Nirsevimab effectiveness, number needed to immunize and impact on severe RSV outcomes, a test-negative study in Quebec, Canada

Background In 2024-25, Quebec implemented a universally publicly funded infant nirsevimab program.We estimated effectiveness, number-needed-to-immunize (NNI) and impact against severe respiratory syncytial virus (RSV) outcomes. MethodsA test-negative study estimated adjusted effectiveness among nirsevimab-eligible children RSV-tested during emergency room (ER) consultation or hospitalization between October 2024 and March 2025.Eligible children were born during the RSV season (at-birth group) or <6-to <19-month-olds healthy, preterm, with chronic conditions or living in remote regions (catch-up groups).We used 2023-24 respiratory hospitalization rates, RSV-positivity from a systematic hospital-based surveillance network, and Quebec 2024-25 coverage estimates to derive the theoretical NNI and averted hospitalizations.Findings Effectiveness analyses included 3172 specimens linked to ER consultations (1775 560% from male and 1397 440% from female participants; 668 211% RSV-positive) and 1758 linked to hospitalizations (988 562% from male and 770 438% from female participants; 549 312% RSV-positive).Effectiveness was 86% (95% CI: 82-90) against ER consultation, 89% (95% CI: 84-92) against hospitalization (79% (95% CI: 60-89) for those with chronic diseases and 93% (95% CI: 83-97) for preterm infants), and 88% (95% CI: 58-97) against ICU admission.We estimated 41 at-birth and 58 catch-up immunizations needed to avert one RSV-associated hospitalization.We estimated that 72% (at-birth group) and 59% (catch-up group with 64% coverage by November) of RSV-associated hospitalizations were prevented, potentially increasing to 82% for a hypothetical coverage of 90% by October.Interpretation Nirsevimab is highly effective and could more substantially impact the RSV burden through broad and timely administration to healthy-term and high-risk infants.