Trial of Vitamin D to Reduce Risk and Severity of COVID-19 and Other Acute Respiratory Infections (CORONAVIT)

Phase 3 Randomised Controlled Trial of Vitamin D Supplementation to Reduce Risk and Severity of COVID-19 and Other Acute Respiratory Infections in the UK Population

Barts & The London NHS Trust, Pharma Nord, Fischer Family Trust, The AIM Foundation, Synergy Biologics Ltd, Cytoplan Ltd

CORONAVIT is an open-label, phase 3, randomised clinical trial testing whether implementation of a test-and-treat approach to correction of sub-optimal vitamin D status results in reduced risk and/or severity of COVID-19 and other acute respiratory infections.

Offer of a daily dose of 800 IU (20 micrograms) cholecalciferol to individuals with 25-hydroxyvitamin D level <75 nmol/L

Offer of a daily dose of 3200 IU (80 micrograms) cholecalciferol to individuals with 25-hydroxyvitamin D level <75 nmol/L

Proportion of participants experiencing at least one doctor-diagnosed or laboratory-confirmed acute respiratory infection of any cause.

Proportion of participants who are prescribed one or more courses of antibiotic treatment for acute respiratory infection

Proportion of participants with asthma who experience one or more exacerbations of asthma requiring treatment with oral corticosteroids and/or requiring hospital treatment

Proportion of participants with COPD who experience one or more exacerbations of COPD requiring treatment with oral corticosteroids and/or antibiotics, and/or requiring hospital treatment

Proportion of participants who have had PCR-, antigen test- or antibody test-confirmed SARS-CoV-2 infection who report symptoms of COVID-19 lasting more than 4 weeks after onset

Mean MRC dyspnoea score at the end of the study in people who have had PCR-, antigen test- or antibody test-confirmed SARS-CoV-2 infection and who report symptoms of COVID-19 lasting more than 4 weeks after onset

Mean FACIT Fatigue Scale score at the end of the study in people with antigen test- or antibody test-confirmed SARS-CoV-2 infection and who report symptoms of COVID-19 lasting more than 4 weeks after onset

Mean COVID-19 Recovery Questionnaire score at the end of the study in people who have had antigen test- or antibody test-confirmed SARS-CoV-2 infection and who report symptoms of COVID-19 lasting more than 4 weeks after onset

Proportion of participants who experience one or more acute respiratory infections requiring hospitalisation

Mean end-study 25(OH)D concentration (sub-set of participants having end-study tests of vitamin D status)

Proportion of participants experiencing a probable or definite adverse reaction to vitamin D supplementation

Proportion of SARS-CoV-2 vaccinated participants with antigen-specific T cell responses to SARS-CoV-2 spike protein (sub-set of participants)

Frequency of antigen-specific T cells reacting to SARS-CoV-2 spike protein in SARS-CoV-2 vaccinated participants (sub-set of participants)

Inclusion criteria: UK resident Age ≥16 years Gives informed consent to participate Exclusion criteria: taking digoxin, alfacalcidol, calcitriol, dihydrotachysterol or paricalcitol known diagnosis of sarcoidosis, primary hyperparathyroidism, renal stones or renal failure requiring dialysis known allergy to any ingredient in the study capsules (vitamin D, olive oil, caramel, gelatine or glycerol) pregnancy

De-identified IPD will be shared with other researchers subject to terms of Data Transfer Agreement and IRB approval

Jolliffe DA, Holt H, Greenig M, Talaei M, Perdek N, Pfeffer P, Vivaldi G, Maltby S, Symons J, Barlow NL, Normandale A, Garcha R, Richter AG, Faustini SE, Orton C, Ford D, Lyons RA, Davies GA, Kee F, Griffiths CJ, Norrie J, Sheikh A, Shaheen SO, Relton C, Martineau AR. Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT). BMJ. 2022 Sep 7;378:e071230. doi: 10.1136/bmj-2022-071230.