Urbanski Alysson Henrique, Freitas Flávia Cristina de Paula, Gomes Tiago Minuzzi Freire da Fontoura, Schemberger Michelle Orane, Reis Bárbara Carvalho Santos Dos, Carvalho Flavia Amêndola Anísio de, Faccion Roberta Soares, Machado Lucas de Almeida, Santos Deborah Antunes Dos, Cunha Daniela Prado, Salú Margarida Dos Santos, Moore Daniella Campelo Batalha Cox, Presibella Mayra Marinho, Noguchi Juliana Fontes, Borges Henrique Lira, Tomiura Lais Kimie, Silva de Castro Luiza, Santos Letícia Graziela Costa, Silva Esdras Matheus Gomes da, Parreira Vinícius Da Silva Coutinho, Morello Luis Gustavo, Marchini Fabricio Klerynton, Tizzot Maria Regina, Ribas Mauricio Marcondes, Pascolat Gilberto, Ribas Carmen Australia Paredes Marcondes, Vicente Fábio Fernandes da Rocha, Paschoal Alexandre Rossi, Cat Rubens, Carvalho Benilton de Sá, Carvalho de Oliveira Jaqueline, Oliveira Marcus F, Coutinho Luiz Lehmann, Nasr Acácia Maria Lourenço Francisco, Riediger Irina Nastassja, Nardin Jeanine Marie, Mikami Liya Regina, Guimarães Ana Carolina Ramos, Savio de Araujo-Souza Patricia, Prata-Barbosa Arnaldo, Vasconcelos Zilton Farias Meira de, Faoro Helisson, Geremias Dos Santos Hellen, Passetti Fabio
Instituto Carlos Chagas, FIOCRUZ, Curitiba, Paraná, Brazil.
Universidade Federal de São Carlos, São Carlos, São Paulo, Brazil.
J Med Virol. 2025 Aug;97(8):e70556. doi: 10.1002/jmv.70556.
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.
2019年冠状病毒病（COVID-19）大流行引发了一场全球健康危机，到2024年初，全球报告的确诊病例超过7亿例，死亡人数至少700万。儿童比成人更不容易受到严重的严重急性呼吸综合征冠状病毒2感染，通常表现出较轻的呼吸道症状。然而，一种罕见但严重的并发症，即儿童多系统炎症综合征（MIS-C），可能在感染数周后出现，其特征是一系列炎症症状。本研究采用全外显子组测序和过度表达分析，在一组患有急性呼吸窘迫综合征（ARDS）的儿童中识别与MIS-C或严重COVID-19相关的具有潜在临床意义的基因变异，这些儿童均未接种COVID-19疫苗。我们观察到，在严重COVID-19儿科患者中，与碳水化合物代谢相关的基因，特别是糖原分解相关基因中，潜在致病基因变异富集；在MIS-C患者中，与胆固醇和脂蛋白代谢相关的基因中也有潜在致病基因变异富集。这些发现为MIS-C和严重COVID-19的遗传基础提供了见解，为进一步研究指明了潜在的基因和生物学途径。
