Symptomatic and Asymptomatic Norovirus Infections in Early Life; the PREVAIL Cohort, 2017–2020

INTRODUCTION: Norovirus is the leading cause of medically attended acute gastroenteritis in the United States. Efforts to reduce the disease burden are constrained by uncertainty around fundamental aspects of norovirus epidemiology. This study describes characteristics of norovirus infections and explores potential risk factors for symptomatic infections in early life. METHODS: The Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal (PREVAIL) birth cohort study followed 245 children from birth to 2 years of age with weekly stool sample collection and symptom surveys. Stool samples were tested by reverse transcriptase-realtime polymerase chain reaction to detect norovirus genogroup (G)I and GII; positive samples were genotyped. Infections accompanied by diarrhea and/or vomiting were considered symptomatic. Children were categorized as adherent if they participated for ≥18 months and submitted ≥70% of samples. RESULTS: A total of 72 GI and 330 GII norovirus infections (among 156 children) were identified. One-fifth (20.8%) of adherent children experienced ≥1 norovirus infection by 6 months of age, increasing to 84.2% of children by 2 years of age. About one-third of infections were symptomatic, including half of infections with cycle threshold values <25. Infection with norovirus genotype GII.4 Sydney was the strongest predictor of symptomatic infection in adjusted analyses, as was older age and higher viral load. Childcare attendance, breastfeeding, mother's secretor status, and prior infections were not predictive of symptom status. CONCLUSIONS: This study highlights fundamental characteristics of norovirus epidemiology in early life with implications for understanding the full natural history of the disease, disease transmission, and prevention approaches.