Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C
Conor Loy, Alicia Sotomayor-González, Venice Servellita, Jenny Nguyen, Joan Sesing Lenz, Sanchita Bhattacharya, Meagan E. Williams, Alexandre Pellan Cheng, Andrew Bliss, Prachi Saldhi, Noah Brazer, Jessica Streithorst, William Suslovic, Charlotte Hsieh, Burak Bahar, Nathan Wood, Abiodun Foresythe, Amelia S. Gliwa, Kushmita Bhakta, María A. Pérez, Laila Hussaini, Evan J. Anderson, Ann Chahroudi, Meghan Delaney, Atul J. Butte, Roberta L. DeBiasi, Christina A. Rostad, Iwijn De Vlaminck, Charles Y. Chiu
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.