Covid19 disease is often accompanied by neurological symptoms. In many patients fatigue and lassitude do usually not appear until months after an infection has been overcome. Since these 'long covid' symptoms may be long lasting, it is debated if they may be associated with an increased risk of Parkinson's or Alzheimer's disease later on.
Zhou and colleagues showed in an important paper last year that Covid19 infection are accompanied by increased expression of Alzheimer's disease-associated genes (e.g., with RAB7A, TGFß1, or VCAM1). Parkinson's disease may also be a direct consequence of infection with corona viruses. To date, three cases of typical symptomatology occurring 2-5 weeks after Covid19 infection have been described (Cohen et al., 2020; Faber et al., 2020; Méndez-Guerrero et al., 2020). The patients were 35, 45, and 58 years old. They had no history of PD and neither were family members affected by the disease. All three showed severe symptoms and had to be hospitalized with respiratory distress. With the help of imaging techniques, a defect in the nigrostriatal dopamine system was then detected. In two patients, Parkinson's medications provided improvement in symptoms, and one recovered without medication.
It is important to emphasize that this does not imply causality, i.e., we do not know at this point whether or not more Parkinson's or Alzheimer's cases will occur in the future as a result of the global corona pandemic. However, available data suggest that Covid19 may trigger neurodegeneration or bring forward the onset of neurological disease in some patients.
The inflammatory processes associated with covid infection probably play a critical role in the development of neurologic symptoms. The lining of the vessel walls, the endothelium, can be damaged by the SARS virus. Monocytes, the precursors of macrophages, migrate from the blood into the brain and, together with the immunologically competent microglia, may damage neurons. In addition, the dopaminergic neurons in the midbrain produce high levels of the receptor ACE2 (angiotensin-converting enzyme receptor), which is necessary for the virus to enter the cells, so that the substantia nigra can be directly affected. In addition, increased α-synuclein aggregates are detectable in infected neurons, which are typical for Parkinson's disease.
With regard to the development of dementia, it has been known for some time that frequent infections in old age accelerate cognitive decline. This can be explained by an increased expression of tumor necrosis factor (TNFα). An important source of TNFα in the brain is the above mentioned microglia. It can ingest (phagocytose) whole cells, cell components, but also synaptic contacts or α-synuclein and amyloid aggregates. Consideration should therefore be given to the use of anti-inflammatory drugs in long-covoid patients, for example, of the non-steroidal anti-inflammatory drug type. They may favorably influence the course of neurodegenerative disease. However, clinical studies in corona patients would still be needed to confirm this hypothesis.
References:
Baig AM (2022) Counting the neurological cost of COVID-19. Nature Reviews Neurology 18:5-6
Brundin P, Nath A, Beckham JD (2020) Is COVID-19 a perfect storm for Parkinson’s disease? Trends in Neurosciences 43:931-933
Cohen ME, Eichel R, Steiner-Birmanns B, ..., Yahalom G (2020) A case of probable Parkinson's disease after SARS-CoV-2 infection. The Lancet Neurology 19:804-805
Faber I, Brandão PRP, Menegatti F, ... , Cardoso F (2020) Coronavirus disease 2019 and Parkinsonism: A non-post-encephalitic case. Movement Disorders 35:1721-1722
Haidar M, Shakkour Z, Reslan M, ... , Bizri M (2022) SARS-CoV-2 involvement in central nervous system tissue damage. Neural Regeneration Research 17:1228-1239
Méndez-Guerrero A, Laespada-García MI, ... , González de la Aleja J (2020) Acute hypokinetic-rigid syndrome following SARS-CoV-2 infection. Neurology 95:e2109-e2118
Merello M, Bhatia KP, Obeso JA (2021) SARS-CoV-2 and the risk of Parkinson's disease: facts and fantasy. The Lancet Neurology 20:94-95
Zhou Y, Xu J, Hou Y, Leverenz JB, ... , Cheng F (2021) Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment. Alzheimer's Research & Therapy 13:110
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