D3

Vitamin D deficiency has been shown to potentially increase the risk of severe respiratory infections.^[205] This has led to investigations of the role of vitamin D deficiency and the potential for use of vitamin D supplements during the COVID-19 pandemic.

Several systematic reviews and meta-analyses of multiple studies have described the associations of vitamin D deficiency with adverse outcomes in COVID-19.<^{[206][207][208]} One found that while deficiency was not associated with a higher probability of becoming infected with COVID-19, there were significant associations between vitamin D deficiency or insufficiency with more severe disease, including increases in hospitalization and mortality rates by about 80%.^[208] Two other meta-analyses of around 40 studies have shown that the risk of infection was higher in those with vitamin D deficiency.^[206][207] The vitamin D deficient group had about a two-fold risk of disease with greater severity, and on some analyses, a significant association with higher rates of mortality.^[206][207] Another, reviewing 31 studies, reported that patients with COVID-19 tend to have lower 25(OH)D levels than healthy subjects but stated that the trend for associations with health outcomes was limited by the low quality of the studies and by the possibility of reverse causality mechanisms.^[209]

In July 2020, the US National Institutes of Health found insufficient evidence to recommend for or against using vitamin D supplementation to prevent or treat COVID-19.^[210] The UK National Institute for Health and Care Excellence (NICE) does not recommend to offer a vitamin D supplement to people solely to prevent or treat COVID‑19.^[211][212] Both organizations included recommendations to continue the previous established recommendations on vitamin D supplementation for other reasons, such as bone and muscle health, as applicable. Both organizations noted that more people may require supplementation due to lower amounts of sun exposure during the pandemic.^[210][211]

The major complication of COVID-19 is acute respiratory distress syndrome (ARDS), which may be aggravated by vitamin D deficiency,^[213] an association that is not specific to coronavirus infections.^[213]

A number of trials in different countries are underway or have been published, looking at the use of vitamin D, and its metabolites such as calcifediol, in the prevention and treatment of SARS-CoV-2 infections.^[213][214] A meta-analysis of three studies on the effect of oral vitamin D or calcifediol supplementation indicated a lower intensive care unit (ICU) admission rate (odds ratio: 0.36) compared to those without supplementation, but without a change in mortality.^[215] A Cochrane review, also of three studies, found the evidence for the effectiveness of vitamin D supplementation for the treatment of COVID-19 to be very uncertain.^[216] They found there was substantial clinical and methodological heterogeneity in the three studies that were included, mainly because of different supplementation strategies, vitamin D formulations (one using calcifediol), pre-treatment status and reported outcomes.^[216] Another meta-analysis stated that the use of high doses of vitamin D in COVID-19 patients is not based on solid evidence although calcifediol supplementation may have a protective effect on ICU admissions.^[209]

1. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, et al. (February 2017). "Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data". BMJ. 356: i6583. doi:10.1136/bmj.i6583. PMC 5310969. PMID 28202713.
2. ^ ^a b c Kazemi A, Mohammadi V, Aghababaee SK, Golzarand M, Clark CC, Babajafari S (March 2021). "Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis". Advances in Nutrition. doi:10.1093/advances/nmab012. PMC 7989595. PMID 33751020.
3. ^ ^a b c Petrelli F, Luciani A, Perego G, Dognini G, Colombelli PL, Ghidini A (March 2021). "Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analysis of 43 observational studies". The Journal of Steroid Biochemistry and Molecular Biology. 211: 105883. doi:10.1016/j.jsbmb.2021.105883. PMC 7997262. PMID 33775818.
4. ^ ^a b Damascena AD, Azevedo LM, Oliveira TA, Santana JD, Pereira M (August 2021). "Addendum to vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis". Critical Reviews in Food Science and Nutrition: 1–6. doi:10.1080/10408398.2021.1951652. PMID 34384300. S2CID 236997712.
5. ^ ^a b Bassatne A, Basbous M, Chakhtoura M, Zein OE, Rahme M, Fuleihan GE (March 2021). "The link between COVID-19 and Vitamin D (VIVID): a systematic review and meta-analysis". Metabolism (Systematic review). 119: 154753. doi:10.1016/j.metabol.2021.154753. PMC 7989070. PMID 33774074.
6. ^ ^a b "Vitamin D". Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health (NIH). July 17, 2020. Retrieved February 22, 2021.  This article incorporates text from this source, which is in the public domain.
7. ^ ^a b COVID-19 rapid guideline: vitamin D (PDF)(Technical report). National Institute for Health and Care Excellence (NICE). December 2020. ISBN 978-1-4731-3942-8. NG187. Retrieved February 22,2021.
8. ^ Evidence reviews for the use of vitamin D supplementation as prevention and treatment of COVID-19 (PDF) (Report). National Institute for Health and Care Excellence (NICE). December 2020.
9. ^ ^a b c Quesada-Gomez JM, Entrenas-Castillo M, Bouillon R (September 2020). "Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166". The Journal of Steroid Biochemistry and Molecular Biology. 202: 105719. doi:10.1016/j.jsbmb.2020.105719. PMC 7289092. PMID 32535032.
10. ^ "International clinical trials assessing vitamin D in people with COVID-19". ClinicalTrials.gov, US National Library of Medicine. May 2020. Retrieved June 11, 2021.
11. ^ Shah K, Saxena D, Mavalankar D (January 2021). "Vitamin D supplementation, COVID-19 & Disease Severity: A meta-analysis". QJM : Monthly Journal of the Association of Physicians. 114 (3):