Host: Elizabeth Esty, MD. At this point, with so many of the studies we’ve digested exploring correlations, associations, observational studies and anecdotal reports and speculation, we could subtitle the show: what we don’t know about COVID. And so, today, we’ll look at what we don’t know about Vitamin D and COVID. There have been a number of studies and a fair amount of media coverage in recent weeks that look at a possible link between low Vitamin D levels and severity of COVID.  Vitamin D plays a role in both adaptive and innate immunity, which we discussed at some length in our episode on the BCG vaccine and COVID. Macrophages starved for Vitamin D can’t produce peroxide to kill microbes, and some of the toll-like receptors crucial to innate immunity that recognize pathogen molecules don't work right without Vitamin D. Finally, Vitamin D modulates the immune response, preventing release of too many cytokines. The potential for Vitamin D to play a role in preventing severe COVID-19 seems plausible, but what does the science say? Research By: Elizabeth Esty and Nathan Novotny. Sound Editing By: Nathan Novotny. References: [1] Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, et al., editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011. 3, Overview of Vitamin D. Available from: https://www.ncbi.nlm.nih.gov/books/NBK56061/ [2] Helming L, Böse J, Ehrchen J, et al. 1α,25-dihydroxyvitamin D3 is a potent suppressor of interferon γ–mediated macrophage activation. Blood. 2005;106(13):4351-4358. doi:10.1182/blood-2005-03-1029   [3] Parva NR, Tadepalli S, Singh P, et al. Prevalence of Vitamin D Deficiency and Associated Risk Factors in the US Population (2011-2012). Cureus. 10(6). doi:10.7759/cureus.2741 [4] Sizar O, Khare S, Goyal A, Bansal P, Givler A. Vitamin D Deficiency. In: StatPearls. StatPearls Publishing; 2020. Accessed May 21, 2020. http://www.ncbi.nlm.nih.gov/books/NBK532266/ [5] Ilie PC, Stefanescu S, Smith L. The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality. Aging Clin Exp Res. Published online May 6, 2020. doi:10.1007/s40520-020-01570-8 [6] Vitamin D and Inflammation – Potential Implications for Severity of Covid-19 – Irish Medical Journal. Accessed May 21, 2020. http://imj.ie/vitamin-d-and-inflammation-potential-implications-for-severity-of-covid-19/ [7] Raharusun P, Priambada S, Budiarti C, Agung E, Budi C. Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study. Social Science Research Network; 2020. doi:10.2139/ssrn.3585561 [8] The Center for Evidence Based Medicine. Vitamin D: A rapid review of the evidence for treatment or prevention in COVID-19. CEBM. Accessed May 21, 2020. https://www.cebm.net/covid-19/vitamin-d-a-rapid-review-of-the-evidence-for-treatment-or-prevention-in-covid-19/ [9] Hastie CE, Mackay DF, Ho F, et al. Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2020;14(4):561-565. doi:10.1016/j.dsx.2020.04.050