Role of SARS-CoV-2 in Modifying Neurodegenerative Processes in Parkinson's Disease: A Narrative Review

Abstract

The COVID-19 pandemic, caused by SARS-CoV-2, continues to impact global health regarding both morbidity and mortality. Although SARS-CoV-2 primarily causes acute respiratory distress syndrome (ARDS), the virus interacts with and influences other organs and tissues, including blood vessel endothelium, heart, gastrointestinal tract, and brain. We are learning much about the pathophysiology of SARS-CoV-2 infection; however, we are just beginning to study and understand the long-term and chronic health consequences. Since the pandemic's beginning in late 2019, older adults, those with pre-existing illnesses, or both, have an increased risk of contracting COVID-19 and developing severe COVID-19. Furthermore, older adults are also more likely to develop the neurodegenerative disorder Parkinson's disease (PD), with advanced age as the most significant risk factor. Thus, does SARS-CoV-2 potentially influence, promote, or accelerate the development of PD in older adults? Our initial focus was aimed at understanding SARS-CoV-2 pathophysiology and the connection to neurodegenerative disorders. We then completed a literature review to assess the relationship between PD and COVID-19. We described potential molecular and cellular pathways that indicate dopaminergic neurons are susceptible, both directly and indirectly, to SARS-CoV-2 infection. We concluded that under certain pathological circumstances, in vulnerable persons-with-Parkinson's disease (PwP), SARS-CoV-2 acts as a neurodegenerative enhancer to potentially support the development or progression of PD and its related motor and non-motor symptoms.

Keywords: COVID-19; Parkinson’s disease; SARS-CoV-2; alpha-synuclein; angiotensin converting enzyme 2 receptor; brain; neurodegenerative disorder; neuroinflammation; older adults.

Figure 1

Etiology of Parkinson’s disease showing the major causes of the disorder that promote the loss of dopaminergic neurons in the substantia nigra pars compacta mid-brain region. Abbreviation used: CNS, central nervous system.

Figure 2

Overview of oxidative stress in PD and in SARS-CoV-2 infection. Abbreviations used: ROS, reactive oxidative species; NF-kB, nuclear factor kB; IL, interleukin; TNF, tumor necrosis factor; NAD, Nicotinamide adenine dinucleotide phosphate; Nrf2, nuclear factor-erythroid factor 2-related factor 2; ROS, reactive oxygen species.

Figure 3

The role of the immune system in the development of PD. The top-left panel shows the adaptive immune system in promoting a pro-inflammatory state. The middle-left panel is the anti-inflammatory reaction to temper down the first reaction. The bottom-left panel shows the activation of adapting immune cells from SARS-CoV-2 hyper-inflammation. The top-, middle-, and bottom-right panels show the immunological consequences of the appropriate and inappropriate reactions of the immune system cells, respectively (dark-colored dots represent aggregated αSYN).

Figure 4

Potential pathways for SARS-CoV-2 to promote neurodegeneration, Parkinson’s disease, or related disorders.