No evidence that vitamin D is able to prevent or affect the severity of COVID-19 in individuals with European ancestry: a Mendelian randomisation study of open data
BMJ Nutrition, Prevention & Health, doi:10.1136/bmjnph-2020-000151
Background Upper respiratory tract infections are reportedly more frequent and more severe in individuals with lower vitamin D levels. Based on these findings, it has been suggested that vitamin D can prevent or reduce the severity of COVID-19. Methods We used two-sample Mendelian randomisation (MR) to assess the causal effect of vitamin D levels on SARS-CoV-2 infection risk and COVID-19 severity using publicly available data. We also carried out a genome-wide association analysis (GWA) of vitamin D deficiency in the UK Biobank (UKB) and used these results and two-sample MR to assess the causal effect of vitamin D deficiency on SARS-CoV-2 infection risk and COVID-19 severity. Results We found no evidence that vitamin D levels causally affect the risk of SARS-CoV-2 infection (ln(OR)=0.17 (95% CI −0.22 to 0.57, p=0.39)) nor did we find evidence that vitamin D levels causally affect COVID-19 severity (ln(OR)=0.36 (95% CI −0.89 to 1.61, p=0.57)). Based on our GWA analysis, we found that 17 independent variants are associated with vitamin D deficiency in the UKB. Using these variants as instruments for our two-sample MR analyses, we found no evidence that vitamin D deficiency causally affects the risk of SARS-CoV-2 infection (ln(OR)=−0.04 (95% CI −0.1 to 0.03, p=0.25)) nor did we find evidence that vitamin D deficiency causally affects COVID-19 severity (ln(OR)=−0.24 (95% CI −0.55 to 0.08, p=0.14)). Conclusions In conclusion, we found no evidence that vitamin D is protective against SARS-CoV-2 infection or COVID-19 severity. Our data support the recent statement by the National Institute for Health and Care Excellence that the use of vitamin D supplementation to mitigate COVID-19 is not supported by the available data.
What this paper adds ► Uncertainty remains over the use of Vitamin D for the prevention of COVID-19 and the moderation of its symptoms. ► Genetic predisposition for higher levels of vitamin D and for lower chance of vitamin D insufficiency do not have evidence of association with infection from SARS-CoV-2 or severity of COVID-19 following infection. ► Our work supports the current NICE statement that, based on the available evidence, vitamin D should not be considered as protective of infection from SARS-CoV-2 or a way to mitigate its severity.
Competing interests None declared. Patient consent for publication Not required. Provenance and peer review Not commissioned; externally peer reviewed by Dr Emmanuel Baah University of North Carolina System, USA. Data availability statement Data from the COVID-19 Host Genetics Initiative are available in a public, open access repository. UK Biobank data may be obtained from a third party and are not publicly available. The data from the COVID-19 Host Genetics Initiative that were used in this study are available here: https://www. covid19hg. org/ results/. UK Biobank data are available to all bona fide researchers for all types of health-related research which is in the public interest. 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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