Abstract
Background
Longitudinal respiratory syncytial virus (RSV) dynamics have not been well studied despite the existence of factors favoring prolonged RSV replication including high mutation rates allowing rapid evolution and potential escape from immune control. We therefore measured viral load in previously RSV-naive infants over prolonged time spans.
Methods
During 2014–2015, quantitative nasal aspirates were collected from 51 RSV-PCR+ infants. Multiple parallel assessments of viral loads were quantified at each collected time point using a well-validated real-time quantitative reverse transcriptase polymerase chain reaction assay. After observing viral load rebound phenomenon in some infants, the viral dynamics of 27 infants with sufficient longitudinal viral load data points were analyzed using the pre-defined criteria for viral rebound. Additional analyses were performed comparing age with viral rebound, viral clearance rates, and viral load area-under-the-curve (AUCVL).
Results
The 51 infants (303 nasal aspirate samples; mean of 5.9 per patient) exhibited slower than expected viral clearance. Lower age trended toward slower viral clearance and greater AUCVL. Six infants had detectable viral loads ≥1 month after symptom onset. Ten of twenty-seven evaluable subjects exhibited viral rebound and this rebound was age-dependent (P=0.0259). All but one rebounder were <70 days old.
Conclusion
Infants struggle to control primary RSV infections allowing prolonged viral replication and previously undescribed viral rebound; likely representing viral mutational immune escape.
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Acknowledgements
We thank the parents and caregivers of the participating infants for their altruism. Without whom, we could not make advancements toward a better understanding of RSV infections, their treatment, and prevention. Dr. DeVincenzo and Dr. Cormier also thank the Department of Pediatrics at University of Tennessee Health Science Center, the Department of Microbiology, Immunology, and Biochemistry at University of Tennessee Health Science Center, Children's Foundation Research Institute and Le Bonheur Children's Hospital for the opportunity to conduct our research and expand the knowledge of RSV infections in the pediatric population.
Statement of financial support
This work was supported by internal funds (Grant number: RO73230070) from the DeVincenzo laboratory and University of Tennessee Health Science Center; no external financial support was received for this study. J.H. was supported by a University of Tennessee Health Science Center College of Medicine-sponsored Medical Students Research Fellowship funded by the University of Tennessee Department of Pediatrics and the LeBonheur Children’s Hospital.
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Brint, M., Hughes, J., Shah, A. et al. Prolonged viral replication and longitudinal viral dynamic differences among respiratory syncytial virus infected infants. Pediatr Res 82, 872–880 (2017). https://doi.org/10.1038/pr.2017.173
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DOI: https://doi.org/10.1038/pr.2017.173
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