Allison Lulov

COVID-19 and Multiple Sclerosis Relapse Initiation: Single-Cell Analysis of CD4 and CD8 T cells in Human Cerebrospinal Fluid with Correlate to COVID-19

Started Aug. 3, 2022

Abstract or project description

2.8 million people worldwide have Multiple Sclerosis, and over 1 million people died due to infection of COVID-19. Multiple Sclerosis (MS) is an autoimmune disease that prompts the immune system to attack nerve fibers and the myelin sheath, ultimately leading to decreased neural communication. Relapsing Remitting Multiple Sclerosis (RRMS) is the most common type of MS and manifests itself in relapses-- bouts of neurological symptoms. Cytokines, specifically interleukins and interferon (IFN), have been observed as key factors in the pathogenesis of RRMS and COVID-19. COVID-19 has been speculated to incite relapse in MS because of the observed relapse seen in RRMS by other viruses, dysfunction of toll-like receptors (TLRs), alteration of T cell inflammatory response, and disruption of the blood brain barrier (BBB) via cytokine storms. The goal of this project was to identify the biomarkers that could link RRMS to COVID-19 to support the idea that COVID-19 can incite relapse in RRMS. To further investigate this, a single-cell dataset from the CSF of RRMS patients was analyzed via Python. COVID-19 literature containing information about the marker genes defined in the single-cell analysis were also investigated. Running an analysis of both CD4 and CD8 T cells, 3 rank tests were performed and qualitative graphs were produced. Combining both parts of the analysis, C1QA, C1QB, C1QC, NEAT1, TMSB4X, and IFITM1 were defined as the most interconnected genes between the two conditions. Immunoglobulin genes had similar expression to the classical complement genes, possibly displaying how the two work together to compose the immune response. Highly expressed TMSB4X was observed in the RRMS analysis and in COVID-19 literature, distinguishing how gender differences in the development of COVID-19 and RRMS could serve as a gateway to investigate the two conditions conjointly. Additionally, the IFN 1 pathway serves as another method to discover how relapses could be connected to the enhanced IFN 1 response in COVID-19. In conclusion, this study serves as an important step in developing the relationship between COVID-19 and MS relapse, and the evidence and therapeutics provided in this study strengthen the relationship of COVID-19 induced relapse.