Immunomodulatory role of Vitamin D should be further investigated. Methods: We reviewed the literature about the immunomodulatory role of Vitamin D collecting data from the databases Medline and Embase.
Vitamin D proved to interact both with the innate immune system, by activating Toll-like receptors (TLRs) or increasing the levels of cathelicidins and β-defensins, and adaptive immune system, by reducing immunoglobulin secretion by plasma cells and pro-inflammatory cytokines production, thus modulating T cells function. Promising results have been extensively described as regards the supplementation of vitamin D in respiratory tract infections, autoimmune diseases and even pulmonary fibrosis.
In this review, we suggest that vitamin D supplementation might play a role in the prevention and/or treatment to SARS-CoV-2 infection disease, by modulating the immune response to the virus both in the adult and pediatric population.
The demographics of the Covid-19 outbreak proves that elderly males, with or without comorbidities, are the most affected across all populations. The available data on the epidemic are also showing a lesser involvement of vast areas lying in the tropics. Although this could easily relate to the lower median age of the population of developing countries, it is harder to make such an inference when looking at the markedly slow march of the Covid-19 epidemic in countries of the southern hemisphere, such as Australia. Just recently, it has been directly hypothesized that vitamin D supplementation could be used as a therapeutic combination in Covid-19, based on the epidemiology of the disease, and on the decreased vitamin D status observed in calves infected with bovine coronavirus .
In the emergency setting that followed the spread of the Covid-19 pandemic new therapeutics have been empirically administered on the basis of former experience in the management of diseases sharing a few similarities with Covid-19-associated ARDS, such as inflammatory autoimmune diseases. A growing interest in the role of tocilizumab, a monoclonal antibody directed against interleukin-6 (IL-6), which is commonly used in the treatment of rheumatoid arthritis, ensued the publication of works regarding its potential use in the prevention of severe cytokine release syndromes, such as in Car-T cell treated pediatric oncologic patients. This so-called cytokine storm has been postulated and confirmed as the main responsible for the lethal pulmonary involvement that is being observed in Covid-19 and was thoroughly studied in former 2009 SARS epidemic. In order to confirm tocilizumab therapeutic potential in ventilator-assisted Covid-19 patients, a clinical trial is currently ongoing in China and in Europe. Just recently, normal to high blood levels of vitamin D proved to act synergistically with tocilizumab in patients with rheumatoid arthritis by suppressing IL-6 enhanced osteocyte-mediated osteoclastogenesis and reducing disease activity.
Although the data on Covid-19 survivors are still lacking, a further downside of the pandemic might be the development of pulmonary fibrosis, which has been widely described as a common complication of ARDS . Here, vitamin D supplementation before and after the infection could play an antifibrotic role that yet need to be delved into.Finally, we would highlight some points that should be further investigated. There is, in fact, a vast literature that shows how obesity in children is closely related with low levels of vitamin D, reaching the prevalence of 92% in the United States. Interestingly, in a recent review, it was also showed that increased adipose tissue, altered adipocyte function and development of adipocyte hypertrophy is linked to an altered adipokine secretion profile, with increase in TNF-alpha, IL-6, and IL-1b levels. Even more interestingly, the study proved that patients receiving long-term vitamin D supplementation had a reduction in adipose tissue inflammation by inhibition of TNF-alpha activity .
Prepubertal children have generally lower androgen levels, with an elevated estrogen to androgen ratio. It has been demonstrated that low estrogen levels are related with an increased IL-1beta, IL-6, and TNF, increased activity of Th1 cells and high androgen levels are related with an increase in IL-1beta, IL-6, and a reduction in TNF, IFN-gamma, IL-4, IL-5, GATA3. It is also clear that sex hormones can differentially influence, along with other genetic polymorphisms and environmental factors, development of innate and adaptive immune responses. In a murine model, the hormonal changes of puberty upregulated the expression of genes associated with innate and adaptive immune responses in males and females, respectively. It has also been demonstrated that high levels of vitamin D seem to reduce aromatase activity (which is in turn increased by high levels of pro-inflammatory cytokines levels), thus containing the effects related to increased peripheral estrogen metabolism, such as B cell overactivity. That means that low levels of vitamin D can increase the risk of developing autoimmune diseases in young women.
Conclusion Till date, only one recent paper addressed the relationship between vitamin D levels and the clinical outcomes of patients with Covid-19. The author conducted a multinomial logistic regression to explore the association between serum 25(OH)D level and clinical outcomes of 212 cases with laboratory-confirmed infection of SARS–CoV-2. Interestingly, serum 25(OH)D proved to be a predictor of severe (OR 0.126, p < 0.001) and critical (OR 0.051, p < 0.001) Covid-19. A recent review proposes the supplementation of vitamin D in Covid-19 patients based on the promising findings of RCTs conducted in other viral infections. According to the emerging relationship between vitamin D status and alleged Covid-19 infection, vitamin D supplementation has already been proposed elsewhere. Although we do not assume that vitamin D plays a role in the pathogenesis of Covid-19, we do believe that its putative role in preventing or even treating the disease urgently needs to be further addressed. At the moment of writing, an interventional randomized clinical trial has been proposed at the University of Granada, with enrollment of 200 participants, proposing vitamin D supplementations (a single dose of 25,000 UI of vitamin D) in preventing and treating mild forms of suspected Covid-19. In a recent paper, it is assumed that vitamin D prophylaxis (without overdosing) could reduce, especially in patients with hypovitaminosis D, the severity of illness caused by SARS–CoV-2. The importance of treating the hypovitaminosis D along with an early nutritional supplementation has been highlighted for the potential preventing role of malnutrition sequelae in these patients. On the basis of the possible direct and indirect effect of vitamin D on immune system and cytokines production, we speculate a possible influence of this vitamin on the immunologic response to the virus and/or a modulating effect on the drugs being administered, namely hydroxychloroquine and anti-IL 6 and anti-IL 1 agents.
Reference & Source information: https://link.springer.com/
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