Vitamin D and immunity in Covid-19

                                           Vitamin D and immunity in Covid-19

                                                  Introduction

Public health experts are recommending people take daily vitamin D supplements through the spring and summer because of the coronavirus lockdown restrictions.


Vitamin D is produced in the skin through the action of UVB radiation reaching 7-dehydrocholesterol in the skin, followed by a thermal reaction.

Vitamin D is important for the absorption of calcium – which is essential to maintaining healthy bones and teeth.

Vitamin D may be best known for the role it plays in helping to build and maintain healthy bones, but since the coronavirus crisis started, many people have been wondering which nutrients are involved in supporting the immune system — and vitamin D happens to be one such nutrient.

While the current evidence doesn’t support claims that any particular vitamin (or other nutrient or supplement) can help prevent, treat or cure COVID-19, vitamin D plays an important role in how your immune system functions, and notably, in its fight against viruses.

What is most top-of-mind for many right now is how Vitamin D is involved in enabling you to mount a healthy defense against immune system invaders, like viruses. Studies have suggested that people with low levels of this nutrient are more likely to catch upper respiratory infections, like colds and flus. A recent analysis concluded that people taking a daily vitamin D supplement are more likely to stay infection-free. This benefit was even more pronounced among those who had extremely low vitamin D levels to begin with.

                                                        

                                                     Sources of vitamin D

It’s always a good idea to think about food before supplements, but the reality is that vitamin D is hard to come by in foods. It’s found naturally in oily fish, like salmon and to a lesser extent, sardines, as well as in certain mushrooms and egg yolks. It’s also in select fortified foods, such as milk and certain fortified yogurt, orange juice and cereals.

                             Effect of Vitamin-D on different categories of immunity

Vitamin D has many mechanisms by which it reduces the risk of microbial infection and death. A recent review regarding the role of vitamin D in reducing the risk of the common cold grouped those mechanisms into three categories: physical barrier, cellular natural immunity, and adaptive immunity. Vitamin D helps maintain tight junctions, gap junctions, and adherens junctions (e.g., by E-cadherin). Several articles discussed how viruses disturb junction integrity, increasing infection by the virus and other microorganisms. 

Vitamin D in cellular immunity

According to Bruce Hollis, Ph.D., a professor of pediatrics, biochemistry and molecular biology and the director of pediatric nutritional sciences at the Medical University of South Carolina, vitamin D is one of the most potent immune-regulating hormones. When your body senses a viral intruder, your immune cells release cells called cytokines. Some of these cells cause an inflammatory process and when your immune system is operating well, this process is slowed down by the release of other cytokine cells.

In people with severe illness from COVID-19, however, one of the factors that leads to death is a cytokine storm — a type of response in which the body’s immune system goes haywire because the inflammatory cells are operating in overdrive. “Vitamin D acts to bring this action under control,” says Hollis.

                                        

Vitamin D in cellular innate immunity

Vitamin D enhances cellular innate immunity partly through the induction of antimicrobial peptides, including human cathelicidin, LL-37, by 1,25-dihdroxyvitamin D, and defensins. Cathelicidins exhibit direct antimicrobial activities against a spectrum of microbes, including Gram-positive and Gram-negative bacteria, enveloped and nonenveloped viruses, and fungi. Those host-derived peptides kill the invading pathogens by perturbing their cell membranes and can neutralize the biological activities of endotoxins. They have many more important functions, as described therein. In a mouse model, LL-37 reduced influenza A virus replication. In another laboratory study, 1,25(OH)2D reduced the replication of rotavirus both in vitro and in vivo by another process. A clinical trial reported that supplementation with 4000 IU/d of vitamin D decreased dengue virus infection.

Vitamin D in adaptive immunity

Vitamin D is a modulator of adaptive immunity; 1,25(OH)2D3 suppresses responses mediated by the T helper cell type 1 (Th1), by primarily repressing production of inflammatory cytokines IL-2 and interferon gamma (INFγ). Additionally, 1,25(OH)2D3 promotes cytokine production by the T helper type 2 (Th2) cells, which helps enhance the indirect suppression of Th1 cells by complementing this with actions mediated by a multitude of cell types. Furthermore, 1,25(OH)2D3 promotes induction of the T regulatory cells, thereby inhibiting inflammatory processes.

                                                         Role of Vitamin-D in Covid-19

Serum 25(OH)D concentrations tend to decrease with age, which may be important for COVID-19 because case-fatality rates (CFRs) increase with age. Reasons include less time spent in the sun and reduced production of vitamin D as a result of lower levels of 7-dehydrocholesterol in the skin.

Vitamin D supplementation also enhances the expression of genes related to antioxidation (glutathione reductase and glutamate–cysteine ligase modifier subunit). The increased glutathione production spares the use of ascorbic acid (vitamin C), which has antimicrobial activities, and has been proposed to prevent and treat COVID-19.

Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. 

To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.