Evidence describing paediatric COVID-19 and influenza co-infection is limited because influenza circulation was minimal during the early COVID-19 pandemic. We used the National Clinical Cohort Collaborative, a multicentre electronic health record repository, to describe the characteristics and clinical outcomes of paediatric COVID-19 and influenza co-infections in the United States from March 2020-April 2024. We defined co-infection as COVID-19 and influenza identified <7 days apart. We reported demographics, pre-existing diagnoses, and clinical outcomes and used generalized estimating equation models. We defined clinical outcomes as Severe/Moderate disease (hospitalization, critical care, or death) versus emergency department/outpatient encounters. We repeated analyses using varying co-infection definitions to assess robustness of findings. Among 1.53 million patients, 10,277 were co-infected, and 647 (6%) were hospitalized. Co-infections occurred predominantly among children aged <12 years. The most common pre-existing diagnoses were obesity (24%), asthma (10%), and congenital/genetic conditions (5%). The risk for Severe/Moderate disease was greatest among persons aged 0-4 years (adjusted risk ratio (aRR) 3.05; 95% confidence interval (CI): 2.35-3.97) and those with ≥2 pre-existing diagnoses (aRR 2.89; 95% CI: 2.43-3.43). Similar distributions of disease severity were observed across varying co-infection definitions. This study provides a large-scale epidemiological characterization of paediatric COVID-19 and influenza co-infection and successfully implemented a practical EHR-based co-infection case definition for future analyses.
Keywords: COVID-19; co-infection; influenza; paediatrics.