Abstract: nutrients Article Vitamin D Status and Mortality from SARS CoV-2: A Prospective Study of Unvaccinated Caucasian Adults Robert Barrett 1 , Modar Youssef 2 , Irfan Shah 2 , Julia Ioana 2 , Abdullah Al Lawati 2 , Abdullah Bukhari 2 , Suzanne Hegarty 2 , Liam J. Cormican 2 , Eoin Judge 2 , Conor M. Burke 2,3 , Catriona Cody 4 , Joseph Feely 5 , Katrina Hutchinson 6 , William Tormey 5 , Eoghan O’ Neill 7 , Aoife O’ Shea 1 , Meabh Connolly 1 , Daniel M. A. McCartney 1 and John L. Faul 2,3,8, * 1 2 3 4 5 6 7 8 * Citation: Barrett, R.; Youssef, M.; Shah, I.; Ioana, J.; Lawati, A.A.; Bukhari, A.; Hegarty, S.; Cormican, L.J.; Judge, E.; Burke, C.M.; et al. Vitamin D Status and Mortality from SARS CoV-2: A Prospective Study of Unvaccinated Caucasian Adults. Nutrients 2022, 14, 3252. https:// doi.org/10.3390/nu14163252 Academic Editors: Andrea P. Rossi and Marwan El Ghoch Received: 24 June 2022 School of Biological and Health Sciences, Technological University Dublin, D08 NF82 Dublin, Ireland Department of Respiratory and Sleep Medicine, Connolly Hospital Dublin, D15 X40D Dublin, Ireland Department of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland Department of Intensive Care Medicine, Connolly Hospital Dublin, D15 X40D Dublin, Ireland Department of Biochemistry, Connolly Hospital Dublin, D15 X40D Dublin, Ireland Eurofins Biomnis, Sandyford, Co. Dublin, D18 A4CO Dublin, Ireland Department of Microbiology, Connolly Hospital Dublin, D15 X40D Dublin, Ireland Department of Medicine, Royal College of Surgeons in Ireland, D02 YN 77 Dublin, Ireland Correspondence: johnfaul@rcsi.ie Abstract: COVID-19 and a low vitamin D state share common risk factors, which might explain why vitamin D deficiency has been linked with higher COVID-19 mortality. Moreover, measures of serum vitamin D may become lower during systemic inflammatory responses, further confounding the association via reverse causality. In this prospective study (recruited over 12 months), we examined whether the association between a low vitamin D state and in-hospital mortality due to SARS-CoV-2 pneumonia in unvaccinated subjects is explained by (i) the presence of shared risk factors (e.g., obesity, advanced age) or (ii) a reduction in serum 25(OH)D due to COVID-19 (i.e., reverse causality). In this cohort of 232 (mean age = 56 years) patients (all had SARS-CoV-2 diagnosed via PCR AND required supplemental oxygen therapy), we failed to find an association between serum vitamin D and levels of CRP, or other inflammatory markers. However, the hazard ratio for mortality for subjects over 70 years of age (13.2) and for subjects with a serum 25(OH)D level less than 30 nmol·L−1 (4.6) remained significantly elevated even after adjustment for gender, obesity and the presence of diabetes mellitus. Subjects <70 years and >70 years had significantly higher mortality with a serum 25(OH)D less than 30 nmol·L−1 (11.8% and 55%), than with a serum 25(OH)D greater than 30 nmol·L−1 (2.2% and 25%). Unvaccinated Caucasian adults with a low vitamin D state have higher mortality due to SARS CoV-2 pneumonia, which is not explained by confounders and is not closely linked with elevated serum CRP. Accepted: 3 August 2022 Published: 9 August 2022 Keywords: COVID-19; vitamin D; hospitalization; mortality; Ireland Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2022 by the authors. Licensee MDPI, Basel,..