High BAME COVID-19 Mortality - Ethnicity a Factor? – Yet: Cardiovascular Disease – Hypertension – Diabetes - were rare in 1920-60’s in Indigenous Africans – Vitamin D an underrated factor?
Rapid response to:
Editorials
Is ethnicity linked to incidence or outcomes of covid-19?
High BAME COVID-19 Mortality - Ethnicity a Factor? – Yet: Cardiovascular Disease – Hypertension – Diabetes - were rare in 1920-60’s in Indigenous Africans – Vitamin D an underrated factor?
Dear Editor,
‘Western’ BAME Persons, including African Americans, Elderly and Obese, have greater risk of; COVID-19 related ICU referral, and mortality.[1-3] BAME Children face increased risk of COVID-19 related PIMS-TS.[4]
The Public Health England (PHE) report ‘Disparities in the risk and outcomes of COVID-19’ [5] (herein ‘DIROC’) observes “Comparing to previous years, all-cause mortality was almost 4 times higher than expected among Black males for this period, almost 3 times higher in Asian males and almost 2 times higher in White males. Among females, deaths were almost 3 times higher in Black, Mixed and Other females, and 2.4 times higher in Asian females compared with 1.6 times in White females” DIROC Fig. 4.5, “age standardised COVID-19 case mortality rates”, indicates increased death rate substantially relates to COVID-19. Increased BAME COVID-19 mortality risk is also recorded in Sweden and the USA.[6 7]
DIROC Fig 4.3, ‘Disparities in the risk and outcomes of COVID-19’,5 indicates; independent of social or employment related increased risk of infection, or comorbidities, the proportion of hospital admitted COVID-19 cases, that ultimately required ICU care, was approximately[8] 3-times higher in Black British, and 2.5-times higher in Asian British, than in White British
.
Multifamily dwelling, employment, and other social factors logically impact comparative initial infection risk. However, disease outcome severity, including ICU requirement and mortality, more likely relates to other factors, such as general health, diet, vitamin D status, and related comorbidities.
Hypertension, cardiovascular disease, and diabetes were flagged by the CDC as COVID-19 risk-factors, increasing hospitalisation and mortality, 6 and 12 times respectively.[9]
The NHS observes inter-alia “You are more at risk of CVD if you . . . are from a black, Asian, minority ethnic (BAME) background”.[10] Ethnic polymorphisms may factor in comorbidities. For example, DHCR7 rs12785878,[11 12] is a cholesterol pathway polymorphism common in non-Europeans, that both, reduces vitamin D,[13] and increases production of cholesterol.[14]
However, historical health data suggests genetics are not the major determinant, but that western lifestyle, latitude, and nutritional changes, are.
Donnison MRCP.[15] in Kenya (1920s) examined 1000 indigenous Africans, without access to shops and money, or Western refined foods. He found not one case of hypertension. Average systolic and diastolic pressure fell with age. Highest average systolic was 126.37, and in the 25-29 age group. (Table [15])
British hospital data for a year, in the 1930s records 2,001,211 “cases-attended” in East Africa; hypertension, nil; atherosclerosis, 9; angina, 21; and diabetes, 70. ‘Western’ diseases were marginally more common in West Africa: 882,558 cases-attended: hypertension, nil; atherosclerosis, 90; angina, 11; and diabetes, 115: and a little more common in Malaya; 134,644 cases-attended – hypertension, 29; atherosclerosis, 120; angina, 9, diabetes 251. (Table [15])
‘Western Diseases: Their Emergence and Prevention’[16] by Burkitt, FRCSE. [17] and Trowell OBE, FRCP.[18] reports; hypertension, ischemic heart disease, myocardial infarction, and angina, did not significantly emerge in indigenous Africans until the 1960s. “Vint reported no CHD in 1000 Kenya autopsies (1936-37).” Davies, during 2994 Uganda autopsies (1931-46), found clear infarction in only one case. Diabetes was not seen in the 1930s, starting to appear in the 1950s. Until the 1950s only half-a-dozen Ugandan diabetic patients were disclosed each year.[16]
Similar scenarios were seen in poor urban and rural areas in South Africa.[16] Ergo, ‘poverty-per-se’ is not determinant in; hypertension, cardiovascular disease, and diabetes; but industrialised, nutrient insufficient and damaged, diet clearly is.
These historical reports by skilled-highly-respected doctors, indicate, increased risk of; hypertension, atherosclerosis, and diabetes, actually, is not an endemic characteristic of African Persons, begging the question why these diverse genetic groups today suffer so heavily with these conditions. Sadly, early Asiatic data pre-westernisation is limited.
Modern industrialised nutrient damaged and depleted westernised diet, as a communal factor for excess COVID-19 mortality, equally is not an obvious explanation; BAME Groups, and White Persons, consume a wide range of diets, albeit commonly impacted by poverty, and industrialisation. Equally, whilst social factors, including poverty, likely factor in infection, high COVID-19 death rates are seen in BAME Doctors and Medics, who are not ‘poor’.
Vitamin D status, is consistently low in BAME, including African Americans, the Elderly and Obese, and acknowledged as a potential factor in COVID.[19] Vitamin D, like oestrogen,[20 21] also a sterol -based hormone, is central to function, including; immune-response, reproduction, development, gene transcription, and mitochondrial regulation. Unlike other internally produced hormones, dependent on nutrient availability, vitamin D is made primarily by UVB sunshine-action on sterols; albeit diet can also be a source.
It is underappreciated that vitamin deficiency disease D exacerbates a range of diseases[22 23] including hypertension atherosclerosis[24] and diabetes.[25] Study results are often inconsistent, because they include supplementation of vitamin D sufficient persons, and often do not measure blood levels. In contrast, studies involving supplementation of the deficient, generally show consistent benefit. Expert consensus observed Vitamin D may factor in COVID.19[19]
Increased risk of comorbidities, are likely primarily due to diet and environmental factors, rather than ‘poverty per-se’, or genetics. Negative polymorphic effects, including of vitamin D,26-28] are magnified by latitude and deficiency,[29] thus secondary factors consequent on failure to maintain sufficiency through diet and supplementation.[30] Social inequalities factors of course, but given Medics and Doctors are also badly impacted, logically are not the dominant factor.
Further, diets and lifestyles, are not consistent across BAME in; Sweden, UK and USA, thus not likely common causative agents; in contrast low vitamin D is, and factors in increased comorbidities risk.
BAME Persons including African Americans, are at greater risk of COVID-19 severity and mortality. However, death rate adjustment for ethnicity arguably has limited rationale, because, historical data, as above, suggests Africans, and possibly wider related ethnic groups, (absent specific ‘familial’ polymorphisms), are not inherently at significant greater ethnic risk of these diseases.
Ultimately, Communities, and Hospitals, daily face proportionately greater numbers of BAME and African Americans in ICU beds and mortuaries. Stark, sad, realities of excess BAME and African American COVID-19 related deaths, are not dimmed by statistical adjustments, which cannot reverse COVID-19’s toll. Each death is a death.
Thus, urgent determination of the extent vitamin D deficiency factors in COVID-19 BAME mortality, by COVID-19-patient-blood-measurement, is required.
Rapid Response:
High BAME COVID-19 Mortality - Ethnicity a Factor? – Yet: Cardiovascular Disease – Hypertension – Diabetes - were rare in 1920-60’s in Indigenous Africans – Vitamin D an underrated factor?
Dear Editor,
‘Western’ BAME Persons, including African Americans, Elderly and Obese, have greater risk of; COVID-19 related ICU referral, and mortality.[1-3] BAME Children face increased risk of COVID-19 related PIMS-TS.[4]
The Public Health England (PHE) report ‘Disparities in the risk and outcomes of COVID-19’ [5] (herein ‘DIROC’) observes “Comparing to previous years, all-cause mortality was almost 4 times higher than expected among Black males for this period, almost 3 times higher in Asian males and almost 2 times higher in White males. Among females, deaths were almost 3 times higher in Black, Mixed and Other females, and 2.4 times higher in Asian females compared with 1.6 times in White females” DIROC Fig. 4.5, “age standardised COVID-19 case mortality rates”, indicates increased death rate substantially relates to COVID-19. Increased BAME COVID-19 mortality risk is also recorded in Sweden and the USA.[6 7]
DIROC Fig 4.3, ‘Disparities in the risk and outcomes of COVID-19’,5 indicates; independent of social or employment related increased risk of infection, or comorbidities, the proportion of hospital admitted COVID-19 cases, that ultimately required ICU care, was approximately[8] 3-times higher in Black British, and 2.5-times higher in Asian British, than in White British
.
Multifamily dwelling, employment, and other social factors logically impact comparative initial infection risk. However, disease outcome severity, including ICU requirement and mortality, more likely relates to other factors, such as general health, diet, vitamin D status, and related comorbidities.
Hypertension, cardiovascular disease, and diabetes were flagged by the CDC as COVID-19 risk-factors, increasing hospitalisation and mortality, 6 and 12 times respectively.[9]
The NHS observes inter-alia “You are more at risk of CVD if you . . . are from a black, Asian, minority ethnic (BAME) background”.[10] Ethnic polymorphisms may factor in comorbidities. For example, DHCR7 rs12785878,[11 12] is a cholesterol pathway polymorphism common in non-Europeans, that both, reduces vitamin D,[13] and increases production of cholesterol.[14]
However, historical health data suggests genetics are not the major determinant, but that western lifestyle, latitude, and nutritional changes, are.
Donnison MRCP.[15] in Kenya (1920s) examined 1000 indigenous Africans, without access to shops and money, or Western refined foods. He found not one case of hypertension. Average systolic and diastolic pressure fell with age. Highest average systolic was 126.37, and in the 25-29 age group. (Table [15])
British hospital data for a year, in the 1930s records 2,001,211 “cases-attended” in East Africa; hypertension, nil; atherosclerosis, 9; angina, 21; and diabetes, 70. ‘Western’ diseases were marginally more common in West Africa: 882,558 cases-attended: hypertension, nil; atherosclerosis, 90; angina, 11; and diabetes, 115: and a little more common in Malaya; 134,644 cases-attended – hypertension, 29; atherosclerosis, 120; angina, 9, diabetes 251. (Table [15])
‘Western Diseases: Their Emergence and Prevention’[16] by Burkitt, FRCSE. [17] and Trowell OBE, FRCP.[18] reports; hypertension, ischemic heart disease, myocardial infarction, and angina, did not significantly emerge in indigenous Africans until the 1960s. “Vint reported no CHD in 1000 Kenya autopsies (1936-37).” Davies, during 2994 Uganda autopsies (1931-46), found clear infarction in only one case. Diabetes was not seen in the 1930s, starting to appear in the 1950s. Until the 1950s only half-a-dozen Ugandan diabetic patients were disclosed each year.[16]
Similar scenarios were seen in poor urban and rural areas in South Africa.[16] Ergo, ‘poverty-per-se’ is not determinant in; hypertension, cardiovascular disease, and diabetes; but industrialised, nutrient insufficient and damaged, diet clearly is.
These historical reports by skilled-highly-respected doctors, indicate, increased risk of; hypertension, atherosclerosis, and diabetes, actually, is not an endemic characteristic of African Persons, begging the question why these diverse genetic groups today suffer so heavily with these conditions. Sadly, early Asiatic data pre-westernisation is limited.
Modern industrialised nutrient damaged and depleted westernised diet, as a communal factor for excess COVID-19 mortality, equally is not an obvious explanation; BAME Groups, and White Persons, consume a wide range of diets, albeit commonly impacted by poverty, and industrialisation. Equally, whilst social factors, including poverty, likely factor in infection, high COVID-19 death rates are seen in BAME Doctors and Medics, who are not ‘poor’.
Vitamin D status, is consistently low in BAME, including African Americans, the Elderly and Obese, and acknowledged as a potential factor in COVID.[19] Vitamin D, like oestrogen,[20 21] also a sterol -based hormone, is central to function, including; immune-response, reproduction, development, gene transcription, and mitochondrial regulation. Unlike other internally produced hormones, dependent on nutrient availability, vitamin D is made primarily by UVB sunshine-action on sterols; albeit diet can also be a source.
It is underappreciated that vitamin deficiency disease D exacerbates a range of diseases[22 23] including hypertension atherosclerosis[24] and diabetes.[25] Study results are often inconsistent, because they include supplementation of vitamin D sufficient persons, and often do not measure blood levels. In contrast, studies involving supplementation of the deficient, generally show consistent benefit. Expert consensus observed Vitamin D may factor in COVID.19[19]
Increased risk of comorbidities, are likely primarily due to diet and environmental factors, rather than ‘poverty per-se’, or genetics. Negative polymorphic effects, including of vitamin D,26-28] are magnified by latitude and deficiency,[29] thus secondary factors consequent on failure to maintain sufficiency through diet and supplementation.[30] Social inequalities factors of course, but given Medics and Doctors are also badly impacted, logically are not the dominant factor.
Further, diets and lifestyles, are not consistent across BAME in; Sweden, UK and USA, thus not likely common causative agents; in contrast low vitamin D is, and factors in increased comorbidities risk.
BAME Persons including African Americans, are at greater risk of COVID-19 severity and mortality. However, death rate adjustment for ethnicity arguably has limited rationale, because, historical data, as above, suggests Africans, and possibly wider related ethnic groups, (absent specific ‘familial’ polymorphisms), are not inherently at significant greater ethnic risk of these diseases.
Ultimately, Communities, and Hospitals, daily face proportionately greater numbers of BAME and African Americans in ICU beds and mortuaries. Stark, sad, realities of excess BAME and African American COVID-19 related deaths, are not dimmed by statistical adjustments, which cannot reverse COVID-19’s toll. Each death is a death.
Thus, urgent determination of the extent vitamin D deficiency factors in COVID-19 BAME mortality, by COVID-19-patient-blood-measurement, is required.
1. Brown, R., & Sarkar, A. (19th May 2020). Is ethnicity linked to incidence or outcomes of covid-19? 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 2020;369:m1548 doi: https://doi.org/10.1136/bmj.m1548 Available from https://www.bmj.com/content/369/bmj.m1548/rr-19
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
3. 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
4. Brown, R. Is ethnicity linked to incidence or outcomes of covid-19? BAME Children at High Risk of PIMS-TS, a Covid-19 Kawasaki-Like Disease - Vitamin D, a Factor? – Testing and Data Urgently Required. (10th June 2020) BMJ 2020;369:m1548 doi: https://doi.org/10.1136/bmj.m1548 Available at https://www.bmj.com/content/369/bmj.m1548/rr-25
5. PHE. (2nd June 2020). Disparities in the risk and outcomes of COVID-19PHE publications PHE gateway number: GW-1311. Available at https://www.gov.uk/government/publications/covid-19-review-of-disparitie...
6. CDC. (2020). COVID-19 in Racial and Ethnic Minority Groups. Centers for Disease Control and Prevention, (Retrieved 16th June 2020). https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/racial-...
7. APM Lab Research Staff. (10th June 2020). The color of coronavirus:COVID-19 deaths by race and ethnicity in the U.S. (Retrieved 10th June 2020) https://www.apmresearchlab.org/covid/deaths-by-race
“The latest overall COVID-19 mortality rate for Black Americans is 2.3 times as high as the rate for Whites and Asians, and 2.2 times as high as the Latino rate. Relative to White rates, Black rates are most dramatically higher in the District of Columbia (6 times as high), Kansas (5 times), Wisconsin (5 times), Michigan (4 times), Missouri (4 times), New York (3 times) and South Carolina (3 times).”
8. Data visually estimated from graph – actual figures I understand are not currently available to public (private correspondence with PHE 17th June 2020).
9. Stokes, E., Zambrano, L., Anderson, K., et al. (15th June 2020). Coronavirus Disease 2019 Case Surveillance — United States, January 22–May 30, 2020. MMWR Morb Mortal Wkly Rep. ePub: 15 June 2020. DOI: http://dx.doi.org/10.15585/mmwr.mm6924e2 Available at https://www.cdc.gov/mmwr/volumes/69/wr/mm6924e2.htm?s_cid=mm6924e2_w
10. NHS. (June 2020). Cardiovascular disease (CVD). (Retrieved 12th June 2020). https://www.england.nhs.uk/ourwork/clinical-policy/cvd/
11. Takahashi H, Cornish A, Sud A, et al. (2019). Mendelian randomisation study of the relationship between vitamin D and risk of glioma [published correction appears in Sci Rep. 2019 May 23;9(1):7924]. Sci Rep. 2018;8(1):2339. Published 2018 Feb 5. doi:10.1038/s41598-018-20844-w Available at https://repository.icr.ac.uk/bitstream/handle/internal/1045/Manuscript.p...
12. Moon, R., Harvey, N., Cooper, C., D'Angelo, S., Curtis, E., Crozier, S., et. Al. (2017). Maternal Vitamin D Osteoporosis Study Trial Group (2017). Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D-Related Genetic Variants. The Journal of clinical endocrinology and metabolism, 102(8), 2941–2949. https://doi.org/10.1210/jc.2017-00682 Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546866/
13. Slow, S., Pearson, J., Florkowski, C., et al. (2020). Effect of genetic factors on the response to vitamin D3 supplementation in the VIDARIS randomized controlled trial. Nutrition. 2020;75-76:110761. doi:10.1016/j.nut.2020.110761
14. Prabhu, A., Luu, W., Sharpe, L., & Brown, J. (2016). See Fig 1. Cholesterol-mediated Degradation of 7-Dehydrocholesterol Reductase Switches the Balance from Cholesterol to Vitamin D Synthesis. The Journal of biological chemistry, 291(16), 8363–8373. https://doi.org/10.1074/jbc.M115.699546 Available at https://www.jbc.org/content/early/2016/02/17/jbc.M115.699546.full.pdf
15. Donnison C. MD. MCRP. (1938). Baillière, Tindall and Cox, Civilisation and Disease. Table - The ethnology of Disease Table. Available at https://mccarrison.com/resources/other-sources-on-western-disease-on-non...
16. Trowell, H., & Burkitt, P. (1981). Western Diseases, Their Emergence and Prevention. Harvard University Press / Edward Arnold. ISBN 0674950208. Abstract available at https://mccarrison.com/resources/other-sources-on-western-disease-on-non...
17. Wikipedia. (2020). Denis Parsons Burkitt MD, FRCSE, FRS. (Retrieved 12th June 2020) https://en.wikipedia.org/w/index.php?title=Denis_Parsons_Burkitt&oldid=9...
18. Wikipedia. (2020) Hugh Carey Trowell OBE, FRCP https://en.wikipedia.org/w/index.php?title=Hubert_Carey_Trowell&oldid=89... (Retrieved 12th June 2020) https://en.wikipedia.org/w/index.php?title=Hubert_Carey_Trowell&oldid=89...
19. Lanham-New, S., Webb, A., Cashman, K., et al. (June 2020 Amended). Vitamin D and SARS-CoV-2 virus/COVID-19 disease. BMJ Nutrition, Prevention & Health. doi: 10.1136/bmjnph-2020-000089 Available at https://nutrition.bmj.com/content/early/2020/06/10/bmjnph-2020-000089
20. Lejri, I., Grimm, A., & Eckert, A. (2018). Mitochondria, Estrogen and Female Brain Aging. Frontiers in aging neuroscience, 10, 124. https://doi.org/10.3389/fnagi.2018.00124 Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934418/
21. Klinge, C. (2008). Estrogenic control of mitochondrial function and biogenesis. Journal of cellular biochemistry, 105(6), 1342–1351. https://doi.org/10.1002/jcb.21936 Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2593138/
22. Heaney, R. (2008). Vitamin D in health and disease. Clinical journal of the American Society of Nephrology : CJASN, 3(5), 1535–1541. https://doi.org/10.2215/CJN.01160308 Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571146/
23. VitmainDwiki – curated vitamin d related material including research papers. https://vitamindwiki.com/Overview+Diabetes+and+vitamin+D#less_T2_Diabete...
24. Gholami, F., Moradi, G., Zareei, B. et al. (2019). The association between circulating 25-hydroxyvitamin D and cardiovascular diseases: a meta-analysis of prospective cohort studies. BMC Cardiovasc Disord 19, 248. https://doi.org/10.1186/s12872-019-1236-7 Available at https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-01...
25. Harinarayan, C. (2014). Vitamin D and diabetes mellitus. Hormones 2014, 13(2):163-181. Available at https://vitamindwiki.com/Vitamin+D+and+diabetes+mellitus+%E2%80%93+massi...
26. Wikipedia. (2020). CYP2R1 Vitamin D 25-hydroxylase also known as cytochrome P450 2R1. (Retrieved 12th June 2020). https://en.wikipedia.org/w/index.php?title=CYP2R1&oldid=951229917
27. Wikipedia. (2020). CYP24A1 Vitamin D 24-hydroxylase. (Retrieved 12th June 2020). https://en.wikipedia.org/w/index.php?title=CYP24A1&oldid=958687419
28. Wikipedia. (2020). CYP27B1 25-Hydroxyvitamin D3 1-alpha-hydroxylase. (Retrieved 12th June 2020). https://en.wikipedia.org/w/index.php?title=25-Hydroxyvitamin_D3_1-alpha-...
29. Signorello, L, Shi, J., Cai, Q., Zheng, W., Williams, S., Long, J., et. al. (2011). Common variation in vitamin D pathway genes predicts circulating 25-hydroxyvitamin D Levels among African Americans. PloS one, 6(12), e28623. https://doi.org/10.1371/journal.pone.0028623 Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244405/
30. Hansen, J., Tang, W., Hootman, K., Brannon, P., Houston, K., et al. (2015). Genetic and Environmental Factors Are Associated with Serum 25-Hydroxyvitamin D Concentrations in Older African Americans, The Journal of Nutrition, 145, 4, 799–805. https://doi.org/10.3945/jn.114.202093 Available From https://academic.oup.com/jn/article/145/4/799/4616066
Competing interests: No competing interests