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1
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Hu X, Li Y, Qu H, He C, Chen Z, Zhan M, Du Y, Wang H, Chen W, Sun L, Ning X. No genetic link between Parkinson's disease and SARS-CoV-2 infection: a two-sample Mendelian randomization study. Front Neurol 2024; 15:1393888. [PMID: 39006236 PMCID: PMC11239547 DOI: 10.3389/fneur.2024.1393888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 06/13/2024] [Indexed: 07/16/2024] Open
Abstract
Objective Existing literature has not clearly elucidated whether SARS-CoV-2 infection increases the incidence of Parkinson's disease or if Parkinson's disease patients are more susceptible to the effects of SARS-CoV-2 infection. To clarify the issue, this study employs a genetic epidemiological approach to investigate the association. Methods This study utilizes a two-sample Mendelian randomization analysis. The primary analysis employs the inverse variance-weighted (IVW) method, supplemented by secondary analyses including MR-Egger regression, weighted median, IVW radial method, and weighted mode, to evaluate the bidirectional causal relationship between Parkinson's disease and SARS-CoV-2 infection. Results IVW results showed no genetic causality between SARS-CoV-2 susceptibility, hospitalization rate and severity and Parkinson's disease. (IVW method: p = 0.408 OR = 1.10 95% CI: 0.87 ~ 1.39; p = 0.744 OR = 1.11 95% CI: 0.94 ~ 1.09; p = 0.436 OR = 1.05 95% CI: 0.93 ~ 1.17). Parkinson's disease was not genetically associated with susceptibility to new crown infections, hospitalization rates, and severity (IVW method: p = 0.173 OR = 1.01 95% CI: 0.99 ~ 1.03; p = 0.109 OR = 1.05 95% CI: 0.99 ~ 1.12; p = 0.209 OR = 1.03 95% CI: 0.99 ~ 1.07). MR-Egger regression, weighted median, IVW radial method, and weighted mode results are consistent with the results of the IVW method. Conclusion This study does not support a genetic link between Parkinson's disease and SARS-CoV-2 infection, and the association observed in previous cohort studies and observational studies may be due to other confounding factors.
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Affiliation(s)
- Xiaohua Hu
- Graduate School, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yutong Li
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Hua Qu
- National Research Center for Cardiovascular Diseases of Traditional Chinese, Beijing, China
- Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing, China
| | - Chunying He
- Graduate School, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zhiyan Chen
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Min Zhan
- Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing, China
| | - Yida Du
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Huan Wang
- Graduate School, China Academy of Chinese Medical Sciences, Beijing, China
| | - Wenjie Chen
- Ezhou Traditional Chinese Medicine Hospital, Ezhou, China
| | - Linjuan Sun
- Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing, China
| | - Xia Ning
- Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing, China
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2
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Meinhardt J, Streit S, Dittmayer C, Manitius RV, Radbruch H, Heppner FL. The neurobiology of SARS-CoV-2 infection. Nat Rev Neurosci 2024; 25:30-42. [PMID: 38049610 DOI: 10.1038/s41583-023-00769-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/01/2023] [Indexed: 12/06/2023]
Abstract
Worldwide, over 694 million people have been infected with SARS-CoV-2, with an estimated 55-60% of those infected developing COVID-19. Since the beginning of the pandemic in December 2019, different variants of concern have appeared and continue to occur. With the emergence of different variants, an increasing rate of vaccination and previous infections, the acute neurological symptomatology of COVID-19 changed. Moreover, 10-45% of individuals with a history of SARS-CoV-2 infection experience symptoms even 3 months after disease onset, a condition that has been defined as 'post-COVID-19' by the World Health Organization and that occurs independently of the virus variant. The pathomechanisms of COVID-19-related neurological complaints have become clearer during the past 3 years. To date, there is no overt - that is, truly convincing - evidence for SARS-CoV-2 particles in the brain. In this Review, we put special emphasis on discussing the methodological difficulties of viral detection in CNS tissue and discuss immune-based (systemic and central) effects contributing to COVID-19-related CNS affection. We sequentially review the reported changes to CNS cells in COVID-19, starting with the blood-brain barrier and blood-cerebrospinal fluid barrier - as systemic factors from the periphery appear to primarily influence barriers and conduits - before we describe changes in brain parenchymal cells, including microglia, astrocytes, neurons and oligodendrocytes as well as cerebral lymphocytes. These findings are critical to understanding CNS affection in acute COVID-19 and post-COVID-19 in order to translate these findings into treatment options, which are still very limited.
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Affiliation(s)
- Jenny Meinhardt
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Simon Streit
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Carsten Dittmayer
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Regina V Manitius
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Helena Radbruch
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
| | - Frank L Heppner
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
- Cluster of Excellence, NeuroCure, Berlin, Germany.
- German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
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3
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Graf K, Gustke A, Mösle M, Armann J, Schneider J, Schumm L, Roessner V, Beste C, Bluschke A. Preserved perception-action integration in adolescents after a COVID-19 infection. Sci Rep 2023; 13:13287. [PMID: 37587175 PMCID: PMC10432494 DOI: 10.1038/s41598-023-40534-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 08/11/2023] [Indexed: 08/18/2023] Open
Abstract
Evidence is accumulating that the Coronavirus disease (COVID-19) can bring forth deficits in executive functioning via alterations in the dopaminergic system. Importantly, dopaminergic pathways have been shown to modulate how actions and perceptions are integrated within the brain. Such alterations in event file binding could thus underlie the cognitive deficits developing after a COVID-19 infection. We examined action-perception integration in a group of young people (11-19 years of age) that had been infected with COVID-19 before study participation (n = 34) and compared them to a group of uninfected healthy controls (n = 29) on the behavioral (i.e., task accuracy, reaction time) and neurophysiological (EEG) level using an established event file binding paradigm. Groups did not differ from each other regarding demographic variables or in reporting psychiatric symptoms. Overall, multiple lines of evidence (behavioral and neurophysiological) suggest that action-perception integration is preserved in adolescents who suffered from COVID-19 prior to study participation. Event file binding processes were intact in both groups on all levels. While cognitive impairments can occur following a COVID-19 infection, the study demonstrates that action-perception integration as one of the basic building blocks of cognition seems to be largely unaffected in adolescents with a rather mild course of the disease.
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Affiliation(s)
- Katharina Graf
- Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Schubertstrasse 42, 01309, Dresden, Germany
- University Neuropsychology Center (UNC), Faculty of Medicine, TU Dresden, Dresden, Germany
| | - Alena Gustke
- Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Schubertstrasse 42, 01309, Dresden, Germany
- University Neuropsychology Center (UNC), Faculty of Medicine, TU Dresden, Dresden, Germany
| | - Mariella Mösle
- Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Schubertstrasse 42, 01309, Dresden, Germany
- University Neuropsychology Center (UNC), Faculty of Medicine, TU Dresden, Dresden, Germany
| | - Jakob Armann
- Department of Paediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Josephine Schneider
- Department of Paediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Leonie Schumm
- Department of Paediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Veit Roessner
- Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Schubertstrasse 42, 01309, Dresden, Germany
| | - Christian Beste
- Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Schubertstrasse 42, 01309, Dresden, Germany.
- University Neuropsychology Center (UNC), Faculty of Medicine, TU Dresden, Dresden, Germany.
| | - Annet Bluschke
- Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Schubertstrasse 42, 01309, Dresden, Germany
- University Neuropsychology Center (UNC), Faculty of Medicine, TU Dresden, Dresden, Germany
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4
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Xi X, Han L. Exploring the relationship between novel Coronavirus pneumonia and Parkinson's disease. Medicine (Baltimore) 2022; 101:e31813. [PMID: 36401405 PMCID: PMC9678520 DOI: 10.1097/md.0000000000031813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
The hypothesis is that there is 0a relationship between Parkinson's disease and coronavirus disease 2019 (COVID-19). By summarizing the pathogenesis of Parkinson's disease and COVID-19 and the impact of COVID-19 on the central nervous system, the relationship between Parkinson's disease and COVID-19 was analyzed, including whether Parkinson's disease is a predisposition factor for COVID-19 and whether COVID-19 causes the occurrence of Parkinson's disease. Discuss the impact of COVID-19 on patients with Parkinson's disease, including symptoms and life impact. To summarize the principles, goals and methods of home rehabilitation for Parkinson's disease patients during COVID-19. Through the analysis of this paper, it is believed that COVID-19 may cause Parkinson's disease. Parkinson's disease has the condition of susceptibility to COVID-19, but this conclusion is still controversial.
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Affiliation(s)
- Xiaoming Xi
- Rehabilitation Center,Beijing Rehabilitation Hospital Affiliated to Capital Medical University, Beijing
- * Correspondence: Xiaoming Xi, Beijing Rehabilitation Hospital Affiliated to Capital Medical University, No.15, Badachu Xixizhuang, Shijingshan District, Beijing (e-mail: )
| | - Liang Han
- Shandong University of Traditional Chinese Medicine
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5
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Rossi E, Mutti L, Morrione A, Giordano A. Neuro-Immune Interactions in Severe COVID-19 Infection. Pathogens 2022; 11:1256. [PMID: 36365007 PMCID: PMC9699641 DOI: 10.3390/pathogens11111256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/26/2022] [Accepted: 10/28/2022] [Indexed: 12/15/2022] Open
Abstract
SARS-CoV-2 is a new coronavirus that has affected the world since 2019. Interstitial pneumonia is the most common clinical presentation, but additional symptoms have been reported, including neurological manifestations. Severe forms of infection, especially in elderly patients, present as an excessive inflammatory response called "cytokine storm", which can lead to acute respiratory distress syndrome (ARDS), multiorgan failure and death. Little is known about the relationship between symptoms and clinical outcomes or the characteristics of virus-host interactions. The aim of this narrative review is to highlight possible links between neurological involvement and respiratory damage mediated by pathological inflammatory pathways in SARS-CoV-2 infection. We will focus on neuro-immune interactions and age-related immunity decline and discuss some pathological mechanisms that contribute to negative outcomes in COVID-19 patients. Furthermore, we will describe available therapeutic strategies and their effects on COVID-19 neurological symptoms.
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Affiliation(s)
- Elena Rossi
- Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
| | - Luciano Mutti
- Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
- Italian Group for Research and Therapy for Mesothelioma (GIMe), 27058 Voghera, Italy
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, Coppito 2, 67100 L’Aquila, Italy
| | - Andrea Morrione
- Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
| | - Antonio Giordano
- Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
- Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
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6
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Bunaciu AA, Aboul-Enein HY. DETERMINATION OF COVID-19 VIRUSES IN SALIVA USING FOURIER TRANSFORM INFRARED SPECTROSCOPY. CHINESE JOURNAL OF ANALYTICAL CHEMISTRY 2022. [PMCID: PMC9519369 DOI: 10.1016/j.cjac.2022.100178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
The rapid spread of severe syndrome coronavirus 2 (SARS-CoV-2) has led to the coronavirus disease 2019 (COVID-19) worldwide pandemic. Scientists and researchers all over the world studied different methods in order to accelerate the testing results. In this review, we present some of the most important papers related to the determination of COVID – 19 in saliva using the Fourier Transform Infrared Spectroscopy technique.
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7
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Mysiris DS, Vavougios GD, Karamichali E, Papoutsopoulou S, Stavrou VT, Papayianni E, Boutlas S, Mavridis T, Foka P, Zarogiannis SG, Gourgoulianis K, Xiromerisiou G. Post-COVID-19 Parkinsonism and Parkinson's Disease Pathogenesis: The Exosomal Cargo Hypothesis. Int J Mol Sci 2022; 23:9739. [PMID: 36077138 PMCID: PMC9456372 DOI: 10.3390/ijms23179739] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 08/21/2022] [Accepted: 08/26/2022] [Indexed: 11/16/2022] Open
Abstract
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer's disease, globally. Dopaminergic neuron degeneration in substantia nigra pars compacta and aggregation of misfolded alpha-synuclein are the PD hallmarks, accompanied by motor and non-motor symptoms. Several viruses have been linked to the appearance of a post-infection parkinsonian phenotype. Coronavirus disease 2019 (COVID-19), caused by emerging severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, has evolved from a novel pneumonia to a multifaceted syndrome with multiple clinical manifestations, among which neurological sequalae appear insidious and potentially long-lasting. Exosomes are extracellular nanovesicles bearing a complex cargo of active biomolecules and playing crucial roles in intercellular communication under pathophysiological conditions. Exosomes constitute a reliable route for misfolded protein transmission, contributing to PD pathogenesis and diagnosis. Herein, we summarize recent evidence suggesting that SARS-CoV-2 infection shares numerous clinical manifestations and inflammatory and molecular pathways with PD. We carry on hypothesizing that these similarities may be reflected in exosomal cargo modulated by the virus in correlation with disease severity. Travelling from the periphery to the brain, SARS-CoV-2-related exosomal cargo contains SARS-CoV-2 RNA, viral proteins, inflammatory mediators, and modified host proteins that could operate as promoters of neurodegenerative and neuroinflammatory cascades, potentially leading to a future parkinsonism and PD development.
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Affiliation(s)
| | - George D. Vavougios
- Department of Neurology, Faculty of Medicine, University of Cyprus, Lefkosia 1678, Cyprus
- Laboratory of Pulmonary Testing and Rehabilitation, Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece
| | - Eirini Karamichali
- Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece
| | - Stamatia Papoutsopoulou
- Department of Biochemistry and Biotechnology, Faculty of Life Sciences, University of Thessaly, Mezourlo, 41500 Larissa, Greece
| | - Vasileios T. Stavrou
- Laboratory of Pulmonary Testing and Rehabilitation, Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece
| | - Eirini Papayianni
- Laboratory of Pulmonary Testing and Rehabilitation, Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece
| | - Stylianos Boutlas
- Laboratory of Pulmonary Testing and Rehabilitation, Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece
| | - Theodoros Mavridis
- 1st Neurology Department, Eginition Hospital, Medical School, National & Kapodistrian University of Athens, 11528 Athens, Greece
| | - Pelagia Foka
- Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece
| | - Sotirios G. Zarogiannis
- Department of Physiology, Faculty of Medicine, University of Thessaly, Biopolis, 41500 Larissa, Greece
| | - Konstantinos Gourgoulianis
- Laboratory of Pulmonary Testing and Rehabilitation, Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece
| | - Georgia Xiromerisiou
- Department of Neurology, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece
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8
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Leta V, Boura I, van Wamelen DJ, Rodriguez-Violante M, Antonini A, Chaudhuri KR. Covid-19 and Parkinson's disease: Acute clinical implications, long-COVID and post-COVID-19 parkinsonism. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2022; 165:63-89. [PMID: 36208907 PMCID: PMC9357514 DOI: 10.1016/bs.irn.2022.04.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
The Coronavirus Disease 2019 (Covid-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has led to unprecedented challenges for the delivery of healthcare and has had a clear impact on people with chronic neurological conditions such as Parkinson's disease (PD). Acute worsening of motor and non-motor symptoms and long-term sequalae have been described during and after SARS-CoV-2 infections in people with Parkinson's (PwP), which are likely to be multifactorial in their origin. On the one hand, it is likely that worsening of symptoms has been related to the viral infection itself, whereas social restrictions imposed over the course of the Covid-19 pandemic might also have had such an effect. Twenty cases of post-Covid-19 para-infectious or post-infectious parkinsonism have been described so far where a variety of pathophysiological mechanisms seem to be involved; however, a Covid-19-induced wave of post-viral parkinsonism seems rather unlikely at the moment. Here, we describe the interaction between SARS-CoV-2 and PD in the short- and long-term and summarize the clinical features of post-Covid-19 cases of parkinsonism observed so far.
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Affiliation(s)
- Valentina Leta
- Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Parkinson's Foundation Centre of Excellence, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Iro Boura
- Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Parkinson's Foundation Centre of Excellence, King's College Hospital NHS Foundation Trust, London, United Kingdom; Medical School, University of Crete, Heraklion, Crete, Greece
| | - Daniel J van Wamelen
- Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Parkinson's Foundation Centre of Excellence, King's College Hospital NHS Foundation Trust, London, United Kingdom; Department of Neurology, Centre of Expertise for Parkinson & Movement Disorders, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
| | | | - Angelo Antonini
- Parkinson and Movement Disorders Unit, Department of Neuroscience, Centre for Rare Neurological Diseases (ERN-RND), University of Padova, Padova, Italy
| | - Kallol Ray Chaudhuri
- Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Parkinson's Foundation Centre of Excellence, King's College Hospital NHS Foundation Trust, London, United Kingdom.
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9
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Boura I, Ray Chaudhuri K. Coronavirus Disease 2019 and related Parkinsonism: the clinical evidence thus far. Mov Disord Clin Pract 2022; 9:584-593. [PMID: 35601258 PMCID: PMC9111006 DOI: 10.1002/mdc3.13461] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 03/11/2022] [Accepted: 04/09/2022] [Indexed: 11/10/2022] Open
Abstract
Background The Coronavirus disease 2019 (Covid‐19) pandemic has fueled both research and speculation, as to whether it could be a “perfect storm” for a post‐Covid emergence of parkinsonism in some susceptible individuals, analogous to the post‐encephalitic parkinsonism reported after the 1918 influenza epidemic. This theory is further augmented by reports of a pathogenic effect of the Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) on the central nervous system with specific impact on the dopaminergic pathway, as well as the possibility of the virus to selectively bind to Angiotensin‐Converting Enzyme‐2 (ACE‐2); these molecules are expressed abundantly in the midbrain dopamine neurons and, are likely involved in several cellular mechanisms cited in Parkinson's Disease (PD) pathophysiology. Objectives—Methods Therefore, we performed a review of the literature up to February 2022 to explore the current landscape considering published cases of new‐onset parkinsonism after a SARS‐CoV‐2 infection in otherwise healthy individuals. We summarized their clinical features, diagnostic and treatment approaches, discussing potential underlying mechanisms in light of PD pathogenesis theories. Results Twenty cases that developed parkinsonian features simultaneously or shortly after a reported SARS‐CoV‐2 infection were reviewed. In 11 of them, parkinsonism appeared in the context of encephalopathy, while four patients developed post‐infectious parkinsonism without encephalopathy, and four bore similarities to idiopathic PD. Nine patients exhibited a good response to dopaminergic therapy, while four responded to immunomodulatory treatment. Conclusions Available data does not yet justify a clear association between the Covid‐19 pandemic and a parkinsonism wave. However, vigilance is necessary, as long‐term effects might have not been revealed.
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Affiliation(s)
- Iro Boura
- University of Crete, Medical School Heraklion Greece
- King's College London, Department of Neurosciences Institute of Psychiatry, Psychology & Neuroscience, Denmark Hill London United Kingdom
- Parkinson's Foundation Centre of Excellence, King's College Hospital, Denmark Hill London United Kingdom
| | - K. Ray Chaudhuri
- King's College London, Department of Neurosciences Institute of Psychiatry, Psychology & Neuroscience, Denmark Hill London United Kingdom
- Parkinson's Foundation Centre of Excellence, King's College Hospital, Denmark Hill London United Kingdom
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10
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Emmi A, Boura I, Raeder V, Mathew D, Sulzer D, Goldman JE, Leta V. Covid-19, nervous system pathology, and Parkinson's disease: Bench to bedside. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2022; 165:17-34. [PMID: 36208899 PMCID: PMC9361071 DOI: 10.1016/bs.irn.2022.06.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Coronavirus disease 2019 (Covid-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is primarily regarded as a respiratory disease; however, multisystemic involvement accompanied by a variety of clinical manifestations, including neurological symptoms, are commonly observed. There is, however, little evidence supporting SARS-CoV-2 infection of central nervous system cells, and neurological symptoms for the most part appear to be due to damage mediated by hypoxic/ischemic and/or inflammatory insults. In this chapter, we report evidence on candidate neuropathological mechanisms underlying neurological manifestations in Covid-19, suggesting that while there is mostly evidence against SARS-CoV-2 entry into brain parenchymal cells as a mechanism that may trigger Parkinson's disease and parkinsonism, that there are multiple means by which the virus may cause neurological symptoms.
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Affiliation(s)
- Aron Emmi
- Institute of Human Anatomy, Department of Neuroscience, University of Padova, Padova, Italy
| | - Iro Boura
- Department of Neurology, University Hospital of Heraklion, Crete, Greece
| | - Vanessa Raeder
- Parkinson's Foundation Centre of Excellence, King's College Hospital NHS Foundation Trust, London, United Kingdom; Department of Neurology, Technical University Dresden, Dresden, Germany; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom
| | - Donna Mathew
- Neuroscience and Mental Health Research Institute, School of Medicine, Cardiff University, Cardiff, United Kingdom
| | - David Sulzer
- Departments of Psychiatry, Neurology, Pharmacology, Columbia University Medical Center, New York State Psychiatric Institute, New York, United States
| | - James E Goldman
- Department of Pathology and Cell Biology, and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University and the New York Presbyterian Hospital, New York, NY, United States
| | - Valentina Leta
- Parkinson's Foundation Centre of Excellence, King's College Hospital NHS Foundation Trust, London, United Kingdom; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
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11
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Kukkle PL. COVID-19: The cynosure of rise of Parkinson's disease. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2022; 165:251-262. [PMID: 36208903 PMCID: PMC9303069 DOI: 10.1016/bs.irn.2022.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Parkinson's disease (PD) is one of the most common age-related disorders globally. The pathophysiological mechanisms and precipitating factors underlying PD manifestations, including genetic and environmental parameters, inflammation/stress and ageing, remain elusive. Speculations about whether the Coronavirus Disease 2019 (Covid-19) pandemic could be a pivotal factor in affecting the prevalence and severity of PD or triggering a wave of new-onset parkinsonism in both the near and distant future have recently become very popular, with researchers wondering if there is a changing trend in current parkinsonism cases. Could the current understanding of the Covid-19 pathophysiology provide clues for an impending rise of parkinsonism cases in the future? Are there any lessons to learn from previous pandemics? Our aim was to look into these questions and available current literature in order to investigate if Covid-19 could constitute a cardinal event affecting the parkinsonism landscape.
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Affiliation(s)
- Prashanth Lingappa Kukkle
- Parkinson's Disease and Movement Disorders Clinic, Bangalore, India; Center for Parkinson's Disease and Movement Disorders, Manipal Hospital, Miller's Road, Bangalore, India.
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12
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Cavallieri F, Sellner J, Zedde M, Moro E. Neurologic complications of coronavirus and other respiratory viral infections. HANDBOOK OF CLINICAL NEUROLOGY 2022; 189:331-358. [PMID: 36031313 PMCID: PMC9418023 DOI: 10.1016/b978-0-323-91532-8.00004-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
In humans, several respiratory viruses can have neurologic implications affecting both central and peripheral nervous system. Neurologic manifestations can be linked to viral neurotropism and/or indirect effects of the infection due to endothelitis with vascular damage and ischemia, hypercoagulation state with thrombosis and hemorrhages, systemic inflammatory response, autoimmune reactions, and other damages. Among these respiratory viruses, recent and huge attention has been given to the coronaviruses, especially the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic started in 2020. Besides the common respiratory symptoms and the lung tropism of SARS-CoV-2 (COVID-19), neurologic manifestations are not rare and often present in the severe forms of the infection. The most common acute and subacute symptoms and signs include headache, fatigue, myalgia, anosmia, ageusia, sleep disturbances, whereas clinical syndromes include mainly encephalopathy, ischemic stroke, seizures, and autoimmune peripheral neuropathies. Although the pathogenetic mechanisms of COVID-19 in the various acute neurologic manifestations are partially understood, little is known about long-term consequences of the infection. These consequences concern both the so-called long-COVID (characterized by the persistence of neurological manifestations after the resolution of the acute viral phase), and the onset of new neurological symptoms that may be linked to the previous infection.
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Affiliation(s)
- Francesco Cavallieri
- Neurology Unit, Neuromotor and Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy,Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Johann Sellner
- Department of Neurology, Landesklinikum Mistelbach-Gänserndorf, Mistelbach, Austria,Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, Salzburg, Austria
| | - Marialuisa Zedde
- Neurology Unit, Neuromotor and Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Elena Moro
- Division of Neurology, CHU of Grenoble, Grenoble Alpes University, Grenoble Institute of Neurosciences, Grenoble, France,Correspondence to: Elena Moro, Service de neurologie, CHU de Grenoble (Hôpital Nord), Boulevard de la Chantourne, 38043 La Tronche, France. Tel: + 33-4-76-76-94-52, Fax: +33-4-76-76-56-31
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