Uncovering associations of variant infection with COVID-19 disease severity in children

Project Abstract Under parent grant R61HD105618 (PI Chiu, University of California, San Francisco), we proposed to define panels of diagnostic and predictive host markers of COVID-19 in children, with a focus on severe clinical manifestations of disease, including COVID-19 associated pneumonia, myocarditis, and multisystem inflammatory syndrome in children (MIS-C). Our aims were to collect and biobank clinical samples from pediatric patients with COVID-19 and MIS-C, perform RNA transcriptome profiling and cell-free DNA analyses to identify host biomarkers, and generate predictive models of clinical severity and outcomes. Here we propose a supplemental project in response to the threat posed by newly emerging SARS-CoV-2 variants, such as Delta. We will perform SARS-CoV-2 viral whole-genome sequencing of >4,000 samples across 5 pediatric hospital systems and correlate variant identification with clinical and laboratory metadata. We aim to determine whether infection from specific variants is associated with more severe illness or complications of COVID-19 disease such as MIS-C. Uncovering potential differences in clinical severity due to infection from specific variants is critical to understanding surges in pediatric hospitalizations associated with SARS-CoV-2 and to informing development of host biomarkers for diagnosing and monitoring disease complications such as COVID-19 pneumonia, myocarditis, and MIS-C. .