Transcriptome analysis of cell lines and human PBMCs to investigate the immunopathology of SARS-CoV-2-related multisystem inflammatory syndrome in children.

MIS-C patients with autosomal recessive deficiencies in the OAS-RNase L pathway have been identified. A series of experiments were conducted to study how OAS-RNase L deficiency leads to MIS-C, and consequently understand the immunopathological basis of MIS-C. In this project, we performed bulk RNA-seq of THP-1 cells with KO of OAS1, OAS2, or RNASEL vs. WT after intracellular polyIC stimulation, SARS-CoV-2 stimulation, after co-culture with Vero cells infected with SARS-CoV-2, or after transfection with RNA of Vero cells infected with SARS-CoV-2. In addition, single-cell RNA-seq (scRNAseq) was performed for a MIS-C patient with RNase L deficiency during and after MIS-C and healthy controls. Finally, scRNAseq was performed in PBMCs from patients with OAS-RNASEL deficiency, type I IFN pathway deficiency, and healthy controls, with and without SARS-CoV-2 stimulation.