By Qadeer Mir
WHEN we move from one place to another, during that time our body requires energy not only for the movement but also for respiration and other metabolic activities. We get this energy from nutrients like carbohydrates, fats and proteins which are called micronutrients. On the other end, Vitamins and minerals don't provide us energy but are essential for the normal functioning of the body. Vitamins include Vitamin A,D,E,K,C and B-complex.
One of the important vitamins is vitamin D. It plays an important role in calcium homeostasis. In 2020 during the peak of the COVID-19 crisis, many studies were done on vitamin D and its role in curing COVID-19.
Vitamin D is a fat soluble vitamin. Its availability, absorption and transportation is associated with fats. It functions like a steroid hormone. For its functioning, it requires a site where it should hold fast. The site where it binds on a cell is called a receptor. The receptor for vitamin D is present inside the cell.
Vitamin D is found in animals in the form vitamin D3 (Cholecalciferol) and in plants it is found in the form of vitamin D2 (Ergocalciferol).
Vitamin D3 is also made in the human body. During cholesterol synthesis, a product called 7-Dehydrocholesterol is formed. This 7-Dehydrocholesterol is present in our skin and on its exposure to ultraviolet B rays, it gets converted to cholecalciferol.
Major sources of vitamin D include fish, liver and mushroom. Cholecalciferol when taken from diet or produced in skin is transported to the liver. In the liver there is an enzyme called 25-hydroxylase. It hydroxylates(adds hydrogen) at the 25th position and forms 25-hydroxycholecalciferol. In kidney 25-hydroxycholecalciferol is hydroxylated at position 1, forming 1,25-dihydroxycholecalciferol (1,25-DHCC) or calcitriol. The main function of calcitriol is to regulate calcium absorption and homeostasis. Calcitriol can also perform other functions. It can bind to its receptor called Vitamin D receptor in immune cells like macrophages.
After this interaction, certain genes will get activated and mRNA will be formed by a process known as transcription. This mRNA undergoes a process called translation to form protein. These proteins formed are of different types but some of them are Cathelicidins and Defensins. They both are antimicrobial peptides.
Cathelicidins are mostly found in cells like neutrophils, monocytes, mast cells, dendritic cells and macrophages. Cathelicidins increase vascular permeability and can also stimulate macrophages. They damage cell membranes of microorganisms like SARS-coV2 by cleaving viral structures.
Cathelicidins range in size from 12 to 80 amino acid residues and have a wide range of structures. Defensins are small protein. They are typically 10-15 amino acid in length. They also damage cell membrane by punching holes in viruses like RSV,Rhinovirus,SARS-coV2.
Anti Inflammatory Pathway
Both anti inflammatory and pro inflammatory pathways involve many cells and substances like cytokines.A student with good knowledge of immunology will be able to understand it much more easily but I will try to make it more understandable.
Phagocytosis is the process of engulfing any substance. Cells called Macrophage are the major phagocytic cells in the human body. When they encounter any virus like SARS-CoV2 they engulf it.SARS-CoV2 virus has a crown like appearance and its due to s-peptide. These s-peptides are present on outside of SARS-coV2 which give the virus crown like appearance. This is the reason virus is called corona virus. Corona means crown like.
So, after phagocytosis macrophages express a piece of dead virus like s-peptide of SARS-coV2 outside on MHC-II. There is another cell called naive helper-T cell that binds with macrophag. For this interaction receptors are required.There is a CD4 receptor on a naive helper-T cell that will bind with MCH-II on macrophages.
After this interaction some chemical substances called cytokines are released like Interleukin(IL-4) from macrophages. When these IL-4 come in contact with naïve helper-T cells, they get converted to T-helper 2 (TH2). Now,this T-helper 2 cell will start releasing cytokines like IL-5.
These cytokines will activate another cell called B- lymphocytes and will differentiate B-lymphocytes into memory cells and plasma cells. Plasma cells will start releasing antibodies. These antibodies can activate the complement system. Complement system will lead to punching holes in the virus and kill it. These antibodies can even bind to s-peptide of another SARS-coV2 and stop it from attaching to host cells. So,this pathway is fighting against the virus and protecting us against it.
This pathway is very important to understand the deficiency of vitamin-D and its effects on the body, especially on immune system cells. If a person has a deficiency of vitamin-D,a pro-inflammatory pathway will be activated more. Here again, after phagocytosis macrophage will express a piece of s-peptide of SARS-coV2 on MHC-II. Again ,MHC-II will bind to CD4 receptor of naive helper-T cell.
Naive helper-T cell will start releasing cytokines IL-12 not IL-4.These IL-12 will convert naïve helper-T cell to T-helper 1 cell (TH1) not T-helper 2 cell.
Now,TH1 cells will start releasing cytokines like gamma interferon. These cytokines will attract more macrophages for phagocytosis of microorganisms like SARS-coV2. In turn macrophages will start releasing a lot of cytokines like IL-1,TNF-a,IL-6-IL-8.
These cytokines will lead to massive inflammation and lead to a condition called cytokine storm. These cytokines can also act on many organs and can lead to multi-organ failure.IL-6 can act on heart cells and can lead to myocardial infarction.
In lungs, massive inflammation can lead to acute respiratory distress syndrome. In the liver, it can lead to increase in fibrinogen, ferritin, CRP and D-dimer. They all are acute phase reactive proteins. Increase in CRP will lead to inflammation of blood vessels and leads to atherosclerosis which can lead to formation of blood clots.
According to an article titled “Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19”, in The New England Journal of Medicine.
According to the study, 7 lungs were obtained during autopsy from patients who died from Covid-19 and compared them with 7 lungs obtained during autopsy from patients who died from acute respiratory distress syndrome (ARDS) secondary to influenza A(H1N1) infection and 10 age-matched, uninfected control lungs.
Results showed that the lungs from patients with Covid-19 showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza.
So, cytokine storms play an important role in clot formation. Optimal quantity of vitamin D in blood will stimulate macrophages more. Vitamin D will stimulate an anti inflammatory pathway more than a proinflammatory pathway. T-helper 2 cell will release IL-10 which will also stop the pro inflammatory pathway.
By decreasing inflammatory pathways, there are less chances of multi organ failure and other complications. Vitamin D deficiency is widespread. The main risk factors were attributed to elderly women, higher latitude, winter season, less sunlight exposure, dark skin, less intake of vitamin D. Vitamin D deficiency is also associated with diabetes, CVD and hypertension. Vitamin D deficiency has been linked to the onset of diabetes. Diabetes is initiated by the onset of insulin resistance. B-cells can overcome the resistance by releasing more insulin. Thus, preventing hyperglycaemia.
Due to excessive reactive oxygen species(RAS) and Ca** results in massive cell death and leads to onset of diabetes. Due to optimal quantity of vitamin D normal level of ROS and Ca** can be maintained.
Vitamin D deficiency is also associated with hypertension. The prevalence of hypertension in adults is approximately 29% with an estimated 1.6 billion cases of hypertension expected in 2025.
Kidneys produce an important hormone called renin. Renin converts a protein called angiotensinogen into angiotensin -1 and ,angiotensin 1 is converted to angiotensin-2 by angiotensin converting enzyme 1 (ACE-1). This angiotensin-2 can lead to many problems. It causes vasoconstriction thereby increasing blood pressure.
Angiotensin-2 also causes inflammation and fibrosis in lungs. There is another enzyme called angiotensin converting enzyme 2 (ACE-2) that converts angiotensin-2 to angiotensin 1-7. It’s a vasodilator substance, it also decreases inflammation and fibrosis. In patients affected by SARS-coV2,virus inhibits ACE-2 and due to that there is less formation of angiotensin 1-7,due to which there will be hypertension, fibrosis and injury to lungs.
The Optimum amount of vitamin D in the body can increase the activity of ACE2 and can prevent hypertension. It also stops viruses from damaging lungs. Different parts of the world measure Vitamin D in blood by using different units.
Deficient being > 30ng/ml or 75nmol/l.
Optimal being 51-70ng/ml or 126-175nmol/l.
Views expressed in the article are the author’s own responsibility and is not a substitute for medical advice
- The author can be reached at [email protected]
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