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

Authors

• 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.

APA Citation

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.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2706

Department

Pediatrics