Increased Pediatric Respiratory Syncytial Virus Case Counts Following the Emergence of SARS-CoV-2 Can Be Attributed to Changes in Testing

Author:

Petros Brittany A1234ORCID,Milliren Carly E5ORCID,Sabeti Pardis C1678ORCID,Ozonoff Al1910ORCID

Affiliation:

1. Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard , Cambridge, Massachusetts , USA

2. Health Sciences & Technology Program, Harvard Medical School and Massachusetts Institute of Technology , Cambridge, Massachusetts , USA

3. Harvard–Massachusetts Institute of Technology MD-PhD Program , Boston, Massachusetts , USA

4. Department of Systems Biology, Harvard Medical School , Boston, Massachusetts , USA

5. Institutional Centers for Clinical and Translational Research, Boston Children's Hospital , Boston, Massachusetts , USA

6. Department of Organismic and Evolutionary Biology, Harvard University , Cambridge, Massachusetts , USA

7. Department of Immunology & Infectious Diseases, Harvard T. H. Chan School of Public Health , Boston, Massachusetts , USA

8. Howard Hughes Medical Institute , Chevy Chase, Maryland , USA

9. Precision Vaccines Program, Boston Children's Hospital , Boston, Massachusetts , USA

10. Department of Pediatrics, Harvard Medical School , Boston, Massachusetts , USA

Abstract

Abstract Background Respiratory syncytial virus (RSV) circulation dropped markedly early in the COVID-19 pandemic, followed by a resurgence with heightened case counts. The “immunity debt” hypothesis proposes that the RSV-naїve pediatric population increased during the period of low transmission. However, the evidence supporting this hypothesis is limited, and the role of changing testing practices in the perceived surge has not been comprehensively evaluated. Methods We conducted a multicenter, retrospective analysis of 342 530 RSV encounters and 980 546 RSV diagnostic tests occurring at 32 US pediatric hospitals in 2013–2023. We used interrupted time series analysis to estimate pandemic-associated changes in RSV patient and test volume and to quantify changes in the proportions of patients requiring hospitalization, intensive care, or mechanical ventilation. We quantified the fraction of the shifts in case counts and in the age of diagnosed patients attributable to changes in testing. Results RSV patient volume increased 2.4-fold (95% confidence interval [CI]: 1.7, 3.5) in 2021–2023 relative to the pre-pandemic phase and was accompanied by an 18.9-fold increase (95% CI: 15.0, 23.9) in RSV test volume. Shifts in patient volume and in patient age were largely attributable to increased testing. The proportions of patients with RSV that required hospitalization, intensive care, or mechanical ventilation declined significantly across all patient age groups. Conclusions A surge in RSV testing, rather than in viral circulation, likely underlies the increased case counts observed in 2021–2023. These findings warrant a critical assessment of the immunity debt hypothesis and highlight the importance of considering the testing denominator when surveillance strategies are dynamic.

Funder

National Institute of General Medical Sciences

Howard Hughes Medical Institute

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Publisher

Oxford University Press (OUP)

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