Impact of SARS-CoV2 infection on the neuropathogenic potential of myelin-primed Th17 cells in an animal model of MS 2436

Abstract Description Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS). Comparison of COVID-19 and MS brain autopsies showed similar neuropathology and preliminary work in our lab revealed the presence of immune cell aggregates in the meningeal layers surrounding the brain of Syrian Hamsters infected with SARS-CoV2. As such, it is critical to learn whether SARS-CoV2-induced brain pathology augments MS disease severity or accelerates progression. More specifically, we wish to determine whether SARS-CoV2 infection augments the neuropathogenic potential of myelin-primed Th17 cells in animal models of MS. I have established a working model in humanized ACE2 knock-in (hACE2-KI) mice that combines experimental autoimmune encephalomyelitis (EAE) with SARS-CoV-2 infection. Following resolution of infection with a non-lethal dose of the delta strain of SARS-CoV2, I induce passive EAE and assess: (1) clinical presentation of disease and (2) CNS pathology. Thus far, we have seen that mice with prior SARS-CoV2 infection exhibited reduced incidence of EAE by approximately 50% and less severe EAE clinical symptoms during the chronic phase of EAE. Immunophenotyping of the spinal cord revealed a reduction in CD4+ T cell numbers in these mice. These findings suggest that SARS-CoV2 infection prior to EAE reduces the impact of encephalogenic T cells and/or delays their progression to the CNS. We wish to further investigate the mechanism behind this observed phenotype. Funding Sources Supported by the Coronavirus Variants Rapid Response Network (CoVaRR-Net), the MS Society of Canada, and the Emerging and Pandemic Infections Consortium Topic Categories Neuroimmunology (NEUR)