It is an undisputed fact, that the complex interaction between the cells and proteins that constitute the immune system is the very reason we, as a species, have survived so long. Millions of years of evolution, adaptation and understanding of both physiological and environmental determinants of health have equipped us to thrive in a world filled with other organisms competing for dominance – Including bacteria, fungi and viruses. In a previous blog, a summary of some of the key findings relating to the Sars-Cov-2 virus was made. The sars-Cov-2 virus is a beta-coronavirus that exploits RDB-ACE2 interaction to gain entry to host cells before using host transcription and translation machinery to manufacture copies. The outcome of damage caused by budding from host type II pneumocytes initiates a severe immune response contributing to a cytokine storm that, in some cases, has a detrimental effect on the host. Case reports have identified multi-system organ failure, Severe acute respiratory syndrome, atrophy of spleen and lymph nodes, upregulation of pro-inflammatory cytokines (IL-6) and pro-apoptotic receptors (FAS) within macrophages, and widespread local perenchymal damage due to neutrophil generated Reactive Oxygen Species. Other reports have established a clear correlation in haematological markers on patient outcomes in infected patients. These changes in some patients, include a DIC-like condition that results in consumptive coagulation disorders and Pulmonary emolisms. Other phenomenon associated with elevated D-dimers and increased fibrin quantities are also observed.
The recent emergence of questions relating to the disproportionate number of bla k and minority ethnic (BAME) patients associated with poorer clinical outcomes has to lead to scientists leading a line of enquiry that seeks to explore whether this correlation has a phenotypical basis, or whether this basis is a combination of both physiology and environment. Early reports from china and Italy demonstrate a significant correlation between ethnicity and disease outcome, and more recently, the United kingdom also reports the same effect. The difficulties presented with these hypotheses relate to a lack of confirmatory data; however, in the UK, it is thought that over one-third of patients who die from Sars-Cov2 are from BAME backgrounds[i]. There are, however, other contributing factors to be considered when predicting disease outcome. There are well-established inverse relationships between socio-economic status and health, as well as environmental, occupational and lifestyle risk factors.
One of the difficulties in establishing relationships between two or more variables is having the understanding that correlation and causation are not synonymous. Biomedical research often emphasises ethnic differences in terms of disease outcome, but there is little clarity on how these differences are measured. Moreover, they could be misconstrued as an attempt to overlook the stark inequalities that exist amongst cross-sections of society, particularly in BAME patients [ii].
The Johns Hopkins University American community survey highlights that in predominantly black communities, the Sars-Cov-2 infection rate is 3 fold that of white communities. Also, the death rate is sixfold, respectively. In addition to examining whether these differences are biological, efforts should be made equally to analyse social and environmental factors. These patterns are not solely exclusive to Sars-Cov-2; they are representative of a large number of morbidity and mortality case rates. Choosing solely to focus on genetic disparities would provide only a partial glimpse into the nature of health inequality when a Bio-psycho-social approach should be applied [iii].
These health disparities have been documented for many diseases in the United States, and globally. HIV death rates are reported to be 11 times higher in the black community. Age-adjusted corrections for cancer show incidence to be significantly higher amongst black females, including colorectal, pancreatic. In males prostate cancer, lung and stomach cancers were higher in black men compared to white men and are more likely to suffer from diabetes and cardiovascular disease. It is known that the conditions mentioned are likely to increase the rate of fatality in patients infected with Sars-Cov-2 [iv].
There is recent speculation about the role of vitamin D in the inhibition of cytokine storms associated with Sars-Cov-2. The results from an unpublished paper, show that in a comparison of previous studies on vitamin D and C-reactive protein, data shows the risk of severity for Sars-Cov-2 for patients with low vitamin D was estimated at 17.3% compared with Healthy vitamin D levels 14.6%[v]. Physiologically, Vitamin D is largely involved in calcium metabolism and sources are derived from the diet and integumentary conversion of 25-hydroxylase to its active form 1,25-hydroxylase. This conversion is facilitated by a CYP450 enzyme (1-alpha hydroxylase) synthesised by the proximal tubules of the renal system. Several studies have shown the vitamin D insufficiency is more prevalent amongst BAME groups as a direct result of inhibition caused by Eumelanin, which serves as an evolutionary protective trait from excessive UV exposure[vi] [vii]. The information released in peer-reviewed articles suggests that modulation of IL-6 is thought to be the mechanism underpinning its potential efficacy; however, much of the evidence is anecdotal and should be viewed cautiously until further data has been supplied to determine whether melanogenesis has an impact on mortality outcomes in BAME patients infected with Sars-Cov-2 [viii].
To summarise, there is a much-needed investigation into the multifactorial variables affecting the clinical outcome of BAME patients with severe Sars-Cov-2, taking into account environmental risk factors. There is cause for concern that too much of an emphasis on seeking genetic determinants may have severe social ramifications from extremist groups. These groups are keen to promote the ideology of racial/genetic superiority, which also has social and ethical ramifications that may move to promote the improvement of the genetic composition of other ethnicities (an extreme scenario, but historically, not an inconceivable notion).
[i] Pareek, Manish et al. (2020) Ethnicity and COVID-19: an urgent public health research priority The Lancet, Volume 395, Issue 10234, 1421 – 1422
[ii] Lee C, (2009) “Race” and “ethnicity” in biomedical research: How do scientists construct and explain differences in health? Social Science & Medicine, Volume 68, Issue 6, p 1183-1190
[iii] Yancy CW (2020) COVID-19 and African Americans. JAMA.. doi:10.1001/jama.2020.6548
[iv] JAMA (2005)Health Disparities Experienced by Black or African Americans—United States; im293(8):922–923. doi:10.1001/jama.293.8.922
[v] Ali Daneshkhah, Vasundhara Agrawal, Adam Eshein, Hariharan Subramanian, HemantKumar Roy, Vadim Backman (2020) The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients. medRxiv 2020.04.08.20058578; doi: https://doi.org/10.1101/2020.04.08.20058578 (unpunished manuscript)
[vi] Harris SS (2006) Vitamin D and African Americans. J Nutr.136(4):1126‐1129. doi:10.1093/jn/136.4.1126
[vii] Correia, Aline, Azevedo, Maria do Socorro, Gondim, Fernando, & Bandeira, Francisco. (2014). Ethnic aspects of vitamin D deficiency. Arquivos Brasileiros de Endocrinologia & Metabologia, 58(5), 540-544. https://dx.doi.org/10.1590/0004-2730000003320
[viii] Silberstein M. Vitamin D: A simpler alternative to tocilizumab for trial in COVID-19? [published online ahead of print, 2020 Apr 23]. Med Hypotheses. 2020;140:109767. doi:10.1016/j.mehy.2020.109767