# Genetic Variants Affect Distinct Metabolic Pathways in Pediatric Multisystem Inflammatory Syndrome and Severe COVID‐19

## TL;DR

This study finds that genetic variants linked to specific metabolic pathways are associated with severe pediatric cases of MIS-C and severe COVID-19.

## Contribution

The study identifies distinct genetic variants related to carbohydrate and cholesterol metabolism in severe pediatric MIS-C and COVID-19.

## Key findings

- Severe pediatric COVID-19 cases show enriched variants in genes related to glycogen breakdown.
- MIS-C patients exhibit enriched variants in genes involved in cholesterol and lipoprotein metabolism.
- The findings highlight potential genetic targets for understanding and treating these conditions.

## Abstract

The coronavirus disease 2019 (COVID‐19) pandemic has triggered a global health crisis, with over 700 million confirmed cases and at least 7 million deaths reported by early 2024. Children are less vulnerable to severe SARS‐CoV‐2 infection than adults and typically experience milder respiratory symptoms. However, a rare but significant complication, known as multisystem inflammatory syndrome in children (MIS‐C), can develop weeks after infection, characterized by a spectrum of inflammatory symptoms. This study employed whole‐exome sequencing and over‐representation analysis to identify genetic variants of potential clinical significance related to MIS‐C or severe COVID‐19 in a group of children with acute respiratory distress syndrome (ARDS), all of whom were unvaccinated for COVID‐19. We observed the enrichment of potentially pathogenic genetic variants in genes related to carbohydrate metabolism, particularly glycogen breakdown, in severe COVID‐19 pediatric patients, and in genes related to cholesterol and lipoprotein metabolism in MIS‐C patients. These findings offer insights into the genetic underpinnings of MIS‐C and severe COVID‐19, suggesting potential genes and biological pathways for further research.