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Vitamin D concentrations and COVID-19 infection in UK Biobank

Hastie et al., Diabetes and Metabolic Syndrome: Clinical Research and Reviews, 14:4, 561–565, doi:10.1016/j.dsx.2020.04.050
Aug 2020  
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Mortality 17% Improvement Relative Risk Hospitalization 9% Vitamin D for COVID-19  Hastie et al.  Sufficiency Are vitamin D levels associated with COVID-19 outcomes? Retrospective 341,484 patients in the United Kingdom Lower mortality with higher vitamin D levels (not stat. sig., p=0.31) Hastie et al., Diabetes and Metabolic .., Aug 2020 Favorsvitamin D Favorscontrol 0 0.5 1 1.5 2+
Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020
*, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments.
Database analysis of 341,484 patients in the UK with 656 hospitalized confirmed COVID-19 patients and 203 deaths, not showing a statistically significant difference after adjustment. Since adjustment factors may be correlated with vitamin D deficiency, the extent of any causal contribution of both vitamin D and the adjustment factors is unclear.
There was an ~10 year time period between baseline 25(OH)D measurement and COVID-19 infection, with 84% concordance for a subsample with measurements ~4.3 years later. Vitamin D levels may change significantly across seasons and years. People that discovered they had low vitamin D levels may have been encouraged to take steps to correct the deficiency.
Davies et al. raise a number of concerns with this study1, reporting that it lacked power, suffered low precision and high bias, used flawed models, and contained many serious statistical errors. 1. Mislabelled data artificially inflated the control set, creating an illusion of high power & precision in an underpowered data set study, 2. Logistic regression violated multiple prerequisite conditions, creating biased results and a further reduction of power (overfit, over-adjusted, poor variable types, and poor handling), and 3. Unreliable data in the logistic regressions caused regression dilution bias, bias amplification, and further loss of power and precision.
See also2.
This is the 11th of 199 COVID-19 sufficiency studies for vitamin D, which collectively show higher levels reduce risk with p<0.0000000001 (1 in 835,162 vigintillion).
risk of death, 17.4% lower, RR 0.83, p = 0.31, cutoff 25nmol/L, adjusted per study, inverted to make RR<1 favor high D levels (≥25nmol/L), multivariable Cox.
risk of hospitalization, 9.1% lower, RR 0.91, p = 0.40, cutoff 25nmol/L, adjusted per study, inverted to make RR<1 favor high D levels (≥25nmol/L), multivariable Cox.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Hastie et al., 26 Aug 2020, retrospective, population-based cohort, database analysis, United Kingdom, peer-reviewed, 14 authors.
This PaperVitamin DAll
Vitamin D and COVID-19 infection and mortality in UK Biobank
Claire E Hastie, Jill P Pell, Naveed Sattar
European Journal of Nutrition, doi:10.1007/s00394-020-02372-4
Purpose Low blood 25-hydroxyvitamin D (25(OH)D) concentration has been proposed as a potential causal factor in COVID-19 risk. We aimed to establish whether baseline serum 25(OH)D concentration was associated with COVID-19 mortality, and inpatient confirmed COVID-19 infection, in UK Biobank participants. Methods UK Biobank recruited 502,624 participants aged 37-73 years between 2006 and 2010. Baseline exposure data, including serum 25(OH)D concentration, were linked to COVID-19 mortality. Univariable and multivariable Cox proportional hazards regression analyses were performed for the association between 25(OH)D and COVID-19 death, and Poisson regression analyses for the association between 25(OH)D and severe COVID-19 infection. Results Complete data were available for 341,484 UK Biobank participants, of which 656 had inpatient confirmed COVID-19 infection and 203 died of COVID-19 infection. 25(OH)D concentration was associated with severe COVID-19 infection and mortality univariably (mortality per 10 nmol/L 25(OH)D HR 0.92; 95% CI 0.86-0.98; p = 0.016), but not after adjustment for confounders (mortality per 10 nmol/L 25(OH)D HR 0.98; 95% CI = 0.91-1.06; p = 0.696). Vitamin D insufficiency or deficiency was also not independently associated with either COVID-19 infection or linked mortality. Conclusions Our findings do not support a potential link between 25(OH)D concentrations and risk of severe COVID-19 infection and mortality. Randomised trials are needed to prove a beneficial role for vitamin D in the prevention of severe COVID-19 reactions or death.
Conflict of interest The authors declare that they have no conflict of interest. Ethics approval UK Biobank received ethical approval from the North West Multi-Centre Research Ethics Committee (REC reference: 16/ NW/0274) and was conducted in accordance with the principles of the Declaration of Helsinki. Informed consent All participants gave written informed consent for data collection, analysis, and record linkage. All participants gave written informed consent for publication of research. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/.
Hastie, Mackay, Ho, Vitamin D concentrations and COVID-19 infection in UK Biobank, Diabetes Metab Syndr Clin Res Rev, doi:10.1016/j.dsx.2020.04.050
Mitchell, Vitamin-D and COVID-19: do deficient risk a poorer outcome?, Lancet Diabetes Endocrinol, doi:10.1016/S2213-8587(20)30183-2
Nhs, Vitamins and minerals: Vitamin D
Nice, COVID-19 rapid evidence summary:vitamin D for COVID-19
Raisi-Estabragh, Mccracken, Bethell, Greater risk of severe COVID-19 in Black, Asian and Minority Ethnic populations is not explained by cardiometabolic, socioeconomic or behavioural factors, or by 25(OH)-vitamin D status: study of 1326 cases from the UK Biobank, doi:10.1093/pubmed/fdaa095
Sattar, Welsh, Panarelli, Forouhi, Increasing requests for vitamin D measurement: costly, confusing, and without credibility, Lancet, doi:10.1016/S0140-6736(11)61816-3
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