COVID-19 in age-related neurodegenerative diseases: is there a role for vitamin D3 as a possible therapeutic strategy?

Abstract

The coronavirus disease (COVID-19), identified in Wuhan, China, on December 2019, was declared a pandemic by the World Health Organization, on March, 2020. Since then, efforts have been gathered to describe its clinical course and to determine preventive measures and treatment strategies. Adults older than 65 years of age are more susceptible to serious clinical symptoms and present higher mortality rates. Angiotensin-converting enzyme 2 (ACE2) is a major receptor for some coronavirus infection, including SARS-COV-2, but is also a crucial determinant in anti-inflammation processes during the renin–angiotensin system (RAS) functioning – converting angiotensin II to angiotensin 1–7. The decline in ACE2 expression that occurs with aging has been associated to the higher morbidity and mortality rates in older adults. These observations highlight the importance of investigating the association between COVID-19 and age-related neurodegenerative disorders, i.e., Parkinson’s and Alzheimer’s diseases. A possible option to reduce the risk of COVID-19 is vitamin D supplementation, due to its anti-inflammatory and immune-system-modulating effects. It has also been suggested that vitamin D supplementation plays a role in slowing progression of Parkinson and Alzheimer. The present study is a literature review of articles published on the theme COVID-19, Parkinson and Alzheimer’s diseases, and the role played by vitamin D. PUBMED, MEDLINE, and EMBASE databases were consulted. Results confirm neurodegenerative and neuroinflammatory effects of COVID-19, aggravated in Parkinson’s and Alzheimer’s patients, and the important role of vitamin D as a possible therapeutic strategy. Nevertheless, randomized controlled trials and large population studies are still warranted.

COVID-19 and neurological sequelae: Vitamin D as a possible neuroprotective and/or neuroreparative agent

“…These effects were accompanied by a decrease in amyloid β-protein formation and an increase in memory performance [96] . Taken together, these findings reinforce the hypothesis that vitamin D supplementation could be an effective option to avoid the development and progression of neurodegenerative pathologies such as Parkinson's and AD in post-COVID-19 patients [97] , [98] , [99] , [100] .

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Pharmacological Efficacy and Mechanism of Vitamin D in the Treatment of “Kidney-Brain” Disorders

“…Our research articles have reported that active vitamin D analog paricalcitol could dramatically improve LPS-induced depressive-like behavior of mice by abolishing neuroinflammation via diminishing RAS activity in the hypothalamus [104], and the kidney-tonifying traditional herb Fructus Ligustri Lucidi displayed the suppressive effects on levels of pro-inflammatory cytokines by improving vitamin D metabolism [105]. Consistent with these findings, vitamin D supplementation appeared to reverse COVID-19-related neurodegeneration and neuroinflammation, which are aggravated in Parkinson's and Alzheimer's patients [95]. These pieces of evidence heighten the key role of vitamin D as a neuroprotective and neuroreparative agent against the neurological sequelae of COVID-19.…”

“…The identification of the ACE homolog, ACE2 as a key Ang(1-7)-forming enzyme, unravels the existence of a distinct enzymatic pathway for the production of Ang(1-7), which has a broad range of effects in different organs and tissues that goes beyond its initially described cardiovascular and renal actions [94]. The decline in ACE2 expression that occurs with aging has been associated with higher morbidity and mortality rates in older adults [95]. Furthermore, numerous studies discovered that the cross talk and the interaction between the dual-axis systems of RAS contribute to tissue homeostasis.…”

The Prediction Model of Risk Factors for COVID-19 Developing into Severe Illness Based on 1046 Patients with COVID-19

“…Yang et al [ 11 ] found that some COVID-19 patients with coronary heart disease complications had serious conditions and extremely high mortality, which is consistent with the results of our study. Studies [ 11 , 23 ] have shown that ACE2, the key receptor of the new coronavirus, is expressed at a high level in the human kidney (nearly 100 times higher than that of the lungs), and ACE2 is one of the main receptors that mediate the entry of the new coronavirus into human cells. The new coronavirus can enter renal tubular cells by binding to ACE2, causing cytotoxicity and abnormal renal function.…”