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J Med Virol . Genetic Variants Affect Distinct Metabolic Pathways in Pediatric Multisystem Inflammatory Syndrome and Severe COVID-19

tetano

Editor, Senior Moderator
J Med Virol


. 2025 Aug;97(8):e70556.
doi: 10.1002/jmv.70556. Genetic Variants Affect Distinct Metabolic Pathways in Pediatric Multisystem Inflammatory Syndrome and Severe COVID-19

Alysson Henrique Urbanski[SUP] 1 [/SUP], Flávia Cristina de Paula Freitas[SUP] 1 2 3 [/SUP], Tiago Minuzzi Freire da Fontoura Gomes[SUP] 1 [/SUP], Michelle Orane Schemberger[SUP] 1 [/SUP], Bárbara Carvalho Santos Dos Reis[SUP] 4 [/SUP], Flavia Amêndola Anísio de Carvalho[SUP] 4 [/SUP], Roberta Soares Faccion[SUP] 4 [/SUP], Lucas de Almeida Machado[SUP] 4 5 [/SUP], Deborah Antunes Dos Santos[SUP] 5 [/SUP], Daniela Prado Cunha[SUP] 4 [/SUP], Margarida Dos Santos Salú[SUP] 4 6 7 [/SUP], Daniella Campelo Batalha Cox Moore[SUP] 8 9 [/SUP], Mayra Marinho Presibella[SUP] 10 [/SUP], Juliana Fontes Noguchi[SUP] 11 [/SUP], Henrique Lira Borges[SUP] 11 [/SUP], Lais Kimie Tomiura[SUP] 11 [/SUP], Luiza Silva de Castro[SUP] 11 [/SUP], Letícia Graziela Costa Santos[SUP] 1 [/SUP], Esdras Matheus Gomes da Silva[SUP] 1 [/SUP], Vinícius Da Silva Coutinho Parreira[SUP] 1 [/SUP], Luis Gustavo Morello[SUP] 1 [/SUP], Fabricio Klerynton Marchini[SUP] 1 [/SUP], Maria Regina Tizzot[SUP] 11 [/SUP], Mauricio Marcondes Ribas[SUP] 12 [/SUP], Gilberto Pascolat[SUP] 12 [/SUP], Carmen Australia Paredes Marcondes Ribas[SUP] 11 12 [/SUP], Fábio Fernandes da Rocha Vicente[SUP] 13 [/SUP], Alexandre Rossi Paschoal[SUP] 13 [/SUP], Rubens Cat[SUP] 14 [/SUP], Benilton de Sá Carvalho[SUP] 15 [/SUP], Jaqueline Carvalho de Oliveira[SUP] 16 [/SUP], Marcus F Oliveira[SUP] 17 18 [/SUP], Luiz Lehmann Coutinho[SUP] 19 [/SUP], Acácia Maria Lourenço Francisco Nasr[SUP] 20 [/SUP], Irina Nastassja Riediger[SUP] 10 [/SUP], Jeanine Marie Nardin[SUP] 21 [/SUP], Liya Regina Mikami[SUP] 11 [/SUP], Ana Carolina Ramos Guimarães[SUP] 5 [/SUP], Patricia Savio de Araujo-Souza[SUP] 22 [/SUP], Arnaldo Prata-Barbosa[SUP] 23 [/SUP], Zilton Farias Meira de Vasconcelos[SUP] 4 [/SUP], Helisson Faoro[SUP] 1 [/SUP], Hellen Geremias Dos Santos[SUP] 1 [/SUP], Fabio Passetti[SUP] 1 [/SUP]



Affiliations
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.

Keywords: COVID‐19; MIS‐C (multisystem inflammatory syndrome in children); carbohydrate metabolism; cholesterol metabolism; genetic variants; whole‐exome sequencing.

 
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