Nirsevimab linked to lower RSV hospitalization risk in high-risk infants

A nationwide case-control analysis from Chile found that nirsevimab was associated with substantial reductions in respiratory syncytial virus (RSV)–related lower respiratory tract infection (LRTI) hospitalizations among infants at elevated risk, including those born preterm or with congenital heart disease (CHD).¹ The findings, derived from linked national registry data during the 2024 RSV season, add real-world evidence to support use of the long-acting monoclonal antibody in populations historically prioritized for prophylaxis.

RSV remains a leading cause of hospitalization in infants, particularly among those born prematurely or with underlying cardiopulmonary conditions.² Chile implemented a universal infant immunization strategy with nirsevimab in 2024, replacing a targeted palivizumab program.¹ The current subgroup analysis of the NIRSE-CL study evaluated outcomes specifically in higher-risk infants, a group underrepresented in prior observational studies.

“To date, most observational studies have reported the outcomes associated with nirsevimab in healthy infants in the northern hemisphere and in Chile, whereas evidence in populations with a higher risk of RSV disease has been limited to clinical trials,” wrote investigators.

Real-world effectiveness in high-risk infants

Investigators conducted a population-based, matched case-control study using nationwide birth, immunization, and hospital discharge registries. The analysis included 177 infants hospitalized for RSV-related LRTI and 708 matched controls. Matching accounted for prematurity, CHD, region, and age, with additional adjustments for sex, gestational age, and birth weight.

The study population comprised several risk strata, including extremely preterm infants with gestational age less than 32 weeks or birth weight below 1500 g, infants with CHD, and a broader at-risk group that included preterm infants born before 36 weeks. Median age at the end of follow-up was approximately 210 days.

Overall, nirsevimab was associated with an 84.3% reduction in the risk of RSV-related LRTI hospitalization among at-risk infants (95% CI, 67.0% to 92.5%). Among high-risk infants, defined as those with extreme prematurity or CHD, the estimated risk reduction was 85.1% (95% CI, 60.2% to 94.4%).

Subgroup analyses showed variability across risk categories. Among infants with CHD, nirsevimab was associated with a 96.3% reduction in hospitalization risk (95% CI, 65.5% to 99.6%). In contrast, estimates for extremely preterm infants were lower and not statistically significant, with a 65.9% reduction (95% CI, −10.8% to 89.5%). Investigators noted that smaller sample sizes may have limited precision in this subgroup.

Among preterm infants without additional high-risk conditions, the estimated reduction in hospitalization risk was 85.1% (95% CI, 55.1% to 95.1%).

Population-level impact and safety signals

Using historical hospitalization patterns, investigators conducted a counterfactual analysis to estimate population-level impact. Among at-risk infants, universal immunization with nirsevimab was associated with an estimated 71.5% relative reduction in RSV-related hospitalizations compared with a projected palivizumab-only scenario. This corresponded to approximately 482 hospitalizations averted and a number needed to immunize of 22.

In high-risk infants, the estimated relative reduction reached 81.2%, with a number needed to immunize of approximately 19. For non–high-risk preterm infants, the reduction was more modest at 51.8%.

Safety data were derived from passive surveillance. A total of 18 adverse events following immunization were reported, including 4 classified as serious. No new safety concerns were identified, although detailed characterization of events was limited.

Clinical context and interpretation

Palivizumab has historically been reserved for a small subset of infants at highest risk because of the cost and the need for monthly dosing. Nirsevimab, administered as a single dose, offers a broader preventive strategy that may simplify implementation and expand coverage.

These findings align with prior clinical trial data demonstrating efficacy of nirsevimab in preventing RSV-related hospitalization, though most earlier real-world studies focused on healthy infants. The current analysis extends those observations to higher-risk populations, including those previously eligible for targeted prophylaxis.

“However, future work should evaluate maternal RSV immunization alongside infant monoclonal antibody strategies to inform optimal prevention policies across risk groups,” wrote investigators.

References

1. Sauré D, Torres JP, Goic M, et al. Nirsevimab in high-risk infants in a respiratory syncytial virus prevention strategy. JAMA Netw Open. 2026;9(4):e266042. doi:10.1001/jamanetworkopen.2026.6042
2. Li Y, Wang X, Blau DM, et al; Respiratory Virus Global Epidemiology Network; RESCEU investigators. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis. Lancet. 2022;399(10340):2047-2064. doi:10.1016/S0140-6736(22)00478-0