id author title date pages extension mime words sentences flesch summary cache txt cord-329855-pr7g6ivu Kalfaoglu, Bahire T-cell hyperactivation and paralysis in severe COVID-19 infection revealed by single-cell analysis 2020-05-30 .txt text/plain 5344 301 50 By in silico sorting CD4+ T-cells from a single cell RNA-seq dataset, we found that CD4+ T-cells were highly activated and showed unique differentiation pathways in the lung of severe COVID-19 patients. Notably, those T-cells in severe COVID-19 patients highly expressed immunoregulatory receptors and CD25, whilst repressing the expression of the transcription factor FOXP3 and interestingly, both the differentiation of regulatory T-cells (Tregs) and Th17 was inhibited. Collectively, CD4+ T-cells from severe COVID-19 patients are hyperactivated and FOXP3-mediated negative feedback mechanisms are impaired in the lung, while activated CD4+ T-cells continue to promote further viral infection through the production of Furin. These CD25 + activated T-cells are likely to be short-lived and do not initiate FOXP3 transcription in severe COVID-19 patients, while they can differentiate into Tregs in moderate infections. These collectively support that FURIN expression is induced in highly activated non-regulatory CD25 + CD4 + T-cells in severe COVIDOur study has shown that CD4 + T-cells in severe COVID-19 patients have dysregulated activation and differentiation mechanisms. ./cache/cord-329855-pr7g6ivu.txt ./txt/cord-329855-pr7g6ivu.txt