Molecular mechanisms highlighting the potential role of COVID-19 in the development of neurodegenerative diseases

Abstract

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to the pulmonary manifestations, COVID-19 patients may present a wide range of neurological disorders as extrapulmonary presentations. In this view, several studies have recently documented the worsening of neurological symptoms within COVID-19 morbidity in patients previously diagnosed with neurodegenerative diseases (NDs). Moreover, several cases have also been reported in which the patients presented parkinsonian features after initial COVID-19 symptoms. These data raise a major concern about the possibility of communication between SARS-CoV-2 infection and the initiation and/or worsening of NDs. In this review, we have collected compelling evidence suggesting SARS-CoV-2, as an environmental factor, may be capable of developing NDs. In this respect, the possible links between SARS-CoV-2 infection and molecular pathways related to most NDs and the pathophysiological mechanisms of the NDs such as Alzheimer's disease, vascular dementia, frontotemporal dementia, Parkinson's disease, and amyotrophic lateral sclerosis will be explained.

Cerebral small vessel disease pathology in COVID-19 patients: A systematic review

“…There is a strong link between COVID-19 severity and increased age ( Neves et al, 2021 ). The elderly population has a greater amount of acute and post-COVID-19 complications, with two of the most prominent being neurological and vascular chronic complications ( Alimohamadi et al, 2020 , Mehandru and Merad, 2022 , Mueller et al, 2020 , Rahmani et al, 2022 , SeyedAlinaghi et al, 2021 ). Aging is also a risk factor for developing long-COVID ( Raveendran et al, 2021 ), in which the majority of patients experience cognitive impairment ( Guo et al, 2022 ).…”

Long COVID and its association with neurodegenerative diseases: pathogenesis, neuroimaging, and treatment

“…This inflammatory state can result in increased permeability of the BBB, dysfunction of cerebrovascular endothelial cells, and disruption of BBB integrity. Consequently, more inflammatory factors can enter the CNS, impacting cognitive function and potentially leading to the development of neurodegenerative diseases ( 31 ). These effects are supported by histopathological examinations of the brains of SARS-CoV-2-infected patients, which revealed the presence of CD 3+ T lymphocytes and CD 68+ monocytes/macrophages within the brain’s mesenchymal cells ( 32 ).…”

Significance of Catecholamine Biosynthetic/Metabolic Pathway in SARS-CoV-2 Infection and COVID-19 Severity

“…Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that emerged in Wuhan in December 2019 is a positive sense, single-stranded, RNA virus, which may cause severe respiratory infections in humans [1,2]. Symptoms of the disease provoked by the virus (coronavirus disease 2019 or COVID-19) may typically include fever, cough, myalgia or fatigue, sputum, headache, hemoptysis, and diarrhea, as well as dysregulation of the nervous system (loss of smell and taste, consciousness impairment, parkinsonism), and in the most severe cases may also lead to respiratory failure [3][4][5]. Virus infection activates the host immune response, causes dysfunction of the lung epithelial-endothelial barrier, and produces lung and airway hypoxia resulting in oxidative stress [6][7][8].…”