Abstract
BACKGROUND: When coronavirus disease 2019 (COVID-19) mitigation efforts waned, viral respiratory infections (VRIs) surged, potentially increasing the risk of postviral invasive bacterial infections (IBIs). We sought to evaluate the change in epidemiology and relationships between specific VRIs and IBIs [complicated pneumonia, complicated sinusitis and invasive group A streptococcus (iGAS)] over time using the National COVID Cohort Collaborative (N3C) dataset. METHODS: We performed a secondary analysis of all prospectively collected pediatric (<19 years old) and adult encounters at 58 N3C institutions, stratified by era: pre-pandemic (January 1, 2018, to February 28, 2020) versus pandemic (March 1, 2020, to June 1, 2023). We compared the characteristics and outcomes of patients with prespecified VRIs and IBIs, including correlation between VRI cases and subsequent IBI cases. RESULTS: We identified 965,777 pediatric and 9,336,737 adult hospitalizations. Compared with pre-pandemic, pandemic-era children demonstrated higher mean monthly cases of adenovirus (121 vs. 79.1), iGAS (5.8 vs. 3.3), complicated pneumonia (282 vs. 178) and complicated sinusitis (29.8 vs. 16.3), P < 0.005 for all. Among pandemic-era children, peak correlation between RSV cases and subsequent complicated sinusitis cases occurred with a 60-day lag (correlation coefficient 0.56, 95% confidence interval: 0.52-0.59, P < 0.001) while peak correlation between influenza and complicated sinusitis occurred with a 33-day lag (0.55, 0.51-0.58, P < 0.001). Correlation among other VRI-IBI pairs was modest during the pandemic and often lower than during the pre-pandemic era. CONCLUSIONS: Since COVID-19 emerged, mean monthly cases of iGAS, complicated pneumonia, and complicated sinusitis have been higher. Pandemic-era RSV and influenza cases were correlated with subsequent cases of complicated sinusitis in children. However, many other VRI-IBI correlations decreased during the pandemic.