Abstract: AJCP / Original Article Serum 25(OH)D Level on Hospital Admission Associated With COVID-19 Stage and Mortality Dieter De Smet, MD,1 Kristof De Smet, MD,2 Pauline Herroelen, MSc,1 Stefaan Gryspeerdt, MD,2 and Geert A. Martens, MD, PhD1,3,4, From the 1AZ Delta Medical Laboratories and 2Department of Radiology, AZ Delta General Hospital, Roeselare, Belgium; 3VUB Metabolomics Platform, Brussels Free University, Brussels, Belgium; and 4Department of Biomolecular Medicine, Ghent University, Ghent, Belgium. Am J Clin Pathol March 2021;155:381-388 DOI: 10.1093/AJCP/AQAA252 ABSTRACT Objectives: Vitamin D deficiency was previously correlated with incidence and severity of coronavirus disease 2019 (COVID-19). We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) level on admission and radiologic stage and outcome of COVID-19 pneumonia. Methods: A retrospective observational trial was done on 186 severe acute respiratory syndrome coronavirus 2 (SARSCoV-2)–infected individuals hospitalized from March 1, 2020, to April 7, 2020, with combined chest computed tomography (CT) and 25(OH)D measurement on admission. Multivariate regression analysis was performed to study if vitamin D deficiency (25(OH)D <20 ng/mL) correlates with survival independently of confounding comorbidities. Results: Of the patients with COVID-19, 59% were vitamin D deficient on admission: 47% of females and 67% of males. In particular, male patients with COVID19 showed progressively lower 25(OH)D with advancing radiologic stage, with deficiency rates increasing from 55% in stage 1 to 74% in stage 3. Vitamin D deficiency on admission was not confounded by age, ethnicity, chronic lung disease, coronary artery disease/hypertension, or diabetes and was associated with mortality (odds ratio [OR], 3.87; 95% confidence interval [CI], 1.30-11.55), independent of age (OR, 1.09; 95% CI, 1.03-1.14), chronic lung disease (OR, 3.61; 95% CI, 1.18-11.09), and extent of lung damage expressed by chest CT severity score (OR, 1.12; 95% CI, 1.01-1.25). Conclusions: Low 25(OH)D levels on admission are associated with COVID-19 disease stage and mortality. © American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com Key Points • A remarkably high fraction (59%) of patients with coronavirus disease 2019 (COVID-19) are vitamin D deficient (25(OH)D <20 ng/mL) on admission. Deficiency was most pronounced in men with advanced radiologic stages of COVID-19 pneumonia. • Vitamin D deficiency on admission was associated with COVID-19 mortality with an odds ratio of 3.87, independent of age, chronic lung disease, coronary artery disease, hypertension, or diabetes. In a subset of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, excessive recruitment of proinflammatory cells and cytokine release contribute to alveolar and endothelial damage, triggering a vicious cycle that evolves toward severe coronavirus disease 2019 (COVID-19).1,2 Beside its role in calcium metabolism, 1,25-dihydroxyvitamin D is a pleiotropic regulator of the immune system.3-5 It stimulates the expression of cathelicidins and β-defensins in respiratory epithelia as a barrier to pathogen invasion.6,7 It acts as a protolerogenic and anti-inflammatory cytokine by inhibiting T helper 1 (Th1) proliferation and switching Th1 CD4 T cells and M1-polarized macrophages toward a type II immunity. Vitamin D deficiency (25-hydroxyvitamin D..