COVID ‐19 Infection Enhances Susceptibility to Oxidative Stress–Induced Parkinsonism
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Abstract
Background
Viral 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 after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection with those observed after pandemic influenza, there is a question whether a similar syndrome of postencephalic parkinsonism could follow coronavirus disease 2019 infection.
Objective
The goal of this study was to determine whether prior infection with SARS‐CoV‐2 increased sensitivity to a mitochondrial toxin known to induce parkinsonism.
Methods
K18‐hACE2 mice were infected with SARS‐CoV‐2 to induce mild‐to‐moderate disease. After 38 days of recovery, mice were administered a non‐lesion‐inducing dose of the parkinsonian toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) and euthanized 7 days later. Subsequent neuroinflammation and substantia nigra pars compacta (SNpc) dopaminergic (DA) neuron loss were determined and compared with SARS‐CoV‐2 or MPTP alone.
Results
K18‐hACE2 mice infected with SARS‐CoV‐2 or MPTP showed no SNpc DA neuron loss after MPTP. In mice infected and recovered from SARS‐CoV‐2 infection, MPTP induced a 23% or 19% greater loss of SNpc DA neurons than SARS‐CoV‐2 or MPTP, respectively ( P < 0.05). Examination of microglial activation showed a significant increase in the number of activated microglia in both the SNpc and striatum of the SARS‐CoV‐2 + MPTP group compared with SARS‐CoV‐2 or MPTP alone.
Conclusions
Our observations have important implications for long‐term public health, given the number of people who have survived SARS‐CoV‐2 infection, as well as for future public policy regarding infection mitigation. However, it will be critical to determine whether other agents known to increase risk for PD also have synergistic effects with SARS‐CoV‐2 and are abrogated by vaccination. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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SciScore for 10.1101/2022.02.02.478719: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Euthanasia Agents: Forty-five days after active or sham infection and 14 days after MPTP or saline administration, the animals were anesthetized and euthanized by transcardial perfusion with 3% paraformaldehyde. Sex as a biological variable not detected. Randomization 0, hACE2 mice) were randomly assigned to a dose-finding study and then four study arms. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Antibody titers were measured in plasma using the Mouse Anti-SARS-CoV-2 IgG Antibody ELISA Kit (DEIASL240) from CD Creative Diagnostics (www.creative-diagnostics.com) according to manufacture instructions. Anti-SARS-CoV…SciScore for 10.1101/2022.02.02.478719: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Euthanasia Agents: Forty-five days after active or sham infection and 14 days after MPTP or saline administration, the animals were anesthetized and euthanized by transcardial perfusion with 3% paraformaldehyde. Sex as a biological variable not detected. Randomization 0, hACE2 mice) were randomly assigned to a dose-finding study and then four study arms. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Antibody titers were measured in plasma using the Mouse Anti-SARS-CoV-2 IgG Antibody ELISA Kit (DEIASL240) from CD Creative Diagnostics (www.creative-diagnostics.com) according to manufacture instructions. Anti-SARS-CoV-2 IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources SARS-CoV-2 (isolate USA-WA1/2020), obtained from bei RESOURCES (Manassas, VA), was propagated in Vero cells using a 10-30% sucrose gradient in an ultracentrifuge (Beckman L8-55), and the yield titrated using the classic Reed and Muench formula 20. Verosuggested: NoneExperimental Models: Organisms/Strains Sentences Resources , SARS-CoV2 susceptible mice (B6.Cg-Tg(K18-ACE2)2Prlmn/J, Jackson Labs, Strain #034860 B6.Cg-Tg(K18-ACE2)2Prlmn/Jsuggested: RRID:IMSR_JAX:034860)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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