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Covid-19: Public health agencies review whether vitamin D supplements could reduce risk

BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m2475 (Published 19 June 2020) Cite this as: BMJ 2020;369:m2475

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COVID-19 and Vitamin-D – NICE; Unthinking discrimination against BAME, Elderly and Obese? Affirmative-action needed to mitigate D deficiency, in high-COVID-risk groups.

Dear Editor

In response to the comments of Dr Paul Crisp, Director of Nice, https://www.bmj.com/content/369/bmj.m2475/rr-8:

Multiple preprints suggest vitamin D deficiency factors in COVID-19 severity and mortality risk in BAME Persons, Elderly and Obese, COVID-19 patients. Vitamin D is a steroid hormone family (cheap, well-researched, natural, with limited side-effects, and a million-year evolutionary efficacy and safety-history), sharing many VDR (vitamin D receptor) pathways[1] with Dexamethasone (a useful pharmaceutical steroid, 60 years old but not part of our evolutionary history, with a long list of potential side effects). Given VDR commonalities with Dexamethasone; immune biology, and wider emerging evidence; it might logically be expected vitamin D, like Dexamethasone, will likely, reduce immediate impact of COVID-10 severity and mortality. Vitamin D may further have longer term beneficial effects – longer term outcomes of Dexamethasone in COVID-19 have yet to be announced.

Thus, did NICE/NHS/PHE, our health guardians, in the fog and darkness of COVID-19, leave their ‘pandemic-act-decisively’ hat in the dexamethasone draw, when considering the needs:

- to test COVID-19 patients for vitamin D deficiency;

- to widen clinical recommendations for clinical testing;

- and or increase provision for automatic higher vitamin D repletion dosing;

thus ensuring better repletion of groups most at risk of Vitamin D deficiency.

This hesitancy ironically manifests, despite Vitamin D deficiency disease being a recognised, NICE defined, clinical condition; with NICE advice on; testing, repletion, and wider parameters. https://cks.nice.org.uk/vitamin-d-deficiency-in-adults-treatment-and-pre...

Within this framework, it is NICE, who delineates the very narrow parameters within which NHS clinical practitioners may test, in the terms;

- “Only test vitamin D status if someone has symptoms of deficiency or is at very high risk”[2];

- recommended supplementation is limited to RNI[2], unless the patient is deficient (which requires a test – hence the catch-22).

Thus, perversely, UK Doctors are discouraged from testing, and or sufficiently supplementing, those at greatest risk of both D-deficiency and COVID-19 mortality, namely; BAME Persons, Elderly, Obese, the Institutionalised, and Hospitalised; with their higher D repletion requirements – confusing / limiting the capacity of Doctors to address vitamin D deficiency in those that are most in need.

NICE unquestionably has authority and capacity to swiftly widen the groups who may be tested for vitamin D levels; and/or facilitate GPs administering, without testing, higher vitamin-D-boluses to all patients at medium-risk of deficiency (BAME, Elderly, Obese, Pregnant et al.).

As below,[3] Australia tests more widely; and New Zealand recommends routine administration of 50,000iu per month; for medium-risk patients.

In contrast to the more visionary pragmatic Antipodean approach, NICE/SACN/PHE have arguably failed to address, with sufficient granularity, the niche-needs of minority groups, BAME, Elderly and Obese Persons, relying instead on generalised-population-based statistics. COVID mortality and infection rates are interestingly lower in the Antipodes, and a recent Australian spike has occurred in a complex with a high minority ethic populous.

NICE, by their failure to decisively address, both; the long-standing-high-risk of vitamin D deficiency; and likely related increased COVID-19 mortality rates, in these groups, arguably sadly open themselves to criticisms of discrimination by; Ethnicity, Age, Fat-mass, Institutionalised and Hospitalised Status, as well as failure to act D-decisively in a pandemic, based on likely benefits v harms.

A recommendation by NICE to vitamin D test COVID-19 Patients in hospitals and care homes, would have both; helped address D deficiencies in COVID-mortality-at-risk-group patients; and also provided valuable population data, including as to D status of the most COVID-mortality vulnerable; namely BAME Persons including those of African Americans origin, Elderly, Obese and Hospitalised– thus further and usefully informing public health policy.

A wider and a final search before NICE publication on 29th June, would have revealed omitted preprints, which together suggest a strong direction of emerging research; reflected in approximately 12 preprints including one in England (134 COVID-19+ patients), and more widely a German paper looked at D and respiratory function.[4] Preprints were relatively easily found; as many were listed in the BMJ Rapid Response Letter dated 25th June 2020.[3] https://www.bmj.com/content/369/bmj.m2475/rr-1

Subsequent known studies include; Cincinnati[5] (689 Covid-19+ patients); Israel[6] (14,832; 7087 COVID-19+ patients), and a military hospital in Brazil[7] (172 COVID-19+ patients). Two of the original seven[8] are no longer available; one of them following the sad death of the lead, Prabowo Raharusun GP, whilst working on the COVID-19 front-line.

A late NICE addendum would have allowed their listing/consideration on 29th June, in final summary conclusions. Adjustment for factors impacted by vitamin D such as hypertension, cardiovascular disease and obesity are complex,[9] with limited value if not suitably nuanced. Hill criteria offer an alternative assessment protocol.[10]

Is it not time for pandemic-urgent recognition of the need for vitamin-D-clinical-sufficiency equality for all, including BAME Persons, the Elderly and Obese.

1. Navarro-Barriuso, J., Mansilla, M.J., Naranjo-Gómez, M. et al. (2018). Comparative transcriptomic profile of tolerogenic dendritic cells differentiated with vitamin D3, dexamethasone and rapamycin. Sci Rep 8, 14985 (2018). https://doi.org/10.1038/s41598-018-33248-7 Available at https://www.nature.com/articles/s41598-018-33248-7 (Accessed: 13 July 2020).
2. NICE. (2017). Vitamin D: supplement use in specific population groups. Public health guideline [PH56] Published date: 26 November 2014 Last updated: 30 August 2017. https://www.nice.org.uk/guidance/ph56/chapter/1-Recommendations#recommen... (Accessed: 10 July 2020).
3. Brown, R. (June 25 2020). Pandemic - ‘Action This Day’ – Measure Vitamin D in COVID-19 Patients – Time is of Essence – BAME, Elderly and Obese are Disproportionately Dying. In response to Covid-19: Public health agencies review whether vitamin D supplements could reduce risk. BMJ 2020;369:m2475
doi: https://doi.org/10.1136/bmj.m2475 (Published 19 June 2020). Available at https://www.bmj.com/content/369/bmj.m2475/rr-1 (Accessed: 10 July 2020).
4. Brenner, B., Holleczek, B., & Schoettker, B. (June 23 2020). Vitamin D insufficiency and deficiency and mortality from respiratory diseases in a cohort of older adults: potential for limiting the death toll during and beyond the COVID-19 pandemic. medRxiv 2020.06.22.20137299; doi: https://doi.org/10.1101/2020.06.22.20137299 Available at https://www.medrxiv.org/content/10.1101/2020.06.22.20137299v1 (Accessed: 10 July 2020).
5. Mendy, A., Apewokin, S., Wells, A., & Morrow, A. (2020). Factors Associated with Hospitalization and Disease Severity in a Racially and Ethnically Diverse Population of COVID-19 Patients. medRxiv : the preprint server for health sciences, 2020.06.25.20137323. https://doi.org/10.1101/2020.06.25.20137323 Available at https://www.medrxiv.org/content/10.1101/2020.06.25.20137323v2 (Accessed: 10 July 2020).
6. Merzon, E., Tworowski, D., Gorohovski, A., Vinker, S., Cohen, A., Green, I., & Morgenstern, M. (July 3 2020). Low plasma 25(OH) vitamin D3 level is associated with increased risk of COVID-19 infection: an Israeli population-based study. medRxiv 2020.07.01.20144329; doi: https://doi.org/10.1101/2020.07.01.20144329. Available at https://www.medrxiv.org/content/10.1101/2020.07.01.20144329v1 (Accessed: 10 July 2020).
7. Tort, A., Mercado, E., Martínez‑Cuazitl, Nieto, A., & Pérez, R. (April 30 2020). La deficiencia de vitamina D es un factor de riesgo de mortalidad en pacientes con COVID-19. (Deficiency of vitamin D is a risk factor of mortality in patients with COVID-19) https://dx.doi.org/10.35366/93773 doi: 10.35366/93773 Available at https://www.medigraphic.com/pdfs/sanmil/sm-2020/sm201_2za.pdf (Accessed: 10 July 2020).
8. Brown, R. (May 19, 2020). ‘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, 369(m1548). DOI: 10.1136/bmj.m1548 Available at: https://www.bmj.com/content/369/bmj.m1548/rr-19 (Accessed:10 July 2020).
9. Fan, X., Wang, J., Song, M., Giovannucci, E., Ma, H., Jin, G,. Hu, Z., Shen, H,. & Hang, D. (July 4 2020). Vitamin D status and risk of all-cause and cause-specific mortality in a large cohort: results from the UK Biobank, The Journal of Clinical Endocrinology & Metabolism, , dgaa432, https://doi.org/10.1210/clinem/dgaa432 Available at https://academic.oup.com/jcem/article-abstract/doi/10.1210/clinem/dgaa43... (Accessed: 10 July 2020).
10. Annweiler, C., Cao, Z., Sabatier J. (June 7 2020). Point of view: Should COVID-19 patients be supplemented with vitamin D? Review article| Volume 140, P24-26, October 01, 2020. DOI:https://doi.org/10.1016/j.maturitas.2020.06.003 Available at https://www.maturitas.org/article/S0378-5122(20)30292-9/abstract (Accessed: 10 July 2020).

Competing interests: No competing interests

14 July 2020
Robert A Brown
Reasearcher
McCarrison Society
La Route de Mont Cochon, St Lawrence, Jersey. C.I.