J Korean Med Sci.  2024 Jul;39(28):e206. 10.3346/jkms.2024.39.e206.

Genotype Analysis of Respiratory Syncytial Virus Before and After the COVID-19 Pandemic Using WholeGenome Sequencing: A Prospective, Single-Center Study in Korea From 2019 to 2022

• Na B
• Park YJ
• Seo J
• Park M
• Baek JY
• Lee JY
• Kim M
• Ahn JG
• Lee ST
• Kang JM

• KMID: 2558244
• DOI: http://doi.org/10.3346/jkms.2024.39.e206

Abstract

Background
Respiratory syncytial virus (RSV), a highly transmissible virus, is the leading cause of lower respiratory tract infections. We examined molecular changes in the RSV genome before and after the coronavirus disease 2019 (COVID-19) pandemic in Korea, and investigated whether drug-resistant mutations were present.
Methods
In this prospective, single-center study, RSV-positive respiratory samples were collected between September 2019 and December 2022. Long-read whole-genome sequencing (WGS) was performed, and the presence of known drug-resistant substitutions for palivizumab, nirsevimab, and suptavumab was investigated.
Results
Overall, 288 respiratory samples were collected from 276 children. WGS data were available for 133 samples (71 and 62 samples from the pre- and post-pandemic periods, respectively). All RSV-A strains (n = 56) belonged to the GA2.3.5 (ON1) genotype, whereas all RSV-B strains (n = 77) belonged to the GB5.0.5a (BA) genotype. No significant differences in genotypes were observed between the pre- and post-pandemic periods. In addition, no notable mutations related to nirsevimab or palivizumab resistance were detected in the F gene. However, the L172Q and S173L substitutions, which are known to confer resistance to suptavumab, were present in all RSV-B samples.
Conclusion
Despite the unprecedented interruption of RSV seasonality, there were no significant molecular changes in circulating RSV strains in Korea related to nirsevimab or palivizumab resistance before and after the COVID-19 pandemic. However, RSV-specific drug-resistance substitutions for suptavumab were identified.

Keyword

RSV; Genotype; Whole-Genome Sequencing; Resistance; Palivizumab; Nirsevimab; Suptavumab; COVID-19 Pandemic; Children; Korea

Figure

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  Fig. 1 Flowchart of study population selection and monthly trend of RSV hospitalizations. (A) Selection schematic of study population and samples. (B) Monthly RSV hospitalization data at SCH during the study period. The shaded portion represents clinical surveillance data on RSV hospitalizations from the KDCA.PCR = polymerase chain reaction, RSV = respiratory syncytial virus, COVID-19 = coronavirus disease 2019, WGS = whole-genome sequencing, SCH = Severance Children’s Hospital, KDCA = Korea Disease Control and Prevention Agency.

• 

  Fig. 2 Phylogenetic tree of RSV-A and RSV-B before and after the coronavirus disease 2019 pandemic based on whole-genome sequencing. (A, C) depict the phylogenetic tree of pre-pandemic RSV (from September 2019 to February 2020), whereas (B, D) represent the phylogenetic tree of post-pandemic RSV (from November 2021 to December 2022). The red circles represent RSV samples from the 2019–2020 season, the blue circles represent samples from the 2021–2022 season, and the circles with blue borders represent samples from the 2022–2023 season.RSV = respiratory syncytial virus.

• 

  Fig. 3 Estimates of nucleotide substitution rates for RSV-A and RSV-B using whole-genome sequencing. The analysis was conducted using the search-thinned datasets and was carried out using the BEAST program.RSV = respiratory syncytial virus.

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