The impact of SARS-CoV-2 infection/COVID-19 and microglial contribution on the development and severity of Parkinson’s disease

Parkinson’s disease (PD) globally affects 1 in 100 adults above 60. Exposure to environmental agents including viral infection increases vulnerability to PD. Hyperactivity of brain immune cells named microglia is also a strong determinant of PD onset and progression. Altered brain functions persist in patients during and after COVID-19. Evidence in the brains of patients who died of COVID-19 show dysfunctional microglia in brain areas affected by PD. These abnormal microglia were also observed in infected monkeys without breathing difficulty. In BC, where above 89% of total SARS-CoV-2 cases do not require hospitalization, older adults totaling 41% of the population, account for 31% of total cases. In mice, SARS-CoV-2 failed to multiply in microglia but initiated robust deleterious microglial functions, which were intensified by the exposure to PD-associated abnormal proteins. Thus, we propose that COVID-19 may precipitate PD onset or exacerbate its progression. We aim to study the impact of COVID-19 pathology on PD onset/progression and microglial implication in a mouse model expressing the human receptors of SARS-COV-2. This study will inform on COVID-19 long-term effects and may position microglia as a future therapeutic target.