This in-depth and detailed article is provided by Eshani King, a researcher in immunology and health. Part two of this blog can be found here.

It is now widely known that a disproportionate number of COVID-19 related mortalities in the UK have been in non-white, BAME populations [2]. The obese, diabetics, hypertensives and the elderly have also been disproportionately affected. BAME doctors account for 94% of total deaths of doctors but comprise 44% of doctors [1]. The suggestion that these deaths result from deprivation does not fit with the high numbers of deaths of doctors and others in higher socio-economic classes; there must be a different and perhaps more comprehensive explanation.

This review examines the compelling body of evidence strongly implicating varying levels of serum vitamin D levels in the significantly disparate outcomes between different groups of people and between different countries. It explores the extent of vitamin D deficiency, highlighting countries and categories of people most likely to be deficient. It demonstrates that the UK suffers from exceptionally high levels of vitamin D deficiency with serum levels averaging only 20ng/ml, half the optimal level; It examines the strong body of existing evidence connecting vitamin D deficiency to increased respiratory tract infections highlighting the central epigenetic role of vitamin D in immune system responses during a respiratory tract infection with SARS-CoV-2; It reviews research flagging correlations between COVID-19 outcomes and vitamin D deficiency and studies providing the first direct evidence linking low vitamin D status with worse outcomes from COVID-19. Cautions regarding future trial designs and lack of evidence for toxicity concerns are both discussed. Current UK guidelines recommend 400 IU of vitamin D per day whereas 6,000-10,000 IU per day is required to maintain blood levels of 40ng/ml, widely accepted as being the level required to support immunity, optimal health, and reduction in all-cause mortality. The financial cost of vitamin D deficiency in the UK has been estimated at around £20 billion per annum.

2. Introduction to Vitamin D

Vitamin D3 (cholecalciferol), a fat-soluble vitamin, is made by the action of UVB sunlight on 7-dehydrocholesterol in the skin and converted in the liver to 25(OH)D or 25-hydroxyvitamin D, occasionally referred to as calcidiol. This is the form that circulates in the blood at detectable levels and measured in order to determine serum vitamin D status. The kidneys carry out a second hydroxylation by the enzyme 1-α-hydroxylase to convert 25(OH)D to 1,25 (OH)D or 1,25-di-hydroxyvitamin D, also referred to as calcitriol or active vitamin D [17]. This second hydroxylation to make the active form, calcitriol, has also been found to occur in many other cells including those in the respiratory tract epithelia and cells involved in the immune response. Calcitriol is 1000 times as potent as the inactive circulating 25(OH)D form but there is around 1,000 times less of it. Please note that, except where otherwise stated, the term vitamin D has been used interchangeably throughout to refer to any of the three forms.

The calcitriol form of vitamin D functions as a hormone in every cell of the body, all of which have vitamin D receptors (VDR). VDRs are nuclear transcription factors that epigenetically control the expression of up to 2,000 different genes including almost 300 genes just in white blood cells involved in the immune response [79]. There is no doubt that Vitamin D is of critical importance to many aspects of health. In addition to its long-known role in bone health, it also plays an important and central role in immune-enhancement and immune-modulation.