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'''Vitamin-D status in Ireland is 45 to 65 nmol/l by season. The immune system wants it over 125nmol/l'''

https://pubmed.ncbi.nlm.nih.gov/32878330/ Nutrients 2020 Aug 31;12(9):2663. doi: 10.3390/nu12092663. Geomapping Vitamin D Status in a Large City and Surrounding Population-Exploring the Impact of Location and Demographics Helena Scully 1, Eamon Laird  2 , Martin Healy  3 , James Bernard Walsh  1 , Vivion Crowley  3 , Kevin McCarroll  1 Affiliations PMID: 32878330 PMCID: PMC7551618 DOI: 10.3390/nu12092663

'''To determine the factor triggering the sudden surge of daily new COVID-19 cases arising in most European countries during the autumn of 2020. The dates of the surge were determined using a fitting of the two last months of reported daily new cases in 18 European countries with latitude ranging from 39° to 62°. The study proves no correlation between the country surge date and the 2 weeks preceding temperature or humidity but shows an impressive linear correlation with latitude. The country surge date corresponds to the time when its sun UV daily dose drops below ≈ 34% of that of 0° latitude. Introducing reported seasonal blood 25-hydroxyvitamin D (25(OH)D) concentration variation into the reported link between acute respiratory tract infection risk and 25(OH)D concentration quantitatively explains the surge dynamics. Several studies have already substantiated a 25(OH)D concentration impact on COVID-19 severity. However, by comparing different patient populations, discriminating whether a low 25(OH)D concentration is a real factor underlying COVID-19 severity or only a marker of another weakness that is the primary severity factor can be challenging. The date of the surge is an intrapopulation observation and has the benefit of being triggered only by a parameter globally affecting the population, i.e. decreases in the sun UV daily dose. The results indicate that a low 25(OH)D concentration is a contributing factor to COVID-19 severity, which, combined with previous studies, provides a convincing set of evidence.'''

https://pubmed.ncbi.nlm.nih.gov/33479261/

Sci Rep 2021 Jan 21;11(1):1981. doi: 10.1038/s41598-021-81419-w. Autumn COVID-19 surge dates in Europe correlated to latitudes, not to temperature-humidity, pointing to vitamin D as contributing factor Stephan Walrand 1 PMID: 33479261 PMCID: PMC7820009 DOI: 10.1038/s41598-021-81419-w

J Clin Endocrinol Metab. 2013 Dec; 98(12): 4619–4628. Published online 2013 Oct 8. doi: 10.1210/jc.2013-2653 PMCID: PMC3849670 PMID: 24106283 Clinical Review The Role of the Parent Compound Vitamin D with Respect to Metabolism and Function: Why Clinical Dose Intervals Can Affect Clinical Outcomes Bruce W. Holliscorresponding author and Carol L. Wagner

Indeed, any high-dose, long-interval dosing schedule can be considered pharmacological rather than physiological.

'''Circulating vitamin D, the parent compound for tissue vitamin D activation, likely has an important direct physiological role beyond what was originally anticipated through the local tissue autocrine system. Based on emerging data from the laboratory and from clinical trials and on available knowledge of vitamin D axis metabolism, it appears likely that for the optimal benefits of vitamin D supplementation, enough vitamin D should be provided on a daily basis to ensure that stable circulating concentrations are maintained over time. This view implies that schedules for vitamin D dosing could have profound effects on the outcomes of clinical trials, due to the short circulating half-life of vitamin D'''

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849670/

FEBS J. 2020 Jul 23 : 10.1111/febs.15495. doi: 10.1111/febs.15495 [Epub ahead of print] PMCID: PMC7404739 PMID: 32700398 Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: an Israeli population‐based study Eugene Merzon,corresponding author 1, 2 Dmitry Tworowski, 3 Alessandro Gorohovski, 3 Shlomo Vinker, 1 , 2 Avivit Golan Cohen, 1 , 2 Ilan Green, 1 , 2 and Milana Frenkel Morgensterncorresponding author 3

'''Of 7,807 individuals, 782 (10.1%) were COVID‐19‐positive, and 7,025 (89.9%) COVID‐19‐negative. The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID‐19 [19.00 ng/mL (95% confidence interval [CI] 18.41‐19.59) vs. 20.55 (95% CI 20.32‐20.78)]. Univariate analysis demonstrated an association between low plasma 25(OH)D level and increased likelihood of COVID‐19 infection [crude odds ratio (OR) of 1.58 (95% CI 1.24‐2.01, p<0.001)], and of hospitalization due to the SARS‐CoV‐2 virus [crude OR of 2.09 (95% CI 1.01‐ 4.30, p<0.05)]. In multivariate analyses that controlled for demographic variables, and psychiatric and somatic disorders, the adjusted OR of COVID‐19 infection [1.45 (95% CI 1.08‐1.95, p<0.001)], and of hospitalization due to the SARS‐CoV‐2 virus [1.95 (95% CI 0.98‐4.845, p=0.061)] were preserved. In the multivariate analyses, age over 50 years, male gender and low‐medium socioeconomic status were also positively associated with the risk of COVID‐19 infection; age over 50 years was positively associated with the likelihood of hospitalization due to COVID‐19. Conclusion

Low plasma 25(OH)D level appears to be an independent risk factor for COVID‐19 infection and hospitalization.'''

Wien Klin Wochenschr

. 2021 Mar 15;1-3. doi: 10.1007/s00508-021-01833-y. Online ahead of print. Strong correlation between prevalence of severe vitamin D deficiency and population mortality rate from COVID-19 in Europe Isaac Z Pugach 1, Sofya Pugach  2 Affiliations

PMID: 33721102 PMCID: PMC7957444 DOI: 10.1007/s00508-021-01833-y

'''Results: There were data sets from 10 countries that fitted the criteria and were analyzed. Severe vitamin D deficiency was defined as 25(OH)D less than 25 nmol/L (10 ng/dL). Pearson correlation analysis between death rate per million of population from coronavirus disease 2019 (COVID-19) and prevalence of severe vitamin D deficiency showed a strong correlation with r = 0.79, p = 0.007. Over time, correlation strengthened, and r coefficient asymptotically increased. After adjusting for countries' age structure and per capita health expenditures, multiple linear regression analysis showed that higher prevalence of severe vitamin D deficiency is associated with increased mortality. Each 1% increase in prevalence increased deaths by 55 per million (95% confidence interval, CI 8-102), p = 0.03.

Conclusion: The authors recommend universal screening for vitamin D deficiency, and further investigation of Vitamin D supplementation in randomized control studies, which may lead to possible treatment or prevention of COVID-19.'''