Abstract: VITAMIN D TREATMENT IS ASSOCIATED WITH REDUCED RISK OF MORTALITY IN PATIENTS WITH COVID-19: A CROSS-SECTIONAL MULTI-CENTRE OBSERVATIONAL STUDY Stephanie F Ling MBChB1,2, Eleanor Broad MBChB1, Rebecca Murphy MBChB1, Joseph M Pappachan MD 2,3,4, Satveer Pardesi-Newton BM5, Marie-France Kong DM6, Edward B Jude MD1,2,4. 1. Tameside and Glossop Integrated Care NHS Foundation Trust, Fountain Street, Ashton-underLyne, OL6 9RW, UK. 2. The University of Manchester, Oxford Road, Manchester, M13 9PL, UK. 3. Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Preston Road, Chorley, PR7 1PP, UK. 4. Manchester Metropolitan University, All Saints Building, Manchester, M15 6BH, UK. 5. Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Infirmary Square, Leicester, LE1 5WW, UK. 6. Leicester General Hospital, University Hospitals of Leicester NHS Trust, Gwendolen Road, Leicester, LE5 4PW, UK. Corresponding author: Professor Edward Jude Tameside and Glossop Integrated Care NHS Foundation Trust Fountain Street Ashton-under-Lyne OL6 9RW Edward.jude@tgh.nhs.uk Telephone: +44 (0) 161 922 5189 Word limit: 3,500 1 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3690902 ABSTRACT Background: The 2019 novel coronavirus disease (Covid-19) worldwide pandemic has posed the most substantial and severe public health issue for several generations, and therapeutic options for it have not yet been optimised. Vitamin D has been proposed in the pharmacological management of Covid-19 by various sources. This study aimed to determine whether Covid-19 disease outcomes were affected by vitamin D status, and to elucidate any predictors of Covid-19 outcomes. Methods: Patients hospitalised with Covid-19 were opportunistically recruited from three different UK hospitals and their data were collected. Logistic regression was used to determine any relationships between vitamin D status and various predictors, including mortality and ventilation, and to determine any relationships between mortality, ventilation, and various predictors. Findings: Vitamin D status was not associated with any outcomes of Covid-19 investigated, following adjustment for age and sex. However, treatment with vitamin D was significantly associated with a reduced risk of death, following adjustment for age and sex (ORadj 0·48, 95% CI 0·32 – 0·70, p = 1·79x10-4). This relationship remained significant when also adjusted for baseline vitamin D levels (ORadj 0·47, 95% CI 0·33 – 0·70, p = 1·27x10-4). Interpretation: Treatment with vitamin D, regardless of baseline serum vitamin D levels, appears to be associated with a reduced risk of mortality in acute in-patients admitted with Covid-19. Further work on large population studies needs to be carried out to determine adequate serum levels of vitamin D, as well as multi-dose clinical trials of vitamin D treatment to assess maximum efficacy. Funding: None. 2 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3690902 RESEARCH IN CONTEXT Evidence before this study: We searched PubMed for articles published between 1st January 2020 and 4th September 2020, with the terms “Covid-19,” “SARS-CoV2,” “vitamin D,” “cholecalciferol,” and “25-hydroxyvitamin D.” We did not restrict outr search by language or type of publication. Due to the rapid onset and clinical severity of Covid-19, large amounts of..