Commentary: Vitamin D for reduction in Covid-19 risks for south Asian and other vitamin D deficient groups?

Barbara A Boucher OPEN ACCESS PUBLISHED: 31 January 2025 CITATION: BOUCHER, Barbara J. Commentary:- Vitamin D for reduction in Covid-19 risks for south Asian and other vitamin D deficient groups?. Medical Research Archives. Available at: <https://esmed.org/MRA/mra/article/view/6173>. COPYRIGHT: © 2025 European Society of Medicine. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. DOI: https://doi.org/10.18103/mra.v13i1.6173 ISSN 2375-1924

Abstract

Over 7 million people died of COVID-19 globally in the current pandemic. Westernised countries reported increased COVID-19 illness with increased mortality rates in their South Asian and Black communities, while dark-skinned communities are more severely vitamin D deficient than others in westernised countries. Vitamin D has many proven mechanistic effects protective against infections and against the ‘acute respiratory distress syndrome’ that caused many COVID-19 deaths. This ‘commentary’, therefore, considers prospective evidence for reductions in COVID-19 risks with better vitamin D repletion; whether treating deficiency reduces COVID-19 risks, and discusses the many actions of vitamin D that could lead to such risk reductions. Better pre-pandemic vitamin D status predicted ~50% COVID-19 risk reductions in each US state [in ~400,000 adults] and in health care staff. Governments generally resisted calls for higher vitamin D intakes [at 1000-2000 IU/day], quoting ‘lack of randomised controlled trials’, and fear of vitamin D ‘toxicity’, despite safe unsupervised population intake generally advised being ‘up to 4000 IU/day’. The UK has since recommended daily adult intakes of 400 IU/day, helpful, but too small to correct deficiency. American rules on ‘medical need’ meant banning treatment of COVID-19 with vitamin D so that the new mRNA vaccines could be used. More recently, trials treating COVID-19 illness with vitamin D₃ [at 1,000,000 IU over 2 weeks] or with the vitamin D 25(OH)D metabolite, calcifediol [at ~2.0mg over 1 month] have shown significantly reduced Covid-19 severity and mortality. This information makes a cogent case for ensuring vitamin D sufficiency globally, most especially in dark skinned communities, as a cost-effective measure for reducing the risks from future COVID-19 variants and from the future health risks of newly emergent pathogenic viruses.

Keywords

• COVID-19
• Vitamin D
• South Asian
• Black communities
• Deficiency

Introduction

Introduction The World Health Organization reported over 775 million cases of COVID-19 illness with >7 million deaths in the recent pandemic by mid-July 2024.1 The UK and other Westemised countries first reported higher COVID-19 illness and mortality rates in their South Asian and Black communities early in 2020.2 Factors thought to account for those increases included socio-economic deprivation, overcrowded living conditions, working in crowded sites and care homes, shops and other essential services where self- isolating was virtually impossible.3 Chronic illnesses were also associated with increased COVID-19 morbidity and mortality across 51 countries.* Obesity and type 2 diabetes [T2DM] are more common amongst Black and south Asian peoples than in indigenous White communities in Westernized countries and are associated with increased risks of severe COVID-19 illness and with hospital admission for ventilatory support.257 British national health service [NHS] hospital staff of Black and south Asian origin had higher COVID-19 mortality rates than White staff working in identical conditions, possibly reflecting their increased T2DM, obesity and chronic illness rates. Chronic ill- health was also associated with increased COVID-19 risks in UK Biobank data on ~400,000 representative adults.” Socio-economic deprivation was not an independent predictor of COVID-19 in UK Biobank data analysis.10 However, a baseline record of regular consumption of vitamin D supplements in the UK-Biobank study was associated, prospectively, with significantly reduced COVID-19 risks.11 The vitamin D deficiency pandemic is another health problem, globally, and most severe in Black and south Asian groups. 12 14 Deficiency rates are also high in economically disadvantaged countries. The aim of the present commentary is, therefore, to report on current evidence for the associations between vitamin D provision and the risks of COVID- 19, on the mechanisms that could account for such associations, and on the use of vitamin D for treating COVID-19 illness.

Methods

Data bases [mainly PubMed] were searched for relevant reports using the terms ‘vitamin D’ and ‘COVID-19’, together with combinations of the terms ‘deficiency, supplementation, health care staff, Black, south Asian, trials, randomized controlled trials, mortality, UK-Biobank, immune responses, mechanisms, acute respiratory distress syndrome, ‘cytokine storm’.

Results

Many Asian countries show vitamin D deficiency rates that relate directly to COVID-19 infection rates and to COVID-19 mortality rates. Those rates also relate inversely to vitamin D status [serum 25(OH)D concentration], even after adjustment for confounders, across many Asian countries.16 Data from 47 countries reported vitamin D deficiency rates of 6.9-81.8% and 2.0-87.5% in 21 European and 24 Asian countries respectively. The direct correlations between deficiency rates and those of COVID-19 illness and of COVID-19 mortality were significant in the Asian but not in the European countries.17 African American deficiency rates are 15-20 times higher than those of other Americans.18 Genetic variation within vitamin D pathways may account for some of the differences seen in vitamin D status between south Asian, Black, and other subjects,” but such staff have consistently been the most deficient amongst NHS workers, as in one large NHS Hospital Trust; that trust later found a U-shaped association of serum 25(OH)D with COVID-19 Sero-positivity, while confirming the findings for south Asian and Black workers.20 That unconfirmed U-shaped association might reflect increased COVID-19 risks, [or better antibody responses to COVID-19 exposure] with higher vitamin D status. South Asian and Black Britons have needed COVID- 19-related critical care more often than others.

Vitamin D and COVID-19

Vitamin D for reduction in Covid-19 risks for south Asian and other vitamin D deficient groups? July 2020, 260 UK hospitals data showed that Black and south-Asian people had had 36% and 26% higher age-adjusted admission rates, respectively, for COVID-19-related critical care than other groups and had accounted for 25% of all the COVID-19 admissions though being only 11% of the population.?1 UK Biobank data for >500,000 representative UK adults revealed significant associations between baseline vitamin D deficiency and COVID-19 diagnoses that were abolished by adjustment for ethnicity, obesity and T2DM.22 But, since each of those 3 factors specifically increase deficiency rates, (reduced 25-hydroxylation of vitamin D in hepatic and other tissues being a feature of both obesity and T2DM], those adjustments have been challenged.23 25 Vitamin D prescribing habits [between mid-January and mid-February 2021] reported by questionnaire from 44,440 active clinicians, mostly in Asia, showed that vitamin D had been prescribed by >80% of general practitioner’s pre-pandemic and that 72.8% of them planned to prescribe it for COVID-19 illness.26 VITAMIN D AND VACCINATION. Adequate vitamin D status improves antibody responses to immunization in the elderly.27 While antibody responses to SARS-CoV-2 vaccines were affected by many factors in the COVIDENCE trial, the risks of remaining Sero-negative post-COVID- 19-vaccination were significantly reduced by vitamin D supplementation (aOR 0.7; 95% Cls, 0.50-0.9].” MECHANISTIC EFFECTS OF VITAMIN D RELEVANT TO COVID-19 RISK. Vitamin D has well-understood protective effects against bacterial and viral infection and against the ‘acute respiratory distress syndrome’ [ARDS] that caused many COVID-19 deaths. These effects include increasing the secretion of the microbiocidal defensins and catholicizing (LL-37).29 Vitamin D also reduces pro-inflammatory cytokine production, increases anti-inflammatory cytokine production and prevents excessive innate immune reactions, thereby reducing the risks of cytokine storms,30,31 Sars-CO-V-2 organisms may evade early innate immune responses through spike-protein binding to membrane-bound ACE-2 molecules, which reduces lung ACE-2 secretion, causing endothelial lung damage. Vitamin D stimulates ACE-2 secretion which reduces this lung damage, as has been confirmed experimentally 32.33 Over-activation of the renin-angiotensin system [RAS] by COVID-19 infections damages the lungs and their vasculature but vitamin D reduces this damage by inhibiting renin secretion.34,35 The Vitamin D-induced increases in ACE2 secretion also suppress many adverse effects of RAS overactivity, which helps to reduce ARDS risks, as already mentioned. Different genetic profiles of the RAS in Black people could contribute to their increased susceptibility to COVID-19.36 A further recently identified protective mechanism is that calcifediol suppresses the secretion of a papain-like protease enzyme (PLpro) by COVID- 19 organisms, since that enzyme is critical for inducing lung damage. EPIDEMIOLOGIC EVIDENCE FROM PRE- PANDEMIC DATA. Baseline serum 25(OH)D concentrations up to ~50 nmol/l in the pre-pandemic year marked significant and progressive reductions in later COVID-19 illness rates, across all regions and all states in the USA, using data on ~400,000 adults.38 These data together with other similar studies have suggested that repletion of whole populations could greatly reduce COVID- 19 illness rates39

Discussion

Despite all the evidence, concerted calls by vitamin D workers for modest improvement of vitamin D provision in the UK [to 1000-2000 IU/day] were resisted, governmental bodies citing the lack of relevant RCTs and quoting the potential for vitamin D toxicity, even though maximum unsupervised intakes advised for the general population in the UK [and by the American National Institutes of Health], are 4000 IU/d.40,41 Current vitamin D intakes advised for UK adults were raised to 400 IU/day all year round.42 That intake, however, is much less than is 2024 European Society of Medicine.

References

• 1. Sabih H, Abdelghany S, Abdallah MS, et al. Vitamin D: A key player in COVID-19 immunity and infection. Nutrients. 2021;13(7):2021.
• 2. Sorarakachorn P, Jeyakumar D, King N, Jayavardhana R. Impact of vitamin D deficiency on COVID-19. Clin Nutr ESPEN. 2021;44:372-378.
• 3. Aldridge RW, Lower D, Katikireddi SV, et al. Health inequalities in the United Kingdom and the role of vitamin D. BMC Public Health. 2021;21:2004234.
• 4. Amels BN, Grant WB, Willett WC. Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities? Nutrients. 2021;13(12):499.
• 5. Janjua A, Luiggs SJ, Faustini SE, Webster C, Duffy E, Haysom M, et al. Genetic polymorphisms, vitamin D binding protein and risk of severe COVID-19. BMC Infect Dis. 2021;21:200.