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

Conor J. Loy, Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14850, USA.
Alicia Sotomayor-Gonzalez, Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Venice Servellita, Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Jenny Nguyen, Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Joan Lenz, Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14850, USA.
Sanchita Bhattacharya, Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Meagan E. Williams, Children's National Hospital, Washington, DC 20010, USA.
Alexandre P. Cheng, Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14850, USA.
Andrew Bliss, Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14850, USA.
Prachi Saldhi, Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Noah Brazer, Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Jessica Streithorst, Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
William Suslovic, Children's National Hospital, Washington, DC 20010, USA.
Charlotte J. Hsieh, Division of Pediatric Infectious Diseases and Global Health, Department of Pediatrics, University of California San Francisco, Oakland, CA 94609.
Burak Bahar, Children's National Hospital, Washington, DC 20010, USA.
Nathan Wood, UCSF Benioff Children's Hospital, Oakland, CA 94609, USA.
Abiodun Foresythe, Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Amelia Gliwa, Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Kushmita Bhakta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA; Children's Healthcare of Atlanta, Atlanta, GA, 30322, USA.
Maria A. Perez, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA; Children's Healthcare of Atlanta, Atlanta, GA, 30322, USA.
Laila Hussaini, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA; Children's Healthcare of Atlanta, Atlanta, GA, 30322, USA.
Evan J. Anderson, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA; Children's Healthcare of Atlanta, Atlanta, GA, 30322, USA; Department of Medicine, Emory University School of Medicine, Atlanta, GA 30307, USA.
Ann Chahroudi, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA; Children's Healthcare of Atlanta, Atlanta, GA, 30322, USA.
Meghan Delaney, Children's National Hospital, Washington, DC 20010, USA; The George Washington University School of Medicine, Washington, DC 20052, USA.
Atul J. Butte, Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Roberta L. DeBiasi, Children's National Hospital, Washington, DC 20010, USA; The George Washington University School of Medicine, Washington, DC 20052, USA.
Christina A. Rostad, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA; Children's Healthcare of Atlanta, Atlanta, GA, 30322, USA.
Iwijn De Vlaminck, Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14850, USA. Electronic address: id93@cornell.edu.
Charles Y. Chiu, Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: charles.chiu@ucsf.edu.

Document Type

Journal Article

Publication Date

6-20-2023

Journal

Cell reports. Medicine

Volume

4

Issue

6

DOI

10.1016/j.xcrm.2023.101034

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

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.

Department

Pediatrics

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