Increased pediatric RSV case counts following the emergence of SARS-CoV-2 are attributable to increased testing

Abstract

Background: The incidence of respiratory syncytial virus (RSV) dropped markedly early in the COVID-19 pandemic, followed by a resurgence with heightened case counts. The immunity debt hypothesis proposes that the RSV-naive pediatric population increased during the period of low transmission, resulting in a subsequent increased risk of infection. However, the evidence supporting this hypothesis is limited, and no studies have comprehensively evaluated the role of changing respiratory viral testing practices in the perceived surge. Methods: We conducted a multicenter, retrospective analysis of 342,530 RSV encounters and 980,546 RSV diagnostic tests occurring at 32 United States pediatric hospitals between 2013 and 2023. We used interrupted time series analysis to estimate pandemic-associated changes in RSV patient and testing volume, and to quantify changes in the proportions of patients admitted from the emergency department (ED), admitted to the intensive care unit (ICU), and receiving mechanical ventilation. We quantified the fraction of the observed shifts in case counts and in the age of diagnosed patients attributable to changes in RSV testing practices. Finally, we analyzed 524,404 influenza virus encounters and 1,768,526 influenza diagnostic tests to address the specificity of the findings to RSV. Findings: RSV patient volume increased 2.4-fold (95% 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. Over two-thirds of the apparent shifts in patient volume and in patient age were attributable to increased testing, which was concentrated among older pediatric patients. The proportions of patients with RSV requiring hospitalization, intensive care, or mechanical ventilation declined significantly across all patient age groups. These declines were not observed for patients with influenza virus. Interpretation: A surge in RSV testing, rather than in viral circulation, likely underlies the increased case counts observed in 2021-2023. We identify expected consequences of increased testing, including the diagnosis of less severe cases and a shift in the patient age distribution. These findings warrant a critical assessment of the immunity debt hypothesis, while highlighting the importance of considering the testing denominator when surveillance strategies are dynamic.

Clinical validation of an RSV neutralization assay and testing of cross-sectional sera pre- and post- RSV outbreaks from 2021-2023

“…Moreover, a recent study attributed approximately two-thirds of the increase in RSV cases to significant increases in volume of RSV testing [49]. Other possible theories behind post-pandemic RSV resurgence, such as SARS-CoV-2-induced immune dysregulation [50][51][52][53], changes in population-wide health-seeking behavior [54], and loosening of public health safety measures [8] should also be investigated to inform future vaccination and immunotherapeutic development.…”