Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C
Cell reports. Medicine
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
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.
Loy, Conor J.; Sotomayor-Gonzalez, Alicia; Servellita, Venice; Nguyen, Jenny; Lenz, Joan; Bhattacharya, Sanchita; Williams, Meagan E.; Cheng, Alexandre P.; Bliss, Andrew; Saldhi, Prachi; Brazer, Noah; Streithorst, Jessica; Suslovic, William; Hsieh, Charlotte J.; Bahar, Burak; Wood, Nathan; Foresythe, Abiodun; Gliwa, Amelia; Bhakta, Kushmita; Perez, Maria A.; Hussaini, Laila; Anderson, Evan J.; Chahroudi, Ann; Delaney, Meghan; Butte, Atul J.; DeBiasi, Roberta L.; Rostad, Christina A.; De Vlaminck, Iwijn; and Chiu, Charles Y., "Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C" (2023). GW Authored Works. Paper 2706.