The Influence of Coronavirus Disease-2019 (COVID-19) On Parkinson’s Disease: An Updated Systematic Review

Abstract

Background COVID-19 has affected global communities with multiple neurological complications in addition to other critical medical issues. COVID-19 binds to the host’s angiotensin-converting enzyme 2 (ACE2) receptors, which are expressed in the neurons and glial cells, acting as an entry port to the central nervous system (CNS). ACE2 receptors are abundantly expressed on dopamine neurons, which may worsen the prognosis of motor symptoms in Parkinson’s disease (PD). SARS-CoV-2 may lead to an indirect response via immune-mediated cytokine storms and propagate through the CNS leading to damage. In this systematic review, we aim to provide thorough analyses of associations between COVID-19 and neurological outcomes for patients with PD. Methods Using PRISMA statement 2020, a systematic review was conducted to isolate confirmed COVID-19 patients and analyze the PD-associated neurological outcomes using the following databases: PubMed, Science Direct, Google Scholar, and Cochrane databases. The following keywords were used “COVID19, SARS-CoV-2, Parkinson’s disease, Pandemic, Mortality.” A modified Delphi process was employed. Results Of the 355 studies located during the initial round of screening, 16 were included in the final synthesis. Of PD patients who tested positive for SARS-CoV-2, worsening motor symptoms and other viral-associated symptoms were reported. These symptoms included bradykinesia, tremors, gait disturbances, delirium and dementia, and severe spasms of arms and legs. Encephalopathy was presented in 2 of the included studies. Increased mortality rates were identified for hospitalized patients due to COVID-19 and PD as compared to other patient groups. Conclusion Patients with PD may experience substantial worsening of symptoms due to COVID 19. Given the novelty of neurological-viral associations, clinical studies in the future ought to explore the disease severity and neurological outcomes in COVID-19 positive patients with PD as compared to non-PD patients, in addition to understanding the role of ACE2 in increased vulnerability to contracting the infection and as a treatment modality.

Demographic Features, Physical Examination Findings, and Medication Use in Hospitalized, Delirious Patients With and Without COVID-19 Infection: A Retrospective Study

“…One possible explanation for this overrepresentation of AM signs is that the high degree of inflammation seen in many COVID-19+ patients disrupts dopamine synthesis and function. This could lead to a state of dopamine depletion and create a vulnerability to AM through impairment of mesocorticolimbic dopamine signaling required for motivation and movement ( 39 , 40 ). The high rates of AM could also represent a subtype of delayed post-hypoxic leukoencephalopathy which can clinically present with features of dopamine dysfunction such as parkinsonian tremor and rigidity ( 41 ).…”

Encephalitis as a clinical manifestation of COVID-19: A Case Series

“…The primary effect of COVID-19 on the human body is on the respiratory system but it can inflict certain neurological manifestations as well [12]. Although the evidence on the neurological manifestations of COVID-19 is still scarce as it is rare, a study has documented that 36 of the patients having ARDS caused by COVID-19 had some forms of neurological manifestations [6].…”

Does SARS-CoV-2 affect neurodegenerative disorders? TLR2, a potential receptor for SARS-CoV-2 in the CNS

“…A case study by Lee and colleagues suggested the potential effects of SARS-CoV-2 infection on the dopaminergic mechanisms that led to the development of dysphagia in PD patients 69 . In addition, a recent study reported that infection with SARS-CoV-2 may worsen the symptoms of PD 70 . It was demonstrated that the nucleocapsid (N) protein of SARS-CoV-2 sped up the process of α-syn aggregation in vitro 71 .…”