Article Text

Original research
Association between vitamin D supplementation or serum vitamin D level and susceptibility to SARS-CoV-2 infection or COVID-19 including clinical course, morbidity and mortality outcomes? A systematic review
  1. Amy Grove1,
  2. Osemeke Osokogu1,
  3. Lena Al-Khudairy1,
  4. Amin Mehrabian1,2,
  5. Mandana Zanganeh1,
  6. Anna Brown1,
  7. Rachel Court1,
  8. Sian Taylor-Phillips1,
  9. Olalekan A Uthman3,
  10. Noel McCarthy1,
  11. Sudhesh Kumar4,
  12. Aileen Clarke1
  1. 1Division of Health Sciences, Warwick Medical School, The University of Warwick, Coventry, UK
  2. 2Department of Pharmaceutical Nanotechnology, University of Medical Sciences, Mashhad, Iran (the Islamic Republic of)
  3. 3Warwick-Centre for Applied Health Research (WCAHRD), University of Warwick, Coventry, UK
  4. 4Warwick Medical School, The University of Warwick, Coventry, UK
  1. Correspondence to Dr Amy Grove; A.L.Grove{at}warwick.ac.uk

Abstract

Objective To systemically review and critically appraise published studies of the association between vitamin D supplementation or serum vitamin D level and susceptibility to SARS-CoV-2 infection or COVID-19, including clinical course, morbidity and mortality outcomes.

Design Systematic review.

Data sources MEDLINE (OVID), Embase (OVID), Cochrane Central Register of Controlled Trials, MedRxiv and BioRxiv preprint databases. COVID-19 databases of the WHO, Cochrane, CEBM Oxford and Bern University up to 10 June 2020.

Study selection Studies that assessed vitamin D supplementation and/or low serum vitamin D in patients acutely ill with, or at risk of, severe betacoronavirus infection (SARS-CoV, MERS-CoV, SARS-CoV-2).

Data extraction Two authors independently extracted data using a predefined data extraction form and assessed risk of bias using the Downs and Black Quality Assessment Checklist.

Results Searches elicited 449 papers, 59 studies were eligible full-text assessment and 4 met the eligibility criteria of this review. The four studies were narratively synthesised and included (1) a cross-sectional study (n=107) suggesting an inverse association between serum vitamin D and SARS-CoV-2; (2) a retrospective cohort study (348 598 participants, 449 cases) in which univariable analysis showed that vitamin D protects against COVID-19; (3) an ecological country level study demonstrating a negative correlation between vitamin D and COVID-19 case numbers and mortality; and (4) a case–control survey (n=1486) showing cases with confirmed/probable COVID-19 reported lower vitamin D supplementation. All studies were at high/unclear risk of bias.

Conclusion There is no robust evidence of a negative association between vitamin D and COVID-19. No relevant randomised controlled trials were identified and there is no robust peer-reviewed published evidence of association between vitamin D levels and severity of symptoms or mortality due to COVID-19. Guideline producers should acknowledge that benefits of vitamin D supplementation in COVID-19 are as yet unproven despite increasing interest.

  • COVID-19
  • public health
  • nutrition & dietetics

Data availability statement

Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. The study protocol is available systematic review protocol registration: CRD42020182876 available online via PROSPERO at https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020182876. All included studies are publicly available. Additional data are available on reasonable request by emailing the corresponding author.

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Data availability statement

Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. The study protocol is available systematic review protocol registration: CRD42020182876 available online via PROSPERO at https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020182876. All included studies are publicly available. Additional data are available on reasonable request by emailing the corresponding author.

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Footnotes

  • Contributors SK, AG and AC conceived the study. AG, AC, NM, SK, ST-P and OAU designed the study. RC and AB developed the search strategies, performed all searches and database management, and created the bibliography. AG, AC, AM, OO, MZ screened titles and abstracts for inclusion. AG, OO, AM, MZ, LA-K and AC screened at full text and extracted and analysed data. OO, AM, MZ and LA-K performed risk of bias assessments. AC, SK and NM assisted in the interpretation from a clinical perspective. ST-P, LA-K and OU offered technical and methodological support. AG, OO and MZ wrote the first draft, all authors revised content. All authors approved the final manuscript. AG and AC are the guarantors. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding Dr AG is supported by the National Institute for Health Research (NIHR) Advanced Fellowship Programme Reference (AF-300060). Dr ST-P is supported by an NIHR Career Development Fellowship (CDF-2016-09-018). Professor AC and Dr LA-K are supported by the NIHR Applied Research Centre West Midlands (ARC-WM). All other authors, with the exception of Professor Uthman, Professor SK and Professor NMC, are supported by the NIHR, Evidence Synthesis Programme (HTA 14.25.05). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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