Razi Journal of Medical Sciences

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After its occurrence in December 2019 in Wuhan, China, the coronavirus disease 2019 (COVID-19) rapidly became a pandemic, but there is still no effective treatment for the disease (1). The novel coronavirus known as SARS-CoV2 destroys the lung epithelial cells and results in acute respiratory problems. A cytokine storm after overactivation of immune cells due to the virus infection along with acute respiratory distress are the major causes of adverse conditions of hospitalized patient in the intensive care units (3). Despite using antiviral and anti-inflammatory drugs for patients, at least in some cases, the medicinal efforts are not effective and the disease leads to death. Therefore, it is necessary to propose novel treatment options with immunomodulatory effects. Vitamin D is a critical regulator of the immune system that increases the production of antioxidants and anti-microbial factors (11). A growing body of reports indicates that vitamin D not only is a useful supplement for the prevention of COVID‑19 complications but also may have therapeutic effects in the patients (18, 19, 48). The seasonal prevalence of particular viral diseases such as influenza along with decreased serum levels of vitamin D in the winter season suggests an association between vitamin D deficiency and the increased risk of viral respiratory diseases (44).
Beyond its classic role in calcium homeostasis and bone metabolism, vitamin D has an important role in boosting and regulating the immune system (11, 12). The active form of vitamin D (1,25-dihydroxy vitamin D) is produced from 25-hydroxy vitamin D by action of an enzyme known as 1-alpha hydroxylase, which along with vitamin D receptors are present in all cells of the innate immune system. By activation of macrophages, 1-alpha hydroxylase enzyme is activated and turns vitamin D into its active form. The increased amount of vitamin D in macrophages leads to the release of a large number of antimicrobial agents such as cathelicidin and defensin, which in turn enhance the microbicidal effects of macrophages and monocytes (12). Vitamin D receptors are absent in inactive B and T lymphocytes but by activation, they will express these receptors. Therefore, the release of vitamin D from macrophages also affects the function of surrounding lymphocytes, which in turn will be effective in defense against viruses (12). Vitamin D also exerts its anti-inflammatory effects through various mechanisms. First, vitamin D inhibits prostaglandins production by inhibiting the enzyme cyclooxygenase 2, and therefore, exerts an anti-inflammatory effect. Prostaglandins facilitate the migration of immune cells into the tissue and increase the symptoms of inflammation due to increasing the permeability of postcapillary venules. Second, vitamin D through activation of the enzyme phosphatase-5 inhibits the phosphorylation and activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway, which is a specific pathway for the production of inflammatory cytokines. Further, vitamin D also reduces the transcription of inflammatory cytokine genes by inhibiting the nuclear factor kappa B (NFκB) (13). The antioxidant role of vitamin D is attributed to the increased expression of enzymes that produce antioxidants such as superoxide dismutase 1 and 2, thioredoxin reductases, and glutathione (13). Taken together, vitamin D via modulating and improving the function of innate and adaptive immune cells, and also reducing the inflammation caused by the overactivation of the immune cells could decrease the COVID-19 symptoms.
According to different studies, a sufficient amount of serum levels of vitamin D should be more than 30 ng/ml and the optimal amount is between 40 and 60 ng/ml (11, 18). Vitamin D is synthesized in the skin under the influence of sunlight UV radiation (23, 25). However, due to the special climatic conditions and religious and cultural beliefs, most of the population especially women in Iran are at a higher risk of vitamin D deficiency (28, 36). Iran's geographical location is between 25- and 40-degrees north latitude of the equator, and therefore the northern half of Iran is faced with a lack of sunlight needed to produce a sufficient amount of vitamin D in most seasons (37). Also, in large urban areas with high levels of nitrogen dioxide, people receive less UV radiation that is not enough for adequate vitamin D synthesis in the skin (37).
Considering the current COVID-19 pandemic condition, it can be suggested that measuring the serum level of vitamin D, and compensation of the possible deficiencies via dietary and drug supplementation can be effective in preventing COVID-19. This study aimed to review the factors involved in vitamin D production, the role and underlying mechanisms of action of this vitamin in preventing COVID-19 and decreasing the severe symptoms of the disease in the patients..
 

Keywords: Vitamin D, COVID-19, Inflammation, Immune system, Preventive medicine s

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