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

• Type of Material: Article
• Authors: Conor J Loy, Cornell University College of Engineering; Alicia Sotomayor-Gonzalez, University of California, San Francisco; Venice Servellita, University of California, San Francisco; Jenny Nguyen, UCSF School of Medicine; Joan Lenz, Cornell University College of Engineering; Sanchita Bhattacharya, University of California, San Francisco; Meagan E Williams, Childrens National Health System; Alexandre P Cheng, Cornell University College of Engineering; Andrew Bliss, Cornell University College of Engineering; Prachi Saldhi, University of California, San Francisco; Noah Brazer, University of California, San Francisco; Jessica Streithorst, University of California, San Francisco (UCSF); William Suslovic, Childrens National Health System; Charlotte J Hsieh, University of California, San Francisco; Burak Bahar, Childrens National Health System; Nathan Wood, UCSF Benioff Children's Hospital Oakland; Abiodun Foresythe, University of California, San Francisco; Amelia Gliwa, University of California, San Francisco; Kushmita Bhakta, Emory University; Maria A Perez, Emory University; Laila Hussaini, Emory University; Evan Anderson, Emory University; Ann Chahroudi, Emory University; Meghan Delaney, Childrens National Health System; Atul J Butte, University of California, San Francisco; Roberta L DeBiasi, Childrens National Health System; Christina Rostad, Emory University; Iwijin De Vlaminck, Cornell University College of Engineering; Charles Y Chiu, University of California, San Francisco
• Language: English
• Date: 2023-06-20
• Publisher: Elsevier Inc
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors
• Final Published Version (URL): http://dx.doi.org/10.1016/j.xcrm.2023.101034
• Title of Journal or Parent Work: Cell Reports Medicine
• Volume: 4
• Issue: 6
• Start Page: 101034
• End Page: 101034
• Keywords: Humans; disease biomarkers; whole-blood RNA; multisystem inflammatory syndrome in children; coronavirus disease 2019; bisulfite sequencing; immune response; cell-free DNA; Biomarkers; Nucleic Acids; RNA-seq; RNA; Child; nucleic acid sequencing; COVID-19; DNA damage; clinical severity; cell damage; tissue damage; pediatric; systems biology; SARS-CoV-2; RNA sequencing; signaling pathways; host response; Cell-Free Nucleic Acids; cell-free RNA
• Research Categories: Health Sciences, Medicine and Surgery; Engineering, Biomedical

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.