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:m1548Read our latest coverage of the coronavirus pandemic
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Dear Editor,
Last year, I responded suggesting that a specific gene variant related to human ACE2 receptor functionality, most frequent in South Asians, could explain the high death rates in certain racial groups..
See https://www.bmj.com/content/369/bmj.m1548/rr-20
An Oxford group has now confirmed this conjecture, in a detailed Original Research paper published in Nature..
"The biological relevance of SLC6A20 to COVID-19 is unclear... its function as an imino acid transporter is modulated by levels of angiotensin-converting enzyme 2 (ref. 68) (ACE2), which is a cell receptor for SARS-CoV-2 (ref. 69). Conversely, LZTFL1 is widely expressed in pulmonary epithelial cells, including ciliated epithelial cells, which have been identified as one of the main cellular targets for SARS-CoV-2 infection (ref 70)."
Competing interests: No competing interests
Dear Editor,
Sars-Cov-2 may infect primarily the respiratory system, but its weakest target has been proven to be our societies. The first true pandemic in the era of globalisation, has left the world facing off its inequalities which were brought into the surface, and posed an existential dilemma: what are we willing to do to protect our communities, even if we, personally, are not affected by the injustice.
According to reports by the Office of National Statistics (ONS) and Public Health England (PHE) Covid-19 has disproportionally affected members of the BAME (Black, Asian and Minority Ethnic) communities (1), (2). The factors contributing to these differences were multifarious. BAME people usually live in urban areas (where there are higher rates of infection). They tend to come from a lower socio-economic status; hence they reside in more deprived areas, usually in overcrowded households, holding jobs that can more easily expose them to the risk of infection (2). Issues were also identified to the level of care BAME people were provided with. The main ones were effective communication and cultural differences between the healthcare professionals and their patients, along with poor quality ethnicity data and accessibility to health care services (2).
The census of 2011 informs us that, within London, Lambeth has the largest black population and Newham hosts the most Asian people. I wanted to compare their accessibility to primary care services to that of the affluent borough of Kensington and Chelsea (K&C) (4).
Borough Area (km2) Total population BAME % GP practices
Kensington & Chelsea 12.12 156.197 7% Black, 4.9% Asian 43
Lambeth 26.83 325.917 25% Black, 7.8% Asian 47
Newham 36.21 352.005 72.9 % BAME (14% Indians) 69
Lambeth, with double the size of K&C, and twice its total population, has almost the same number of registered GP practices. In Newham, with triple the size of K&C, and twice its total population, there are no more than 1.5 times more practices.
If you live in an area, like Lambeth, where your closest GP practice requires a mean of 20 minutes travel with public transport (9), you even probably have to face severe delays once you get there, since a small number of practices has to care for a much larger population, and you cannot afford to miss a day or even some hours of work, then you would probably not choose to visit the health care services, unless absolutely necessary. It is this fundamental inequality in the accessibility of healthcare, between boroughs of different BAME populations, that feeds systemic racism.
How it does that? By creating two-lane citizens. On the one lane, there is better access to healthcare, that results to earlier diagnosis, treatment and recovery, a generally healthier community, that can invest their time and resources to further growth and influence. On the other lane, with a much more difficult access to healthcare, people are trying to balance between physical and economic survival, finding little space to contemplate any idea of growth and bettering of their community.
How did this reality translate during the pandemic? People failed to get their diagnosis early, therefore, they didn’t get the treatment they required, they could not self-isolate appropriately, and ultimately, they could not protect their family and communities.
What can we do to address this issue? We urgently need to improve access to healthcare for the BAME population, with more primary care services to more deprived areas.
Why? Because access to healthcare, stems from the most intrinsic parts of our humanity, and by denying it to some, actively or passively, we deny ourselves of any decent collective future.
References:
1. Ons.gov.uk. 2020. Coronavirus (COVID-19) Related Deaths By Ethnic Group, England And Wales - Office For National Statistics. [online] Available at:
2. Assets.publishing.service.gov.uk. 2020. Disparities In The Risk And Outcome Of Covid-19. [online] Available at:
3. 2020. [online] Available at:
4. Data.gov.uk. 2020. 2011 Census - Data.Gov.Uk. [online] Available at:
5. Royal Borough of Kensington and Chelsea, 2011. Health Care Services. Royal Borough of Kensington and Chelsea.
6. Nhs.uk. 2020. Gps - NHS West London (K&C & Qpp) CCG - NHS. [online] Available at:
7. Lambethccg.nhs.uk. 2020. GP Surgeries In Lambeth. [online] Available at:
8. Lmc.org.uk. 2020. List Of Newham GP Practices. [online] Available at:
9. Kanaroglou, P. and Delmelle, E., 2016. Spatial Analysis In Health Geography. International Journal of Geographical Information Systems.
Competing interests: No competing interests
Dear Editor
There are a number of well meaning articles about including some the articles and these letters but I wonder about some of the prevailing "dogma".
A lot is being said about vulnerabilities and the need to protect BAME people. It is evidently important to protect people who are at risk but what does that actually mean, particularly at an individual level.
I am of BAME origin and a frontline worker. I have had COVID and been fortunate to recover. Since then I have worked for two months on a COVID ward. All of a sudden I am now bombarded which all this information which tells me that I should be afraid and consider myself "vulnerable". The current narrative also suggests that I should be removed from frontline work.
Interestingly, I also see that in countries that are overwhelming populated by people of BAME origin the rates of infection and mortality are nowhere near the figures we are seeing in western countries.
I am forced to question the narrative that people of BAME origin are inherently more susceptible to this disease and I am more inclined to believe that there are other factors at play. I think it is reasonable to consider how previous health and social factors and occupational exposure may play a role.
However, the approach taken by many organisations now risks depriving an underfunded health service the skills of people who are able to continue contributing to the safe delivery of care. In the current climate it is understandable that some of these reactive approaches are being taken in order to show that people of BAME origin are valued.
However, removing me from frontline duty will not make me feel more valued. It is more relevant to me that there is a safe environment for all patients and staff.
Competing interests: No competing interests
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
Dear Editor,
Seven observational preprints, [1-8] from a variety of countries, based on COVID-19 positive patients, note significant links between; low vitamin D status and, COVID-19 severity, ICU risk and mortality rates.
Higher rates of COVID-19 are observed in; BAME Persons including African Americans, as well as the Obese, and Elderly.[9]
Similarly, higher occurrence of COVID-19 Kawasaki like disease [10 11] (‘Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2’: PIMS-TS) are reported in BAME children; of 70 admissions, “The Evelina London Children’s Hospital says around 70-80 per cent of the children it has treated for the syndrome are from a black, Asian and minority ethnic background.” Consistent with this, The Necker-Enfants Malades Hospital in Paris, noted BAME children represented 67% of 21 PIMS-TS admissions.[12]
Thus COVID (COVID-19) Kawasaki-like-disease PIMS-TS, in children, appears to be associated with darker skin type, as is Kawasaki disease. Kawasaki disease is reported to be exacerbated by low vitamin D. [13-15] The review ‘Seasonality of Kawasaki Disease: A Global Perspective’ noted, occurrence was higher (40% northern hemisphere extra Tropics, 30% southern hemisphere extra Tropics) in late winter and Spring[16] when vitamin D levels would be expected to be lower. Seasonality may vary by country.[17]
Those with darker skin types living in upper latitudes are widely recognised to be at greater risk of vitamin D deficiency. Vitamin D deficiency rates in the young are often increasing due to more indoor screen-related lifestyles. Low vitamin D risk is significantly greater in African American children,[18] and BAME children in the UK.[19]
Vitamin D is an ancient hormone, derived from exposure of sterols to sunshine (UVB): vitamin D may also be acquired from a limited range of foods. Skin sunshine exposure is the main route of acquisition by most. UVB incident on exposed skin is diminished, when absorbed by melanin. Thus, those with darker skin types are more protected from UVB exposure, but require greater exposure to make an equivalent amount of Vitamin D precursor.
Vitamin D features widely in human physiology including in; immune, metabolic, reproductive, and developmental, pathways; via a multitude of mechanisms including gene transcription, and mitochondrial regulation. Such mechanisms are well and widely reported; some such references may be found in earlier related BMJ Rapid responses.[1, 9] Research is ongoing.
It is inescapable that vitamin D features heavily in disease pathways, because it features at such basal and fundamental levels in human physiology including in immune function. Thus, in relation to COVID-19 and related disease conditions, the question is not; does vitamin D play a role: but, how, by how much, and what is the quantum of impact of insufficiency and deficiency?
On the issue of the often-underappreciated importance of deficiencies, Hugh MacDonald Sinclair FRCP presciently and succinctly observed[20 21]:
“The deficiency of any nutrient which is essential for every tissue will eventually lead to abnormal function in every tissue. That is so incontrovertibly obvious that I am continually astonished by the eminence of the medical scientists to whom it must be forcefully restated.”
“The second is that when deprivation of an essential nutrient occurs, not all tissues will be simultaneously and equally affected, and not all individuals will react in the same way. Which tissue shows symptoms first will depend on the genetic inheritance of the individual and on his or her exposure to environmental factors and lifestyle events. “
At least seven observational studies suggest a link between vitamin D deficiency and COVID-19. If we frail humans are to avoid the risk of a 21st century repetition of the Semmelweis effect, [22 23] it is surely time that vitamin D assay (and even better, also tests for other key nutrients) become standard for all COVID-19, and COVID-19 Kawasaki-like PIMS-TS, patients, so the relationship between, PIMS-TS, COVID-19, Vitamin D and wider nutrients could be better quantified. The information gathered may not generate short term profits, but it might help prevent destruction of economies, lives and social stability.
Simple observations have greatly factored in remediation of impactful diseases – is it not time to let the sunlight in?[24]
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. 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 2nd June 2020).
3. 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 2nd June 2020).
4. 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 2nd June 2020).
5. De Smet, D., De Smet, K., Herroelen, P., Gryspeerdt, S. & Martens, D. (Version 1 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: 2nd June 2020).
(Version 2 19 May 2020). https://doi.org/10.1101/2020.05.01.20079376
6. 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 Available at https://www.mdpi.com/2072-6643/12/5/1359/htm (Accessed: 2nd June 2020).
7. 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: 2nd June 2020).
8. 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 2nd June 2020).
9. 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)
10. 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] Available from https://hosppeds.aappublications.org/content/hosppeds/early/2020/04/06/h...
11. 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’. https://www.aa.com.tr/en/europe/new-global-trend-of-covid-19-linked-dise... (Accessed: 8th June 2020).
12. McNamara A. (4th June 2020) BAME children ‘more at risk’ of rare COVID-19-related syndrome. PA Science. BBC Science Focus Magazine. https://www.sciencefocus.com/news/bame-children-more-at-risk-of-rare-cov... (Retrieved 4th June 2020)
13. 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.
14. 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.
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
15. Burns, J. C., Herzog, L., Fabri, O., Tremoulet, A. H., Rodó, X., et.al. Kawasaki Disease Global Climate Consortium (2013). Seasonality of Kawasaki disease: a global perspective. PloS one, 8(9), e74529. https://doi.org/10.1371/journal.pone.0074529
16. Burgner, D., & Harnden, A. (2005). Kawasaki disease: What is the epidemiology telling us about the etiology? International Journal of Infectious Diseases 9, 4, 185-194. https://doi.org/10.1016/j.ijid.2005.03.002. Available from https://www.sciencedirect.com/science/article/pii/S1201971205000597
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18. Basatemur, E., Horsfall, L., Marston, L., Rait, G., & Sutcliffe, A. (2017). Trends in the Diagnosis of Vitamin D Deficiency. Pediatrics, 139(3), e20162748. https://doi.org/10.1542/peds.2016-2748 Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5337117/
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Competing interests: No competing interests
Dear Editor
What has been apparent for many years is that many of the UK population are totally unaware of the advice for Vitamin D supplementation in the UK (pretty much all of us over the age of 1 for winter months except bottle fed babies but see official guidance from Public health England).
Supplementation after diagnosis seems for most illness of no value and covid will pass one hopes, but multiple other problems are associated with low vitamin D, especially bone health, and it is surprising that the NHS spends no money on this health promotion advice.
Competing interests: No competing interests
Dear Editor,
The role of vitamin D deficiency as a cause of predisposition to Covid-19 is an interesting one, but it is one of several explanations, the prime one being genetic. I would also be interested to see whether there is a religious, rather than an ethnic difference. I am not aware that the Asian subgroup has been divided this way. It is of interest because one would expect a higher incidence of Vitamin D deficiency among vegetarian Hindus than among non-vegetarian Muslims.
Competing interests: No competing interests
Dear Editor:
The recent BMJ editorial by Khunti et al. asks “Is ethnicity linked to incidence or outcomes of covid-19?” [1] Here we outline how ethnicity relates to incidence and outcomes of COVID-19 due, in part, to lack of vitamin D because of increased skin pigmentation and diet.
Public Health England’s (PHE) recent report is a descriptive review of data on the risks, and outcomes, of COVID-19 [2], finding that these risks were higher in Black, Asian, and Minority Ethnic (BAME) groups than with White ethnicity. People in Black ethnic groups had the highest confirmed diagnosis rates, but people of Bangladeshi ethnicity had the highest death rates [80% higher than the death rates with White ethnicity].
The PHE report considered several risk-modifying factors in their analyses [age, sex, deprivation, region, and ethnicity], but not other factors mentioned that might contribute to these disparities [place of birth, occupation, living in care homes, co-morbidities or obesity]. A potentially important factor not considered in the PHE report was vitamin D deficiency, though mounting evidence suggests that vitamin D deficiency is an important risk factor for acute respiratory tract infections and for COVID-19. Meta-analysis of individual participant data from randomized double blind, placebo-controlled trials of vitamin D supplementation showed adjusted odds ratios (OR) of 0.88, [95% confidence interval (CI); 0.81-0.96; P for heterogeneity <0.001] for reduction in acute respiratory tract infection risks with supplementation overall, [3] but reductions were greatest in those with baseline serum 25(OH)D values < 25 nmol/l [deficiency] vs. those with baseline values > 25nmol/l (adjusted OR 0.30 (95% CI; 0.25-0.6) vs. 0.75 (95% CI; 0.60-0.95: P for interaction, 0.006).
Mounting evidence demonstrates that vitamin D has important roles in regulating the immune system that should reduce COVID-19 risks; primarily by reducing survival and replication of the SARS-CoV-2 virus and by reducing the risks of “cytokine storms” by reducing pro-inflammatory cytokine production and increasing anti-inflammatory cytokine productcion [4]. Vitamin D also promotes local ACE2 formation in the lungs, an effect known to reduce the severity of acute respiratory distress syndrome [5]. Furthermore, higher baseline serum 25(OH)D concentrations are currently being reported to be associated with reduced rates of severe COVID-19 and of mortality. 212 COVID-19 patients from three hospitals in southern Asian countries demonstrated an inverse correlation between baseline serum 25(OH)D concentration and clinical outcomes; with mean 25(OH)D values of 78 nmol/l, 69 nmol/l, 53 nmol/l, and 43 nmol/l for ‘mild’, ordinary’, ‘severe’ and ‘critical’ outcomes, respectively, and the differences in those mean 25OH)D values were statistically significant (p<0.001) [6].
An Indonesian study of 780 COVID-19 patients found adjusted OR for death of x7.6 (P<0.001) for 25(OH)D values of 50-75 nmol/l vs. patients with 25(OH)D values >75 nmol/l, rising to x10.1 for 25(OH)D values <50 nmol/l [7].
Nearer England, 25(OH)D concentrations of 186 consecutive COVID-19 patients from Roeselare, Belgium were inversely correlated with COVID-19 severity in males but not females, with median baseline 25(OH)D values in men with Stage 1 disease on CT = 49 nmol/l (P<0.05), with stage 2 = 44 nmol/l, and with CT Stage 3 = 40 nmol/l (P<0.05) versus 51 nmol/l in inpatients with non-covid related illnesses.
BAME in England have higher rates of vitamin D deficiency [25(OH)D concentration <50 nmol/l)] than other UK citizens, for example, the UK-based National Diet and Nutrition Survey for 2008-2012 found that 20.2% of whites aged 18-70 y had serum 25(OH)D concentrations <33 nmol/l vs. 50.5% of BAME 8, the 25(OH)D concentrations being confirmed by accurate modelling of 25(OH)D responses to ultraviolet B exposure and vitamin D intakes [9].
Another recent publication using 25(OH)D concentrations sampled between 2006 and 2010 for the UK Biobank confirmed that values <25 nmol/l were significantly correlated with increased risk for COVID-19 [OR = 1.37 (95% CI; 1.07-1.76)] [10]. Further adjustment for race and ethnicity reduced the OR to 0.92 (95% CI; 0.71-1.21) though median 25(OH)D concentrations were 34 nmol/l in white, 21 nmol/l in black and 14.5 nmol/l in South Asian participants. However, a letter to the editor [in press] points out that adjustment for ethnicity was likely an over-adjustment, since this factor is probably causal rather than a confounder [11].
Reasons for South Asian vitamin D deficiency include increased skin pigmentation, providing natural sun-screening, and that many are vegetarians or vegans, but vegetables other than fungi do not contain vitamin D, while animal products [meat, wild oily fish and eggs] contain vitamin D, both as vitamin D3 and its 25(OH)D metabolite [12]. Thus, mean 25(OH)D concentrations in 2109 white men and women in winter were 63 nmol/l for meat eaters, 57 nmol/l for fish eaters, 52 nmol/l for vegetarians, and 38 nmol/l for vegans [13].
There are many further benefits of vitamin D repletion. Secondary analyses of two recent vitamin D RCTs, for example, report significant benefits - reduced cancer rates for supplemented non-obese participants [BMI <25 kg/m2] and reduced rates of cancer deaths with supplementation, overall [14,15]. Reduced risk of progressing from prediabetes to diabetes was found in non-obese participants [BMI<30 kg/m2] and in those not given additional calcium supplements [16,15].
What should be done about this problem? Studies in the UK should assess correlations between baseline serum 25(OH)D values and COVID-19 infection severity; should trial adequate vitamin D supplementation of newly hospitalized patients for effects on disease progression [if not already on-going] [17] and BAME and others populations groups well-known to be at high risk of vitamin D deficiency [indoor and shift workers, the elderly, those in residential care or currently confined to their homes, and the obese] should be advised to take daily supplementation that might reduce COVID-19 severity. Vitamin D is readily available in the UK ‘over the counter’ at supermarkets, chemists and on-line, but could be provided free to those in financial hardship or unable to access supplies. Doses of 1000 IU/day in general and of 4000 IU/day for those at high risk of deficiency, as above, including the BAME groups, should be advised for the duration of the Covid-19 outbreak, since those doses are within NICE safety limits and would help avoid deficiency.
References
1. Khunti K, Singh AK, Pareek M, et al. Is ethnicity linked to incidence or outcomes of covid-19? BMJ 2020;369:m1548. doi: 10.1136/bmj.m1548
2. Public Health England. Disparities in the risk and outcomes of COVID-19. , 2020:1-89.
3. 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. doi: 10.1136/bmj.i6583
4. Grant WB, Lahore H, McDonnell SL, et al. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients 2020;12(4):E988. doi: 10.3390/nu12040988
5. Annweiler C, Cao Z, Wu Y, et al. Counter-regulatory 'Renin-Angiotensin' System-based Candidate Drugs to Treat COVID-19 Diseases in SARS-CoV-2-infected patients. Infect Disord Drug Targets 2020 doi: 10.2174/1871526520666200518073329
6. Alipio MM. Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-2019), 2020.
7. Raharusuna P, Priamgada S, Budiarti C, et al. Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study. Coronavirus & Infectious Disease Research eJournal 2020:14. [published Online First: May 6, 2020]
8. Public Health England. National Diet and Nutrition Survey Results from Years 1, 2, 3 and 4 (combined) of the Rolling Programme (2008/2009 – 2011/2012). 14 May 2014 ed: Public Health England, 2017:1-160.
9. O'Neill CM, Kazantzidis A, Kiely M, et al. A predictive model of serum 25-hydroxyvitamin D in UK white as well as black and Asian minority ethnic population groups for application in food fortification strategy development towards vitamin D deficiency prevention. J Steroid Biochem Mol Biol 2017;173:245-52. doi: 10.1016/j.jsbmb.2016.09.010
10. Hastie CE, Mackay DF, Ho F, et al. Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes Metab Syndr 2020;14(4):561-65. doi: 10.1016/j.dsx.2020.04.050
11. Grant WB, McDonnell SL. Statistical error in “Vitamin D concentrations and COVID-19 infection in UK Biobank”. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 2020;14
12. Grant WB, Fakhoury HMA, Karras SN, et al. Variations in 25-Hydroxyvitamin D in Countries from the Middle East and Europe: The Roles of UVB Exposure and Diet. Nutrients 2019;11(9):E2065. doi: 10.3390/nu11092065
13. Crowe FL, Steur M, Allen NE, et al. Plasma concentrations of 25-hydroxyvitamin D in meat eaters, fish eaters, vegetarians and vegans: results from the EPIC-Oxford study. Public Health Nutr 2011;14(2):340-6. doi: 10.1017/S1368980010002454
14. Manson JE, Cook NR, Lee IM, et al. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med 2019;380(1):33-44. doi: 10.1056/NEJMoa1809944
15. Grant WB, Boucher BJ. Why Secondary Analyses in Vitamin D Clinical Trials Are Important and How to Improve Vitamin D Clinical Trial Outcome Analyses-A Comment on "Extra-Skeletal Effects of Vitamin D, Nutrients 2019, 11, 1460". Nutrients 2019;11(9) doi: 10.3390/nu11092182
16. Pittas AG, Dawson-Hughes B, Sheehan P, et al. Vitamin D Supplementation and Prevention of Type 2 Diabetes. N Engl J Med 2019;381(6):520-30. doi: 10.1056/NEJMoa1900906
17. Grant WB, Baggerly CA, Lahore H. Response to Comments Regarding “Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths”. Nutrients 2020;12(6):1620. doi: 10.3390/nu12061620
Competing interests: WBG receives funding from Bio-Tech Pharmacal, Inc. (Fayetteville, AR, USA). BJB has no conflicts of interest to report.
Dear Editor,
Recent studies [1, 2] and BMJ rapid responses [3-5] have correlated vitamin D deficiency with severity and mortality risks in COVID-19. Supporting references [6-8] highlighted atmospheric pollution as possible independent epidemiological determinant of COVID-19.
In this commentary the combination of vitamin D deficiency and environmental pollutants are hypothesized as a unique epidemiologic cofactor. The aim is to highlight the hypothesis that a vitamin D deficiency exacerbated by environmental pollution could underlie the severity of the COVID-19 epidemic in certain geographies. The concept that underlies the hypothesis is that the virus could use environmental pollutants like particulate matter and gases as a gateway to spread in the environment and the individual deficit of vit D as a key to attack the human body and particularly the respiratory system.
The WHO indicated that 3.7 million premature deaths globally were attributable to ambient air pollution and placed air pollution as the world’s largest environmental health risk factor [9]. Primary pollutants can be divided into two groups: particulate matter (PM) and gases.
A study [6] in the United States showed that a small increase in long-term exposure to PM2.5 lead to a large increase in COVID-19 death rate and a long-term exposure to air pollution increased vulnerability to severe COVID-19 outcomes. A similar situation was suggested by a study in China where higher concentration of PM10 and PM2.5 had a positive correlation with deaths caused by COVID-19 [7]. Another study found an association of air quality and COVID-19 outbreak in northern Italy [8].
Some studies revealed a negative association between air quality and vitamin D status [10-13]. Among the mechanisms studied it was also shown that air pollution, in particular ozone and nitrogen dioxide, is capable of reducing ultraviolet B radiation [14]. Living in a polluted area plays a significant role in vitamin D deficiency for healthy adults and children. This may affect immune response [15] and contribute to the different morbidity and mortality of the disease observed in some areas.
There is a probable correlation between onset, virulence, diffusion, and characteristics of COVID-19 and environmental pollutants that could be modulated by a vitamin D deficiency. Further studies are needed to support this combined hypothesis. However, it is important to consider the urgent need of some global interventions both in reducing emissions and in correcting vitamin D deficiency to mitigate the negative effects on this and future pandemics.
References
1. Grant, W.B.; Lahore, H.; McDonnell, S.L.; Baggerly, C.A.; French, C.B.; Aliano, J.L.; Bhattoa, H.P. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients 2020, 12, 988.
2. 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
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 (accessed June 2, 2020)
4. 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 June 2, 2020)
5. Haroon S (April 27, 2020) ‘Rapid Response: Rapid response re: Is ethnicity linked to incidence or outcomes of COVID-19?’: Should Vitamin D supplementation be recommended to prevent COVID-19? BMJ 2020;369:m1548 https://doi.org/10.1136/bmj.m1548 Available at: https://www.bmj.com/content/369/bmj.m1548/rr-12
6. Wu, Xiao, Rachel C. Nethery, Benjamin M. Sabath, Danielle Braun, e Francesca Dominici. «Exposure to Air Pollution and COVID-19 Mortality in the United States: A Nationwide Cross-Sectional Study». Preprint. Epidemiology, 7 aprile 2020. https://doi.org/10.1101/2020.04.05.20054502.
7. Ye Yao, Jinhua Pan, Zhixi Liu, Xia Meng, Weidong Wang, Haidong Kan, and Weibing Wang. 2020. “Temporal Association Between Particulate Matter Pollution and Case Fatality Rate of COVID-19 in Wuhan, China.” medRxiv.
8. Fattorini D, Regoli F. Role of the chronic air pollution levels in the Covid-19 outbreak risk in Italy [published online ahead of print, 2020 May 4]. Environ Pollut. 2020;264:114732. doi:10.1016/j.envpol.2020.114732
9. World Health Organisation. Media Centre. https://www.who.int/phe/health_topics/outdoorair/databases/FINAL_HAP_AAP.... (accessed June 2, 2020)
10. Z E. Hoseinzadeh, P. Taha, C. Wei, H. Godini, G.M. Ashraf, M. Taghavi, M. Miri The impact of air pollutants, UV exposure and geographic location on vitamin D deficiency Food Chem. Toxicol., 113 (2018), pp. 241-254
11. Hosseinpanah F, Pour SH, Heibatollahi M, Moghbel N, Asefzade S, Azizi F. The effects of air pollution on vitamin D status in healthy women: a cross sectional study. BMC Public Health 2010;10:519.
12. Mousavi, Sayed Esmaeil, Heresh Amini, Pouria Heydarpour, Fatemeh Amini Chermahini, e Lode Godderis. «Air Pollution, Environmental Chemicals, and Smoking May Trigger Vitamin D Deficiency: Evidence and Potential Mechanisms». Environment International 122 (1 gennaio 2019): 67–90. https://doi.org/10.1016/j.envint.2018.11.052.
13. Feizabad E, Hossein-Nezhad A, Maghbooli Z, Ramezani M, Hashemian R, Moattari S. Impact of air pollution on vitamin D deficiency and bone health in adolescents. Arch Osteoporos. 2017;12(1):34. doi:10.1007/s11657-017-0323-6
14. Barnard, William F., e Brian N. Wenny. «Ultraviolet Radiation and Its Interaction with Air Pollution». In UV Radiation in Global Climate Change: Measurements, Modeling and Effects on Ecosystems, a cura di Wei Gao, James R. Slusser, e Daniel L. Schmoldt, 291–330. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. https://doi.org/10.1007/978-3-642-03313-1_11.
15. Daniel D. Bikle, Chapter one - Vitamin D Regulation of Immune Function,
Editor(s): Gerald Litwack, Vitamins & Hormones, Academic Press, Volume 86, 2011.
Competing interests: No competing interests
Re: Is ethnicity linked to incidence or outcomes of covid-19?; Oxford covid-gene study should be treated with caution
Dear Editor
With reference to the article in Nature[1] cited by Leslie Lewis (04 November 2021), it is reported that this study "should be treated with caution"[2]. Among others, it is said that "Immune defences in lungs can vary with ethnicity – but doubts remain over data quality and socio-economic factors"[2].
Further it is reported[2], "the claim that the LZTFL1 gene is present in 60% of those of south Asian backgrounds and 2% of those with an African background derives from a database of nearly 200,000 genomes, 85% of which come from those of European descent" and "without better representation in these databases, scientists cannot be confident that these figures apply across whole swathes of society – especially because social definitions of ethnicity rarely map neatly on to the distribution of risk genes through the population".
References
[1] https://www.nature.com/articles/s41588-021-00955-3
[2] https://www.theguardian.com/science/2021/nov/04/human-genetic-variant-ca...
Competing interests: No competing interests