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

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. Respiratory samples were collected through 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. A total of 251 WGS (HRSV-A: 165; HRSV-B: 86) and 27F 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 12F 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 suggested a shift toward neutral evolution in immunised samples. Mutations N63S, K65R, I206T, and K209E (HRSV-A) and K68E, R209Q, and S211N (HRSV-B) were detected in nirsevimab epitope, with K209E and K68E absent in non-immunised samples. Nirsevimab immunisation may influence HRSV evolution, particularly in HRSV-B. Continued genomic surveillance is crucial for early mAb-resistant mutants detection.