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

Conor J. Loy; Alicia Sotomayor-Gonzalez; Venice Servellita; Jenny Nguyen; Joan Lenz; Sanchita Bhattacharya; Meagan E. Williams; Alexandre P. Cheng; Andrew Bliss; Prachi Saldhi; Noah Brazer; Jessica Streithorst; William Suslovic; Charlotte J. Hsieh; Burak Bahar; Nathan Wood; Abiodun Foresythe; Amelia Gliwa; Kushmita Bhakta; Maria A. Perez; Laila Hussaini; Evan J. Anderson; Ann Chahroudi; Meghan Delaney; Atul J. Butte; Roberta L. DeBiasi; Christina A. Rostad; Iwijn De Vlaminck; Charles Y. Chiu

doi:10.1016/j.xcrm.2023.101034

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

Conor J. Loy
, Alicia Sotomayor-Gonzalez
, Venice Servellita
, Jenny Nguyen
, Joan Lenz
, Sanchita Bhattacharya
, Meagan E. Williams
, Alexandre P. Cheng
, Andrew Bliss
, Prachi Saldhi
, Noah Brazer
, Jessica Streithorst
, William Suslovic
, Charlotte J. Hsieh
, Burak Bahar
, Nathan Wood
, Abiodun Foresythe
, Amelia Gliwa
, Kushmita Bhakta
, Maria A. Perez

Laila Hussaini, Evan J. Anderson, Ann Chahroudi, Meghan Delaney, Atul J. Butte, Roberta L. DeBiasi, Christina A. Rostad, Iwijn De Vlaminck, Charles Y. Chiu

Research output: Contribution to journal › Journal Article › peer-review

17 Citations (Scopus)

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.

Original language	English
Article number	101034
Journal	Cell Reports Medicine
Volume	4
Issue number	6
DOIs	https://doi.org/10.1016/j.xcrm.2023.101034
Publication status	Published - 20 Jun 2023
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

!!!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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10.1016/j.xcrm.2023.101034

Cite this

Loy, C. J., Sotomayor-Gonzalez, A., Servellita, V., Nguyen, J., Lenz, J., Bhattacharya, S., Williams, M. E., Cheng, A. P., Bliss, A., Saldhi, P., Brazer, N., Streithorst, J., Suslovic, W., Hsieh, C. J., Bahar, B., Wood, N., Foresythe, A., Gliwa, A., Bhakta, K., ... Chiu, C. Y. (2023). Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C. Cell Reports Medicine, 4(6), Article 101034. https://doi.org/10.1016/j.xcrm.2023.101034

@article{46ad108740544eb6a56ea84213edd05c,

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

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",

author = "Loy, \{Conor J.\} and Alicia Sotomayor-Gonzalez and Venice Servellita and Jenny Nguyen and Joan Lenz and Sanchita Bhattacharya and Williams, \{Meagan E.\} and Cheng, \{Alexandre P.\} and Andrew Bliss and Prachi Saldhi and Noah Brazer and Jessica Streithorst and William Suslovic and Hsieh, \{Charlotte J.\} and Burak Bahar and Nathan Wood and Abiodun Foresythe and Amelia Gliwa and Kushmita Bhakta and Perez, \{Maria A.\} and Laila Hussaini and Anderson, \{Evan J.\} and Ann Chahroudi and Meghan Delaney and Butte, \{Atul J.\} and DeBiasi, \{Roberta L.\} and Rostad, \{Christina A.\} and \{De Vlaminck\}, Iwijn and Chiu, \{Charles Y.\}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = jun,

day = "20",

doi = "10.1016/j.xcrm.2023.101034",

language = "English",

volume = "4",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "6",

}

Loy, CJ, Sotomayor-Gonzalez, A, Servellita, V, Nguyen, J, Lenz, J, Bhattacharya, S, Williams, ME, Cheng, AP, Bliss, A, Saldhi, P, Brazer, N, Streithorst, J, Suslovic, W, Hsieh, CJ, Bahar, B, Wood, N, Foresythe, A, Gliwa, A, Bhakta, K, Perez, MA, Hussaini, L, Anderson, EJ, Chahroudi, A, Delaney, M, Butte, AJ, DeBiasi, RL, Rostad, CA, De Vlaminck, I & Chiu, CY 2023, 'Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C', Cell Reports Medicine, vol. 4, no. 6, 101034. https://doi.org/10.1016/j.xcrm.2023.101034

TY - JOUR

T1 - Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C

AU - Loy, Conor J.

AU - Sotomayor-Gonzalez, Alicia

AU - Servellita, Venice

AU - Nguyen, Jenny

AU - Lenz, Joan

AU - Bhattacharya, Sanchita

AU - Williams, Meagan E.

AU - Cheng, Alexandre P.

AU - Bliss, Andrew

AU - Saldhi, Prachi

AU - Brazer, Noah

AU - Streithorst, Jessica

AU - Suslovic, William

AU - Hsieh, Charlotte J.

AU - Bahar, Burak

AU - Wood, Nathan

AU - Foresythe, Abiodun

AU - Gliwa, Amelia

AU - Bhakta, Kushmita

AU - Perez, Maria A.

AU - Hussaini, Laila

AU - Anderson, Evan J.

AU - Chahroudi, Ann

AU - Delaney, Meghan

AU - Butte, Atul J.

AU - DeBiasi, Roberta L.

AU - Rostad, Christina A.

AU - De Vlaminck, Iwijn

AU - Chiu, Charles Y.

PY - 2023/6/20

Y1 - 2023/6/20

N2 - 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.

AB - 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.

KW - DNA damage

KW - RNA sequencing

KW - RNA-seq

KW - SARS-CoV-2

KW - bisulfite sequencing

KW - cell damage

KW - cell-free DNA

KW - cell-free RNA

KW - clinical severity

KW - coronavirus disease 2019

KW - disease biomarkers

KW - host response

KW - immune response

KW - multisystem inflammatory syndrome in children

KW - nucleic acid sequencing

KW - pediatric

KW - signaling pathways

KW - systems biology

KW - tissue damage

KW - whole-blood RNA

UR - https://www.scopus.com/pages/publications/85161061029

U2 - 10.1016/j.xcrm.2023.101034

DO - 10.1016/j.xcrm.2023.101034

M3 - Journal Article

C2 - 37279751

AN - SCOPUS:85161061029

SN - 2666-3791

VL - 4

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 6

M1 - 101034

ER -

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

Abstract

UN SDGs

!!!Keywords

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