1. RSV-B fights back: French surveillance flags notable nirsevimab escape, stressing need for smarter long-term RSV strategies This multicenter prospective cohort (POLYRES) from 32 French hospitals (Sept 2024–Apr 2025) included 1,023 RSV-positive infants <1 year of age; 858 yielded high-quality whole genomes, of whom 419 had nirsevimab breakthrough infections, and 439 were nirsevimab-naive. RSV A (n=404) and RSV B (n=454) circulation was well characterized by lineage. Among 184 RSV B breakthroughs, 23 (12.5%) harbored resistance-associated substitutions (RASs) conferring intermediate to highly reduced nirsevimab susceptibility in fusion inhibition assays, whereas only 2/195 RSV A breakthroughs carried an intermediate resistance variant. Resistant RSV B cases were older, more often high risk, and had longer intervals since prophylaxis. No RASs were detected in nirsevimab naive infants, supporting de novo selection under monoclonal antibody pressure. Comment: This is not an unexpected finding and underlines the classic monoclonal antibody dilemma: RSV B resistance emerges under subneutralizing nirsevimab...
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