Estimating the burden of respiratory syncytial virus infection in young children in England: a novel approach to community-based serological surveys through data linkage

Bronchiolitis caused by respiratory syncytial virus (RSV) is the most common reason for hospital admissions in infants. The community burden of RSV is less well understood. We used a unique dataset linking serial serological data, questionnaires, and routinely collected health records to undertake the first community-based serological survey of RSV in England. We used stored blood samples, tested for immunoglobulin G RSV postfusion F antibody, linked to questionnaires and primary and secondary care records from the Born in Bradford cohort study, collected at birth, and ages 1 and 2 years. We used finite mixture models to classify children as RSV infected or not infected according to their antibody concentrations. We fitted multivariable Poisson regression models with robust error variances to identify factors associated with increased risk of primary RSV infection at ages younger than 1 year and 1–2 years. The study included 490 children. By their first birthday, 258 children (53%, 95% CI 48–57%) had serological evidence of past RSV infection, 99 (38%) of whom contacted health-care services during peak RSV season (November–January) due to a respiratory tract infection. Having older siblings (adjusted risk ratio [aRR] 1·52, 95% CI 1·21–1·92, comparing one to no older siblings), Pakistani ethnicity (1·31, 1·04–1·65, compared with White British), blood sample taken outside October–December (1·74, 1·35–2·24 for January–March and 1·60, 1·23–2·08 for April–June, compared with October–December), and attending formal childcare (1·40, 1·12–1·75, compared with no formal childcare) were predictive of RSV infection in infancy. A further 164 children (33%, 95% CI 29–38%) were newly infected at ages 1–2 years, 58 (35%) of whom had contact with health-care services. 14% (95% CI 11–17%) had no evidence of RSV infection by age 2 years. Around half of children are infected with RSV during the first year of life, and one in seven children remain unexposed after their second year. Our findings will inform future analyses to assess the cost-effectiveness of RSV vaccination programmes. Our novel approach reusing stored blood samples and linked data present a time-efficient and cheap method for future serological surveys of RSV. Wellcome Trust Seed Award In Science (grant reference number 207673/Z/17/Z).