Parkinson’s Disease and the COVID-19 Pandemic: A Review Article on the Association between SARS-CoV-2 and α-Synucleinopathy

Abstract

There is an extensive debate on the neurological consequences of 2019 novel coronavirus disease (COVID-19) and its impact on Parkinson’s disease (PD) patients, which seems to puzzle neurologists. Links between viral infections and PD have long been suspected and studied, but the exact relationship remains elusive. Since severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) enters the brain through multiple routes and has a direct impact on the brain, cumulative damage occurs due to the activation of proinflammatory cytokines and chemokines. SARS-CoV-2 seems to aggravate PD due to its effects on α-synuclein, mitochondrial dysfunction, and dopamine depletion. A few studies have even highlighted the higher vulnerability of PD patients to COVID-19. The sudden dramatic change in lifestyle caused by the pandemic and the widespread lockdowns that were implemented have added to the hidden sorrows of PD patients, as they already have a compromised mechanism for coping with stress. This review summarizes insights from basic science and the clinical effect of SARS-CoV-2 infection on the human brain, with a specific focus on PD.

SARS-CoV-2 Proteins Interact with Alpha Synuclein and Induce Lewy Body-like Pathology In Vitro

“…Hence, a single pathogen is unlikely to be responsible for the entire pathogenesis of PD. There is also mounting evidence supporting the association of inflammation, mitochondrial dysfunction, autophagy deficiency, endoplasmic reticulum stress, and loss of proteostasis by SARS-CoV-2 infection with an elevated risk of PD later in life [ 4 ]. Several biochemical pathways, including oxidative stress, inflammation, and protein aggregation, show similarities between PD and COVID-19 [ 2 ].…”

“…The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks known as the 2019 novel coronavirus disease (COVID-19) pandemic has caused high levels of concern and economic crisis around the world [ 1 ]. Previous studies have supported a link between SARS-CoV-2 infection and Parkinson’s diseases (PD) [ 2 , 3 , 4 , 5 ]. More recently, several cases of patients with COVID-19 who developed parkinsonism and responded to levodopa have been reported.…”

“…One of these cases was a 45-year-old Israeli patient who developed PD soon after hospitalization due to SARS-CoV-2 infection [ 10 ]. There is growing evidence in PD patients suffering from COVID-19 that COVID-19 could worsen PD [ 4 ], suggesting that COVID-19 might be associated with an elevated long-term risk of PD.…”

COVID-19 and neurological sequelae: Vitamin D as a possible neuroprotective and/or neuroreparative agent

“…As the mechanisms involved in the neurological symptoms of COVID-19 are progressively elucidated, the concept of “Neuro-COVID-19” is becoming increasingly accepted in research and clinical circles [44] . The most relevant neurological manifestations following SARS-CoV-2 infection include headache, ischemic or hemorrhagic strokes, neuroinflammation, neurodegeneration and neuropsychiatric disorders [45] , [46] , [47] . Some additional neurological-derived manifestations are quite pathognomonic of COVID-19 disease caused by most variants of SARS-CoV-2 (though not others, such as Omicron [48] ).…”

“…Likewise, although the association between the pathophysiology of COVID-19 and Parkinson's disease (PD) is still unknown, SARS-CoV-2 has been reported to cause an increase in alpha-synuclein synthesis which in turn triggers the release of various cytokines and chemokines characteristic of PD [60] , [61] . Furthermore, the binding of SARS-CoV-2 to ACE2 may alter GABA (gamma-aminobutyric acid) neurotransmission in the amygdala and possibly in other parts of the brain, as well as produce alterations in dopaminergic neurotransmission, which may represent another possible target of the virus, possibly related to other neurodegenerative sequelae associated with COVID-19 [46] , [62] . It has also been proposed that antibodies directed against SARS-CoV-2 epitopes also react against the nicotinic acetylcholine receptor or other molecular elements of the neuromuscular junction, thus accelerating neurodegenerative pathologies such as myasthenia gravis, which has also been linked to COVID-19 [63] .…”