Evolutionary dynamics of HRSV following the implementation of nirsevimab immunoprophylaxis in Catalonia (2023-2024)

Abstract

Objectives: To evaluate the effect of the selective pressure exerted by nirsevimab on human respiratory syncytial virus (HRSV) in Catalonia (2023-2024) by analysing viral mutations, diversity, and evolutionary dynamics, based on viruses characterised from non-immunised and previously immunised patients. Methods: Respiratory samples were collected through the SIVIC sentinel network and three hospitals in Catalonia. HRSV-positive samples underwent whole-genome sequencing (WGS), or F gene sequencing when WGS was not feasible. Viral diversity, phylogenetics, and selection pressure were assessed. Results: A total of 251 WGS (HRSV-A: 165; HRSV-B: 86) and 27 F gene sequences (HRSV-A: 13; HRSV-B: 14) were obtained for the non-immunised group. For immunised cases, 79 WGS (HRSV-A: 67; HRSV-B: 12) and 12 F sequences (HRSV-A: 10; HRSV-B: 2) were analysed. Lineage distribution remained similar between groups. Nucleotide diversity was similar for HRSV-A groups, though reduced in immunised HRSV-B. Selection pressure analyses suggested a shift toward neutral evolution in immunised samples. Mutations N63S, K65R, I206T , K209E (HRSV-A) , K68E, R209Q, and S211N (HRSV-B) were detected in nirse- vimab epitope, with K209E and K68E absent in non-immunised samples. Conclusions: Nirsevimab immunisation may influence HRSV evolution, particularly in HRSV-B. Continued genomic surveillance is crucial for early mAb-resistant mutants detection. (c) 2025 Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).