Abstract: International Journal of Environmental Research and Public Health Article The Interaction of Vitamin D and Corticosteroids: A Mortality Analysis of 26,508 Veterans Who Tested Positive for SARS-CoV-2 Jimmy T. Efird 1, *, Ethan J. Anderson 2 , Charulata Jindal 3 , Thomas S. Redding 1 , Andrew D. Thompson 1 , Ashlyn M. Press 1 , Julie Upchurch 1 , Christina D. Williams 1,4,5 , Yuk Ming Choi 6 and Ayako Suzuki 1,7,8 1 2 3 4 5 6 7 8 *



 Citation: Efird, J.T.; Anderson, E.J.; Jindal, C.; Redding, T.S.; Thompson, A.D.; Press, A.M.; Upchurch, J.; Williams, C.D.; Choi, Y.M.; Suzuki, A. The Interaction of Vitamin D and Corticosteroids: A Mortality Analysis of 26,508 Veterans Who Tested Positive for SARS-CoV-2. Int. J. Environ. Res. Public Health 2022, 19, 447. https://doi.org/10.3390/ ijerph19010447 Academic Editor: Oliver Grundmann Received: 5 December 2021 Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, NC 27705, USA; thomas.redding28@va.gov (T.S.R.); andrew.thompson3@va.gov (A.D.T.); ashlyn.press@va.gov (A.M.P.); julie.upchurch@va.gov (J.U.); christina.williams4@va.gov (C.D.W.); ayako.suzuki@duke.edu (A.S.) College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA; ethan-anderson@uiowa.edu Harvard Medical School, Harvard University, Boston, MA 02115, USA; charujindal@gmail.com Department of Medicine, Duke University, Durham, NC 27710, USA Duke Cancer Institute, Duke University, Durham, NC 27710, USA Signify Health, Dallas, TX 75244, USA; ychoi@signifyhealth.com Division of Gastroenterology, Duke University, Durham, NC 27710, USA The Division of Gastroenterology, Durham VA Medical Center, Durham, NC 27705, USA Correspondence: jimmy.efird@va.gov; Tel.: +1-(650)-248-8282 Abstract: This data-based cohort consisted of 26,508 (7%) United States veterans out of the 399,290 who tested positive for SARS-CoV-2 from 1 March to 10 September 2020. We aimed to assess the interaction of post-index vitamin D (Vit D) and corticosteroid (CRT) use on 30-day mortality among hospitalized and non-hospitalized patients with coronavirus disease 2019 (COVID-19). Combination Vit D and CRT drug use was assessed according to four multinomial pairs (−|+, −|−, +|+, +|−). Respective categorical effects were computed on a log-binomial scale as adjusted relative risk (aRR). Approximately 6% of veterans who tested positive for SARS-CoV-2 died within 30 days of their index date. Among hospitalized patients, a significantly decreased aRR was observed for the use of Vit D in the absence of CRTs relative to patients who received CRTs but not Vit D (aRR = 0.30; multiplicity corrected, p = 0.0004). Among patients receiving systemically administered CRTs (e.g., dexamethasone), the use of Vit D was associated with fewer deaths in hospitalized patients (aRR = 0.51) compared with non-hospitalized patients (aRR = 2.5) (P-for-Interaction = 0.0071). Evaluating the effect of modification of these compounds in the context of hospitalization may aid in the management of COVID-19 and provide a better understanding of the pathophysiological mechanisms underlying this and future infectious disease outbreaks. Accepted: 28 December 2021 Published: 31 December 2021 Publisher’s Note: MDPI stays neutral Keywords: anti-inflammatory; corticosteroids; COVID-19; cytokine storm; SARS-CoV-2; vitamin D; veterans with regard to jurisdictional claims in published maps and institutional affiliations.