WITHDRAWN: Nucleic acid biomarkers of immune response and cell and tissue damage in COVID-19 and MIS-C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 acute COVID-19 (n=70) or MIS-C (n=141) across three hospitals. Profiling of plasma cell-free nucleic acids uncovers distinct signatures of cell injury and death between these two disease states, with increased heterogeneity and multi-organ involvement in MIS-C encompassing diverse cell types such as endothelial and neuronal Schwann cells. Whole blood RNA profiling reveals upregulation of similar pro-inflammatory signaling 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 yet complementary signatures for each disease state. Our work provides a systems-level, multi-analyte view of immune responses and tissue damage in COVID-19 and MIS-C and informs the future development of new disease biomarkers.

WITHDRAWN: A gene expression-based diagnostic classifier for identification of severe COVID-19 and multisystem inflammatory syndrome in children (MIS-C)

“…In a previous study 11 , analysis of plasma cell-free RNA from patients with MIS-C or severe COVID-19 yielded distinct signatures of cell injury and death between these two disease states, including the involvement of unexpected pathways such as endothelial and neuronal Schwann cell signaling. These signatures were different from those from whole blood RNA profiling [10][11][12][13] , which showed upregulation of pro-inflammatory signaling pathways in . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.…”

“…Transcriptome analysis by RNA sequencing (RNA-Seq) has been shown to be useful in the diagnosis of rare genetic diseases 7 and infections such as Lyme disease 8 , influenza 9 , and COVID-19 10 . In a previous study 11 , analysis of plasma cell-free RNA from patients with MIS-C or severe COVID-19 yielded distinct signatures of cell injury and death between these two disease states, including the involvement of unexpected pathways such as endothelial and neuronal Schwann cell signaling. These signatures were different from those from whole blood RNA profiling [10][11][12][13] , which showed upregulation of pro-inflammatory signaling pathways in 4 COVID-19 but downregulation of T cell-associated pathways in MIS-C.…”

“…In a previous study 11 , analysis of plasma cell-free RNA from patients with MIS-C or severe COVID-19 yielded distinct signatures of cell injury and death between these two disease states, including the involvement of unexpected pathways such as endothelial and neuronal Schwann cell signaling. These signatures were different from those from whole blood RNA profiling [10][11][12][13] , which showed upregulation of pro-inflammatory signaling pathways in 4 COVID-19 but downregulation of T cell-associated pathways in MIS-C. Given the findings of distinct signaling pathways 11 , we hypothesized that whole blood and plasma would be promising analytes for the development of diagnostic assays for severe COVID-19 and MIS-C.…”

“…26.22280395 doi: medRxiv preprint COVID-19 but downregulation of T cell-associated pathways in MIS-C. Given the findings of distinct signaling pathways 11 , we hypothesized that whole blood and plasma would be promising analytes for the development of diagnostic assays for severe COVID-19 and MIS-C.…”

“…Sample Acquisition Children's National. Samples were acquired from Children's National as previously described 11 . Briefly, pediatric patients were classified as having MIS-C if they met the CDC case definition.…”