Nirsevimab Benefits Beyond the First Year After Birth

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract (LRTI) globally and the second leading pathogen to cause infant mortality.1,2 Most deaths occur in low- and middle-income countries.1,3 In the United States, an estimated 58 000–80 000 young children are hospitalized annually with RSV, with the highest incidence in infants aged less than 6 months,4,5 most of whom are healthy. RSV prevention has been long recognized as a priority to improve children’s health; however, the path to achieve this has been defined by both significant breakthroughs and setbacks.4In 1998, palivizumab, a humanized monoclonal antibody, was developed.6 It proved to be very effective at preventing severe RSV disease but remained costly and required multiple doses per season because of its short half-life. Therefore, its use was restricted to high-risk populations (eg, those with chronic lung disease), leading to implementation challenges domestically and globally.7In 2013, the structural detail of RSV’s prefusion F protein, the key protein against which neutralizing antibody is formed following infection, was described.8,9 This finding led to the development of the 3 licensed RSV vaccines and 2 long-acting monoclonal antibodies: nirsevimab and clesrovimab.10,11 With the advent of these new, safe, and more affordable tools, the RSV-prevention landscape changed and the opportunity arose to broaden its indications from only high-risk patients to all young infants. Spain was one of the first countries to implement nirsevimab for all infants aged less than 6 months during their first RSV season. This resulted in a dramatic decrease in medically attended RSV-associated illness and hospitalization in the first year nirsevimab was available12–14 and a high-product effectiveness against RSV-severe disease. However, our understanding of the longer-term benefits of nirsevimab beyond the first year of age remain limited.In this issue of Pediatrics, Moreno-Perez and colleagues15 report a multicenter case-control study designed to assess the association between nirsevimab administration in infants aged less than 6 months during the 2023–2024 season and the risk of hospitalizations because of LRTI during the 2024–2025 season. Infants who received nirsevimab during their first RSV season had a 17% reduction in risk of hospitalization caused by any LRTI in their second RSV season compared with the group that did not. This impact was greater, with a 25.4% reduction, for those with confirmed RSV infection and a 27.7% reduction for infants with history of inhaler use before admission. Therefore, nirsevimab immunoprophylaxis appears to last into infants’ second RSV season. The authors hypothesize this prevention is because of lung damage averted from severe RSV infections or potentially nirsevimab antibodies still being present during the second season.Three prior studies have evaluated the impact of nirsevimab on infants’ second season. Two studies did not find a statistically significant benefit in the second season, but a third one did.16–18 Coma and colleagues found a decrease in the rate of RSV pediatric intensive care unit admission days in the second season, but the study was underpowered to find a significant difference.19 The study by Gonzalez-Bertolin and colleagues focused on safety and was also underpowered to assess benefit.20 However, Razzini and colleagues found that, compared with historical cohorts, nirsevimab decreased RSV-LRTI–related hospitalizations by 55.3% in the second season.18The findings from Moreno-Perez and colleagues underscore the importance of improving nirsevimab uptake. The initial uptake of the RSV prophylaxis in the United States was slow. Because of shortages and late availability during the 2023–2024 RSV season, only 4%–12% of all eligible infants received nirsevimab.19,20 Infant protection from nirsevimab or maternal vaccination ranged from an estimated 11% to 53%, with disparities by race and ethnicity, across the United States during the initial season following their approval.21–23 Rates of prophylaxis have improved somewhat, but the disparities persist.24Currently, these monoclonals are recommended ONLY for a selected group of high-risk children including those with chronic lung disease or those who are severely immunocompromised.25 Because these agents are more affordable and longer-acting, other high-risk children may benefit from a second-season dose (eg, children who sustained prior lung injury following a severe LRTI in their first year of life because of another pathogen despite being otherwise healthy).26The study by Moreno-Perez and colleagues provides compelling evidence that RSV prophylaxis with nirsevimab is both safe and effective beyond the initial season of administration, an important addition to the growing body of real-world evidence supporting the strategy to prevent significant RSV infection. Clinicians should counsel families on this long duration of benefit. In an era in which public trust in science and vaccine-related communication is increasingly challenged, these findings carry particular significance. Robust, accessible evidence is essential to empower meaningful shared decision-making with families. These findings may also help with developing interventions to address the persistent disparities and improve outcomes for all.