Authors: Kunling Shen, Lance Rodewald, Yonghong Yang, Gary Wong, Leyla Namazova Baranova, Lanny Rosenwasser, Adel Alharbi, Anne Chang, Anne Goh, Antonella Muraro, Basil Elnazir, Bernard Kinane, Chris O'callaghan, Eitan Kerem, Hilary Hoey, Jim Buttery, Jiu-yao Wang, Kazunobu Ouchi, Rosemary Horne, Rina Triasih, Ruth Etzel, Varinder Singh, Spencer Li, Yu Guan
Description:Respiratory syncytial virus (RSV) is the leading cause of severe acute lower respiratory tract infection (LRTI) in infants and young children, resulting in an estimated 33 million infections annually, >3 million hospitalizations, and >100 000 deaths in children under 5 years globally, with a mortality rate of up to 9% in low-resource countries, which have 99% of the global RSV mortality.1 RSV infection is associated with an increased risk of respiratory failure, admission to the ICU, mechanical ventilation, use of oxygen therapy, and death.2, 3 Severe RSV-LRTI in early childhood increases the risk of long-term respiratory disorders such as repeated wheezing or asthma.4-6 Most children have had serologically proven RSV infection by age 2 years, representing a major healthcare burden.7, 8 RSV epidemics increase health resource utilization (HRU). For example, the early arrivals of the RSV epidemic seasons during 2022 and 2023 overlapped with the coronavirus disease 2019 (COVID-19) and influenza epidemics and resulted in severe pressure and impact on the healthcare systems of multiple countries.9-12
Risk factors such as socio-economic status influence morbidity and mortality from acute RSV infection, with low- and middle-income countries being disproportionately impacted.13 Young age at time of infection is a key risk factor. A systematic analysis of the global burden of RSV mortality found that 45% of the 101 400 RSV-caused deaths in children under 5 years of age occurred in infants during the first 6 months of life and that 3.6% of all deaths among infants 2–6 months of age were caused by RSV.1 Premature infants and infants with underlying disease are at high risk for severe RSV infection; however, most of the RSV burden occurs in previously healthy infants.14, 15 There is therefore a need to protect all infants from RSV infection, which can greatly reduce HRU, thereby reducing pressure on the healthcare system, especially during the RSV epidemic season.
RSV infection in infants has been identified as a major global priority, but currently, there are no effective anti-RSV drugs or vaccines licensed for infants. An earlier RSV monoclonal antibody (mAb) product, palivizumab, is available but needs to be given intramuscular monthly and is recommended for only a small proportion of infants with certain underlying medical conditions. A solution to tackle this unmet need for all-infant protection (AIP) against RSV has yet to be widely implemented.16 Recent advances in RSV prevention, including long-acting prophylactic mAbs and maternal RSV vaccination, show significant promise. We are on the cusp of a new era in RSV prevention. Maternal vaccination can protect infants born during or immediately before RSV season, with protection waning after a few months. Real-world evidence has shown that prophylactic mAbs represent an avenue for effectively protecting all infants during their first RSV season.17-19 Pivotal clinical trials and real-world evidence during the first RSV season demonstrated good safety and effectiveness of prophylactic mAbs for preventing LRTIs and associated hospitalizations.19-22 As of June 2024, more than a dozen countries, including the United States, Spain, the United Kingdom, Luxembourg, and Austria, recommend prophylactic mAbs for the prevention of RSV in infants and young children. These evidence-based recommendations are from national immunization technical advisory groups. Countries will conduct evaluations in their immunization programs to ensure the accessibility of prophylactic mAbs for all infants and some young children.23-36
In view of the global burden of RSV disease among infants, in September 2024, the World Health Organization and its Strategic Advisory Group of Experts on Immunization (SAGE) recommended that “all countries introduce passive immunization for the prevention of severe RSV disease in young infants.”37
Thus, all infants are the key target population for protection from RSV-LRTI, and prophylactic mAbs represent the best available preventive measure.