Nirsevimab cuts RSV burden in newborns

A retrospective study from Italy shows an association between nirsevimab prophylaxis and a lower risk of respiratory syncytial virus (RSV) hospitalizations and a milder disease course.

“[W]e found robust evidence that nirsevimab was associated with a significant reduction in RSV-related hospitalizations during the first winter of life. With 79.2 percent prophylaxis coverage of the study population, nirsevimab was associated with a 68 percent relative reduction in RSV hospitalization risk, closely mirroring the efficacy reported in pivotal clinical trials and prior studies,” the investigators said.

Nirsevimab prophylaxis was associated with a reduction in within-month individual hazard of RSV hospitalization (hazard ratio [HR], 0.11; p<0.001), as supported by logistic regression (odds ratio [OR], 0.11; p<0.001). [JAMA Netw Open 2025;8:e2544679]

Looking at the population level, there was a lower hazard of RSV hospitalization during the post-nirsevimab season, which was between April 1, 2024 and March 31, 2025 (HR, 0.32; p<0.001).

In infants hospitalized with RSV lower respiratory tract infection* (LRTI), nirsevimab prophylaxis was associated with a substantial reduction in the need for high-flow nasal cannula (OR, 0.33; p=0.04), but not with shorter length of stay (incidence rate ratio, 0.81; p=0.09).

Prematurity, household exposure

The risk of RSV hospitalization was markedly higher among premature infants (HR, 2.93; p<0.001 [OR, 2.85; p<0.001 on logistic regression]), which was similarly observed in the population-level analysis (HR, 2.96; p<0.001). Prematurity was also associated with a substantially higher risk of non-RSV hospitalization (HR, 6.58; p<0.001).

There was also an association between living with older siblings and increased risk of RSV hospitalization (HR, 4.57; p<0.001 [OR, 4.71; p<0.001 on logistic regression]). This pattern was also seen in the population-level model (HR, 4.37; p<0.001). The association remained for non-RSV LRTI (HR, 6.88; p<0.001).

“[T]he residual risk observed among preterm infants and those with older siblings suggests that nirsevimab alone may not fully address the heightened susceptibility associated with these factors,” the researchers explained.

The susceptibility of preterm infants to RSV may be attributed to immature immune responses. Household transmission is also considered a major driver of infant RSV, with evidence consistently demonstrating a higher risk in larger households and in the presence of older siblings. [BMC Pediatr 2023;23:326; Ital J Pediatr 2015;41:40; Lancet 2024;403:1241-1253]

These risk factors underscore the need for additional targeted prevention measures to optimize RSV prevention in these susceptible groups, they noted.

Public health strategy

The study included 13,624 newborns (mean gestational age 39.4 weeks, 51.4 percent boys) from five participating hospitals. Of these, ~50 percent had an older sibling within the household, and 4.8 percent were born preterm. About 51 percent of births occurred during the pre-nirsevimab season (April 1, 2023 to March 31, 2024), while the remaining 49 percent occurred during the post-nirsevimab season.

After the universal nirsevimab prophylaxis implementation and after obtaining informed parental consent, all newborns received nirsevimab before hospital discharge after birth.

Overall, 292 infants (2.1 percent) were hospitalized for an RSV-related event, which primarily occurred during the pre- vs post-nirsevimab season (75.3 percent vs 24.7 percent; p<0.001). Of the 72 hospitalizations during the post-nirsevimab season, 54 (75 percent) occurred in infants who had not received prophylaxis.

“Collectively, our results strongly endorse the integration of nirsevimab into routine immunization schedules and emphasize the need for continued surveillance to maximize its benefits on infant health outcomes,” the investigators said.

Despite the substantially lower RSV hospitalization risk with nirsevimab prophylaxis, the findings underscore the need for targeted supplemental strategies in high-risk infants to further alleviate the RSV disease burden, they added.

Complementary public health interventions may include different nirsevimab dosing regimens, maternal vaccination, and reinforced infection-control practices in households with high-risk infants, they noted.