Treg cell epigenetic modifications controlling Brain fog in Long COVID 9015

Abstract Description It has been estimated that around 65 million people has experienced post COVID19 sequelae. Patients with COVID19 have been shown to have an increased Notch4 expression on their regulatory T-cells (Tregs), which lead to a decreased immune tolerance and a worsening of symptoms. In this study, we investigated the role of Tregs in brain fog. In this study, PBMCs were collected from either healthy or Long COVID (LC) probands. Cells were stained and measured for various biomarkers. RNAseq of Tregs from healthy probands and LC patients was conducted. Furthermore, a mouse model of post-viral infection model based on H1N1 infection was established to investigate Brain fog. RNAseq, MRI and Pharmascan were conducted to understand the role of Tregs in brain fog. Patients with LC showed a significant increase in Notch4 on their Tregs cells, paralleled with increased senescence markers on these Tregs. In animal model of post viral infection, Notch4+Tregs, were able to induce cytotoxicity in the brain, exhibited by increase lactate and pyruvate production measured in the MRI and Pharmascan. RNAseq of Tregs from patients showed a pattern of dysfunction and senescence marked by increased IL-17 pathway and DUSP4 a main marker for senescence. Treg specific deletion of DUSP4 in the mouse model showed a drastic significant reduction in brain cytotoxicity and brain fog. Dysfunctional Tregs during COVID19 syndrome develop to retain their proinflammatory profile causing brain fog in LC patients. Funding Sources DFG. 3019/1 DAAD: 91865474 CSC: 202308440122 Topic Categories Viral Immunology (VIR)