Association between vitamin D supplementation and COVID-19 infection and mortality
Jason B Gibbons, Edward C Norton, Jeffrey S Mccullough, David O Meltzer, Jill Lavigne, Virginia C Fiedler, Robert D Gibbons
Scientific Reports, doi:10.1038/s41598-022-24053-4
Vitamin D deficiency has long been associated with reduced immune function that can lead to viral infection. Several studies have shown that Vitamin D deficiency is associated with increases the risk of infection with COVID-19. However, it is unknown if treatment with Vitamin D can reduce the associated risk of COVID-19 infection, which is the focus of this study. In the population of US veterans, we show that Vitamin D 2 and D 3 fills were associated with reductions in COVID-19 infection of 28% and 20%, respectively [(D 3 Hazard Ratio (HR) = 0.80, [95% CI 0.77, 0.83]), D 2 HR = 0.72, [95% CI 0.65, 0.79]]. Mortality within 30-days of COVID-19 infection was similarly 33% lower with Vitamin D 3 and 25% lower with D 2 (D 3 HR = 0.67, [95% CI 0.59, 0.75]; D 2 HR = 0.75, [95% CI 0.55, 1.04]). We also find that after controlling for vitamin D blood levels, veterans receiving higher dosages of Vitamin D obtained greater benefits from supplementation than veterans receiving lower dosages. Veterans with Vitamin D blood levels between 0 and 19 ng/ml exhibited the largest decrease in COVID-19 infection following supplementation. Black veterans received greater associated COVID-19 risk reductions with supplementation than White veterans. As a safe, widely available, and affordable treatment, Vitamin D may help to reduce the severity of the COVID-19 pandemic. Vitamin D insufficiency and deficiency affect approximately half of the US population, with increased rates in people with darker skin, reduced sun exposure, people living in higher latitudes in the winter, nursing home residents, and healthcare workers 1 . Populations with low levels of Vitamin D have also experienced higher rates of COVID-19      . Despite several studies pointing to an association between low levels of vitamin D and COVID-19 2-7 , limited information is available regarding the potential for supplementation with vitamin D to reduce the risk of COVID-19 infection. Expanding supplementation with vitamin D may present a new and unique opportunity to mitigate global infection rates, given that it is a widely available over-the-counter (OTC), inexpensive, and is associated with relatively few side effects. We conducted a large-scale pharmacoepidemiologic study of the association between vitamin D 3 and D 2 supplementation and the probability of COVID-19 infection and COVID-19 infection ending in mortality within 30-days in the Department of Veterans Administration (VA) in the United States. We also studied whether patient sex, race, vitamin D serum levels, and cumulative D 3 supplementation dosage modified the association.
Author contributions J.G. Wrote the manuscript, analyzed the data, planned the analysis, and reviewed the manuscript. E.N. planned the analysis and reviewed the manuscript. J.M. planned the analysis and reviewed the manuscript. D.M. planned the analysis and reviewed the manuscript. J.L. planned the analysis and reviewed the manuscript and obtained the data. V.F.. planned the analysis and reviewed the manuscript. R.G. Wrote the manuscript, planned the analysis, and reviewed the manuscript.
Competing interests Dr. DO Meltzer reported grants from the National Institutes of Health during the conduct of the study. Dr. JB Gibbons, Dr. J Lavigne, Dr. VC Fiedler, Dr. EC Norton, Dr. J McCullough, Dr. RD Gibbons have no conflicts to report.
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1038/ s41598-022-24053-4. Correspondence and requests for materials should be addressed to J.B.G. Reprints and permissions information is available at www.nature.com/reprints. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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