Background: Respiratory Syncytial Virus (RSV) is a major health concern, particularly for infants. In France, Nirsevimab, a long-acting monoclonal antibody to prevent RSV-associated lower respiratory tract infections (LRTI) was available from September 2023. We described RSV-associated LRTI hospitalisations during the 2023-2024 season among infants younger than six months born at the Hospices Civils de Lyon (HCL), and evaluated the effectiveness of Nirsevimab against RSV-LRTI hospitalisation. Methods: This observational study included infants born and hospitalised at the HCL during the 2023-2024 season, along with pre-COVID-19 and 2022-2023 seasons. Information on Nirsevimab immunisation status, clinical and perinatal variables were collected through routine care. Infants’ characteristics and incidence risk of hospitalisation per 100 births during 2023-2024 were compared with the historical periods overall and by delay between birth and the onset of the RSV season. Nirsevimab effectiveness was computed by the screening method. Results: During the 2023-2024 season, 83 infants younger than six months were hospitalised with an RSV-associated LRTI. Compared with the historical periods these infants were older. Incidence risk for infants born during the period when immunisation was available were lower than the previous seasons; incidence risk ratios were 0.45 (95% confidence interval (CI): [0.33;0.62]) in 2023-2024 compared with pre-COVID-19 period and 0.53 (95%CI: [0.36;0.77]) compared with 2022-2023 season. Nirsevimab effectiveness was 78.3% (95%CI: [55.9 ;89.5]) with a coverage of 79.3% in the HCL maternities. Conclusions: This study revealed a change in the epidemiology of RSV-associated LRTI hospitalisations in 2023-2024. High coverage and effectiveness were estimated in real-world setting.

Background: The nucleoprotein (N protein) of respiratory syncytial virus (RSV) is a candidate antigen for new RSV vaccine development. The aim of the present study was to investigate the association between maternal antibody titers against the RSV N protein at birth and the newborns’ risk of developing very-severe lower respiratory tract infection (VS-LRTI). Methods: In this single-center prospective cohort study, 578 infants born during the RSV epidemic season in France were included. Among these, 36 were hospitalized for RSV VS-LRTI. A generalized linear model was used to test the occurrence of a VS-LRTI in function of sex, mode of delivery, parity of the mother, type of pregnancy, date of birth in relation to the peak of the epidemic, and antibody titer against N protein. Results: All cord blood samples had detectable antibodies against N protein. The mean titers were significantly lower in newborns with risk factors for RSV severe LRTI (preterm infants, birth before the peak epidemic, multiparous mother). There was no association between antibody titer against the N protein and a protection against VS-LRTI. Conclusions The present study found that transfer of maternal antibodies against the RSV N protein may not provide a significant immune protection early in infancy. Clinical Trials Registration. NCT04144816.