Clinical Profile of RSV Breakthrough Infections After Nirsevimab Introduction

The introduction of universal prophylaxis with nirsevimab for all children in their first epidemic season has substantially reduced the burden of respiratory syncytial virus (RSV). However, a small number of breakthrough infections continue to occur despite immunization, mostly in previously healthy infants, and these cases remain incompletely characterized. We conducted a retrospective study across three epidemic seasons at a third-level hospital, including 536 RSV-positive children under 12 months of age hospitalised for bronchiolitis. Immunised infants with breakthrough infection showed a higher prevalence of prematurity and comorbidities than unimmunised infants, and were more frequently represented in the 9-12-month age group, with a median of 291 days since nirsevimab administration. Immunised infants had significantly lower odds of requiring supplemental oxygen (aOR 0.33, 95% CI 0.19-0.57, p < 0.001). However, once oxygen therapy was required, immunisation status did not independently predict the need for advanced ventilatory support. Severe breakthrough cases requiring invasive mechanical ventilation occurred even among infants without traditional risk factors. These findings confirm the substantial real-world impact of universal nirsevimab prophylaxis while underscoring the need for continued clinical vigilance and further research into the mechanisms underlying breakthrough disease.