Nirsevimab in High-Risk Infants in a Respiratory Syncytial Virus Prevention Strategy

Nirsevimab is highly effective in preventing respiratory syncytial virus (RSV) infection in healthy infants. Evidence among infants at higher risk of severe RSV disease, such as those born preterm or with congenital heart disease (CHD), remains limited to clinical settings.

To evaluate the association of nirsevimab with the prevention of RSV-related hospitalizations among at-risk infants after implementation of a universal immunization strategy in Chile.

This case-control study used nationwide health registries of all public and private hospitals in Chile during the 2024 RSV season following the launch of a universal RSV immunization program with nirsevimab. The case group included at-risk infants born preterm (gestational age <36 weeks) or with congenital heart disease (CHD) hospitalized for RSV-related lower respiratory tract infection (LRTI), while the control group included infants not hospitalized for RSV-related LRTI. Each case infant was matched to 4 control infants by age, prematurity or CHD status, and geographic region.

A single intramuscular dose of nirsevimab administered to all infants born up to 6 months before April 1, 2024, and those born between April 1 and September 30, 2024.

The main outcome was RSV-related LRTI hospitalization. Associations were assessed for at-risk infants and high-risk infants (born extremely preterm at gestational age <32 weeks or with CHD), with nirsevimab outcomes associated with RSV-related LRTI hospitalization estimated as (1 - adjusted odds ratio) × 100, with 95% CIs.

Of 179 RSV-related LRTI hospitalizations among at-risk infants (including 58 [32.4%] with extreme prematurity, 41 [22.9%] with CHD, and 87 [48.6%] without extreme prematurity and CHD [non-high risk]; categories not mutually exclusive), 177 (median [IQR] age, 210.0 [148.0-266.0] days; 109 male [61.3%]) were successfully matched to 708 control infants (including 55 of 58 [94.8%] with extreme prematurity, 39 of 41 [95.1%] with CHD, and 87 [100%] non-high risk; median [IQR] age, 210.5 [147.8-268.5] days; 393 male [55.5%]). A total of 156 case infants (88.1%) and 689 control infants (97.3%) received nirsevimab. In subgroup analyses, nirsevimab receipt in case vs control infants was 79 of 90 (87.8%) vs 351 of 360 (97.5%) among high-risk infants, 50 of 55 (90.9%) vs 213 of 220 (96.8%) among extremely preterm infants, 33 of 39 (84.6%) vs 153 of 156 (98.1%) among infants with CHD, and 77 of 87 (88.5%) vs 339 of 348 (97.4%) in non-high-risk infants. Nirsevimab was associated with a reduced risk of RSV-related LRTI hospitalization of 84.3% (95% CI, 67.0%-92.5%) among all at-risk infants, 85.1% (95% CI, 60.2%-94.4%) among infants with extreme prematurity and CHD combined, and 96.3% (95% CI, 65.5%-99.6%) among infants with CHD but was not associated with a reduced risk for hospitalization among infants with extreme prematurity alone (65.9%; 95% CI, -10.8% to 89.5%).

This case-control study of Chile's nationwide nirsevimab immunization program found that RSV-related LRTI hospitalizations among infants at higher risk of severe disease were substantially reduced. These findings support replacing targeted palivizumab prophylaxis with a broader, universal nirsevimab strategy as part of RSV prevention policy.