Parkinson’s Disease and SARS-CoV-2 Infection: Particularities of Molecular and Cellular Mechanisms Regarding Pathogenesis and Treatment

Abstract

Accumulating data suggest that chronic neuroinflammation-mediated neurodegeneration is a significant contributing factor for progressive neuronal and glial cell death in age-related neurodegenerative pathology. Furthermore, it could be encountered as long-term consequences in some viral infections, including post-COVID-19 Parkinsonism-related chronic sequelae. The current systematic review is focused on a recent question aroused during the pandemic’s successive waves: are there post-SARS-CoV-2 immune-mediated reactions responsible for promoting neurodegeneration? Does the host’s dysregulated immune counter-offensive contribute to the pathogenesis of neurodegenerative diseases, emerging as Parkinson’s disease, in a complex interrelation between genetic and epigenetic risk factors? A synthetic and systematic literature review was accomplished based on the ”Preferred Reporting Items for Systematic Principles Reviews and Meta-Analyses” (PRISMA) methodology, including registration on the specific online platform: International prospective register of systematic reviews—PROSPERO, no. 312183. Initially, 1894 articles were detected. After fulfilling the five steps of the selection methodology, 104 papers were selected for this synthetic review. Documentation was enhanced with a supplementary 47 bibliographic resources identified in the literature within a non-standardized search connected to the subject. As a final step of the PRISMA method, we have fulfilled a Population-Intervention-Comparison-Outcome-Time (PICOT)/Population-Intervention-Comparison-Outcome-Study type (PICOS)—based metanalysis of clinical trials identified as connected to our search, targeting the outcomes of rehabilitative kinesitherapeutic interventions compared to clinical approaches lacking such kind of treatment. Accordingly, we identified 10 clinical trials related to our article. The multi/interdisciplinary conventional therapy of Parkinson’s disease and non-conventional multitarget approach to an integrative treatment was briefly analyzed. This article synthesizes the current findings on the pathogenic interference between the dysregulated complex mechanisms involved in aging, neuroinflammation, and neurodegeneration, focusing on Parkinson’s disease and the acute and chronic repercussions of COVID-19. Time will tell whether COVID-19 neuroinflammatory events could trigger long-term neurodegenerative effects and contribute to the worsening and/or explosion of new cases of PD. The extent of the interrelated neuropathogenic phenomenon remains obscure, so further clinical observations and prospective longitudinal cohort studies are needed.

Links between COVID-19 and Parkinson’s disease/Alzheimer’s disease: reciprocal impacts, medical care strategies and underlying mechanisms

“…Dopaminergic neurons are considered to be susceptible to SARS-CoV-2 infection since both ACE2 and TMPRSS2 receptors are overexpressed in the substantia nigra [ 76 , 77 ]. Under certain pathological circumstances, SARS-CoV-2 acts as a neurodegenerative enhancer to potentially drive the development or progression of PD and its related motor and non-motor symptoms [ 35 , 78 ]. In direct pathways, SARS-CoV-2 enters the CNS through the olfactory nerve via axonal transport from peripheral nerves, or through the BBB [ 79 ].…”

“…COVID-19 is responsible for severe acute respiratory insufficiency, subsequent hypoxemia, sepsis-induced hyper-coagulation, local thrombosis in brain vessels with hypoperfusion, and cerebral hypoxia. COVID-19 might exacerbate oxidative stress dysregulation at the cellular level and promote neurodegeneration [ 78 ]. Binding of SARS-CoV-2 to ACE2 receptors on microglia decreases mitochondria energy and activates nicotinamide adenine dinucleotide phosphate oxidase, which generates ROS, promoting oxidative stress and neuroinflammation, leading to apoptosis of neighboring dopaminergic neurons [ 93 – 95 ].…”

Life and disease status of patients with Parkinson’s disease during and after zero-COVID in China: an online survey

“…Infection is a common cause of exacerbation of parkinsonian symptoms [ 16 ]. A severe infection such as COVID-19 could have a direct harmful impact on PD motor symptoms, which deteriorate during systemic inflammation [ 17 ]. A large online study (Fox Insight) has investigated the effects of the COVID-19 pandemic on PD patients [ 5 ].…”

Exploring the Role of ACE2 as a Connecting Link between COVID-19 and Parkinson’s Disease

“…A growing body of evidence suggests that ACE2 plays a key role in the pathogenesis of both COVID-19 and PD, via its implication in the shared underlying mechanisms of these diseases: inflammation, immune responses, oxidative stress, cell proliferation and survival, and mitochondrial function. Although the role of ACE2 in neurodegenerative diseases and COVID-19 has been previously discussed [ 17 , 18 , 19 ], there has been no recent extensive review focusing on the latest evidence, particularly for PD. Given the rapidly growing body of research in this field, we intend to provide an updated critical review on the relationship between COVID-19 and PD in particular, using ACE2 as a potential connecting link between these two conditions.…”