当前临床确诊感染情况无法反映该病毒的真实流行态势，其中5岁以下儿童为易感人群，应在疫情防控中予以重点关注。