Viral and Host Genomics Influences on the Phenotypic Expression of COVID-19 Infection and Its Sequelae in Children of Varied Genetic Ancestries

Introduction: After an acute SARS-CoV-2 infection, various longer-term sequelae can occur. In children, two major post-acute conditions identified include Post-acute Sequelae of SARS-CoV-2 (PASC/Long COVID) and Multisystem Inflammatory Syndrome in Children (MIS-C). Long COVID presents with diverse symptomatology that can affect multiple organ systems and lead to significant morbidity in affected children. The marked phenotypic heterogeneity and relatively low incidence of both conditions in children have limited our understanding of why certain patients develop these sequelae while others do not.

Objective: The objective of this study is to investigate associations between rare pathogenic variants in genes of relevance and the development of PASC or MIS-C using comprehensive whole-genome sequencing analysis.

Methods: Design: Cross-sectional study comparing pathogenic variant frequencies across patient cohorts. Setting: Multi-institutional collaboration through RECOVER initiative with sequencing performed at Children's Hospital Los Angeles. Participants: 246 pediatric participants: 108 PASC-negative controls, 107 PASC-positive patients, and 31 MIS-C patients. Methods: Whole-genome sequencing was performed on saliva samples. Variants were called using Illumina Dragen Germline Pipeline and Varseq was used to provide pathogenicity annotation or prediction. Pathogenic variant frequencies were calculated for each cohort and normalized against PASC-negative controls to generate enrichment scores, identifying genes with increased variant burden in sequelae groups. Gene-level enrichment of pathogenic variants in MIS-C and PASC cohorts compared to controls.

Results: Pending.

Conclusion/Discussion: Discussion and conclusions pending final analysis and results. This study identifies distinct pathogenic variant enrichment patterns distinguishing PASC and MIS-C from controls.

Key Topics:

• Understanding the host genomic risk factors for developing long COVID