Aside from the socioeconomic factors, already discussed at length in the media, are there other factors that may increase the susceptibility of the BAME community to severe complications and death from COVID 19 infection

A marked increase of non-Caucasian ethnicities has been observed of healthcare workers who have succumbed fatally to the COVID 19 virus.

A second genetic factor could be considered regarding skin colour and melanin content. Skin type influences vitamin D levels where darker skin has greater amounts of melanin, which competes for UVB photons with 7-dehydrocholesterol (vitamin D making substrate). Several epidemiological studies link higher susceptibility to immune mediated disorders with vitamin D deficiency.

The non-skeletal effects of vitamin D have been of increasing interest with regard to its association with several diseases and, in particular, its role in regulating the immune system at the cellular level. 1,25-dihydoxyvitamin D3, the active form of vitamin D, has a physiological role in immunomodulation targeting several cells of the immune system and is a key factor linking innate and adaptive immunity and both are compromised with vitamin D deficiency. Hypovitaminosis D is associated with several immune and autoimmune disorders in addition to the classical association with osteomalacia.

Several immune cells have the cellular ability to convert 25-hydroxyvitamin D to active 1,25-duhydroxyvitamin D, which promote responses to pathogens in macrophages. Another antimicrobial response is in regulating the maturation of antigen-presenting dendritic cells and this pathway controls T-lymphocyte function. T cells also responds directly to activated vitamin D. Another immunomodulatory function is that cells of the immune system express vitamin D-activating enzymes also enabling the conversion of vitamin D into its active form.

The amount of UV exposure is related to the global UV index is also associated with vitamin D synthesis in skin and thus undergoes activation via a binding protein in the liver and kidney. As higher levels of melanin inhibit vitamin D synthesis from UV exposure and the currently low UV index in the UK, this may influence the demographic findings of healthcare workers that have succumbed to the virus.

Vitamin D insufficiency or deficiency is associated with regulation of insulin secretion and glucose levels. Deficiency also causes the inflammation associated with adipose metabolic diseases, such as obesity, multiple sclerosis, diabetes, and fatty liver.

The vitamin D receptor is expressed in adipose tissue and the vitamin itself is stored there. It is suggested that vitamin D exerts antiadipogenic influence on some preadipocytes and regulates the expression of adipocyte transcription factors, such as, PPARγ, C/EBPα, and LPL. Obesity has also been a factor associated with more severe disease and death from COVID 19 infection.

Having already established that genetic factors determining skin colour may influence disease outcomes to COVID 19 infection, it should also be considered that genetic differences in vitamin D receptor genes (VDR), such as, polymorphisms occur frequently in might influence disease outcomes. Vitamin D receptor (VDR) polymorphisms also alter vitamin D levels and can influence disease but is not necessarily a factor differentiating between different ethnic groups.

Located on chromosome 12q13.11 in humans, the VDR gene consists of eleven exons. Several polymorphisms of the VDR gene have been identified, but four single-nucleotide polymorphisms (SNPs) of this gene are the ones that have been most studied, namely, BsmI (rs1544410), ApaI (rs7975232), TaqI (T> C; rs731236), and FokI (C> T; rs2228570, formerly known as rs10735810).

Another factor in this discussion is that the marked increase of non-Caucasian ethnicities has been observed of healthcare workers who have succumbed fatally to the COVID 19 virus may be related to hypertensive drug treatment regimens, as there is a difference, according to the treatment British Hypertension Society recommendations, for combining blood pressure lowering drugs for different ages and ethnicity, where black patients and older patients tend to be treated with diuretics and calcium channel blockers whereas the younger or non-black patients receive ACEI/ARB and Beta blockers.

In a retrospective study in Hubei province in China, COVID 19 patients, admitted to 9 hospitals in a multi centre study, between December 31st and February 29th 2020. 1128 hospitalised adult patients with hypertension and diagnosed with COVID 19 were included in the study. There were 188 patients taking ACEI/ARB and 940 not taking ACEI/ARB with a median age of 64 years.

ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB non-users (ACEI/ARB group versus the non-ACEI/ARB group (3.7% vs. 9.8%; P = 0.01)).

References

• Hewison M. Vitamin D and immune function: an overview. Proc Nutr Soc. 2012;71(1):50–61. doi:10.1017/S0029665111001650
• Hewison M. Vitamin D and the immune system: new perspectives on an old theme.Endocrinol Metab Clin North Am. 2010;39(2):365–379. doi:10.1016/j.ecl.2010.02.010
• Glass D, Lens M, Swaminathan R, Spector TD, Bataille V. Pigmentation and vitamin D metabolism in Caucasians: low vitamin D serum levels in fair skin types in the UK. PLoS One. 2009;4(8):e6477. Published 2009 Aug 3. doi:10.1371/journal.pone.0006477
• Clemens TL, Adams JS, Henderson SL, Holick MF. Increased skin pigment reduces the capacity of skin to synthesise vitamin D3. Lancet. 1982;1(8263):74–76. doi:10.1016/s0140-6736(82)90214-8
• Jones P, Lucock M, Chaplin G, et al. Distribution of variants in multiple vitamin D-related loci (DHCR7/NADSYN1, GC, CYP2R1, CYP11A1, CYP24A1, VDR, RXRα and RXRγ) vary between European, East-Asian and Sub-Saharan African-ancestry populations. Genes Nutr. 2020;15(1):5. Published 2020 Mar 13. doi:10.1186/s12263-020-00663-3
• Rockell JE, Skeaff CM, Williams SM, Green TJ. Association between quantitative measures of skin color and plasma 25-hydroxyvitamin D. Osteoporos Int. 2008;19(11):1639–1642. doi:10.1007/s00198-008-0620-4
• Miao Z, Wang S, Wang Y, et al. A Potential Linking between Vitamin D and Adipose Metabolic Disorders. Can J Gastroenterol Hepatol. 2020;2020:2656321. Published 2020 Feb 18. doi:10.1155/2020/2656321
• Valdivielso JM, Fernandez E. Vitamin D receptor polymorphisms and diseases. Clin Chim Acta. 2006;371(1-2):1‐12. doi:10.1016/j.cca.2006.02.016