COVID-19 & Vitamin D Deficiency

Dr. Muhammad Torequl Islam :
Vitamin D (vit-D) is a prohormone that facilitates calcium absorption from our gut. The deficiency of this vitamin causes rickets in children and osteomalacia in older people. Vit-D3 (also called calcitriol), a fat-soluble vitamin,mostly found in fish, eggs, liver, butter and margarine. In the liver vit-D3 converts into 25-hydroxy-vit-D3 through hydroxylation, which transfers into 1-a, 25-dihydroxy-vit-D3 in the kidneys. According to the scientific reports the exposure time of the light skin peoples is between 20 and 30 min, while it is 2-10 fold larger for the dark skin peoples for 2-3 times in a week (which produces around 20,000 IU of vit-D3. However, left unexposure of the next day vit-D3 cannot enter into the bloodstreamdue to the rapid degradation into suprasterol1, suprasternal and 5,6 trans-vit-D3 (biologically inactive forms).
Relation between skin melanin content and vitamin D biosynthesis
Approximately 80% people of the world are pigmented. The human skin contains four major types of pigments, such as melanin, hemoglobin, carotene, and bilirubin. However, melanin and hemoglobin are the known skin color contributors. Melanocytes present in the basal layer of the epidermis are responsible for melanin production. Among the natural sunlight (e.g., UVA and UVB) UVB is the most biological active from, which at wavelength 290-315 nm synthesizes vit-D in our skin. Tyrosinase catalyzes hydroxylation of tyrosine and oxidation of dopa, resulting in a formation of melanin through the free radical coupling pathway.
Melanin (e.g., brown or black eumelanin and red or yellow pheomelanin) is a biopolymer complex mixture of quinone/indolequinone derivatives. The elliptical melanosomes produce eumelanin, while rounded melanosomes produce the pheomelanin. The peoples having dark skin contain high level of melanin than the lighter skin peoples. Generally, melanin has photoprotective capacity and it protects our skin from the harmful effects of UV radiation. An increasing in melanin level in the skin, reduces the production of vit-D3 of the dark skin peoples of high latitude. Vit-D deficiency or insufficiency is most common in the UK. Most of the African and Americans having dark skin have vit-D3 deficiency.
Role of vit-D against viral infections
A low serum 25(OH)D level has been found to increase the risk of hypertension prevalence. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme 2 (ACE2) receptor for attaching and entry into human cells. ACE2 catalyzes the hydrolysis of the vasoconstrictor peptide angiotensin II into the vasodilator angiotensin (1-7), thereby reduces the blood pressure. Angiotensin II stimulates the melanogenesis process. Vit-D3 can modulatethe expression of ACE2 and is evident to inhibit angiotensin II-induced nitrogen oxides (NOx) activation and reactive oxygen species (ROS) production. Therefore, an upregulation of ACE2 will negatively affect the melanogenesis process. It is evident that the hyperpigmentation is one of common skin pigmentation disorders in the diabetes mellitus patients. Vit-D receptor gene polymorphisms are also associated with the diabetic nephropathy risk in diabetes mellitus patients. Therefore, serum 25(OH)D levels may serve as a biomarker (due to it has a circulating half-life of 15 days) for these kinds of patients, although it does not indicate the actual amount of vit-D stored in our body tissues.
Vit-D has immunomodulatory effects and itsdeficiency or insufficiency implicates about 53% of deaths from pneumonia of viral and bacterial origins in children worldwide. Research findings demonstrate that a normal to high-serum 25(OH)D level can reduce theincidence and severity of viral infections. On the other hand, the metabolites (both active or inactive)of vit-D do not consistently influence on the replication or clearance processes of viruses. However,these metabolites have been found to reduce the pro-inflammatory cytokines those are reported to augment by SARS-CoV-2 infection in novel coronavirus disease 2019 (COVID-19) patients.
Critical observations and final consideration
The facultative skin color depends on the complex interplay of UV radiation and hormones upon the genetical interference on the melanogenesis process of the individual.Irrespect of skin melanin contents, the breastfed infants may have vit-D deficiency as their vit-D contents depend on the mother’svit-D status. The skin of the peoples (including older adults) cannot synthesize sufficient vit-D, especially who spend more time indoors. Vit-D is fat soluble, which requires some dietary fats in the gut for its proper absorption. Therefore, peoples having reduced ability to absorb dietary fats such those are suffering from liver disease, cystic fibrosis, and Crohn’s disease might be required vit-D supplements. Moreover, peoples having obesity and who have undergone gastric bypass surgery may become vit-D deficient.
The effective supplementation of vit-D needs to start before the onset of respiratory tract infection. Vit-D reduces the risk of viral infections in our body, possibly through the anti-viral immune induction, modulation of immunoregulatory defense processes, induction of autophagy and apoptosis, genetic or epigenetic regulation, and stimulating the defensins and cathelicidins, thereby decreasing the replication of the virus, increasing the levels of anti-inflammatory cytokines, while reducing the concentrations of pro-inflammatory cytokines that induce inflammation-related pneumonia. Vit-D supplementation also reduces the mortality due to chronic disease (e.g., diabetes and hypertension) in COVID-19. Vit-D deficiency is globally prevalent, particularly in the elders. This high prevalence probably contributes to the first outbreak COVID-19 during winter and the high mortality rate in older adults. However, for people at risk of COVID-19, the goal should be to raise the concentrations of 25(OH)D above 40-60?ng/mL (100-150?nM/L) by considering taking 10,000?IU/day of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000?IU/day.Vit-D is known to mitigate the scope of acquired immunity and regenerate endothelial lining. This may be beneficial in minimizing the alveolar damage caused in acute respiratory distress syndrome (ARDS) in COVID-19.
Dark skin contains a high level of melanin. Generally, melanin protects us from many diseases, including skin infections and cancer, however, it inhibits the synthesis of vit-D in the skin. The angiotensin II stimulates melanogenesis process. On the other hand, the angiotensin-converting enzyme 2(ACE2) catalyzes angiotensin II. The SARS-CoV-2 uses ACE2 receptor to enter into the lung cells. However, ACE2 has lung protective capacity and it can reduce blood pressure. Therefore, the peoples having low levels of ACE2 will not get much defensive power over the high ACE2 content peoples. Further, a reduction of ACE2 may upregulate the melanogenesis process, which is inversely related to the vit-D synthesis in our body. Most African and Americans have high levels of melanin in their skin and are usually deficient with vit-D. To overcome this problem, they can eat food supplements those are rich in vit-D.

(Dr. Muhammad Torequl Islam is Assistant Professor, Department of Pharmacy, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology
University).