Balanced on the Biggest Wave: Nirsevimab for Newborns

Respiratory syncytial virus (RSV) is the leading cause of hospitalization in infancy in the United States. Nearly all infants are infected by 2 years of age, with bronchiolitis requiring hospitalization often occurring in previously healthy children and long-term consequences of severe disease including delayed speech development and asthma. Incomplete passage of maternal immunity and a high degree of genetic variability within the virus contribute to morbidity and have also prevented successful neonatal vaccine development. Monoclonal antibodies reduce the risk of hospitalization from severe RSV disease, with palivizumab protecting high-risk newborns with comorbidities including chronic lung disease and congenital heart disease. Unfortunately, palivizumab is costly and requires monthly administration of up to five doses during the RSV season for optimal protection.Rapid advances in the past two decades have facilitated the identification of antibodies with broad neutralizing activity and allowed manipulation of their genetic code to extend half-life. These advances have culminated with nirsevimab, a monoclonal antibody targeting the Ø antigenic site on the RSV prefusion protein and protecting infants from severe disease for an entire 5-month season with a single dose. Four landmark randomized controlled trials, the first published in July 2020, have documented the efficacy and safety of nirsevimab in healthy late-preterm and term infants, healthy preterm infants, and high-risk preterm infants and those with congenital heart disease. Nirsevimab reduces the risk of RSV disease requiring medical attention (number needed to treat [NNT] 14-24) and hospitalization (NNT 33-63) with rare mild rash and injection site reactions. Consequently, the Centers for Disease Control and Prevention has recently recommended nirsevimab for all infants younger than 8 months of age entering or born during the RSV season and high-risk infants 8-19 months of age entering their second season. Implementing this novel therapy in this large population will require close multidisciplinary collaboration. Equitable distribution through minimizing barriers and maximizing uptake must be prioritized.