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Cell Rep Med . Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C

tetano

Editor, Senior Moderator
Cell Rep Med


. 2023 Apr 21;101034.
doi: 10.1016/j.xcrm.2023.101034. Online ahead of print. Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C

Conor J Loy[SUP] 1 [/SUP], Alicia Sotomayor-Gonzalez[SUP] 2 [/SUP], Venice Servellita[SUP] 2 [/SUP], Jenny Nguyen[SUP] 2 [/SUP], Joan Lenz[SUP] 1 [/SUP], Sanchita Bhattacharya[SUP] 3 [/SUP], Meagan E Williams[SUP] 4 [/SUP], Alexandre P Cheng[SUP] 1 [/SUP], Andrew Bliss[SUP] 1 [/SUP], Prachi Saldhi[SUP] 2 [/SUP], Noah Brazer[SUP] 2 [/SUP], Jessica Streithorst[SUP] 2 [/SUP], William Suslovic[SUP] 4 [/SUP], Charlotte J Hsieh[SUP] 5 [/SUP], Burak Bahar[SUP] 4 [/SUP], Nathan Wood[SUP] 6 [/SUP], Abiodun Foresythe[SUP] 2 [/SUP], Amelia Gliwa[SUP] 2 [/SUP], Kushmita Bhakta[SUP] 7 [/SUP], Maria A Perez[SUP] 7 [/SUP], Laila Hussaini[SUP] 7 [/SUP], Evan J Anderson[SUP] 8 [/SUP], Ann Chahroudi[SUP] 7 [/SUP], Meghan Delaney[SUP] 9 [/SUP], Atul J Butte[SUP] 3 [/SUP], Roberta L DeBiasi[SUP] 9 [/SUP], Christina A Rostad[SUP] 7 [/SUP], Iwijn De Vlaminck[SUP] 10 [/SUP], Charles Y Chiu[SUP] 11 [/SUP]



Affiliations
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.

Keywords: 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.

 
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