Second-Season RSV Immunization Worked for Eligible Children

— U.S. study reports 75% effectiveness against RSV-associated hospitalization in the second season

WASHINGTON -- Real-world data backed the effectiveness of second-season nirsevimab (Beyfortus) immunizations against hospitalizations for children at high risk for severe respiratory syncytial virus (RSV) illness.

In the case-control study of nirsevimab-eligible children ages 8 to 23 months who were hospitalized with respiratory symptoms, the rate of RSV-positivity was less common in patients who had received nirsevimab (20% vs 42%, P<0.001), reported Angela Campbell, MD, MPH, of the CDC.

The adjusted estimated effectiveness of the long-acting monoclonal antibody against RSV-associated hospitalizations came out to 75% (86% when given within the 60 days before symptom onset and 66% when given earlier than that), according to findings presented at the IDWeekopens in a new tab or window annual meeting.

"These data provide valuable real-world evidence of nirsevimab effectiveness against RSV hospitalizations for nirsevimab-eligible children in their second RSV season," said Campbell. "Overall, these estimates support the initial recommendation for use of nirsevimab as a preventive strategy in those high-risk groups."

The high-risk groups in questionopens in a new tab or window: children with chronic lung disease of prematurity, those severely immunocompromised, American Indian/Alaska Natives, and those with cystic fibrosis.

"Truly, estimating the effectiveness of nirsevimab among this group of kids is challenging because the proportion of children that actually make up the population in those groups is only estimated to be about 2 to 4% and even that might be an overestimate of the kids that meet those criteria," Campbell told the audience. "And so, because of that, you actually need large surveillance platforms to evaluate effectiveness in this population, and there are really not a lot of effectiveness data in preventing severe RSV disease among high-risk children in this second season."

For her study, the investigators relied on the Overcoming RSV Network of 26 hospitals in 24 U.S. states and covered two seasons of data (November 2024 to March 2026).

Campbell cited prior attempts to estimate nirsevimab's effectiveness against RSV hospitalizations in the second season: Figures around 89% have come out of research on American Indian/Alaska Natives; more concerningly, a recent study from Spain suggested the effectiveness was only 42%.

"I will note that that study is quite different than ours. The recommendations in Spain have a much broader indication. They had a lot of premature children less than 25 weeks, and they had an extremely small sample size, just 22 cases in that. So it is going to be quite different," she cautioned.

Of note, broader indications for RSV immunization in the second season are also in play for Americans starting this season. The American Academy of Pediatrics recently added four new indicationsopens in a new tab or window for immunization in children age 8-19 months: preterm birth (<32 weeks' gestation), hemodynamically significant congenital heart disease, anatomic pulmonary abnormalities or neuromuscular disorders, and Down syndrome or other chromosomal differences.

"So it's a huge group of kids now that are being recommended to receive nirsevimab in that second season," Campbell said.

She said her group does not have plans for further analysis on this expanded group. "We actually don't have ongoing funding for Overcoming. So this was the last season of the network at this time," she lamented. "Other people can carry this on and do that analysis without having to require such a network like we had."

Campbell's group conducted a hospital-based case-control study using caregiver interview and medical record abstraction. Hospitalized kids with respiratory symptoms during their second RSV season and a positive RSV test were matched to controls who had a negative RSV test.

Included were 231 nirsevimab-eligible hospitalized kids: 128 from the 2024-2025 RSV season and 103 from the 2025-2026 RSV season. Median age was 16 years.

The proportion who tested positive for RSV was 55% from the 2024-2025 season and 45% from the 2025-2026 season.

These RSV-positive cases were numerically but not statistically more likely to have a worse clinical course, more commonly involving acute respiratory failure (36% vs 25% for RSV-negative peers, P=0.07). Meanwhile, there was no difference in intensive care unit admission (46% vs 45%), extracorporeal membrane oxygenation (0.9% vs 0.8%), or death during hospitalization (0% vs 0.8%).

Study participants mostly had chronic lung disease of prematurity (84% for RSV-positive kids vs 70% for RSV-negative kids) and less frequently had severe immunocompromise (7% vs 18%).

Campbell suggested that while the study had the inherent limitations of an observational analysis, a randomized trial would probably not be feasible. "The test-negative design does allow us to select cases and controls from the same source population with the same acute respiratory symptoms, so that should reduce confounding and selection bias," she added.