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

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 COVID-19 and MIS-C, with increased multi-organ 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 yet 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 the future development of new disease biomarkers.

TableS5_patient-metadata.csv: Patient metadata from all samples used in the study
TableS6_cfrna-samples.csv: Cell-free RNA sample metadata, QC, and deconvolution results
TableS7_wbrna-samples.csv: Whole-blood RNA sample metadata, QC, and deconvolution results
TableS8_cfdna-samples.csv: Cell-free DNA sample metadata, QC, and deconvolution results
TableS9_cfrna-covid-control.csv: Cell-free RNA COVID-19 vs Control differential abundance table
TableS10_cfrna-misc-control.csv: Cell-free RNA MIS-C vs Control differential abundance table
TableS11_cfrna-misc-covid.csv: Cell-free RNA COVID-19 vs MIS-C differential abundance table
TableS12_wbrna-covid-control.csv: Whole-blood RNA COVID-19 vs Control differential expression table
TableS13_wbrna-misc-control.csv: Whole-blood RNA MIS-C vs Control differential expression table
TableS14_wbrna-misc-covid.csv: Whole-blood RNA MIS-C vs COVID-19 differential expression table