Two-season effectiveness of a single nirsevimab dose against RSV hospitalisation in healthy term-born infants: a population-based case-control study, Spain, October 2023 to March 2025

Abstract

BACKGROUNDIn autumn 2023, Spain recommended nirsevimab to all infants born after 1 April 2023, as catch-up or at-birth immunisation.AIMWe estimated effectiveness of a single nirsevimab dose against respiratory syncytial virus (RSV) hospitalisations throughout two seasons in healthy term-born infants.METHODSCases were children born 1 April 2023 through 31 March 2024 after 35 gestation weeks without major comorbidities and hospitalised for RSV infection between 2023 immunisation campaign onset and 31 March 2025. We selected four healthy population-density controls per case, matched by province and birth date. Using target trial emulation, causal per-protocol effectiveness was estimated for catch-up (within 30 days of 2023 campaign onset) and at-birth immunisation (within 14 days of life) through cloning, censoring and inverse-probability-weighted conditional logistic regression.RESULTSWe included 235/905 cases/controls for catch-up and 334/1,292 cases/controls for at-birth immunisation (first season), and 188/713 cases/controls for catch-up and 328/1,269 cases/controls for at-birth immunisation (second season). Two-season effectiveness was 64% (95%?confidence interval (CI): 52-72) and 67% (95%?CI: 59-74) for catch-up and at-birth immunisation, respectively, compared with 78% (95%?CI: 70-84) and 84% (95%?CI: 79-88) during first season and -8% (95%?CI: -88 to 38) and 20% (95%?CI: -21 to 46) during second season.CONCLUSIONNirsevimab was an effective long-term population-level intervention, decreasing RSV hospitalisations by two-thirds during the first two seasons of life. Effectiveness during second season was low or null, although it may be underestimated due to unavoidable survivor bias. The RSV hospitalisation rate among immunised children did not rebound in the second season.