Tweet
Cell Rep Med
. 2023 Apr 21;101034.
doi: 10.1016/j.xcrm.2023.101034. Online ahead of print. Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C
Conor J Loy 1 , Alicia Sotomayor-Gonzalez 2 , Venice Servellita 2 , Jenny Nguyen 2 , Joan Lenz 1 , Sanchita Bhattacharya 3 , Meagan E Williams 4 , Alexandre P Cheng 1 , Andrew Bliss 1 , Prachi Saldhi 2 , Noah Brazer 2 , Jessica Streithorst 2 , William Suslovic 4 , Charlotte J Hsieh 5 , Burak Bahar 4 , Nathan Wood 6 , Abiodun Foresythe 2 , Amelia Gliwa 2 , Kushmita Bhakta 7 , Maria A Perez 7 , Laila Hussaini 7 , Evan J Anderson 8 , Ann Chahroudi 7 , Meghan Delaney 9 , Atul J Butte 3 , Roberta L DeBiasi 9 , Christina A Rostad 7 , Iwijn De Vlaminck 10 , Charles Y Chiu 11
Affiliations
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.
. 2023 Apr 21;101034.
doi: 10.1016/j.xcrm.2023.101034. Online ahead of print. Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C
Conor J Loy 1 , Alicia Sotomayor-Gonzalez 2 , Venice Servellita 2 , Jenny Nguyen 2 , Joan Lenz 1 , Sanchita Bhattacharya 3 , Meagan E Williams 4 , Alexandre P Cheng 1 , Andrew Bliss 1 , Prachi Saldhi 2 , Noah Brazer 2 , Jessica Streithorst 2 , William Suslovic 4 , Charlotte J Hsieh 5 , Burak Bahar 4 , Nathan Wood 6 , Abiodun Foresythe 2 , Amelia Gliwa 2 , Kushmita Bhakta 7 , Maria A Perez 7 , Laila Hussaini 7 , Evan J Anderson 8 , Ann Chahroudi 7 , Meghan Delaney 9 , Atul J Butte 3 , Roberta L DeBiasi 9 , Christina A Rostad 7 , Iwijn De Vlaminck 10 , Charles Y Chiu 11
Affiliations
- PMID: 37279751
- DOI: 10.1016/j.xcrm.2023.101034
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.