Abstract: The Journal of Clinical Endocrinology & Metabolism, 2021, Vol. 106, No. 11, e4708–e4715 doi:10.1210/clinem/dgab439 Clinical Research Article Clinical Research Article Edward B. Jude,1,2,3 Stephanie F. Ling,1,2 Rebecca Allcock,4 Beverly X. Y. Yeap,2 and Joseph M. Pappachan2,3,4 1 Tameside and Glossop Integrated Care NHS Foundation Trust, Fountain Street, Ashton-under-Lyne, OL6 9RW, UK; 2The University of Manchester, Oxford Road, Manchester, M13 9PL, UK; 3Manchester Metropolitan University, All Saints Building, Manchester, M15 6BH, UK; and 4Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Sharoe Green Lane, Fulwood, Preston, PR2 9HT, UK ORCiD numbers: 0000-0002-3186-4122 (E. B. Jude); 0000-0003-0886-5255 (J. M. Pappachan). Abbreviations: 25(OH)D, 25-hydroxyvitamin D; IQR, interquartile range; NICE, National Institute for Health and Clinical Care Excellence; OR, odds ratio; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. Received: 2 April 2021; Editorial Decision: 11 June 2021; First Published Online: 17 June 2021; Corrected and Typeset: 15 July 2021. Abstract Context: One risk factor for severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) infection is postulated to be vitamin D deficiency. To better understand the role of vitamin D deficiency in the disease course of COVID-19, we undertook a retrospective case-control study in North West England. Objective: To examine whether hospitalization with COVID-19 is more prevalent in individuals with lower vitamin D levels. Methods: The study included individuals with test results for serum 25-hydroxyvitamin D (25[OH]D) between April 1, 2020, and January 29, 2021, from 2 districts in North West England. The last 25(OH)D level in the previous 12 months was categorized as “deficient” if less than 25 nmol/L and “insufficient” if 25 to 50 nmol/L. Results: The study included 80 670 participants. Of these, 1808 were admitted to the hospital with COVID-19, of whom 670 died. In a primary cohort, median serum 25(OH)D in nonhospitalized participants with COVID-19 was 50.0 nmol/L (interquartile range [IQR], 34.0-66.7) vs 35.0 nmol/L (IQR, 21.0-57.0) in those admitted with COVID-19 (P < 0.005). In a validation cohort, median serum 25(OH)D was 47.1 nmol/L (IQR, 31.8-64.7) in nonhospitalized vs 33.0 nmol/L (IQR, 19.4-54.1) in hospitalized patients. Age-, sex-, and season-adjusted odds ratios for hospital admission were 2.3 to 2.4 times higher among participants with serum 25(OH)D <50 nmol/L compared with those with normal serum 25(OH)D levels, without excess mortality risk. ISSN Print 0021-972X e4708   https://academic.oup.com/jcem ISSN Online 1945-7197 Printed in USA © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com Vitamin D Deficiency Is Associated With Higher Hospitalization Risk From COVID-19: A Retrospective Case-Control Study The Journal of Clinical Endocrinology & Metabolism, 2021, Vol. 106, No. 11 e4709 Conclusion: Vitamin D deficiency is associated with higher risk of COVID-19 hospitalization. Widespread measurement of serum 25(OH)D and treatment of insufficiency or deficiency may reduce this risk. Key Words: vitamin D deficiency, COVID-19, hospitalization, severe acute respiratory syndrome coronavirus..