Interference between rhinovirus and other RNA respiratory viruses in the first 2-years of life: A longitudinal community-based birth cohort study.

BACKGROUND: Cross-sectional studies report negative associations between rhinovirus and other RNA respiratory viruses. However, longitudinal studies with frequent, serial sampling are needed to identify the directionality of this relationship and its nature. OBJECTIVE: To investigate the association between rhinovirus and other RNA respiratory viruses detected 1-week apart. METHODS: The Observational Research in Childhood Infectious Diseases cohort study was conducted in Brisbane, Australia (2010-2014). Parents collected nasal swabs weekly from birth until age 2-years. Swabs were analysed by real-time polymerase chain reaction. The association between new rhinovirus detections and five other RNA viruses (influenza, respiratory syncytial virus, parainfluenza viruses, seasonal human coronaviruses, and human metapneumovirus) in paired swabs 1-week apart were investigated. RESULTS: Overall, 157 children provided 8,101 swabs, from which 4,672 paired swabs 1-week apart were analysed. New rhinovirus detections were negatively associated with new pooled RNA respiratory virus detections 1-week later (adjusted odds ratio (aOR) 0.48; 95% confidence interval (CI): 0.13-0.83), as were pooled RNA virus detections with new rhinovirus detections the following week (aOR 0.34; 95%CI: 0.09-0.60). At the individual species level, rhinovirus had the strongest negative association with new seasonal human coronavirus detections in the subsequent week (aOR 0.34; 95%CI: 0.120.95) and respiratory syncytial virus had the strongest negative association with rhinovirus 1-week later (aOR 0.21; 95%CI: 0.050.88). CONCLUSION: A strong, negative bidirectional association was observed between rhinovirus and other RNA viruses in a longitudinal study of a community-based cohort of young Australian children. This suggests within-host interference between RNA respiratory viruses.

Respiratory Syncytial Virus-Associated Neurologic Complications in Children: A Systematic Review and Aggregated Case Series.

OBJECTIVES: To describe the features and frequency of respiratory syncytial virus (RSV)-associated severe acute neurologic disease in children. STUDY DESIGN: We performed a systematic review of the literature to identify reports of severe acute neurologic complications associated with acute RSV infection in children aged <15 years (PROSPERO Registration CRD42019125722). Main outcomes included neurologic, clinical, and demographic features of cases and the frequency of disease. We aggregated available case data from the published literature and from the Australian Acute Childhood Encephalitis (ACE) study. RESULTS: We identified 87 unique studies from 26 countries describing a spectrum of RSV-associated severe acute neurologic syndromes including proven encephalitis, acute encephalopathy, complex seizures, hyponatremic seizures, and immune-mediated disorders. The frequency of RSV infection in acute childhood encephalitis/encephalopathy was 1.2%-6.5%. We aggregated data from 155 individual cases with RSV-associated severe acute neurologic complications; median age was 11.0 months (IQR 2.0-21.5), most were previously healthy (71/104, 68%). Seizure was the most frequently reported neurologic feature (127/150, 85%). RSV was detected in the central nervous system of 12 cases. Most children recovered (81/122, 66%); however, some reports described partial recovery (33/122, 27%) and death (8/122, 7%). CONCLUSIONS: RSV-associated neurologic complications have been widely reported, but there is substantial heterogeneity in the design and quality of existing studies. The findings from our study have implications for the investigation, management, and prevention of RSV-associated neurologic complications. Further, this systematic review can inform the design of future studies aiming to quantify the burden of childhood RSV-associated neurologic disease.