Abstract: nutrients Article Association of Vitamin D Prescribing and Clinical Outcomes in Adults Hospitalized with COVID-19 Kathleen M. Fairfield 1,2, *, Kimberly A. Murray 1 , A. Jerrod Anzalone 3 , William Beasley 4 , Maryam Khodaverdi 5 , Sally L. Hodder 5 , Jeremy Harper 6 , Susan Santangelo 1,2 , Clifford J. Rosen 1,2 and on behalf of the N3C Consortium † 1 2 3 4 5 6 * † Citation: Fairfield, K.M.; Murray, K.A.; Anzalone, A.J.; Beasley, W.; Khodaverdi, M.; Hodder, S.L.; Harper, J.; Santangelo, S.; Rosen, C.J.; on behalf of the N3C Consortium. Association of Vitamin D Prescribing and Clinical Outcomes in Adults Hospitalized with COVID-19. Nutrients 2022, 14, 3073. https:// doi.org/10.3390/nu14153073 Academic Editor: Bruce W. Hollis Received: 22 June 2022 Accepted: 21 July 2022 Published: 26 July 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. MaineHealth Institute for Research, Portland, ME 04074, USA; kimberly.murray@mainehealth.org (K.A.M.); susan.santangelo@mainehealth.org (S.S.); clifford.rosen@mainehealth.org (C.J.R.) Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA; alfred.anzalone@unmc.edu Biomedical and Behavioral Methodology Core, University of Oklahoma, Norman, OK 73019, USA; william-beasley@ouhsc.edu West Virginia Clinical and Translational Science Institute, West Virginia University School of Medicine, Morgantown, WV 26506, USA; makhodaverdi@hsc.wvu.edu (M.K.); slhodder@hsc.wvu.edu (S.L.H.) Owl Health Works LLC, Indianapolis, IN 46278, USA; owlhealthworks@gmail.com Correspondence: kathleen.fairfield@mainehealth.org N3C Consortial contributors: Jeremy Harper, Christopher G. Chute, Carolyn Bramante, Melissa A. Handel, Richard A. Moffitt. Abstract: Abstract: BackgroundIt is unclear whether vitamin D benefits inpatients with COVID-19. Objective: To examine the relationship between vitamin D and COVID-19 outcomes. Design: Cohort study. Setting: National COVID Cohort Collaborative (N3C) database. Patients: 158,835 patients with confirmed COVID-19 and a sub-cohort with severe disease (n = 81,381) hospitalized between 1 January 2020 and 31 July 2021. Methods: We identified vitamin D prescribing using codes for vitamin D and its derivatives. We created a sub-cohort defined as having severe disease as those who required mechanical ventilation or extracorporeal membrane oxygenation (ECMO), had hospitalization >5 days, or hospitalization ending in death or hospice. Using logistic regression, we adjusted for age, sex, race, BMI, Charlson Comorbidity Index, and urban/rural residence, time period, and study site. Outcomes of interest were death or transfer to hospice, longer length of stay, and mechanical ventilation/ECMO. Results: Patients treated with vitamin D were older, had more comorbidities, and higher BMI compared with patients who did not receive vitamin D. Vitamin D treatment was associated with an increased odds of death or referral for hospice (adjusted odds ratio (AOR) 1.10: 95% CI 1.05–1.14), hospital stay >5 days (AOR 1.78: 95% CI 1.74–1.83), and increased odds of mechanical ventilation/ECMO (AOR 1.49: 95% CI 1.44–1.55). In the sub-cohort of severe COVID-19, vitamin D decreased the odds of death or hospice (AOR 0.90, 95% CI 0.86–0.94), but increased the odds of hospital stay longer >5 days (AOR 2.03, 95% CI..