Among the hospitalised Covid-19 patients, 20 per cent develop Acute Respiratory Distress Syndrome (ARDS) and need ICU admission. ARDS, a condition where fluid collects in the lungs, is associated with either a cytokine storm or a bradykinin storm.
Cytokines are proteins that send signals to cells and help call the body’s immune system to action. Bradykinins are proteins that promote inflammation. An overexpression of these proteins — described as a cytokine storm and a bradykinin storm — leads to multiple organ damage and may cause death.
Vitamin D, an immunomodulatory agent, could have protective effects against these severe outcomes in Covid-19 patients.
- Cytokine storm: Vitamin D has been known to play a crucial role in the activation and functioning of the immune system. Vitamin D inhibits the development and function of T helper cell type 1 (Th1), which is involved in cell-mediated inflammation.
Helper T cells — a type of white blood cells — are among the most important components of the immune system. Inhibition of Th1 helps to suppress the progression of inflammation by reducing the generation of inflammatory cytokines such as Interleukin (IL)-6, IL-8, IL-12 etc.
Studies have also found that Calcitriol (1,25(OH)2D), a biologically active form of Vitamin D, is directly associated with inhibition of two cytokines – gamma interferon (IFN-γ) and IL-2.
2. Protection against lung damage: It has been reported that, during viral infection, inactive Vitamin D is converted to active form by the cells in the alveoli — tiny air sacs in our lungs — and leads to increased expression of another compound named cathelicidin. In mice, cathelicidins have been shown to reduce lung injury caused by hyperoxia or excessive oxygen supply.
- Preventing kidney disease in diabetes: Studies in humans with primary and secondary kidney disease, and in mice with diabetes, have demonstrated increased Angiotensin-Converting Enzyme 2 (ACE2) expression. ACE2 is known to facilitate the entry of the SARS-CoV-2 virus into host cells.
A 2018 study showed that Vitamin D supplements can inhibit ACE2 expression in the kidney. Thus, treatment with Vitamin D can reduce ACE2 expression in the kidney tubule cells, thereby preventing the entry of the virus into the cell and protecting the kidney in patients living with diabetes.
- Preventing ARDS and heart injury: Angiotensin II (Ang II) is a natural hormone known for increasing the blood pressure. ACE2 helps in breaking down Ang II and thereby, lowering its levels.
Covid-19 infection may downgrade the ACE2 level, which leads to excessive accumulation of Ang II. A high level of Ang II may cause ARDS and cardiac injuries. Renin, a protein released by the kidney, boosts Ang II accumulation.
A 2015 study reported that mice which do not have Vitamin D receptors, have increased levels of Renin and Ang II. Thus, Vitamin D supplements can prevent inflammatory activity of Ang II by suppressing the release of Renin in Covid-19 patients and decreasing the risk of ARDS, and cardiac injuries.
- Protecting alveolar membrane: Vitamin D deficiency is an important risk factor in ARDS as well as in many diseases. A single high-dose treatment with oral Vitamin D, given before an operation, was reported to prevent ARDS by reducing pulmonary vascular permeability index after surgery.
The pulmonary vascular permeability index describes the permeability of the blood–air barrier in the gas-exchanging region of the lungs. This barrier prevents the formation of air bubbles in the blood, and prevents fluids from entering the air sacs in the lungs.
A 2015 study showed that Vitamin D exhibits direct protective effect on the cells in the alveoli in an artificially-induced ARDS mouse model.
A study conducted in 2017 demonstrated that Vitamin D treatment was shown to have a protective effect on the lungs by inhibiting renin, ACE, and Ang II level, and increased ACE2 level expression in acute lung injury model in animals.
Thus, Vitamin D deficiency may play a role in increasing the risk of developing Covid-19 infection, severity and mortality. More than 15 studies have been published so far to support this hypothesis. Vitamin D increases the level of ACE2 in the lungs. ACE2, as the key SARS receptor, does play a protective role in cardiovascular diseases and SARS-mediated ARDS.
Thus, it’s important to assess one’s existing Vitamin D level and correct any deficiency any after consulting a physician on the dosage of supplements required.
The writer is a clinical and public health nutritionist and researcher