Genomic Epidemiology of Respiratory Syncytial Virus in a New England Hospital System, 2024

Respiratory syncytial virus (RSV) is one of the main seasonal respiratory pathogens in the United States and causes up to 240,000 hospitalizations per year among children under five and adults over 60. RSV is classified into two subtypes, RSV-A and RSV-B. Although several RSV vaccines and a preventative monoclonal antibody, nirsevimab, were recently approved by the FDA, vaccination and prevention measures remain low even among age groups at higher risk for hospitalization. To better understand the epidemiology of RSV, we analyzed RSV-positive nasopharyngeal swabs from Boston Medical Center and its satellite clinics from January to June 2024 using amplicon-based whole-genome sequencing. Of the 59 samples collected, 19 were from children under five years of age, and 17 were from adults over the age of 60. Fifty-four samples sequenced successfully, with over 90% of the genome at a minimum of 20-fold coverage.

We found that over 80% of the samples were RSV-B; 48 RSV-B samples and 6 RSV-A samples. This represents a major switch from 2022, when Boston RSV samples were ~90% RSV-A. 45 of 48 RSV-B samples mapped into a single clade (B.D.E.1). These samples do not cluster to a single source within the B.D.E.1 clade, suggesting that the predominance of RSV-B is multifactorial, not the selective expansion of a single variant. We also found examples of identical/highly related genomes among our samples, suggesting clustered transmission. One infant had documented nirsevimab therapy forty days prior to RSV isolation. None of the adults had documented RSV vaccination, and mutations associated with nirsevimab resistance or vaccine escape were not observed. Our work highlights the importance of genomic surveillance for respiratory pathogens as a means to monitor transmission dynamics, such as the unexpected switch from RSV-A to RSV-B subtype dominance, to identify examples of superspreading events, and to understand the epidemiological changes that may be associated with nirsevimab and RSV vaccines.