Is ethnicity linked to incidence or outcomes of covid-19?BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1548 (Published 20 April 2020) Cite this as: BMJ 2020;369:m1548
All rapid responses
Low vitamin D: high risk COVID-19 mortality? Seven preprints suggest that is case. Does low ‘D’ put BAME and elderly, at particular COVID-19 risk? Testing and Data Required.
BMJ rapid response letters and supporting references[1, 2] posited vitamin D deficiency disease features in COVID-19 severity and mortality risks. Brown and Sakar, in March, suggested vitamin D plasma deficiency differentials may help account for mortality rate differences between European countries.
There are now seven observational preprints (Abstracts and links below), based on COVID-19 positive patient data, indicating vitamin D deficiency and insufficiency, do indeed factor significantly in COVID-19 severity and mortality – for example, and thought provokingly, 10 to 20 times increases were seen in ICU and mortality in Asian studies.[5, 6] One further USA based study observes vitamin D may factor in COVID-19 infection. Whilst differing in, size and exact approach, results of all preprints point clearly in the same direction.
Concerningly, vitamin D is often low in high-risk COVID-19-groups, such as, BAME including African Americans, elderly in care-homes, and the obese. Low vitamin D is also increasingly common in young. Studies suggest low ‘D’ factors in Kawasaki disease[9, 10, 11] ; occurrences are increasingly being linked with COVID-19.[12,13]
Vitamin D is a nutrient-hormone with a multiplicity of roles, well evidenced in voluminous and wide-reaching literature, spanning over a hundred years. The primary, and evolutionarily determined, source of vitamin D, including in; humans (D3), pets, livestock, and plants (D2), is not diet, but appropriate sun exposure. Dietary sources of vitamin D are limited, and particularly so for vegans and non ovo-lacto vegetarians. Twenty minutes of sensible non-burning sunbathing by pale-skinned-humans, can produce 20,000 IU; equivalent to 50 days intake of 400 IU supplementation. Production rate depends on skin pigmentation and other factors including gender. UVB blocking creams inhibit vitamin D production.Fat tissue accretes and stores vitamin D, reducing vitamin D in plasma.
Biology, physiology, and research, has proved that vitamin D has multiple roles, including in regulation of gene transcription, and inter-alia as a crucial factor in immune and respiratory function. The seven observational studies to date, using COVID-19 positive patient data, assessing the impact of vitamin D on COVID-19 severity and mortality, are listed and quoted below:
South Asia (Raharusun)– preprint; ‘Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study’ - 780 COVID-19 positive patient cases concluded, “When controlling for age, sex, and comorbidity, Vitamin D status is strongly associated with COVID-19 mortality outcome of cases.” Unadjusted increased risk of death in ‘D’ insufficient 12.55 (7.63 adjusted) and ‘D’ deficient 19.12 (10.12 adjusted).
South Asia (Alipio) - preprint; ‘Vitamin D supplementation could possibly improve clinical outcomes of patients infected with Coronavirus-2019 (Covid-2019)’ - 212 COVID-19 patients, noted, “the odds of having a mild clinical outcome rather than a severe outcome were approximately 7.94 times (OR=0.126, p<0.001) while interestingly, the odds of having a mild clinical outcome rather than a critical outcome were approximately 19.61 times (OR=0.051, p<0.001).”
India (Glicio)– preprint; ‘Vitamin D Level of Mild and Severe Elderly Cases of COVID-19: A Preliminary Report’ - 176 COVID-19 patients age > 60, noted, “Majority of subjects classified as severe had 25(OH)D level below 30 ng/ml.”
USA (Lau) – preprint; ‘Vitamin D insufficiency is prevalent in severe COVID-19’ – 20 COVID-19 patients noted, “VDI is highly prevalent in severe COVID-19 patients. VDI and severe COVID-19 share numerous associations including hypertension, obesity, male sex, advanced age, concentration in northern climates, coagulopathy, and immune dysfunction.”
Belgium (De Smet) – preprint; ‘Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics’- 186 COVID-19 confirmed patients noted, “Male COVID-19 patients, however, showed markedly higher percentage of vitamin D deficiency than controls (67.0% versus 49.2%, P=0.0006) and this effect was more pronounced with advanced radiological stage ranging from 55.2% in stage 1 to 74% in stage 3.”
Switzerland (D’Avolio) – preprint; ‘25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2’ - 107 patients; 27 were COVID-positive; observed, “significantly lower 25(OH)D levels (p = 0.004) were found in PCR-positive for SARS-CoV-2 (median value 11.1 ng/mL) patients compared with negative patients (24.6 ng/mL); this was also confirmed by stratifying patients according to age >70 years.”
Ireland (Faul) – preprint; ‘Vitamin D Deficiency and ARDS after SARS-CoV-2 Infection’- 33 patients observes, “twelve had a baseline 25OHD level less than 30 nmol.l-1. In patients with SARS-CoV-2 related pneumonia a baseline serum 25OHD level less than 30 nmol.l-1 was associated with a hazard ratio (HR) for intubation of 3.19 (95 percent confidence interval, 1.05 to 9.7), (p = 0.03).”
It is thus urgent, even arguably imperative, vitamin-D-levels in COVID-19 patients in hospitals and care-homes, particularly the most at risk including, BAME, the elderly, obese, and young including those presenting with Kawasaki disease, are collected, related to outcomes, and reported, to determine if the above preprint data holds more widely.
Observations, not RCTs, resolved human deficiency related diseases, such as, goitre, rickets, beriberi, pellagra, and scurvy. RCTs were not completed before; parachute deployment, recommendations to drink only ‘clean’ water, sun cream approval, social distancing, steps to discourage smoking, or hand washing for infection control.[21, 22]
Vitamin D deficiency/insufficiency is referred to by some as a pandemic, and is a recognised disorder obliging prescribed existing recommended treatments and protocols, including by NICE.
1. Brown, R., Rhein, H., Alipio, M., Annweiler, C., Gnaiger, E., Holick M., Boucher, B., Duque, G., Feron, F., Kenny, R., Montero-Odasso, M., Minisola, M., Rhodes, J., Haq., A, Bejerot, S., Reiss, L., Zgaga, L., Crawford, M., Fricker, R., Cobbold, P., Lahore, H., Humble, M., Sakar, A., Karras, S., Iglesias-Gonzalez, J., Gezen-Ak, D., Dursun E., Cooper, I., Grimes, D. & de Voil C. (April 20, 2020). ‘Rapid response re: Is ethnicity linked to incidence or outcomes of COVID-19?’: COVID-19 ’ICU’ risk – 20-fold greater in the Vitamin D Deficient. BAME, African Americans, the Older, Institutionalised and Obese, are at greatest risk. Sun and ‘D’-supplementation – Game-changers? Research urgently required. BMJ, 369(m1548). DOI: 10.1136/bmj.m1548. Available at: https://www.bmj.com/content/369/bmj.m1548/rr-6 (Accessed: 18 May 2020)
2. Brown, R. (April 7, 2020). ‘Rapid Response: Re: Preventing a COVID-19 pandemic - COVID-19: Vitamin D deficiency; and, death rates; are both disproportionately higher in elderly Italians, Spanish, Swedish Somali, and African Americans? A connection? Research urgently required!’, BMJ, 368(m810). DOI: 10.1136/bmj.m810 Available at: https://www.bmj.com/content/368/bmj.m810/rr-46 (Accessed: 18 May 2020).
3. Grant, W., Lahore, H., McDonnell, S., Baggerly, C., French, C., Aliano, J. & Bhattoa, H. (March 30, 2020; 2nd version). ‘Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths’, Nutrients, 12(988). Available at: https://www.preprints.org/manuscript/202003.0235/v2 (Accessed: 18 May 2020).
4. Brown, R. & Sarkar, A. (March 24, 2020). ‘Vitamin D deficiency: a factor in COVID-19, progression, severity and mortality? – An urgent call for research’, MitoFit Preprint Arch. DOI: 10.26124/mitofit:200001. Available at: https://www.mitofit.org/index.php/Brown_2020_MitoFit_Preprint_Arch (Accessed: 18 May 2020).
5. Raharusun, P., Sadiah, P., Cahni, B., Erdie, A., Cipta, B. (April 26, 2020). ‘Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study’, SSRN. DOI: 10.2139/ssrn.3585561 Available at: https://ssrn.com/abstract=3585561 (Accessed: 18 May 2020).
6. Alipio, M. (April 9, 2020). ‘Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-19)’, SSRN. DOI: 10.2139/ssrn.3571484 Available at: https://ssrn.com/abstract=3571484 (Accessed: 18 May 2020).
7. Meltzer, D., Best T., Zhang, H., Vokes, T., Arora, V. & Solway, J. (May 13, 2020). ‘Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence’, MedRxiv. DOI: 10.1101/2020.05.08.20095893 Available at: https://www.medrxiv.org/content/10.1101/2020.05.08.20095893v1 (Accessed: 18 May 2020).
8. Buttriss, J. & Lanham‐New, S. (May 18, 2020). ‘Is a vitamin D fortification strategy needed?’, Nutrition Bulletin, p. 1-8. DOI: 10.1111/nbu.12430
9. Stagi, S., Rigante, D., Lepri, G., Matucci Cerinic, M. & Falcini, F. (2016). ‘Severe vitamin D deficiency in patients with Kawasaki disease: a potential role in the risk to develop heart vascular abnormalities?’, Clin Rheumatol., 35(7), p.1865-1872. DOI: 10.1007/s10067-015-2970-6.
10. Yang, X. & Dong, X. Y. (2016). ‘Research advances in association between vitamin D and Kawasaki disease and related mechanisms of action’, Zhongguo Dang dai er ke za zhi = Chinese Journal of Contemporary Pediatrics, 18(12), p.1319-1323.
11. Jun, J., Jung, Y. & Lee, D. (2017). ‘Relationship between vitamin D levels and intravenous immunoglobulin resistance in Kawasaki disease’, Korean Journal of Pediatrics, 60(7), p.216-220. DOI: 10.3345/kjp.2017.60.7.216
12. Jones, V., Mills, M., Suarez, D., Hogan, C., Yeh, D., Bradley Segal, J., Nguyen, E., Barsh, G., Maskatia, S. & Mathew, R. (April 7, 2020). ‘COVID-19 and Kawasaki Disease: Novel Virus and Novel Case’, Hosp Pediatr. pii: hpeds.2020-0123. doi: 10.1542/hpeds.2020-0123. [Epub ahead of print] https://hosppeds.aappublications.org/content/hosppeds/early/2020/04/06/h...
13. El-Bar, K. (May 14, 2020). ‘New global trend of COVID-19 linked disease in children. Italian doctors report in new article that Kawasaki disease among some patients may be linked to COVID-19. Anadolu Agency’. Available at: https://www.aa.com.tr/en/europe/new-global-trend-of-covid-19-linked-dise... (Accessed: 19 May 2020).
14. Schmid, A. & Walther, B. (2013). ‘Natural vitamin D content in animal products’, Advances in nutrition (Bethesda, Md.), 4(4), p.453–462. DOI: 10.3945/an.113.003780
15. Holick, M. (2011). ‘Vitamin D: a d-lightful solution for health’, Journal of investigative medicine : the official publication of the American Federation for Clinical Research, 59(6), p.872–880. DOI: 10.2310/JIM.0b013e318214ea2d
16. Glicio, El, J. (May 5, 2020). ‘Vitamin D Level of Mild and Severe Elderly Cases of COVID-19: A Preliminary Report’, SSRN. Available at: https://ssrn.com/abstract=3593258 (Accessed: 18 May 2020).
17. Lau, F., Majumder, R., Torabi, R., Saeg, F., Hoffman, R., Cirillo, J. & Greiffenstein, P. (April 28, 2020). ‘Vitamin D Insufficiency is Prevalent in Severe COVID-19’, MedRxiv. DOI: 10.1101/2020.04.24.20075838 Available at: https://www.medrxiv.org/content/10.1101/2020.04.24.20075838v1 (Accessed: 18 May 2020).
18. De Smet, D., De Smet, K., Herroelen, P., Gryspeerdt, S. & Martens, D. (May 5, 2020). ‘Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics’, MedRxiv. DOI: 10.1101/2020.05.01.20079376 Available at: https://www.medrxiv.org/content/10.1101/2020.05.01.20079376v1 (Accessed: 18 May 2020).
19. D’Avolio, A., Avataneo, V., Manca A., Cusato, J., De Nicolò, A., Lucchini, R., Keller, F. & Cantù, M. (2020). ‘25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2’, Nutrients, 12(5) 1359, p. 1-7. DOI: 10.3390/nu12051359
20. Faul, J., Kerley, C., Love, B., O’Neill, E., Cody. C., Tormey, W., Hutchinson, K., Cormican, L. & Burke, C. (2020). ‘Vitamin D Deficiency and ARDS after SARS-CoV-2 Infection’, Ir Med J, 113(5), P84. Available at: http://imj.ie/wp-content/uploads/2020/05/Vitamin-D-Deficiency-and-ARDS-a... (Accessed: 18 May 2020)
21. Davis R. The Doctor Who Championed Hand-Washing and Briefly Saved Lives. NPR Your Health. Available at https://www.npr.org/sections/health-shots/2015/01/12/375663920/the-docto.... (Accessed: 18 May 2020).
22. Acknowledgement: Thanks to William Grant referenced above note 3 for the parachute analogy, and his wider contribution to finding and sharing papers, and to Henry Lahore of https://vitamindwiki.com/ for his tireless cataloguing of all things Vitamin D, with dogged unceasing determination, over very many years.
23. National Institute for Health and Care Excellence (2020). ‘Vitamin D deficiency in adults - treatment and prevention’. Last revised in September 2018. Next planned review by November 2021. Available at: https://cks.nice.org.uk/vitamin-d-deficiency-in-adults-treatment-and-pre... (Accessed: 18 May 2020).
Competing interests: No competing interests
The COVID-19 pandemic has drawn attention to the impact of health inequality on the virus outcome. In response to the important conversations in the BMJ and Lancet around Black and Ethnic Minorities (BAMEs) and the disproportionate severity of COVID-19 among this group in the UK [1,2]. BAMEs account for more than 34% of critically ill patients from COVID-19, keeping in mind that this group only make up 14% of the total population in the UK . In comparison to the White population have only 73.6% of deaths while representing more than 85% of the total population, this brings -14% deaths in this group when compared to the total population representation.
However, we would like to focus this conversation on disproportionate infection and mortality of the black-African population due to COVID-19 in the UK. This is important because Black-African has been reported to be more disadvantaged than other BAMEs . It has been reported that black-Africans make up 5.8% of the cases of COVID deaths while representing only 3.5% of the total population. They have highest hospital deaths with three times that of the White population . In comparison, Asian group made up 7.6% of deaths due to COVID-19 while representing 7.7% of the total population. Similarly in London, black-African accounted for more than 16% of the deaths while only representing 13% of the total population. This is higher in comparison to Whites 55.9% deaths with 59.8% representation of the population and Asian 16.4% deaths while representing 18.5% of the population . This prompted us to review publications in relation to COVID-19 outcome among BAMEs in the UK and found that no study has focused on Black-Africans and the severity of COVID-19 outcome among individuals from this group.
Black- African population in the UK have continuously faced health inequality which has disadvantaged this group in relation to COVID-19 outcome. African population have a higher burden of non-communicable diseases such as diabetes, hypertension, mental health in the UK . Furthermore, cultural beliefs in regard to conditions such as HIV and AIDs and tuberculosis have contributed to the higher burden of these diseases among African populations in the UK . These burdens of chronic disease among black-African populations have implications for the higher burden of COVID-19 reported within these groups.
Other factors such as genetic composition, vitamin D deficiency, vaccine from country of birth, immune system performance might be important in COVID-19 outcome among Africans in the UK . In addition, limited access to health-care services, working in high-risk jobs such as care worker, health worker has made African immigrants more susceptible to COVID-19 infection and mortality. This is in addition to the overly-representation of this group in low socio-economic status which has important implications on health and wellbeing.
Finally, COVID-19 has highlighted the disparity of African population health in the UK as compared to the general population. We feel it is time that policy address this long-overdue inequality in health among BAMEs and African population in particular. It should not be expected as normal that these groups are worse hit by COVID-19 or any other diseases. Targeted research is needed to understanding the implications of inequality on health of Black-Africans that are disproportionately affected by disease conditions.
1. Khunti Kamlesh, Singh Awadhesh Kumar, Pareek Manish, Hanif Wasim. Is ethnicity linked to incidence or outcomes of covid-19? BMJ 2020; 369 :m1548
2. Pareek, M., Bangash, M.N., Pareek, N., Pan, D., Sze, S., Minhas, J.S., Hanif, W. and Khunti, K. Ethnicity and COVID-19: an urgent public health research priority. The Lancet. 2020.
3. Intensive Care National Audit and Research Centre, London 2020 Available from https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports Accessed April, 2020
4. Alloh, F., Hemingway, A. and Turner-Wilson, A.L. Systematic review of diabetes management among black African immigrants, white and South Asian populations. Journal of Global Health Reports. 2019;3.
5. Platt and Warwick 2020 Are some ethnic groups more vulnerable to COVID-19 than others? Available from: https://www.ifs.org.uk/inequality/wp-content/uploads/2020/04/Are-some-et... Accessed May, 2020
6. NHS statistics. COVID-19 Daily Deaths https://www.england.nhs.uk/statistics/statistical-work-areas/covid-19-da... Accessed May, 2020
7. Regmi PR, Alloh F, Pant PR, Simkhada P, Van Teijlingen E. Mental health in BME groups with diabetes: an overlooked issue?. The Lancet. 2017;4;389(10072):904-5.
8. Gerrish, K., Naisby, A. and Ismail, M. The meaning and consequences of tuberculosis among Somali people in the United Kingdom. Journal of advanced nursing. 2012;68(12), pp.2654-2663.
9. Agyemang, C., de-Graft Aikins, A. and Bhopal, R. Ethnicity and cardiovascular health research: pushing the boundaries by including comparison populations in the countries of origin. Ethnicity & health. 2012;17(6), pp.579-596.
Competing interests: No competing interests
It is neglectful to present a dichotomous argument of structural racism versus biological risk to describe the excess COVID19 deaths in BAME groups.
There are still unanswered questions as to why COVID19 causes severe disease and death in some and not in many others.
This editorial and more recently data from the Office of National Statistics summarises the higher risk of death due to COVID19 among Black African and South Asian men and women in the UK, which is additionally observed in the U.S [1, 2]. With a current lack of robust evidence guiding our understanding of this, arguments have often been dichotomous; between structural racism and the poorer social and health risk determinants versus biological. However, these are inextricably linked.
Research must investigate both to ensure they are not just described but more importantly translated and acted upon ethically and equitably. If there is a true excess of severe illness and death associated with COVID19 in people from Black, Asian and mixed ethnicity (BAME) groups, we need to focus on data driven interventions to save lives and improve health in these groups.
If there is a true association between ethnicity and COVID19 severity, is it driven by deprivation; virus exposure; excess of specific co-morbidities; or other social, environmental or biological/immunological risk factors or an interplay? This research needs to involve social science and it is needed urgently.
There are well described historical, systemic structural barriers  that no doubt factor into the excess of many chronic and acute conditions described in BAME groups in industrialised nations, which play deep into U.S and UK society. Structural barriers penetrate further; the vast empire of the commercial food industry, for example, pervades low and middle income Asian and African countries and has contributed to a greater burden of non-communicable conditions such as heart disease and obesity in these settings. Such that these less resourced nations face a double burden of malnutrition .
However, focused arguments on structural racism have been reluctant to accept biological factors; suggesting to discuss them fuels this structural barrier. Biological factors associated with BAME ethnicity are connected to the structural and historical/colonial dynamics of the centuries gone by and to evolved modern-day lifestyles within Western industrialised nations, but we must address them within interventions to improve wellbeing and health in these groups.
An active shift to address structural barriers by equity-oriented initiatives, health policy reform, health sector education and targeted outreach to improve health outcomes in BAME groups are long awaited. The question is, will any such change happen quickly enough to impact outcomes from COVID19 right now?
Whilst awaiting urgently needed data, we can focus on discussing social distancing behaviour in households; evaluating occupational risk and employment rights of key workers; educating healthcare workers; managing lifestyle factors; driving a healthier diet to improve diabetic and blood pressure outcomes; targeted outreach to strengthen and optimise cardiovascular disease, hypertension and diabetes management; stopping smoking; improving exercise capacity; replacing vitamin D nutritionally and through supplementation.
Vitamin D has an immunomodulatory role , deficiency has been associated with a risk of acute pneumonias  and higher rates of deficiency described in BAME groups  living within non-tropical environments. Importantly, encouraging replete levels cannot do harm.
BAME groups should be empowered to make beneficial lifestyle choices rather than be at the mercy of a repressive health rhetoric in the midst of an outbreak. Those choices may be greatly limited due to structural constraints, but we all need to think about our own actions and behaviours to mitigate impact on ourselves and on those in our communities.
1. Khunti Kamlesh, Singh Awadhesh Kumar, Pareek Manish, Hanif Wasim. Is ethnicity linked to incidence or outcomes of covid-19? BMJ 2020; 369:m1548
2. Coronavirus: Black Britons face 'twice the risk' of death, says ONS. BBC News online; 7th May 2020. https://www.bbc.co.uk/news/uk-52574931 [Accessed 12th May 2020]
3. Bailey ZD, Krieger N, Agénor M, Graves J, Linos N, Bassett MT. Structural racism and health inequities in the USA: evidence and interventions. Lancet. 2017;389(10077):1453‐1463.
4. Popkin BM, Corvalan C, Grummer-Strawn LM. Dynamics of the double burden of malnutrition and the changing nutrition reality. Lancet. 2020;395(10217):65‐74. doi:10.1016/S0140-6736(19)32497-3.
5. Zhang Y, Fang F, Tang J, et al. Association between vitamin D supplementation and mortality: systematic review and meta-analysis. BMJ. 2019;366:l4673.
6. Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583.
7. Herrick KA, Storandt RJ, Afful J, et al. Vitamin D status in the United States, 2011-2014. Am J Clin Nutr. 2019;110(1):150‐157
Competing interests: No competing interests
Kamlesh Khunti and colleagues’ editorial came to our attention due to extensive media coverage on the disproportionately high novel coronavirus disease (COVID-19) morbidity and mortality in the black and minority ethnic (BME) population in the UK.
Whilst the BME group is heterogenous as it includes communities such as Black, Indian, Pakistani/Bangladeshi, and Chinese, etc., it is still valid to explore a possible link between ethnicity and prognosis of COVID-19 in view of increasing public concerns and calls for taking action by public health authorities in ethnically diverse countries including the UK and USA.
Statistics published on 7th May 2020 by the Office for National Statistics shows that after age adjustment, the risk of dying from COVID-19 in Black and Bangladeshi/Pakistani groups was more than 4-fold and 3-fold respectively in both males and females compared to the white ethnic group. (1)
It is interesting to point out that in the same Indian ethnicity group, the age-adjusted likelihood of dying from COVD-19 was more than 2-fold compared to the white ethnic group, but it was significantly lower than the South Asian counterpart, Bangladeshi/Pakistani group and differences still remained after full adjustment including socio-economic position. (1)
The risk of COVID-19 related death in the Chinese group was the lowest in the BME population, less than 2-fold of white counterparts when age adjusted. (1) As obesity is implied as one of the emerging predictors of poor outcome for COVID-19, (2) the lowest percentage (34.5%) of being overweight or obese is in the Chinese group (3) compared to overall 62.0% and may explain the above. As higher prevalence of obesity in the BME group is one of the possible susceptibilities in the original editorial, it also shows the heterogeneity of the BME population.
Genetic and environmental factors are two major determinants of biological phenomena, and the COVID-19 pandemic should be researched accordingly. We expect further studies to look for a causative relationship between the outcome of COVID-19 and minority ethnic group including sick behaviours, socio-economic inequality, and genetic variation so as to help public health authorities detect and protect a vulnerable population effectively.
1) Coronavirus(COVID – 19) related deaths by ethnic group, England and Wales: 2 March 2020 to 10 April 2020, 7 May 2020 [accessed 7 May 2020]. Available from:
2) Is adipose Tissue a Reservoir for Viral Spread, Immune Activation and Cytokine Amplification in COVID-19, 21 April 2020 [accessed 7 May 2020] Available from: https://doi.org/10.1002/oby.22843
3) Overweight adults, 25 July 2019 [accessed 7 May 2020] Available from: https://www.ethnicity-facts-figures.service.gov.uk/health/diet-and-exerc...
Competing interests: No competing interests
Interim measures to protect BAME health/social care personnel from covid-19
The recent editorial by Khunti (1) and colleagues explores the linkage between ethnicity and outcomes of covid-19. It rehearsed the usual associations of racial, social and economic inequalities, as well as cultural/lifestyle and genetic predisposition, but did not offer any solutions to dealing with the problem other than advice that more research be done to provide “clear evidence to confirm or rule out an association between ethnicity and outcome in covid-19”.
While we need more research, we do need action now to stem the mortality in this group of front-line workers. Preliminary mortality data thus far show overwhelmingly that BAME front-line staff are disproportionately dying and are more severely affected by covid-19, compared with other ethnicities. We cannot wait for these studies to be concluded while people continue to die. Urgent action is needed on an interim basis while we await the outcome of these studies, the times to completion of which are at yet unknown.
As a matter of urgency, while waiting for complete data set from the ongoing studies, the following actions could be instituted immediately by all health and social care organisations to protect their front-line staff, but particularly BAME staff.
Firstly, all staff, but particularly BAME staff, be risk assessed, recognising their ethnicity as a risk factor, and possibly excluding them from front-line covid -19 duties, depending on their risk score.
Secondly, BAME staff should be prioritised for more protective PPE including FFP3 masks.
Thirdly, all staff, but particularly BAME staff who fall ill/test positive for covid-19 and have to self-isolate, should be monitored by their employer while self-isolating with a view to early hospital admission at the earliest signs of deterioration, to maximise their chances of survival.
1. Khunti K, Singh AK, Pareek M, Hanif W. Is ethnicity linked to outcomes of covid-19? BMJ 2020;369:m1548
Competing interests: No competing interests
The Intensive Care and National Audit and Research Centre (ICNARC) Report on COVID-19 showed that 35% of critically ill patients in the UK were from black and minority ethnic backgrounds (BME). Only 14% of the population in England and Wales are from BME backgrounds, suggesting that they are disproportionately affected by COVID-19. A number of reasons have been postulated, such as higher rates of socioeconomic deprivation, multigenerational living, and cardiometabolic disease in BME communities. Furthermore, major cities like London and Birmingham have been hit hardest by COVID-19 due, in part, to urban density and international travel, but they also have a greater ethnic diversity than the rest of the country.
One alternative hypothesis is the higher prevalence of vitamin D deficiency in those from BME backgrounds. Vitamin D deficiency is common in South Asians and African-Caribbeans in the UK, particularly in inner cities. One study in Birmingham found serum 25-hydroxyvitamin D levels below 10 nanograms/mL (25 nmol/L) in one in four African-Caribbeans and one in three Asians. An analysis of UK primary care records found that two-thirds of Asian/Asian British and half of Black/Black British adults had 25-hydroxyvitamin D levels below 30nmol/L.
Vitamin D is principally obtained following skin exposure to sunlight, leading to ultraviolet (UV) light induction of dermal vitamin D synthesis. Relatively few foods provide a dietary source of vitamin D. The current lock-down to control COVID-19 could potentially exacerbate vitamin D deficiency by reducing UV light exposure at a time of the year when the vitamin D status of most of the UK population is at its lowest following the decline in vitamin D production during the winter.
The effect of vitamin D on immune function and respiratory health has been known for some time. Vitamin D reduces pulmonary inflammation and enhances innate and adaptive immunity to respiratory pathogens.[5,6] Epithelial cells lining the respiratory tract contain enzymes which convert 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, which in turn induces expression of various antibacterial proteins by cells, such as macrophages, from the innate immune system.
Vitamin D also increases the phagocytic potential of macrophages and inhibits the maturation of dendritic cells, which dampens the response of pro-inflammatory cytokines (e.g. IL-12 and IL-23) and enhances the expression of anti-inflammatory cytokines, such as IL-10, thereby shifting the T cell response from pro-inflammatory T helper (TH1) towards a tolerogenic TH2 based profile through support from regulatory T cells. Vitamin D inhibits a potentially harmful chemokine and cytokine response while maintaining antiviral activity, which may prove particularly important in COVID-19, in which critically ill patients experience a cytokine storm.
A number of observational studies have shown independent associations between vitamin D deficiency and incidence of respiratory tract infections (RTIs). A large cohort study in US citizens found that lower vitamin D levels were independently associated with the likelihood of a recent upper respiratory tract infection (URTI) with a clear dose-response relationship. In patients with asthma and COPD, the association between vitamin D deficiency and URTIs was stronger still (odds ratio 5.67 and 2.26, respectively). Vitamin D deficiency is associated with a higher risk of community-acquired pneumonia  and independently predicts mortality and ICU admission among these patients. The extent to which vitamin D deficiency specifically contributes to viral infections has not yet been fully established  although H5N1 virus-infected mice models do suggest a protective effect of calcitriol (an active form of vitamin D) on reducing acute lung injury.
Vitamin D deficiency is common among patients with acute respiratory distress syndrome, which is a hallmark of severe COVID-19 infection, and patients with lower vitamin D levels have a higher odds of developing acute respiratory failure (odds ratio 1.84, 95% CI 1.22 to 2.77). Vitamin D deficiency is associated with increased alveolar inflammation and damage, which may be ameliorated by vitamin D supplementation.
A systematic review and individual patient data meta-analysis of high-quality randomised controlled trials showed that daily or weekly vitamin D supplementation at a standard dose significantly reduces the risk of RTIs. The number needed-to-treat to prevent one RTI was only four when regular vitamin D supplementation is used at a daily dose of under 20 micrograms or 800 IU, among people with vitamin D deficiency. Systematic reviews of RCTs of vitamin D supplementation for patients with asthma and COPD similarly conclude that vitamin D supplementation prevents exacerbations in patients who are vitamin D deficient. Use of high or bolus doses of vitamin D appear to have no effect on preventing RTIs and may even disrupt vitamin D metabolism, and the effect is only statistically significant in people with vitamin D deficiency.
Trials for vitamin D supplementation for the treatment of COVID-19 are currently underway, providing hope that its efficacy for protecting patients from SARS-Coronavirus-2 will be more definitively resolved.[22,23] However, given the substantial epidemiological evidence that vitamin D supplementation is effective at preventing respiratory tract infections and that vitamin D deficiency may be causally related to ARDS, a strong argument could be made to recommend empirical preventative treatment with standard-dose (400 to 800 IU or 10-20 micrograms daily) vitamin D supplementation for high-risk groups, such as people from BME backgrounds, patients with chronic respiratory disease such as COPD and asthma, and any other population groups at risk of vitamin D deficiency.
Regular intake of standard-dose vitamin D is not associated with adverse effects such as hypercalcaemia or renal stones. This would be a safe intervention to recommend to at-risk population groups and strengthens the argument for increased vitamin D fortification at a population level. It is highly questionable to wait for the results of RCTs before this recommendation should be made.
Shamil Haroon, Clinical Lecturer in Primary Care, Institute of Applied Health Research.
Jennifer Cooper, Academic Clinical Fellow, Institute of Applied Health Research.
Astha Anand, Academic Clinical Fellow, Institute of Applied Health Research.
Krishnarajah Nirantharakumar, Senior Clinical Lecturer, Insitute of Applied Health Research.
Martin Hewison, Professor of Molecular Endocrinology, Institute of Metabolism and Systems Research.
Correspondence to: Shamil Haroon, email@example.com, Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham, UK, B15 2TT
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2 Population of England and Wales. 2018.https://www.ethnicity-facts-figures.service.gov.uk/uk-population-by-ethn... (accessed 15 Apr 2020).
3 Ford L, Graham V, Wall A, et al. Vitamin D concentrations in an UK inner-city multicultural outpatient population. Ann Clin Biochem 2006;43:468–73.
4 Crowe FL, Jolly K, MacArthur C, et al. Trends in the incidence of testing for vitamin D deficiency in primary care in the UK: a retrospective analysis of The Health Improvement Network (THIN), 2005–2015. BMJ Open. 2019;9:e028355. doi:10.1136/bmjopen-2018-028355
5 Hughes DA, Norton R. Vitamin D and respiratory health. Clin Exp Immunol 2009;158:20–5.
6 Jiménez-Sousa MÁ, Martínez I, Medrano LM, et al. Vitamin D in Human Immunodeficiency Virus Infection: Influence on Immunity and Disease. Front Immunol 2018;9:458.
7 Hansdottir S, Monick MM, Hinde SL, et al. Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. J Immunol 2008;181:7090–9.
8 Herr C, Greulich T, Koczulla RA, et al. The role of vitamin D in pulmonary disease: COPD, asthma, infection, and cancer. Respir Res 2011;12:1–9.
9 Ginde AA, Mansbach JM, Camargo CA Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med 2009;169:384–90.
10 Zhou Y-F, Luo B-A, Qin L-L. The association between vitamin D deficiency and community-acquired pneumonia: A meta-analysis of observational studies. Medicine 2019;98:e17252.
11 Remmelts H, van de Garde E, Meijvis S, et al. Vitamin D level predicts clinical outcome in community-acquired pneumonia. Eur Respir J 2012;40.https://erj.ersjournals.com/content/40/Suppl_56/1361 (accessed 17 Apr 2020).
12 Lee C. Controversial Effects of Vitamin D and Related Genes on Viral Infections, Pathogenesis, and Treatment Outcomes. Nutrients 2020;12. doi:10.3390/nu12040962
13 Huang F, Zhang C, Liu Q, et al. Identification of amitriptyline HCl, flavin adenine dinucleotide, azacitidine and calcitriol as repurposing drugs for influenza A H5N1 virus-induced lung injury. PLoS Pathog 2020;16:e1008341.
14 Dancer RCA, Parekh D, Lax S, et al. Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS). Thorax 2015;70:617–24.
15 Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory Medicine 2020;8:420–2.
16 Thickett DR, Moromizato T, Litonjua AA, et al. Association between prehospital vitamin D status and incident acute respiratory failure in critically ill patients: a retrospective cohort study. BMJ Open Respir Res 2015;2:e000074.
17 Ilie PC, Stefanescu S, Smith L. The role of Vitamin D in the prevention of Coronavirus Disease 2019 infection and mortality. In Review. 2020. doi:10.21203/rs.3.rs-21211/v1
18 Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017;356:i6583.
19 Jolliffe DA, Greenberg L, Hooper RL, et al. Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials. Thorax 2019;74:337–45.
20 Jolliffe DA, Greenberg L, Hooper RL, et al. Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data. The lancet Respiratory medicine 2017;5:881–90.
21 Netuveli G, Hurwitz B, Sheikh A. Ethnic variations in incidence of asthma episodes in England & Wales: national study of 502,482 patients in primary care. Respir Res 2005;6:120.
22 COvid-19 and Vitamin D Supplementation: a Multicenter Randomized Controlled Trial of High Dose Versus Standard Dose Vitamin D3 in High-risk COVID-19 Patients (CoVitTrial) - Full Text View - ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04344041 (accessed 17 Apr 2020).
23 Vitamin D on Prevention and Treatment of COVID-19 - Full Text View - ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04334005 (accessed 17 Apr 2020).
Competing interests: Shamil Haroon, Jennifer Cooper and Astha Anand have no competing interests. Krishnarajah Nirantharakumar has received research funding from AstraZeneca, Vifor and CSL Behring unrelated to this work and personal fees from MSD, Sanofi and Boehringer Ingelheim outside the submitted work. Martin Hewison has received personal fees from Internis.
Covid-19 is not a "great leveller". But, as history tells us, pandemics never are. One only has to look as far back as the Spanish flu of 1918 which disproportionately affected the poor .
The socioeconomic and health inequalities which are so prevalent within the BAME community are well known[2, 3, 4], and have been well known for quite some time. However, given that the UK government has only recently decided to include ethnicity, along with age, sex, geographical location and co-morbidity, into its national data collection, it will remain some time before we are able to decipher between a correlation and a causation.
What is highly important is that the relevant health authorities act on this information and share it widely, for if we do what many inquiries are guilty of achieving - all talk and no walk - then we run the risk of improperly relaxing social distancing measures and exposing the unknown vulnerable to further harm.
We cannot do anything about the colour of our skins, age, sex, or genetic expression of ACE2, but, if shown that poverty, obesity, vitamin D deficiency, and poorer educational attainment amongst others, correlate to a worse outcome with Covid-19, then surely as a modern society we must enact change which will lessen the impact of these reversible risk factors?
Identify, test and treat is the new public health mantra for this pandemic . I say we should be doing the same for the risk factors associated with poorer outcome. Now that we have the time to reflect on what our society has become, and what we want our society to look like when we eventually re-enter it, it is pertinent that systemic injustices and inequalities are addressed and rectified.
So my question to the UK government is - what are you going to do about it?
It is sadly too late for the people who have died, but, their deaths can help us to understand what we can improve in society. Let their deaths not be in vain.
1. Mamelund SE. 1918 pandemic morbidity: The first wave hits the poor, the second wave hits the rich. Influenza Other Respir Virsus. 2018; 12(3): 307 – 313.
2. Joseph Rowntree Foundation. Poverty, ethnicity and education. May 2011 [accessed 27 Apr 2020]. Available from: https://www.jrf.org.uk/sites/default/files/jrf/migrated/files/poverty-et...
3. Institute of Race Relations. Inequality, Housing and Employment Statistics [accessed 27 Apr 2020]. Available from: http://www.irr.org.uk/research/statistics/poverty/
4. Runnymede Trust. Black and Asian Britons more likely to be homeless or live in overcrowded homes. 11 Feb 2014 [accessed 17 Apr 2020]. Available from: https://www.runnymedetrust.org/news/558/272/Black-and-Asian-Britons-more...
5. Department of Health. Public health matters. 24 Apr 2020 [accessed 27 Apr 2020]. Available from: https://publichealthmatters.blog.gov.uk/2020/04/24/duncan-selbies-friday...
6. World Health Organization. WHO Director-General's opening remarks at the media briefing on COVID-19 - 16 March 2020. 16 Mar 2020 [accessed 27 Apr 2020]. Available from: https://www.who.int/dg/speeches/detail/who-director-general-s-opening-re...
Competing interests: No competing interests
We read with great interest and concern the reports from both sides of the Atlantic suggestive of a disproportionate impact of COVID-19 on people of ethnic minorities [1-3]. Authors have proposed different reasons to explain the observed phenomenon. These include socioeconomic factors related to the living conditions of ethnic minority communities in the West, a higher risk of comorbidities (diabetes, hypertension) and a ‘language barrier’ factor restricting the understanding of some ethnic minority communities to COVID-19 related health instructions and access to medical care when needed [1,3,4]. While these factors could partially explain the variable impact COVID-19 has in the general population, they fall short of explaining the more striking disparity figures reported in doctors’ demise. So far, about 95% of the NHS doctors who died while in the frontline fighting the virus are from an ethnic minority background .
Further investigations are urgently needed within the NHS to explore whether the compounding effect within its medical force could be related to any reversible work-environment or staff behaviour factors (e.g., non-compliance with personal protective equipment or reluctance to confront inadequate supply of them due to fear of recrimination, staff deployment, etc).
1. Yancy CW. COVID-19 and African Americans. JAMA. 2020. Published 15th Apr 2020. doi:10.1001/jama.2020.6548
2. Intensive Care National Audit & Care Centre. ICNARC report on COVID-19 in critical care. https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports (10 April 2020).
3. Khunti K, Singh AK, Pareek M, Hanif W. Is ethnicity linked to incidence or outcomes of covid-19? BMJ. 2020;369:m1548.
4. Nagpaul C. Impact of Covid-19 on the BAME population and doctor workforce. BMA council chair's message to members – 10 April 2020. https://www.bma.org.uk/advice-and-support/covid-19/what-the-bma-is-doing.... (accessed 11th Apr 2020).
5. Ward V, Lyons I. These are the NHS workers who have died from coronavirus. The Telegraph. https://www.telegraph.co.uk/news/0/nhs-died-coronavirus-frontline-worker.... (accessed 27th Apr 2020).
Competing interests: No competing interests
The updated version of the Intensive Care National Audit and Research Centre (ICNARC) report published on 24th April 2020 with 6720 confirmed cases of coronavirus (COVID-19) shows that the condition disproportionately impacts Black, Asian, and Minority Ethnic (BAME) patients (34.3% in intensive care and 34.4% required advanced respiratory support) compared to White Caucasians.  Furthermore, a greater proportion of BAME patients died (55.3% vs. 48.4%) in intensive care thus reflecting a lower survival rate from the pandemic.
Global evidence has concluded that the majority of patients who died due to COVID-19 had one or more pre-existing conditions. In the UK context, it is well established that BAME individuals are more likely to have cardiovascular disease, diabetes and other long-term conditions and the onset of disease is significantly earlier (e.g. gets type 2 diabetes in early 40s) compared to their White counterparts.  Multiple co-morbidities and a longer duration of these long-term conditions among BAME patients may explain the severity of COVID-19 among confirmed cases. The ICNARC report confirms that higher proportions of BAME COVID-19 patients were on ventilators and also required other organ support including renal.
The much greater area of concern is the gender disparity with a greater occurrence of COVID-19 in men (72% male vs. 28% female). Similar differences were also observed for SARS and MERS (previous coronavirus diseases) during the early 21st Century. On the contrary, one finds a gender balance in other respiratory conditions. For example, the ICNARC report has provided comparable cohort data of viral pneumonia cases between 2017 and 2019 where the gender gap was minimal (46% female vs 54% male). The underlying reasons for the gender disparity in COVID-19 cases need to be explored further. Previous research has suggested that the higher smoking rate among men could be a contributory factor. However, a more plausible reason is the differences in immunity levels between men and women. The presence of two X chromosomes in every cell in women naturally strengthens the immunity. A recent article states that: “a number of critical immune genes are located on the X chromosome in particular the gene for a protein called TLR7, which detects single-stranded RNA viruses like the coronavirus. As a result, this protein is expressed at twice the dose on many immune cells in females compared to males, and the immune response to coronavirus is therefore amplified in females” . Another potential explanation could be due to lower levels of hygiene among men. Historically, the frequency and timing of hand washing as well as use of sanitiser is considerably poorer in men. Therefore it is imperative that routine NHS data on COVID-19 is urgently examined to explore gender differences and associated risk factors within each broad category of ethnicity.
The other critical issue is to explore and understand the differences in immunity level as well as underlying diet, nutrition, and exercise factors that are required to raise and maintain immunity levels among BAME groups. Vitamin D deficiencies have been widely reported among the BAME population in the UK. Additionally, BAME individuals particularly those living in deprived areas lack knowledge on the importance of a balanced and healthy diet containing all essential micronutrients that are required to boost immunity and prevent infectious diseases. Understandably, the BAME population in the UK is highly heterogeneous. Hence use of a tool such as the Six G framework4 can enable healthcare providers to deliver culturally-appropriate advice and aid in the development of interventions to promote lifestyle behavioural changes (i.e. diet and exercise) to improve immunity level and combat COVID type viruses in the future.
Competing Interests: We have no competing interests.
1 Intensive Care National Audit and Research Centre. ICNARC report on COVID-19 in critical care 24 April 2020. https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports accessed 25th April 2020.
2 Bellary S, O’Hare JP, Raymond NT, Gumber A et al. Enhanced diabetes care to patients of south Asian ethnic origin (the United Kingdom Asian Diabetes Study): a cluster randomised controlled trial. Lancet 371 (9626):1769-1776. 24 May 2008.
4 Gumber A and Gumber L. Improving Prevention, Monitoring and Management of Diabetes among Ethnic Minorities: Contextualising the Six G’s Approach. BMC Research Notes (2017) 10(1):774. https://doi.org/10.1186/s13104-017-3104-9.
Competing interests: No competing interests
In lieu of of a vaccine targetting an elusive disease and perhaps even better than a vaccine would be to focus on general immunity. I note both the deeply troubling article by Khunti et al  and the response from Brown et al . Might it also be an idea whenever possible to reduce consumption of immunity lowering drugs, as for instance listed in a recent article by Joan-Ramon Laporte ?
 Kamlesh Khunti, Awadhesh Kumar Singh, Manish Pareek, Wasim Hanif, 'Is ethnicity linked to incidence or outcomes of covid-19?', BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1548 (Published 20 April 2020)
 Brown et al, 'COVID-19 ’ICU’ risk – 20-fold greater in the Vitamin D Deficient. BAME, African Americans, the Older, Institutionalised and Obese, are at greatest risk. Sun and ‘D’-supplementation – Game-changers? Research urgently required.', 24 April 2020, https://www.bmj.com/content/369/bmj.m1548/rr-6
 Joan-Ramon Laporte, 'IN THE MIDST OF THE SARS-CoV-2 PANDEMIA, CAUTION IS NEEDED WITH COMMONLY USED DRUGS THAT INCREASE THE RISK OF PNEUMONIA', Rxisk 2 April 2020, https://rxisk.org/medications-compromising-covid-infections/
Competing interests: AgeofAutism.com, an on-line daily journal, concerns itself with the potential environmental sources for the proliferation of autism, neurological impairment, immune dysfunction and chronic disease. I receive no payment as UK Editor