Molecular epidemiology of respiratory syncytial virus illness in children and adults in Seattle, WA over five seasons

Background: Respiratory syncytial virus (RSV) is the most important cause of pneumonia in children aged <5 years worldwide and can cause severe disease in elderly and high-risk adults. Multiple RSV strains co-circulate and evolve over seasons. We seek to describe the molecular epidemiology and evolution of RSV over five seasons in Seattle, WA, USA. Methods: From 2011 to 2016, subjects aged 6 months and older seeking outpatient care for acute respiratory illness (ARI) at Kaiser Permanente Washington were enrolled in the United States Influenza Vaccine Effectiveness Network (Flu VE Network) and a respiratory swab was collected. Real-time polymerase chain reaction (RT-PCR) was performed to identify and subtype RSV positive samples. A subset of RSV samples were sequenced using primer-amplified next generation sequencing. Associations between RSV genotype ON1 and severe disease, defined as illness requiring hospitalization or chest imaging in the following 30 days, were assessed using a multivariable logistic regression model. Results: A total of 8,749 individuals were enrolled in the Flu VE Network and RSV was detected in between 11.0 (2015-6) and 16.4 (2012-3) percent of ARI episodes annually. The predominant RSV subtype switched every 1-2 years. RSV-A cumulative incidence was highest in 2015-6 at 13.7 ARI cases per 1,000 population (confidence interval [CI] 11.3, 16.1) and RSV-B incidence was highest in 2014-5 at 15.4 ARI cases per 1,000 (CI 13.6, 17.3). The ratio of RSV-A to RSV-B incidence differed across age groups (p<0.001). Forty of 43 (93%) RSV-A sequenced specimens were the ON1 genotype and the BA genotype represented 40 of 42 (95%) RSV-B specimens. Of 1133 RSV-positive ARIs, 213 (18%) were categorized as severe disease. Neither RSV subtype A or genotype ON1 was associated with severe disease (p>0.05). Conclusion: There was limited genotype diversity of the RSV genotypes circulating in our outpatient cohort with significant predominance of the ON1 and BA genotypes across all seasons. There was no evidence of an association between molecular subtype or genotype and severe disease. With multiple RSV vaccine candidates in development, understanding the genetic diversity and circulation of RSV viruses within a population is important for analyzing the effects of a vaccine on the evolution and molecular epidemiology of RSV.