Respiratory Syncytial Virus Genotypes and Disease Severity in Young Children Hospitalized with Bronchiolitis

Background: There is limited data on how different RSV genotypes and associated viral loads influence disease phenotypes. We characterized the genetic variability of RSV strains during five non-consecutive respiratory seasons, and evaluated the role of RSV subtypes, genotypes and viral loads on clinical disease severity. Methods: Healthy infants hospitalized with RSV bronchiolitis were prospectively enrolled and nasopharyngeal samples obtained within 24h of hospitalization for RSV load quantitation by PCR, typing and genotyping. Parameters of disease severity were assessed, and multivariate models constructed to identify virologic and clinical factors predictive of clinical outcomes. Results: From March 2004 to April 2011, we enrolled 253 patients (56.5 % males; median age 2.1 (1.1-4.0) months). RSV A infections predominated over RSV B (69% vs. 31%; p<0.001) and showed greater genotype variability. The most common genotypes were RSV A/GA2, A/GA5 and RSV B/BA. Infants infected with RSV GA5 had higher viral loads compared with GA2 or BA infection (p<0.01), independent of duration of symptoms. After adjusting for other covariates, RSV A/GA5 infections were associated with longer hospital stay. Conclusions: RSV A infections were more frequent than RSV B infections and displayed greater genetic variability. Infections with GA5 were independently associated with clinical disease severity. To define the host systemic immune response according to the different RSV types or genotypes identified, blood transcriptional profiles were analyzed in a subset of infants with RSV bronchiolitis enrolled during the last study season (2010-11; n=62) and 12 healthy asymptomatic age-matched controls. Of the 62 infants with RSV LRTI enrolled, 49 (79%) were infected with RSV A (GA2 n=43, GA5 n=5, non-typed n=1) and 13 (21%) with RSV B (BA n=12, non-typed n=1).