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Original article

Vol. 155 No. 12 (2025)

Molecular epidemiology of respiratory syncytial virus in Switzerland 2019–2024 from nucleic acid testing and whole-genome sequencing

Cite this as:
Swiss Med Wkly. 2025;155:4600
Published
23.12.2025

Summary

BACKGROUND AND AIMS: Respiratory syncytial virus (RSV) infection is one of the leading causes of hospitalisation in infants, the elderly and immunocompromised patients, with significant morbidity and mortality rates. Despite its global impact, epidemiological surveillance of RSV in Switzerland has historically been limited compared to the USA and European countries. A significant surge in RSV activity and hospitalisations after the COVID-19 pandemic, along with the introduction of new monoclonal antibodies and RSV vaccines, has led to an increased interest in the molecular epidemiology of RSV. To ensure continued efficacy of the new preventive options, monitoring of the genetic diversity of circulating RSV strains, their evolutionary dynamics and the potential emergence of resistance mutations is of central importance. The present study aimed to characterise the genetic diversity and seasonal trends of RSV dynamics in Switzerland from 2019 to 2024, mainly over the last two post-pandemic winter seasons (2022/23 and 2023/24).

METHODS: A total of 48,897 respiratory clinical specimens from 30,782 patients with respiratory tract infections were tested for RSV at a tertiary care centre in Northwestern Switzerland between July 2019 and June 2024. RSV activity over these seasons was investigated. Amplicon-based whole-genome sequencing was performed on 182 selected samples, with 125 high-quality consensus genomes and phylogenies reconstructed. Lineage distribution and seasonal subtype prevalence were compared to European data.

RESULTS: RSV activity was absent during the 2020/21 pandemic season, but surged with an off-season peak in summer 2021. RSV B predominated during the 2022/23 season, while a shift to RSV A occurred in the 2023/24 winter season, which is in line with neighbouring European countries. Lineage subtype distribution showed high concordance with circulating European strains. RSV A exhibited greater diversity (mean pairwise Hamming distance 0.015, SD 0.006) than RSV B (mean 0.006, 0.003), with all current strains falling within G protein duplication clades A.D.1, 2, 3 and 5 for RSV A, and B.D.E.1 and B.D.4.1.1 for RSV B.

CONCLUSION: By contributing 125 newly assembled RSV genome sequences, we have significantly increased the number of publicly available whole-genome sequences from Switzerland. Our study provides a genomic surveillance of RSV in Switzerland, analysing seasonal patterns, alternating subtype dominance, and consistency with broader European trends. A comprehensive understanding of the molecular epidemiology of RSV enables healthcare providers and public health authorities to monitor the effectiveness of current vaccines and monoclonal antibodies, associate lineages and serotypes with disease severity, implement timely interventions and detect emerging variants, ultimately reducing the burden of RSV-related illnesses.

References

  1. 1. Kaler J, Hussain A, Patel K, Hernandez T, Ray S. Respiratory syncytial virus: A comprehensive review of transmission, pathophysiology, and manifestation. Cureus. 2023 Mar;15(3):e36342. doi: https://doi.org/10.7759/cureus.36342
  2. 2. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 Dec;380(9859):2095–128. doi: https://doi.org/10.1016/S0140-6736(12)61728-0
  3. 3. Stucki M, Lenzin G, Agyeman PK, Posfay-Barbe KM, Ritz N, Trück J, et al. Inpatient burden of respiratory syncytial virus (RSV) in Switzerland, 2003 to 2021: an analysis of administrative data. Euro Surveill. 2024 Sep;29(39):2400119. doi: https://doi.org/10.2807/1560-7917.ES.2024.29.39.2400119
  4. 4. Meslé MM, Sinnathamby M, Mook P, Pebody R, Lakhani A, Zambon M, et al.; WHO European Region Respiratory Network Group. Seasonal and inter-seasonal RSV activity in the European Region during the COVID-19 pandemic from autumn 2020 to summer 2022. Influenza Other Respir Viruses. 2023 Nov;17(11):e13219. doi: https://doi.org/10.1111/irv.13219
  5. 5. Fischli K, Schöbi N, Duppenthaler A, Casaulta C, Riedel T, Kopp MV, et al. Postpandemic fluctuations of regional respiratory syncytial virus hospitalization epidemiology: potential impact on an immunization program in Switzerland. Eur J Pediatr. 2024 Dec;183(12):5149–61. doi: https://doi.org/10.1007/s00431-024-05785-z
  6. 6. Sauteur PM, Plebani M, Trück J, Wagner N, Agyeman PK. Ongoing disruption of RSV epidemiology in children in Switzerland. Lancet Reg Heal; 2024. p. 45.
  7. 7. Rao S, Armistead I, Messacar K, Alden NB, Schmoll E, Austin E, et al. Shifting epidemiology and severity of respiratory syncytial virus in children during the COVID-19 pandemic. JAMA Pediatr. 2023 Jul;177(7):730–2. doi: https://doi.org/10.1001/jamapediatrics.2023.1088
  8. 8. Abu-Raya B, Viñeta Paramo M, Reicherz F, Lavoie PM. Why has the epidemiology of RSV changed during the COVID-19 pandemic? EClinicalMedicine. 2023 Jul;61:102089. doi: https://doi.org/10.1016/j.eclinm.2023.102089
  9. 9. Hammitt LL, Dagan R, Yuan Y, Baca Cots M, Bosheva M, Madhi SA, et al.; MELODY Study Group. Nirsevimab for prevention of RSV in healthy late-preterm and term infants. N Engl J Med. 2022 Mar;386(9):837–46. doi: https://doi.org/10.1056/NEJMoa2110275
  10. 10. Griffin MP, Yuan Y, Takas T, Domachowske JB, Madhi SA, Manzoni P, et al.; Nirsevimab Study Group. Single-dose nirsevimab for prevention of RSV in preterm infants. N Engl J Med. 2020 Jul;383(5):415–25. doi: https://doi.org/10.1056/NEJMoa1913556
  11. 11. Simões EA, Pahud BA, Madhi SA, Kampmann B, Shittu E, Radley D, et al.; MATISSE (Maternal Immunization Study for Safety and Efficacy) Clinical Trial Group. Efficacy, Safety, and Immunogenicity of the MATISSE (Maternal Immunization Study for Safety and Efficacy) Maternal Respiratory Syncytial Virus Prefusion F Protein Vaccine Trial. Obstet Gynecol. 2025 Feb;145(2):157–67. doi: https://doi.org/10.1097/AOG.0000000000005816
  12. 12. Shirley M. RSVPreF3 OA respiratory syncytial virus vaccine in older adults: a profile of its use. Drugs Ther Perspect. 2025;41(1):1–8. doi: https://doi.org/10.1007/s40267-024-01125-1
  13. 13. Papi A, Ison MG, Langley JM, Lee DG, Leroux-Roels I, Martinon-Torres F, et al.; AReSVi-006 Study Group. Respiratory syncytial virus prefusion F protein vaccine in older adults. N Engl J Med. 2023 Feb;388(7):595–608. doi: https://doi.org/10.1056/NEJMoa2209604
  14. 14. Fourati S, Reslan A, Bourret J, Casalegno JS, Rahou Y, Chollet L, et al. Genotypic and phenotypic characterisation of respiratory syncytial virus after nirsevimab breakthrough infections: a large, multicentre, observational, real-world study. Lancet Infect Dis. 2024.
  15. 15. Saito M, Tsukagoshi H, Sada M, Sunagawa S, Shirai T, Okayama K, et al. Detailed evolutionary analyses of the F gene in the respiratory syncytial virus subgroup A. Viruses. 2021 Dec;13(12):2525. doi: https://doi.org/10.3390/v13122525
  16. 16. Goya S, Ruis C, Neher RA, Meijer A, Aziz A, Hinrichs AS, et al. Standardized phylogenetic classification of human respiratory syncytial virus below the subgroup level. Emerg Infect Dis. 2024 Aug;30(8):1631–41. doi: https://doi.org/10.3201/eid3008.240209
  17. 17. Ison MG, Hirsch HH. Community-acquired respiratory viruses in transplant patients: diversity, impact, unmet clinical needs. Clin Microbiol Rev. 2019 Sep;32(4):10–1128. doi: https://doi.org/10.1128/CMR.00042-19
  18. 18. Goldenberger D, Leuzinger K, Sogaard KK, Gosert R, Roloff T, Naegele K, et al. Brief validation of the novel GeneXpert Xpress SARS-CoV-2 PCR assay. J Virol Methods. 2020 Oct;284:113925. doi: https://doi.org/10.1016/j.jviromet.2020.113925
  19. 19. Leuzinger K, Roloff T, Gosert R, Sogaard K, Naegele K, Rentsch K, et al. Epidemiology of severe acute respiratory syndrome coronavirus 2 emergence amidst community-acquired respiratory viruses. J Infect Dis. 2020 Sep;222(8):1270–9. doi: https://doi.org/10.1093/infdis/jiaa464
  20. 20. Leung EC man, Chow VC ying, Lee MK ping, Tang KP san, Li DK cheung, Lai RW man. Evaluation of the Xpert Xpress SARS-CoV-2/Flu/RSV Assay for Simultaneous Detection of SARS-CoV-2, Influenza A and B Viruses, and Respiratory Syncytial Virus in Nasopharyngeal Specimens. Hayden R, editor. J Clin Microbiol. 2021 Mar 19;59(4):e02965-20.
  21. 21. Mostafa HH, Carroll KC, Hicken R, Berry GJ, Manji R, Smith E, et al. Multicenter Evaluation of the Cepheid Xpert Xpress SARS-CoV-2/Flu/RSV Test. McAdam AJ, editor. J Clin Microbiol. 2021 Feb 18;59(3):e02955-20.
  22. 22. Quick J, Grubaugh ND, Pullan ST, Claro IM, Smith AD, Gangavarapu K, et al. Multiplex PCR method for MinION and Illumina sequencing of Zika and other virus genomes directly from clinical samples. Nat Protoc. 2017 Jun;12(6):1261–76. doi: https://doi.org/10.1038/nprot.2017.066
  23. 23. Wang L, Ng TF, Castro CJ, Marine RL, Magaña LC, Esona M, et al. Next-generation sequencing of human respiratory syncytial virus subgroups A and B genomes. J Virol Methods. 2022 Jan;299:114335. doi: https://doi.org/10.1016/j.jviromet.2021.114335
  24. 24. Dyrdak R, Mastafa M, Hodcroft EB, Neher RA, Albert J. Intra- and interpatient evolution of enterovirus D68 analyzed by whole-genome deep sequencing. Virus Evol. 2019 Apr;5(1):vez007. doi: https://doi.org/10.1093/ve/vez007
  25. 25. Hodcroft EB, Dyrdak R, Andrés C, Egli A, Reist J, García Martínez De Artola D, et al. Evolution, geographic spreading, and demographic distribution of Enterovirus D68. Elde NC, editor. PLOS Pathog. 2022 May 31;18(5):e1010515. doi: https://doi.org/10.1371/journal.ppat.1010515
  26. 26. Hadfield J, Megill C, Bell SM, Huddleston J, Potter B, Callender C, et al. Nextstrain: real-time tracking of pathogen evolution. Bioinformatics. 2018 Dec;34(23):4121–3. doi: https://doi.org/10.1093/bioinformatics/bty407
  27. 27. Aksamentov I, Roemer C, Hodcroft EB, Neher RA. Nextclade: clade assignment, mutation calling and quality control for viral genomes. J Open Source Softw. 2021;6(67):3773. doi: https://doi.org/10.21105/joss.03773
  28. 28. Nguyen LT, Schmidt HA, von Haeseler A, Minh BQ. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol. 2015 Jan;32(1):268–74. doi: https://doi.org/10.1093/molbev/msu300
  29. 29. Garcia-Maurino C, Brenes-Chacón H, Halabi KC, Sánchez PJ, Ramilo O, Mejias A. Trends in age and disease severity in children hospitalized with RSV infection before and during the COVID-19 pandemic. JAMA Pediatr. 2024 Feb;178(2):195–7. doi: https://doi.org/10.1001/jamapediatrics.2023.5431
  30. 30. Bourdeau M, Vadlamudi NK, Bastien N, Embree J, Halperin SA, Jadavji T, et al.; Canadian Immunization Monitoring Program Active (IMPACT) Investigators. Pediatric RSV-associated hospitalizations before and during the COVID-19 pandemic. JAMA Netw Open. 2023 Oct;6(10):e2336863–2336863. doi: https://doi.org/10.1001/jamanetworkopen.2023.36863
  31. 31. Eshaghi A, Duvvuri VR, Lai R, Nadarajah JT, Li A, Patel SN, et al. Genetic variability of human respiratory syncytial virus A strains circulating in Ontario: a novel genotype with a 72 nucleotide G gene duplication. PLoS One. 2012;7(3):e32807. doi: https://doi.org/10.1371/journal.pone.0032807
  32. 32. Trento A, Galiano M, Videla C, Carballal G, García-Barreno B, Melero JA, et al. Major changes in the G protein of human respiratory syncytial virus isolates introduced by a duplication of 60 nucleotides. J Gen Virol. 2003 Nov;84(Pt 11):3115–20. doi: https://doi.org/10.1099/vir.0.19357-0
  33. 33. Stein RT, Zar HJ. RSV through the COVID-19 pandemic: Burden, shifting epidemiology, and implications for the future. Pediatr Pulmonol. 2023 Jun;58(6):1631–9. doi: https://doi.org/10.1002/ppul.26370
  34. 34. Heemskerk S, Baliatsas C, Stelma F, Nair H, Paget J, Spreeuwenberg P. Assessing the Impact of Non-Pharmaceutical Interventions During the COVID-19 Pandemic on RSV Seasonality in Europe. Influenza Other Respir Viruses. 2025 Jan;19(1):e70066. doi: https://doi.org/10.1111/irv.70066
  35. 35. Scholz S, Dobrindt K, Tufts J, Adams S, Ghaswalla P, Ultsch B, et al. The Burden of Respiratory Syncytial Virus (RSV) in Germany: A Comprehensive Data Analysis Suggests Underdetection of Hospitalisations and Deaths in Adults 60 Years and Older. Infect Dis Ther. 2024 Aug;13(8):1759–70. doi: https://doi.org/10.1007/s40121-024-01006-0
  36. 36. Kiefer A, Pemmerl S, Kabesch M, Ambrosch A. Comparative analysis of RSV-related hospitalisations in children and adults over a 7 year-period before, during and after the COVID-19 pandemic. J Clin Virol. 2023 Sep;166:105530. doi: https://doi.org/10.1016/j.jcv.2023.105530
  37. 37. Hönemann M, Maier M, Frille A, Thiem S, Bergs S, Williams TC, et al. Respiratory Syncytial Virus in Adult Patients at a Tertiary Care Hospital in Germany: Clinical Features and Molecular Epidemiology of the Fusion Protein in the Severe Respiratory Season of 2022/2023. Viruses. 2024 Jun;16(6):943. doi: https://doi.org/10.3390/v16060943
  38. 38. Lastrucci V, Pacifici M, Puglia M, Alderotti G, Berti E, Del Riccio M, et al. Seasonality and severity of respiratory syncytial virus during the COVID-19 pandemic: a dynamic cohort study. Int J Infect Dis. 2024 Nov;148:107231. doi: https://doi.org/10.1016/j.ijid.2024.107231
  39. 39. Pierangeli A, Nenna R, Fracella M, Scagnolari C, Oliveto G, Sorrentino L, et al. Genetic diversity and its impact on disease severity in respiratory syncytial virus subtype-A and -B bronchiolitis before and after pandemic restrictions in Rome. J Infect. 2023 Oct;87(4):305–14. doi: https://doi.org/10.1016/j.jinf.2023.07.008
  40. 40. Cutrera R, Ciofi Degli Atti ML, Dotta A, D’Amore C, Ravà L, Perno CF, et al. Epidemiology of respiratory syncytial virus in a large pediatric hospital in Central Italy and development of a forecasting model to predict the seasonal peak. Ital J Pediatr. 2024 Apr;50(1):65. doi: https://doi.org/10.1186/s13052-024-01624-x
  41. 41. Redlberger-Fritz M, Springer DN, Aberle SW, Camp JV, Aberle JH. Respiratory syncytial virus surge in 2022 caused by lineages already present before the COVID-19 pandemic. J Med Virol. 2023 Jun;95(6):e28830. doi: https://doi.org/10.1002/jmv.28830
  42. 42. Rios-Guzman E, Simons LM, Dean TJ, Agnes F, Pawlowski A, Alisoltanidehkordi A, et al. Deviations in RSV epidemiological patterns and population structures in the United States following the COVID-19 pandemic. Nat Commun. 2024 Apr;15(1):3374. doi: https://doi.org/10.1038/s41467-024-47757-9
  43. 43. de Korne-Elenbaas J, Rimaite A, Topolsky I, Dreifuss D, Bürki C, Fuhrmann L, et al. Wastewater-based sequencing of Respiratory Syncytial Virus enables tracking of lineages and identifying mutations at antigenic sites. medRxiv [Preprint]. 2025 medRxiv [cited 2025 Mar 7]. p. 2025.02.28.25321637. Available from: https://www.medrxiv.org/content/10.1101/2025.02.28.25321637v1 10.1101/2025.02.28.25321637
  44. 44. Yunker M, Fall A, Norton JM, Abdullah O, Villafuerte DA, Pekosz A, et al. Genomic Evolution and Surveillance of Respiratory Syncytial Virus during the 2023-2024 Season. Viruses. 2024 Jul;16(7):1122. doi: https://doi.org/10.3390/v16071122
  45. 45. de Jesus-Cornejo J, Hechanova-Cruz RA, Sornillo JB, Okamoto M, Oshitani H; Viral Etiology Working Group. Prolonged RSV circulation in 2022 to 2023 associated with the emergence of a novel RSV-B clade in Biliran, Philippines. J Infect. 2025 Apr;90(4):106467. doi: https://doi.org/10.1016/j.jinf.2025.106467
  46. 46. Jafri HS, Wu X, Makari D, Henrickson KJ. Distribution of respiratory syncytial virus subtypes A and B among infants presenting to the emergency department with lower respiratory tract infection or apnea. Pediatr Infect Dis J. 2013 Apr;32(4):335–40. doi: https://doi.org/10.1097/INF.0b013e318282603a
  47. 47. Midulla F, Nenna R, Scagnolari C, Petrarca L, Frassanito A, Viscido A, et al. How respiratory syncytial virus genotypes influence the clinical course in infants hospitalized for bronchiolitis. J Infect Dis. 2019 Jan;219(4):526–34. doi: https://doi.org/10.1093/infdis/jiy496
  48. 48. Jung JA, Wi PH, Kim H. Kim H sol. Comparisons of clinical characteristics between Respiratory Syncytial Virus A and B infection. J Allergy Clin Immunol. 2020;145(2):AB131. doi: https://doi.org/10.1016/j.jaci.2019.12.520
  49. 49. Vos LM, Oosterheert JJ, Kuil SD, Viveen M, Bont LJ, Hoepelman AI, et al. High epidemic burden of RSV disease coinciding with genetic alterations causing amino acid substitutions in the RSV G-protein during the 2016/2017 season in The Netherlands. J Clin Virol. 2019 Mar;112:20–6. doi: https://doi.org/10.1016/j.jcv.2019.01.007
  50. 50. Irwin KK, Renzette N, Kowalik TF, Jensen JD. Antiviral drug resistance as an adaptive process. Virus Evol. 2016 Jun;2(1):vew014. doi: https://doi.org/10.1093/ve/vew014
  51. 51. Gosert R, Leuzinger K, Kuznetsov A, Neher RA. Respiratory syncytial virus A amplicon sequencing dataset, Basel, Switzerland, 2021-2024 [dataset]. 2025 Jun 16 [cited 2025 Sep 23]. Pathoplexus. Available from: 10.62599/PP_SS_201.2
  52. 52. Gosert R, Leuzinger K, Kuznetsov A, Neher RA. Respiratory syncytial virus B amplicon sequencing dataset, Basel, Switzerland, 2020-2024 [dataset]. 2025 Jun 16 [cited 2025 Sep 23]. Pathoplexus. Available from: 10.62599/PP_SS_202.2