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bioRxiv · 10.1101/2022.02.02.478719

COVID-19 infection enhances susceptibility to oxidative-stress induced parkinsonism

Smeyne, R. J.·Eells, J.·Chatterjee, D.·Byrne, M.·Akula, S. M.·Sriramula, S.·O'Rourke, D.·Schmidt, P.
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Abstract

BackgroundViral induction of neurological syndromes has been a concern since parkinsonian-like features were observed in patients diagnosed with encephalitis lethargica subsequent to the 1918 influenza pandemic. Given the similarities in the systemic responses following SARS-CoV-2 infection with those observed after pandemic influenza, there is a question if a similar syndrome of post-encephalic parkinsonism could follow COVID-19 infection. ObjectivesTo determine if prior infection with SARS-CoV-2 increased sensitivity to a mitochondrial toxin known to induce parkinsonism. MethodshACE2 mice were infected with SARS-CoV-2 to induce mild to moderate disease. After 31 days recovery, mice were administered a non-lesion inducing dose of the parkinsonian toxin MPTP. Subsequent neuroinflammation and SNpc dopaminergic neuron loss was determined and compared to SARS-CoV-2 or MPTP alone. ResultshACE2 mice infected with SARS-CoV-2 or MPTP showed no SNpc DA neuron loss following MPTP. In mice infected and recovered from SARS-CoV-2 infection, MPTP induced a 23% or 19% greater loss of SNpc dopaminergic neurons than SARS-CoV-2 or MPTP, respectively (p{square}<{square}0.05). Examination of microglial activation showed a significant increase in the number of activated microglia in the SARS-CoV-2 + MPTP group compared to SARS-CoV-2 or MPTP alone. ConclusionsOur observations have important implications for long-term public health, given the number of people that have survived SARS-CoV-2 infection as well as for future public policy regarding infection mitigation. However, it will be critical to determine if other agents known to increase risk of PD also have synergistic effects with SARS-CoV-2 and if are abrogated by vaccination. FundingThis work was supported by grant from the State of North Carolina (PS, JE, DOR, RJS) and R21 NS122280 (RJS).

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Smeyne, R. J., Eells, J., Chatterjee, D., Byrne, M., Akula, S. M., Sriramula, S., O'Rourke, D., Schmidt, P.. 2022-02-03. COVID-19 infection enhances susceptibility to oxidative-stress induced parkinsonism. https://doi.org/10.1101/2022.02.02.478719

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