Circulation patterns and molecular characteristics of respiratory syncytial virus among hospitalized children in Tianjin, China, before and during the COVID-19 pandemic (2017-2022)

Mengzhu Hou; Guangping Liu; Chao Meng; Lili Dong; Yulian Fang; Lu Wang; Ning Wang; Chunquan Cai; Hanjie Wang

doi:10.1016/j.virs.2024.07.004

October 2024

. doi: 10.1016/j.virs.2024.07.004

Citation: Mengzhu Hou, Guangping Liu, Chao Meng, Lili Dong, Yulian Fang, Lu Wang, Ning Wang, Chunquan Cai, Hanjie Wang. Circulation patterns and molecular characteristics of respiratory syncytial virus among hospitalized children in Tianjin, China, before and during the COVID-19 pandemic (2017-2022) .VIROLOGICA SINICA, 2024, 39(5) : 719-726. http://dx.doi.org/10.1016/j.virs.2024.07.004

新冠疫情前后天津地区儿童呼吸道合胞病毒的流行特征及遗传多样性分析

侯梦珠 ^a ,
刘广平 ^b ,
孟超 ^c ,
东丽丽 ^d ,
方玉莲 ^a ,
王露 ^a ,
王宁 ^a ,
蔡春泉 ^a,, ,
王汉杰 ^e,,

cstr: 32224.14.j.virs.2024.07.004

a. 天津市儿科研究所, 天津市儿童医院(天津大学儿童医院), 天津市出生缺陷防治重点实验室;
b. 天津中医药大学研究生院;
c. 天津市第二人民医院检验科;
d. 呼吸科, 天津市儿童医院(天津大学儿童医院);
e. 天津大学生命科学学院, 天津市微纳生物材料与检疗技术工程中心, 天津市生物大分子结构功能与应用重点实验室

通讯作者： 蔡春泉, cqcns6@126.com; 王汉杰, wanghj@tju.edu.cn
收稿日期： 2023-10-25
录用日期： 2024-07-24

摘要

呼吸道合胞病毒（respiratory syncytial virus，RSV）是引起儿童急性下呼吸道感染住院的主要病原体。随着社区及学校重新开放，COVID-19后时代RSV的卷土重来引起密切关注。为了解COVID-19流行前后天津地区合胞病毒的传播模式、优势毒株和基因型变异，我们对2017年7月至2022年6月间天津市住院儿童共19531份鼻咽拭子样本进行评估。采用直接免疫荧光法和PCR筛选RSV阳性样本并进行亚型鉴定，进一步利用Sanger测序分析G基因的第二高变区(HVR2)突变。研究结果显示，16.46% (3,215/19,531)样本呈现RSV阳性，在2020年12月至2021年2月，RSV出现一个流行高峰，平均阳性率达35.77% (519/1,451)。ON1型和BA9型是天津市2017年7月至2022年6月间高频交替感染的主导株，此外，在COVID-19流行期间，新的替换突变如BA9基因型中的N296Y、K221T、N230K、V251A和ON1基因型的L226I也相继出现。临床特征分析显示，RSV-A组和RSV-B组之间没有显著差异。本研究为临床防治提供理论依据，但还需要进一步探究宿主对ON1和BA9不同谱系的免疫反应的调节机制作用。
- 呼吸道合胞病毒
- , 新冠疫情前后
- , 住院儿童
- , 分子流行病学
- , 基因型

Circulation patterns and molecular characteristics of respiratory syncytial virus among hospitalized children in Tianjin, China, before and during the COVID-19 pandemic (2017-2022)

Mengzhu Hou ^a ,
Guangping Liu ^b ,
Chao Meng ^c ,
Lili Dong ^d ,
Yulian Fang ^a ,
Lu Wang ^a ,
Ning Wang ^a ,
Chunquan Cai ^a,, ,
Hanjie Wang ^e,,

a. Tianjin Pediatric Research Institute, Tianjin Children's Hospital (Children's Hospital of Tianjin University), Tianjin Key Laboratory of Birth Defects for Prevention and Treatment, Tianjin, 300134, China;
b. Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China;
c. Department of Medical Laboratory, Tianjin Second People's Hospital, Tianjin, 300192, China;
d. Department of Respiratory, Tianjin Children's Hospital (Children's Hospital of Tianjin University), Tianjin, 300134, China;
e. School of Life Sciences, Tianjin University and Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin, 300072, China

Corresponding author: Chunquan Cai, cqcns6@126.com Hanjie Wang, wanghj@tju.edu.cn
Received Date: 25 October 2023
Accepted Date: 24 July 2024

Abstract

Respiratory syncytial virus (RSV) is the main pathogen that causes hospitalization for acute lower respiratory tract infections (ALRIs) in children. With the reopening of communities and schools, the resurgence of RSV in the COVID-19 post-pandemic era has become a major concern. To understand the circulation patterns and genotype variability of RSV in Tianjin before and during the COVID-19 pandemic, a total of 19,531 nasopharyngeal aspirate samples from hospitalized children in Tianjin from July 2017 to June 2022 were evaluated. Direct immunofluorescence and polymerase chain reaction (PCR) were used for screening RSV-positive samples and subtyping, respectively. Further analysis of mutations in the second hypervariable region (HVR2) of the G gene was performed through Sanger sequencing. Our results showed that 16.46% (3215/19,531) samples were RSV positive and a delayed increase in the RSV infection rates occurred in the winter season from December 2020 to February 2021, with the average RSV-positive rate of 35.77% (519/1451). The ON1, with H258Q and H266L substitutions, and the BA9, with T290I and T312I substitutions, are dominant strains that alternately circulate every 1-2 years in Tianjin, China, from July 2017 to June 2022. In addition, novel substitutions, such as N296Y, K221T, N230K, V251A in the BA9 genotype, and L226I in the ON1 genotype, emerged during the COVID-19 pandemic. Analysis of clinical characteristics indicated no significant differences between RSV-A and RSV-B groups. This study provides a theoretical basis for clinical prevention and treatment. However, further studies are needed to explore the regulatory mechanism of host immune responses to different lineages of ON1 and BA9 in the future.
- Respiratory syncytial viruse (RSV)
- , Child
- , Hospitalized
- , Molecular epidemiology
- , Genotype
- , COVID-19

References
1. Abrego, L. E., Delfraro, A., Franco, D., Castillo, J., Castillo, M., Moreno, B., Lopez-Verges, S., Pascale, J. M., Arbiza, J., 2017. Genetic variability of human respiratory syncytial virus group B in Panama reveals a novel genotype BA14. J. Med. Virol. 89, 1734-1742.
2. Anderson, L. J., Jadhao, S. J., Paden, C. R., Tong, S., 2021. Functional features of the respiratory syncytial virus G protein. Viruses.13, 1214.
3. Arnott, A., Vong, S., Mardy, S., Chu, S., Naughtin, M., Sovann, L., Buecher, C., Beaute, J., Rith, S., Borand, L., et al., 2011. A study of the genetic variability of human respiratory syncytial virus (HRSV) in Cambodia reveals the existence of a new HRSV group B genotype. J. Clin. Microbiol. 49, 3504-3513.
4. Auksornkitti, V., Kamprasert, N., Thongkomplew, S., Suwannakarn, K., Theamboonlers, A., Samransamruajkij, R., Poovorawan, Y., 2014. Molecular characterization of human respiratory syncytial virus, 2010-2011: identification of genotype ON1 and a new subgroup B genotype in Thailand. Arch. Virol. 159, 499-507.
5. Baek, Y. H., Choi, E. H., Song, M. S., Pascua, P. N., Kwon, H. I., Park, S. J., Lee, J. H., Woo, S. I., Ahn, B. H., Han, H. S., et al., 2012. Prevalence and genetic characterization of respiratory syncytial virus (RSV) in hospitalized children in Korea. Arch. Virol.157, 1039-1050.
6. Bashir, U., Nisar, N., Mahmood, N., Alam, M. M., Sadia, H., Zaidi, S. S., 2017. Molecular detection and characterization of respiratory syncytial virus B genotypes circulating in Pakistani children. Infect. Genet. Evol. 47, 125-131.
7. Blanc, A., Delfraro, A., Frabasile, S., Arbiza, J., 2005. Genotypes of respiratory syncytial virus group B identified in Uruguay. Arch. Virol. 150, 603-609.
8. Canedo-Marroquin, G., Acevedo-Acevedo, O., Rey-Jurado, E., Saavedra, J. M., Lay, M. K., Bueno, S. M., Riedel, C. A., Kalergis, A. M., 2017. Modulation of host immunity by human respiratory syncytial virus virulence factors: a synergic inhibition of both innate and adaptive immunity. Front. Cell. Infect. Microbiol.7, 367.
9. Chen, X., Zhu, Y., Wang, W., Li, C., An, S., Lu, G., Jin, R., Xu, B., Zhou, Y., Chen, A., et al., 2021. A multi-center study on molecular epidemiology of human respiratory syncytial virus from children with acute lower respiratory tract infections in the mainland of China between 2015 and 2019. Virol. Sin. 36, 1475-1483.
10. Chiu, S. S., Cowling, B. J., Peiris, J. S. M., Chan, E. L. Y., Wong, W. H. S., Lee, K. P., 2022. Effects of nonpharmaceutical COVID-19 interventions on pediatric hospitalizations for other respiratory virus infections, Hong Kong. Emerg. Infect. Dis. 28, 62-68.
11. Chuang, Y.-C., Lin, K.-P., Wang, L.-A., Yeh, T.-K., Liu, P.-Y., 2023. The impact of the COVID-19 pandemic on respiratory syncytial virus infection: a narrative review. Infect. Drug Resist. 16, 661-675.
12. Collins, P. L., Melero, J. A., 2011. Progress in understanding and controlling respiratory syncytial virus: still crazy after all these years. Virus Res.162, 80-99.
13. Cui, G., Zhu, R., Qian, Y., Deng, J., Zhao, L., Sun, Y., Wang, F., 2013. Genetic variation in attachment glycoprotein genes of human respiratory syncytial virus subgroups A and B in children in recent five consecutive years. PLoS One. 8, e75020.
14. Dapat, I. C., Shobugawa, Y., Sano, Y., Saito, R., Sasaki, A., Suzuki, Y., Kumaki, A., Zaraket, H., Dapat, C., Oguma, T., et al., 2010. New genotypes within respiratory syncytial virus group B genotype BA in Niigata, Japan. J. Clin. Microbiol. 48, 3423-3427.
15. Eshaghi, A., Duvvuri, V. R., Lai, R., Nadarajah, J. T., Li, A., Patel, S. N., Low, D. E., Gubbay, J. B., 2012. Genetic variability of human respiratory syncytial virus A strains circulating in Ontario: a novel genotype with a 72 nucleotide G gene duplication. PLoS One. 7, e32807.
16. Guo, Y.-j., Wang, B.-h., Li, L., Li, Y.-l., Chu, X.-l., Li, W., 2023. Epidemiological and genetic characteristics of respiratory syncytial virus infection in children from Hangzhou after the peak of COVID-19. J. Clin. Virol. 158, 105354.
17. Jia, R., Lu, L., Su, L., Lin, Z., Gao, D., Lv, H., Xu, M., Liu, P., Cao, L., Xu, J., 2022. Resurgence of respiratory syncytial virus infection during COVID-19 pandemic among children in Shanghai, China. Front. Microbiol. 13, 938372.
18. Li, Y., Wang, X., Blau, D. M., Caballero, M. T., Feikin, D. R., Gill, C. J., Madhi, S. A., Omer, S. B., Simoes, E. A. F., Campbell, H. et al., 2022. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis. Lancet. 399, 2047-2064.
19. Liu, P., Xu, M., Lu, L., Ma, A., Cao, L., Su, L., Dong, N., Jia, R., Zhu, X., Xu, J., 2022. The changing pattern of common respiratory and enteric viruses among outpatient children in Shanghai, China: two years of the COVID-19 pandemic. J. Med. Virol. 94, 4696-4703.
20. Maruo, Y., Ishikawa, S., Oura, K., Shiraishi, H., Sato, N., Suganuma, T., Mikawa, M., Sato, T., 2022. The impact of the coronavirus disease 2019 pandemic on pediatric hospitalization in Kitami, Japan. Pediatr. Int. 64, e14937.
21. Matheson, J. W., Rich, F. J., Cohet, C., Grimwood, K., Huang, Q. S., Penny, D., Hendy, M. D., Kirman, J. R., 2006. Distinct patterns of evolution between respiratory syncytial virus subgroups A and B from New Zealand isolates collected over thirty-seven years. J. Med. Virol. 78, 1354-1364.
22. Mufson, M. A., Orvell, C., Rafnar, B., Norrby, E., 1985. Two distinct subtypes of human respiratory syncytial virus. J. Gen. Virol.66 (Pt 10), 2111-2124.
23. Munoz-Escalante, J. C., Comas-Garcia, A., Bernal-Silva, S., Noyola, D. E., 2021. Respiratory syncytial virus B sequence analysis reveals a novel early genotype. Sci. Rep. 11, 3452.
24. Peret, T. C., Hall, C. B., Schnabel, K. C., Golub, J. A., Anderson, L. J., 1998. Circulation patterns of genetically distinct group A and B strains of human respiratory syncytial virus in a community. J. Gen. Virol.79, 2221-2229.
25. Peret, T. C., Hall, C. B., Hammond, G. W., Piedra, P. A., Storch, G. A., Sullender, W. M., Tsou, C., Anderson, L. J., 2000. Circulation patterns of group A and B human respiratory syncytial virus genotypes in 5 communities in North America. J. Infect. Dis.181, 1891-1896.
26. Redlberger-Fritz, M., Kundi, M., Aberle, S. W., Puchhammer-Stockl, E., 2021. Significant impact of nationwide SARS-CoV-2 lockdown measures on the circulation of other respiratory virus infections in Austria. J. Clin. Virol. 137, 104795.
27. Reiche, J., Schweiger, B., 2009. Genetic variability of group A human respiratory syncytial virus strains circulating in Germany from 1998 to 2007. J. Clin. Microbiol. 47, 1800-1810.
28. Reicherz, F., Xu, R. Y., Abu-Raya, B., Majdoubi, A., Michalski, C., Golding, L., Stojic, A., Vineta, M., Granoski, M., Cieslak, Z., et al., 2022. Waning immunity against respiratory syncytial virus during the coronavirus disease 2019 pandemic. J. Infect. Dis. 226, 2064-2068.
29. Ren, L., Xiao, Q., Zhou, L., Xia, Q., Liu, E., 2015. Molecular characterization of human respiratory syncytial virus subtype B: a novel genotype of subtype B circulating in China. J. Med. Virol. 87, 1-9.
30. Tabatabai, J., Thielen, A., Lehners, N., Daeumer, M., Schnitzler, P., 2018. Respiratory syncytial virus A in haematological patients with prolonged shedding: premature stop codons and deletion of the genotype ON1 72-nucleotide-duplication in the attachment G gene. J. Clin. Virol. 98, 10-17.
31. Tahamtan, A., Samadizadeh, S., Rastegar, M., Nakstad, B., Salimi, V., 2020. Respiratory syncytial virus infection: why does disease severity vary among individuals ? Expert Rev. Respir. Med. 14, 415-423.
32. Thielen, B. K., Bye, E., Wang, X., Maroushek, S., Friedlander, H., Bistodeau, S., Christensen, J., Reisdorf, E., Shilts, M. H., Martin, K., et al., 2020. Summer outbreak of severe RSV-B disease, Minnesota, 2017 associated with emergence of a genetically distinct viral lineage. J. Infect. Dis. 222, 288-297.
33. Trento, A., Galiano, M., Videla, C., Carballal, G., Garcia-Barreno, B., Melero, J. A., Palomo, C., 2003. Major changes in the G protein of human respiratory syncytial virus isolates introduced by a duplication of 60 nucleotides. J. Gen. Virol. 84, 3115-3120.
34. Uhteg, K., Amadi, A., Forman, M., Mostafa, H. H., 2022. Circulation of non-SARS-CoV-2 respiratory pathogens and coinfection with SARS-CoV-2 amid the COVID-19 pandemic. Open Forum Infect. Dis. 9, ofab618.
35. Ujiie, M., Tsuzuki, S., Nakamoto, T., Iwamoto, N., 2021. Resurgence of respiratory syncytial virus infections during COVID-19 pandemic, Tokyo, Japan. Emerg. Infect. Dis. 27, 2969-2970.
36. Umar, S., Yang, R., Wang, X., Liu, Y., Ke, P., Qin, S., 2023. Molecular epidemiology and characteristics of respirator.y syncytial virus among hospitalized children in Guangzhou, China. Virol. J. 20, 272.
37. Venter, M., Madhi, S. A., Tiemessen, C. T., Schoub, B. D., 2001. Genetic diversity and molecular epidemiology of respiratory syncytial virus over four consecutive seasons in South Africa: identification of new subgroup A and B genotypes. J. Gen. Virol. 82, 2117-2124.
38. Zhao, X., Wang, C., Jiang, H., Zhang, H., Fang, F., Chen, M., Yuan, Z., Teng, Z., Liu, J., Zhang, X., 2022. Analysis of circulating respiratory syncytial virus A strains in Shanghai, China identified a new and increasingly prevalent lineage within the dominant ON1 genotype. Front. Microbiol. 13, 966235.
39. Zheng, Y., Liu, L., Wang, S., Li, Z., Hou, M., Li, J., Yu, X. F., Zhang, W., Hua, S., 2017. Prevailing genotype distribution and characteristics of human respiratory syncytial virus in northeastern China. J. Med. Virol. 89, 222-233.
40. Zhu, Y., Lu, G., Jin, R., Sun, Y., Shang, Y. X., Ai, J. H., Wang, R., Chen, X. P., Duan, Y. L., Zhang, M., et al., 2022. Analysis of respiratory syncytial virus infection in hospitalized children with acute lower respiratory tract infection in China from 2017 to 2020. Zhonghua Yu Fang Yi Xue Za Zhi. 56, 1739-1744.
41. Zlateva, K. T., Lemey, P., Moes, E., Vandamme, A. M., Van Ranst, M., 2005. Genetic variability and molecular evolution of the human respiratory syncytial virus subgroup B attachment G protein. J. Virol. 79, 9157-9167.
Proportional views
Electronic Supplementary Material

10.1016j.virs.2024.07.004-ESM.docx