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)
David A Jolliffe, Hayley Holt, Matthew Greenig, Mohammad Talaei, Natalia Perdek, Paul Pfeffer, Giulia Vivaldi, Sheena Maltby, Jane Symons, Nicola L Barlow, Alexa Normandale, Rajvinder Garcha, Alex G Richter, Sian E Faustini, Christopher Orton, David Ford, Ronan A Lyons, Gwyneth A Davies, Frank Kee, Christopher J Griffiths, John Norrie, Aziz Sheikh, Seif O Shaheen, Clare Relton, Adrian R Martineau
BMJ, doi:10.1136/bmj-2022-071230
Objective To determine the effect of population level implementation of a test-and-treat approach to correction of suboptimal vitamin D status (25-hydroxyvitamin D (25(OH)D) <75 nmol/L) on risk of all cause acute respiratory tract infection and covid 19.
Design Phase 3 open label randomised controlled trial. setting United Kingdom. ParticiPants 6200 people aged ≥16 years who were not taking vitamin D supplements at baseline.
interventiOns Offer of a postal finger prick test of blood 25(OH)D concentration with provision of a six month supply of lower dose vitamin D (800 IU/day, n=1550) or higher dose vitamin D (3200 IU/day, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, compared with no offer of testing or supplementation (n=3100). Follow-up was for six months.
Main OutcOMe Measures The primary outcome was the proportion of participants with at least one swab test or doctor confirmed acute respiratory tract infection of any cause. A secondary outcome was the proportion of participants with swab test confirmed covid-19. Logistic regression was used to calculate odds ratios and associated 95% confidence intervals. The primary analysis was conducted by intention to treat.
results Of 3100 participants offered a vitamin D test, 2958 (95.4%) accepted and 2674 (86.3%) had 25(OH) D concentrations <75 nmol/L and received vitamin D supplements (n=1328 lower dose, n=1346 higher dose). Compared with 136/2949 (4.6%) participants in the no offer group, at least one acute respiratory tract infection of any cause occurred in 87/1515 (5.7%) in the lower dose group (odds ratio 1.26, 95% confidence interval 0.96 to 1.66) and 76/1515 (5.0%) in the higher dose group (1.09, 0.82 to 1.46). Compared with 78/2949 (2.6%) participants in the no offer group, 55/1515 (3.6%) developed covid-19 in the lower dose group (1.39, 0.98 to 1.97) and 45/1515 (3.0%) in the higher dose group (1.13, 0.78 to 1.63). cOnclusiOns Among people aged 16 years and older with a high baseline prevalence of suboptimal vitamin D status, implementation of a population level test-and-treat approach to vitamin D supplementation was not associated with a reduction in risk of all cause acute respiratory tract infection or covid-19. trial registratiOn ClinicalTrials.gov NCT04579640.
Contributors: ARM, DAJ, and CR designed the study, with input from PP, JS, DF, RAL, GAD, FK, CJG, JN, AS, SEF, AGR, and SOS. DAJ, HH, NP, SM, MT, and ARM managed the trial. AN, NLB, and RG performed the laboratory assays. DAJ, MG, MT, GV, and CO managed and analysed the data. DAJ and ARM contributed equally and are the guarantors. All the authors vouch for the accuracy and completeness of the data and for the fidelity of the trial to the protocol. ARM wrote the first draft of the paper. All authors contributed to the interpretation of the results, review and approval of the manuscript, and the decision to submit it for publication. There were no agreements concerning confidentiality of the data between the sponsor and the authors or the institutions named in the credit lines. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Funding:
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'abstract': '<jats:title>Abstract</jats:title>\n'
' <jats:sec>\n'
' <jats:title>Objective</jats:title>\n'
' <jats:p>To determine the effect of population level implementation of a '
'test-and-treat approach to correction of suboptimal vitamin D status (25-hydroxyvitamin D '
'(25(OH)D) <75 nmol/L) on risk of all cause acute respiratory tract infection and covid '
'19.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Design</jats:title>\n'
' <jats:p>Phase 3 open label randomised controlled trial.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Setting</jats:title>\n'
' <jats:p>United Kingdom.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Participants</jats:title>\n'
' <jats:p>6200 people aged ≥16 years who were not taking vitamin D supplements at '
'baseline.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Interventions</jats:title>\n'
' <jats:p>Offer of a postal finger prick test of blood 25(OH)D concentration with '
'provision of a six month supply of lower dose vitamin D (800 IU/day, n=1550) or higher dose '
'vitamin D (3200 IU/day, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, '
'compared with no offer of testing or supplementation (n=3100). Follow-up was for six '
'months.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Main outcome measures</jats:title>\n'
' <jats:p>The primary outcome was the proportion of participants with at least one '
'swab test or doctor confirmed acute respiratory tract infection of any cause. A secondary '
'outcome was the proportion of participants with swab test confirmed covid-19. Logistic '
'regression was used to calculate odds ratios and associated 95% confidence intervals. The '
'primary analysis was conducted by intention to treat.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>Of 3100 participants offered a vitamin D test, 2958 (95.4%) accepted and '
'2674 (86.3%) had 25(OH)D concentrations <75 nmol/L and received vitamin D supplements '
'(n=1328 lower dose, n=1346 higher dose). Compared with 136/2949 (4.6%) participants in the no '
'offer group, at least one acute respiratory tract infection of any cause occurred in 87/1515 '
'(5.7%) in the lower dose group (odds ratio 1.26, 95% confidence interval 0.96 to 1.66) and '
'76/1515 (5.0%) in the higher dose group (1.09, 0.82 to 1.46). Compared with 78/2949 (2.6%) '
'participants in the no offer group, 55/1515 (3.6%) developed covid-19 in the lower dose group '
'(1.39, 0.98 to 1.97) and 45/1515 (3.0%) in the higher dose group (1.13, 0.78 to '
'1.63).</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Conclusions</jats:title>\n'
' <jats:p>Among people aged 16 years and older with a high baseline prevalence of '
'suboptimal vitamin D status, implementation of a population level test-and-treat approach to '
'vitamin D supplementation was not associated with a reduction in risk of all cause acute '
'respiratory tract infection or covid-19.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Trial registration</jats:title>\n'
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