Household Transmission and Genomic Diversity of Respiratory Syncytial Virus (RSV) in the United States, 2022-2023

Background Household transmission of respiratory viruses may drive community spread. Few recent studies have examined household respiratory syncytial virus (RSV) transmission in the United States. Methods We conducted a prospective community-based cohort study from 1 June 2022 to 31 May 2023. Participants had blood samples collected and completed nasal swabs and surveys at least weekly, irrespective of symptoms. We tested serum for RSV antibody, nasal swabs by quantitative reverse transcription polymerase chain reaction (RT-qPCR), and performed whole genome sequencing. We evaluated secondary RSV transmission and associated risk factors based on a log-linear Poisson regression model. Results RSV was detected among 310 (10%) participants within 200 (20%) households. Most (94%) index cases were symptomatic. We identified 37 cases of potential secondary transmission within 14 days of a distinct index case (10%, 95% confidence interval [CI]: 7%, 14%); median age of index and secondary cases were 6 (interquartile range [IQR]: 3-10) and 35 (7-41) years, respectively, with 89% (24/27) of index cases aged 6 months to 12 years. Factors associated with increased risk of RSV transmission included index case viral detection >= 1 week and contact age <= 12 years. Of 120 sequenced specimens, the main lineages represented were A.d.5.2 (n = 37) and A.d.1 (n = 30). Sequenced viruses from households with >= 2 RSV infections were similar when occurring within <= 14 days (mean pairwise difference 4 [range 0-13], n = 17 households), compared to those >14 days (137 [37-236], n = 2). Conclusions Most RSV household transmission occurs from infants and young children to adults. Viral genome sequencing demonstrated that multiple household infections within a 14-day period are likely due to within-household transmission.