COVID-19 and possible links with Parkinson's disease and parkinsonism: from bench to bedside

David Sulzer¹, Angelo Antonini², Valentina Leta^{3

4}, Anna Nordvig⁵, Richard J Smeyne⁶, James E Goldman⁷, Osama Al-Dalahmah⁷, Luigi Zecca⁸, Alessandro Sette^{9

10}, Luigi Bubacco¹¹, Olimpia Meucci^{12

13

14}, Elena Moro^{15

16

17}, Ashley S Harms¹⁸, Yaqian Xu¹⁹, Stanley Fahn⁵, K Ray Chaudhuri^{3

4}

Affiliations

¹ Departments of Psychiatry, Neurology, Pharmacology, Columbia University Medical Center, New York State Psychiatric Institute, New York, NY 10032 USA.
² Department of Neuroscience, Parkinson and Movement Disorders Unit, University of Padua, Padua, Italy.
³ King's College London, Institute of Psychiatry, Psychology & Neuroscience, De Crespigny Park, London, SE5 8AF UK.
⁴ Parkinson's Foundation Centre of Excellence, King's College Hospital, Denmark Hill, London, SE5 9RS UK.
⁵ Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University and the New York Presbyterian Hospital, New York, NY 10032 USA.
⁶ Department of Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107 USA.
⁷ Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University and the New York Presbyterian Hospital, New York, NY 10032 USA.
⁸ Institute of Biomedical Technologies, National Research Council of Italy, Segrate, Milan, Italy.
⁹ Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92093 USA.
¹⁰ Department of Medicine, University of California, San Diego, CA 92093 USA.
¹¹ Department of Biology, University of Padova, Padova, Italy.
¹² Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102 USA.
¹³ Center of Neuroimmunology and CNS Therapeutics, Institute of Molecular Medicine and Infectious Diseases, Drexel University College of Medicine, Philadelphia, PA 19102 USA.
¹⁴ Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102 USA.
¹⁵ Department of Neurology, Grenoble Alpes University Hospital, Grenoble, France.
¹⁶ Grenoble Institute of Neurosciences GIN-INSERM U1216/CEA/UGA, Grenoble, France.
¹⁷ Grenoble Alpes University, Grenoble, France.
¹⁸ Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL 35294 USA.
¹⁹ Department of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032 USA.

PMID: 32885037
PMCID: PMC7441399
DOI: 10.1038/s41531-020-00123-0

Review

COVID-19 and possible links with Parkinson's disease and parkinsonism: from bench to bedside

David Sulzer et al. NPJ Parkinsons Dis. 2020.

. 2020 Aug 20:6:18.

doi: 10.1038/s41531-020-00123-0. eCollection 2020.

Authors

Affiliations

¹ Departments of Psychiatry, Neurology, Pharmacology, Columbia University Medical Center, New York State Psychiatric Institute, New York, NY 10032 USA.
² Department of Neuroscience, Parkinson and Movement Disorders Unit, University of Padua, Padua, Italy.
³ King's College London, Institute of Psychiatry, Psychology & Neuroscience, De Crespigny Park, London, SE5 8AF UK.
⁴ Parkinson's Foundation Centre of Excellence, King's College Hospital, Denmark Hill, London, SE5 9RS UK.
⁵ Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University and the New York Presbyterian Hospital, New York, NY 10032 USA.
⁶ Department of Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107 USA.
⁷ Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University and the New York Presbyterian Hospital, New York, NY 10032 USA.
⁸ Institute of Biomedical Technologies, National Research Council of Italy, Segrate, Milan, Italy.
⁹ Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92093 USA.
¹⁰ Department of Medicine, University of California, San Diego, CA 92093 USA.
¹¹ Department of Biology, University of Padova, Padova, Italy.
¹² Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102 USA.
¹³ Center of Neuroimmunology and CNS Therapeutics, Institute of Molecular Medicine and Infectious Diseases, Drexel University College of Medicine, Philadelphia, PA 19102 USA.
¹⁴ Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102 USA.
¹⁵ Department of Neurology, Grenoble Alpes University Hospital, Grenoble, France.
¹⁶ Grenoble Institute of Neurosciences GIN-INSERM U1216/CEA/UGA, Grenoble, France.
¹⁷ Grenoble Alpes University, Grenoble, France.
¹⁸ Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL 35294 USA.
¹⁹ Department of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032 USA.

PMID: 32885037
PMCID: PMC7441399
DOI: 10.1038/s41531-020-00123-0

Abstract

This Viewpoint discusses insights from basic science and clinical perspectives on coronavirus disease 2019 (COVID-19)/severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection in the brain, with a particular focus on Parkinson's disease. Major points include that neuropathology studies have not answered the central issue of whether the virus enters central nervous system neurons, astrocytes or microglia, and the brain vascular cell types that express virus have not yet been identified. Currently, there is no clear evidence for human neuronal or astrocyte expression of angiotensin-converting enzyme 2 (ACE2), the major receptor for viral entry, but ACE2 expression may be activated by inflammation, and a comparison of healthy and infected brains is important. In contrast to the 1918 influenza pandemic and avian flu, reports of encephalopathy in COVID-19 have been slow to emerge, and there are so far no documented reports of parkinsonism apart from a single case report. We recommend consensus guidelines for the clinical treatment of Parkinson's patients with COVID-19. While a role for the virus in causing or exacerbating Parkinson's disease appears unlikely at this time, aggravation of specific motor and non-motor symptoms has been reported, and it will be important to monitor subjects after recovery, particularly for those with persisting hyposmia.

Keywords: Translational research.

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Conflict of interest statement

Competing interestsD.S. and K.R.C. are Editors in Chief for npj Parkinson’s Disease. E.M. is Associate Editor for npj Parkinson’s Disease. A.A has received compensation for consultancy and speaker related activities from UCB, Boehringer Ingelheim, AbbVie, Zambon, Bial, Ever Pharma, Neuroderm, Theravance Biopharma, Biogen, outside the submitted work; he receives research support from Chiesi Pharmaceuticals, Lundbeck, Horizon 2020 - PD_Pal Grant 825785, Ministry of Education University and Research (MIUR) Grant ARS01_01081, Cariparo Foundation, outside the submitted work. He serves as consultant for Boehringer–Ingelheim for legal cases on pathological gambling, outside the submitted work. V.L., A.N., R.J.S., J.E.G., O.A., L.Z., A.S., L.B., O.M., A.S.H., Y.X., and S.F. declare that there are no competing interests.

Figures

**Fig. 1. Possible entry routes for SARS-CoV-2 into central nervous system and potential intracellular consequences.**
There is evidence for SARS-CoV-2 invasion of vasculature in the brain, but little evidence for SARS-CoV-2 in brain parenchyma at this time: this issue will become clearer with results from ongoing autopsy studies. Whether or not the virus is present in neurons or astrocytes, there may be multiple consequences for brain cells, in part through intracellular responses to inflammation that could lead to protein misfolding, a feature of neurodegenerative disorders.

**Fig. 2. Flowchart identifying potential management issues in Parkinson’s disease patients.**
a Parkinson’s disease patients exposed to self-isolation or b, c infection with Coronavirus disease 2019 virus.

See this image and copyright information in PMC

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COVID-19 and possible links with Parkinson's disease and parkinsonism: from bench to bedside

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COVID-19 and possible links with Parkinson's disease and parkinsonism: from bench to bedside

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Conflict of interest statement

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