Examining RSV Breakthrough Infections After Nirsevimab

Key Takeaways

• Among infants hospitalized with RSV bronchiolitis at a Rome hospital, preterm birth was more common in those admitted despite prior nirsevimab than in unimmunized infants (12.3% vs. 5.5%); comorbidities were numerically more common (8.6% vs. 3.5%) but not significantly so.
• Prior nirsevimab was significantly associated with lower odds of supplemental oxygen in the primary model, but the association was not statistically significant after adjustment for epidemic season.
• Among hospitalized infants needing oxygen, prior nirsevimab was not independently associated with advanced respiratory support.
• Three breakthrough infants received invasive mechanical ventilation despite having no documented prematurity or comorbidity.

Vittucci and colleagues retrospectively compared 536 RSV-positive infants younger than 12 months hospitalized at Bambino Gesù Children’s Hospital in Rome, Italy. The study spanned three epidemic seasons, from October 1, 2023, through May 31, 2026; 81 infants had documented prior nirsevimab in the latter two seasons, and the first preceded its availability. RSV was detected by polymerase chain reaction (PCR) on a respiratory specimen within 72 hours of admission, usually with a multiplex panel. Prior exposure required nirsevimab at least 96 hours before symptoms and seven days before admission. Prematurity meant birth before 37 completed weeks. Maximum recorded support ranged from low-flow oxygen and high-flow nasal cannula to helmet continuous positive airway pressure (CPAP)/noninvasive ventilation and invasive mechanical ventilation; the latter two defined advanced support. Of 439 infants identified as receiving oxygen, one lacked an exposure record and was excluded from the advanced-support comparison. Primary logistic models adjusted for age, prematurity, and comorbidities; sensitivity analyses added epidemic season or considered viral coinfection separately.

Comorbidities were more prevalent among breakthrough admissions, and infants aged 9–12 months were more represented in that group than among unimmunized inpatients. Across all breakthrough admissions, the median interval from nirsevimab administration to hospitalization was 53.5 days. Among the 13 breakthrough infants aged 9–12 months, the median was 291 days.

Prior nirsevimab was associated with lower odds of supplemental oxygen after adjustment for age, prematurity, and comorbidities: adjusted odds ratio (aOR) 0.33, 95% confidence interval (CI) 0.19–0.57, p < 0.001.

After additional adjustment for epidemic season, the oxygen association was attenuated and no longer statistically significant: aOR 0.54, 95% CI 0.23–1.25, p = 0.150. Among infants receiving oxygen, prior nirsevimab was not independently associated with advanced support in either the primary or season-adjusted model.

Because the cohort included only hospitalized infants, it had no denominator of all nirsevimab recipients or their time at risk. The findings cannot establish breakthrough incidence, protection duration, population-level effectiveness against hospitalization, or waning from the older subgroup’s interval since immunization. Nirsevimab availability also varied by season, making temporal confounding possible. Single-center retrospective records may be incomplete, while selective immunization or selection into hospitalization could influence the observed case mix. Few severe events also limit interpretation of advanced-support comparisons; a nonsignificant association does not establish equal severity.

The authors described a different profile among hospitalized breakthrough infants than among unimmunized inpatients. The oxygen association was not statistically significant after adjustment for season, and immunization status did not independently distinguish advanced-support needs once oxygen was required.

Clinician Questions

Did viral coinfection change the nirsevimab–respiratory support associations in hospitalized infants with RSV bronchiolitis?

Six infants tested with RSV-only PCR were excluded from coinfection analyses because their coinfection status could not be assessed. Additional adjustment for viral coinfection left the primary-model pattern similar: prior nirsevimab remained associated with lower oxygen requirement but was not independently associated with advanced support among infants already receiving oxygen. This analysis did not resolve possible confounding by epidemic season.

Was age independently associated with advanced ventilation among oxygen-treated infants hospitalized with RSV bronchiolitis?

Among infants receiving oxygen, older age was associated with lower adjusted odds of advanced ventilatory support per month after accounting for nirsevimab status, prematurity, and comorbidities.