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, 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. Conclusions: Nirsevimab immunisation may influence HRSV evolution, particularly in HRSV-B. Continued genomic surveillance is crucial for early mAb-resistant mutants detection.