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

doi:10.1136/bmj-2022-071230

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 GriffithsJohn Norrie, Aziz Sheikh, Seif O Shaheen, Clare Relton, Adrian R Martineau^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Article number	e071230
Number of pages	14
Journal	BMJ
Volume	378
DOIs	https://doi.org/10.1136/bmj-2022-071230
Publication status	Published - 7 Sept 2022

Bibliographical note

Keywords

COVID-19/prevention & control
Cholecalciferol
Dietary Supplements
Double-Blind Method
Humans
Respiratory Tract Infections/drug therapy
Vitamin D/therapeutic use
Vitamin D Deficiency/diagnosis
Vitamins/therapeutic use

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Jolliffe, D. A., Holt, H., Greenig, M., Talaei, M., Perdek, N., Pfeffer, P., Vivaldi, G., Maltby, S., Symons, J., Barlow, N. L., Normandale, A., Garcha, R., Richter, A. G., Faustini, S. E., Orton, C., Ford, D., Lyons, R. A., Davies, G. A., Kee, F., ... Martineau, A. R. (2022). 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, 378, Article e071230. https://doi.org/10.1136/bmj-2022-071230

@article{782ad3d7b9234f12b6f698b230d8ca0a,

title = "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)",

abstract = "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.",

keywords = "COVID-19/prevention & control, Cholecalciferol, Dietary Supplements, Double-Blind Method, Humans, Respiratory Tract Infections/drug therapy, Vitamin D/therapeutic use, Vitamin D Deficiency/diagnosis, Vitamins/therapeutic use",

author = "Jolliffe, {David A} and Hayley Holt and Matthew Greenig and Mohammad Talaei and Natalia Perdek and Paul Pfeffer and Giulia Vivaldi and Sheena Maltby and Jane Symons and Barlow, {Nicola L} and Alexa Normandale and Rajvinder Garcha and Richter, {Alex G} and Faustini, {Sian E} and Christopher Orton and David Ford and Lyons, {Ronan A} and Davies, {Gwyneth A} and Frank Kee and Griffiths, {Christopher J} and John Norrie and Aziz Sheikh and Shaheen, {Seif O} and Clare Relton and Martineau, {Adrian R}",

note = "{\textcopyright} Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",

year = "2022",

month = sep,

day = "7",

doi = "10.1136/bmj-2022-071230",

language = "English",

volume = "378",

journal = "BMJ",

issn = "1756-1833",

publisher = "BMJ Publishing Group",

}

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 2022, '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, vol. 378, e071230. https://doi.org/10.1136/bmj-2022-071230

TY - JOUR

T1 - Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19

T2 - phase 3 randomised controlled trial (CORONAVIT)

AU - Jolliffe, David A

AU - Holt, Hayley

AU - Greenig, Matthew

AU - Talaei, Mohammad

AU - Perdek, Natalia

AU - Pfeffer, Paul

AU - Vivaldi, Giulia

AU - Maltby, Sheena

AU - Symons, Jane

AU - Barlow, Nicola L

AU - Normandale, Alexa

AU - Garcha, Rajvinder

AU - Richter, Alex G

AU - Faustini, Sian E

AU - Orton, Christopher

AU - Ford, David

AU - Lyons, Ronan A

AU - Davies, Gwyneth A

AU - Kee, Frank

AU - Griffiths, Christopher J

AU - Norrie, John

AU - Sheikh, Aziz

AU - Shaheen, Seif O

AU - Relton, Clare

AU - Martineau, Adrian R

PY - 2022/9/7

Y1 - 2022/9/7

N2 - 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.

AB - 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.

KW - COVID-19/prevention & control

KW - Cholecalciferol

KW - Dietary Supplements

KW - Double-Blind Method

KW - Humans

KW - Respiratory Tract Infections/drug therapy

KW - Vitamin D/therapeutic use

KW - Vitamin D Deficiency/diagnosis

KW - Vitamins/therapeutic use

U2 - 10.1136/bmj-2022-071230

DO - 10.1136/bmj-2022-071230

M3 - Article

C2 - 36215226

SN - 1756-1833

VL - 378

JO - BMJ

JF - BMJ

M1 - e071230

ER -

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)

Abstract

Bibliographical note

Keywords

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