Abstract: nutrients Article Correlation between 25-hydroxyvitamin D/D3 Deficiency and COVID-19 Disease Severity in Adults from Northern Colorado Bridget A. Baxter 1 , Michaela G. Ryan 1 , Stephanie M. LaVergne 1 , Sophia Stromberg 1 , Kailey Berry 1 , Madison Tipton 1 , Nicole Natter 1 , Nikiah Nudell 2 , Kim McFann 2 , Julie Dunn 2 , Tracy L. Webb 3 , Michael Armstrong 4 , Nichole Reisdorph 4 and Elizabeth P. Ryan 1, * 1 2 3 4 * Citation: Baxter, B.A.; Ryan, M.G.; LaVergne, S.M.; Stromberg, S.; Berry, K.; Tipton, M.; Natter, N.; Nudell, N.; McFann, K.; Dunn, J.; et al. Correlation between 25-hydroxyvitamin D/D3 Deficiency and COVID-19 Disease Severity in Adults from Northern Colorado. Nutrients 2022, 14, 5204. https://doi.org/10.3390/ nu14245204 Academic Editor: Andrea Fabbri Received: 30 August 2022 Accepted: 20 November 2022 Published: 7 December 2022 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, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ Department of Environmental Radiological Health Science, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA Medical Center of the Rockies, University of Colorado Health, Loveland, CO 80538, USA Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USA Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA Correspondence: e.p.ryan@colostate.edu; Tel.: +1-970-491-1936 Abstract: Vitamin D deficiency is common in the United States and leads to altered immune function, including T cell and macrophage activity that may impact responses to SARS-CoV-2 infection. This study investigated 131 adults with a history of a positive SARS-CoV-2 nasopharyngeal PCR and 18 adults with no COVID-19 diagnosis that were recruited from the community or hospital into the Northern Colorado Coronavirus Biorepository (NoCo-COBIO). Participants consented to enrollment for a period of 6 months and provided biospecimens at multiple visits for longitudinal analysis. Plasma 25-hydroxyvitamin D levels were quantified by LC-MS/MS at the initial visit (n = 149) and after 4 months (n = 89). Adults were classified as deficient (<30 nM or <12 ng/mL), insufficient (<30–50 nM or 12–20 ng/mL), or optimal (50–75 nM or >20 ng/mL) for 25-hydroxyvitamin D status. Fisher’s exact test demonstrated an association between disease severity, gender, and body mass index (BMI) at baseline. Mixed model analyses with Tukey-Kramer were used for longitudinal analysis according to BMI. Sixty-nine percent (n = 103) of the entire cohort had optimal levels of total 25(OH)D, 22% (n = 32) had insufficient levels, and 9% (n = 14) had deficent levels. Participants with severe disease (n = 37) had significantly lower 25-hydroxyvitamin D (total 25(OH)D) when compared to adults with mild disease (p = 0.006) or no COVID-19 diagnosis (p = 0.007). There was 44% of the cohort with post-acute sequalae of COVID-19 (PASC) as defined by experiencing at least one of the following symptoms after 60 days’ post-infection: fatigue, dyspnea, joint pain, chest pain, forgetfulness or absent-mindedness, confusion, or difficulty breathing. While..