Molecular Epidemiology of Herpangina Children in Tongzhou District, Beijing, China, During 2019-2020

Abstract

Background: The changing pattern of pathogen spectrum causing herpangina in the time of coronavirus disease 2019 (COVID-19) pandemic was unknown. The purpose of this study was to investigate the changes on the molecular epidemiology of herpangina children during 2019-2020 in Tongzhou district, Beijing, China.

Method: From January 2019 to December 2020, children diagnosed with herpangina were recruited by the staff from Tongzhou Center for Disease Control and Prevention (CDC) in Beijing. Viral RNA extraction from pharyngeal swabs was used for enterovirus (EV) detection and the complete VP1 gene was sequenced. The phylogenetic analysis was performed based on all VP1 sequences for EV genotypes.

Result: A total of 1,331 herpangina children were identified during 2019-2020 with 1,121 in 2019 and 210 in 2020, respectively. The predominant epidemic peak of herpangina children was in summer and autumn of 2019, but not observed in 2020. Compared to the number of herpangina children reported in 2019, it decreased sharply in 2020. Among 129 samples tested in 2019, 61 (47.3%) children were detected with EV, while 22.5% (20/89) were positive in 2020. The positive rate for EV increased since June 2019, peaked at August 2019, and decreased continuously until February 2020. No cases were observed from February to July in 2020, and the positive rate of EV rebounded to previous level since August 2020. Four genotypes, including coxsackievirus A6 (CV-A6, 9.3%), CV-A4 (7.8%), CV-A10 (2.3%) and CV-A16 (10.1%), were identified in 2019, and only three genotypes, including CV-A6 (9.0%), CV-A10 (6.7%) and CV-A16 (1.1%), were identified in 2020. The phylogenetic analysis showed that all CV-A6 strains from Tongzhou located in Group C, and the predominant strains mainly located in C2-C4 subgroups during 2016-2018 and changed into C1 subgroup during 2018-2020. CV-A16 strains mainly located in Group B, which consisting of strains widely distributed around the world.

Conclusions: The predominant genotypes gradually shifted from CV-A16, CV-A4 and CV-A6 in 2019 to CV-A6 in 2020 under COVID-19 pandemic. Genotype-based surveillance will provide robust evidence and facilitate the development of public health measures.

Keywords: COVID-19 pandemic; China; children; herpangina; molecular epidemiology.

Figure 1

Molecular epidemiology of herpangina children in Tongzhou during 2019-2020. (A) Monthly reported herpangina children in 2019 and 2020; (B) monthly detection of herpangina in 2019 and 2020; (C) composition of enterovirus types by season 2019-2020; (D) composition of enterovirus types in 2019; (E) composition of enterovirus types in 2020. The 2018-2019 winter includes January and February 2019, 2019-2020 winter includes December 2019, January and February 2020, the 2020-2021 winter includes December 2020. PHER, Public health emergency response.

Figure 2

Phylogenetic tree of CV-A4 based on VP1 gene. Different colors represented different groups, and the red branches represented amplified strains from this study. We used maximum likelihood estimation with 1000 bootstrap replications to construct phylogenetic trees. (A) All CV-A4 strains were divided into eight groups; countries and times of the strains with the highest frequency in each group were listed on the right. (B) Group E of the CV-A4 phylogenetic tree. (C) Nucleotide identities between Tongzhou amplified CV-A4 strains and different groups. Each violin graph showed the nucleotide identities between intragroup of amplified strains and different groups based on VP1. Solid line represents median, while the dashed line represents the quartiles.

Figure 3

Phylogenetic tree of CV-A6 based on VP1 gene. Different colors represented different groups, and the red branches represented amplified strains from this study. We used maximum likelihood estimation with 1000 bootstrap replications to construct phylogenetic trees. (A) All CV-A6 strains were divided into five groups; countries and times of the strains with the highest frequency in each group were listed on the right. (B) Group D of the CV-A6 phylogenetic tree. (C) Nucleotide identities between Tongzhou amplified CV-A6 strains and different groups. Each violin graph showed the nucleotide identities between intragroup of amplified strains and different groups based on VP1. Solid line represents median, while the dashed line represents the quartiles.

Figure 4

Phylogenetic tree of CV-A10 based on VP1 gene. Different colors represented different groups, and the red branches represented amplified strains from this study. We used maximum likelihood estimation with 1000 bootstrap replications to construct phylogenetic trees. (A) All CV-A10 strains were divided into five groups; countries and times of the strains with the highest frequency in each group were listed on the right. (B) Group D of the CV-A10 phylogenetic tree. (C) Nucleotide identities between Tongzhou amplified CV-A10 strains and different groups. Each violin graph showed the nucleotide identities between intragroup of amplified strains and different groups based on VP1. Solid line represents median, while the dashed line represents the quartiles.

Figure 5

Phylogenetic tree of CV-A16 based on VP1 gene. Different colors represented different groups, and the red branches represented amplified strains from this study. We used maximum likelihood estimation with 1000 bootstrap replications to construct phylogenetic trees. (A) All CV-A16 strains were divided into five groups; countries and times of the strains with the highest frequency in each group were listed on the right. (B) Group B of the CV-A16 phylogenetic tree. (C) Nucleotide identities between Tongzhou amplified CV-A16 strains and different groups. Each violin graph showed the nucleotide identities between intragroup of amplified strains and different groups based on VP1. Solid line represents median, while the dashed line represents the quartiles.