학술논문

Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C
Document Type
article
Source
Cell Reports Medicine. 4(6)
Subject
Pediatric
Genetics
Rare Diseases
Clinical Research
2.1 Biological and endogenous factors
Aetiology
4.1 Discovery and preclinical testing of markers and technologies
Detection
screening and diagnosis
Inflammatory and immune system
Good Health and Well Being
Humans
Child
Nucleic Acids
COVID-19
RNA
Cell-Free Nucleic Acids
Biomarkers
DNA damage
RNA sequencing
RNA-seq
SARS-CoV-2
bisulfite sequencing
cell damage
cell-free DNA
cell-free RNA
clinical severity
coronavirus disease 2019
disease biomarkers
host response
immune response
multisystem inflammatory syndrome in children
nucleic acid sequencing
pediatric
signaling pathways
systems biology
tissue damage
whole-blood RNA
Language
Abstract
Differential host responses in coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) remain poorly characterized. Here, we use next-generation sequencing to longitudinally analyze blood samples from pediatric patients with COVID-19 or MIS-C across three hospitals. Profiling of plasma cell-free nucleic acids uncovers distinct signatures of cell injury and death between COVID-19 and MIS-C, with increased multiorgan involvement in MIS-C encompassing diverse cell types, including endothelial and neuronal cells, and an enrichment of pyroptosis-related genes. Whole-blood RNA profiling reveals upregulation of similar pro-inflammatory pathways in COVID-19 and MIS-C but also MIS-C-specific downregulation of T cell-associated pathways. Profiling of plasma cell-free RNA and whole-blood RNA in paired samples yields different but complementary signatures for each disease state. Our work provides a systems-level view of immune responses and tissue damage in COVID-19 and MIS-C and informs future development of new disease biomarkers.