What appears to be the first large study of nirsevimab prophylaxis for respiratory syncytial virus (RSV) in newborns found a 68% reduction in risk of hospitalization for RSV respiratory tract infection among more than 13,000 neonates in Northern Italy during their first winter of life.1
Notably, when infants were compared within the same birth month to control for seasonal RSV risk, nirsevimab was associated with an 89% reduction in hospitalization, demonstrating a robust individual-level protective effect rather than a purely population-level seasonal phenomenon. Among the infants who were hospitalized for RSV infection during the first year of life, nirsevimab prophylaxis was associated with a reduction in the odds of needed high-flow nasal cannula (HFNC) respiratory support.
“We see hundreds of infants with RSV in pediatric intensive care every year,” said Christopher Carroll, MD, MS, FCCP, Professor of Pediatrics at the University of Florida and Director of Pediatric Intensive Care at Wolfson Children’s Hospital. “Anything that could reduce the toll of RSV infection would be a real plus for the kids we treat every year and for their families.”
RSV infection is the leading cause of hospital admission for lower respiratory tract infection (LRTI) in newborns and has been associated with recurrent wheezing and asthma later in life. Preterm birth and household transmission are major risk factors for infection, and no studies had previously investigated whether nirsevimab prophylaxis fully offsets these risk factors. Pediatric guidelines in Italy and elsewhere recommend universal RSV prophylaxis with nirsevimab for infants born during the highest risk months for infection, September through March.
Led by investigator Enrico Cocchi, MD, PhD, researchers in Northern Italy used regional health data from five neonatal centers across two successive RSV epidemic seasons before and after nirsevimab was available. Retrospective data were collected for 13,524 live births between April 1, 2023, and March 31, 2025, across five Italian provinces. Infants were followed from birth until the earliest of the first RSV hospitalization, April 1 of the next year (end of RSV season), or their first birthday. Infants received nirsevimab prophylaxis following birth and before initial discharge based on parental consent.
The mean gestational age of infants was 39.4 weeks, and 48.6% were female. About half (49.5%) had older siblings in the household, and 4.8% were born preterm. Half of the infants (50.9%) were born during the pre-nirsevimab season (2023 to 2024), and half (49.1%) were born during the post-nirsevimab season (2024 to 2025). Most eligible newborns (79.2%) received nirsevimab prophylaxis after September 1, 2024.
The primary outcome was RSV-associated hospitalization during the first year of life. Secondary outcomes comprised RSV severity measures, including hospital length of stay, HFNC use, and ICU admission.
A total of 292 infants were hospitalized with RSV infection (2.1%) during the study period. Significantly fewer were hospitalized for RSV during the post-nirsevimab period (24.7%) compared with the pre-nirsevimab period (75.3%), with a population-level reduction in hospitalization HR of 0.32 (95% CI, 0.25-0.44; P < .001).
Among infants who were hospitalized for RSV, nirsevimab was associated with reduced HFNC use, with an OR of 0.33 (95% CI, 0.11-0.97; P = .04). Dr. Cocchi, Assistant Professor and Neonatal and Pediatric Intensivist, University of Bologna, said there was no difference in length of stay or in ICU admission and no reported adverse events associated with nirsevimab prophylaxis.
Among the RSV hospitalizations that occurred during the post-nirsevimab season, 75% were in infants who had not received nirsevimab prophylaxis, he said, and there was no significant difference in non-RSV hospitalizations for LRTI between the pre- and post-nirsevimab periods.
Premature infants made up a larger proportion of RSV admissions in the post-nirsevimab period (15.25%) compared with the pre-nirsevimab period (11.4%), with an HR of 2.93 (95% CI, 2.11-4.07; P < .001). Living with older siblings was also associated with an increased risk of RSV hospitalization, HR of 4.57 (95% CI, 4.15-5.03; P < .001), as well as with non-RSV LRTI admission, HR of 6.88 (95% CI, 3.64-13.01; P < .001).
Dr. Cocchi said that together these findings indicate a persistent residual risk among preterm infants and those living with older siblings, even in the setting of widespread nirsevimab use. While nirsevimab prophylaxis was highly effective at reducing RSV hospitalizations overall, it did not fully offset the elevated baseline susceptibility associated with prematurity and increased household exposure.
He said this pattern suggests that although nirsevimab provides substantial protection, it may not confer uniform risk reduction across all infant subgroups, underscoring the need for complementary or targeted prevention strategies to further protect these higher-risk populations. Ongoing surveillance and continuous monitoring are therefore essential to identify infants who remain at highest risk and to refine prevention strategies as real-world experience with nirsevimab expands, he said.
Dr. Cocchi also said there was no observed interaction between maternal RSV vaccination and the beneficial effects of nirsevimab prophylaxis in infants. However, current guidelines from the US Centers for Disease Control and Prevention say that most infants will not need both maternal vaccination against RSV and infant RSV antibodies (nirsevimab or clesrovimab).
“Vaccination has been a mainstay in the prevention of severe respiratory infections in infants,” Dr. Carroll said. “Before influenza vaccines, ICUs were flooded with children with Haemophilus infections and meningitis. We don’t see that today; we see RSV infections in the ICU. This study suggests that nirsevimab prophylaxis could make a difference.”
References
1. Cocchi E, Bloise S, Lorefice A, et al. Nirsevimab prophylaxis and respiratory syncytial virus hospitalizations among infants. JAMA Netw Open. 2025;8(11):e2544679. doi:10.1001/jamanetworkopen.2025.44679
