Abstract
A growing body of evidence shows that poor vitamin D status has been associated with an increased susceptibility to viral and bacterial respiratory infections. In this study, we aimed to examine the association between vitamin D and COVID-19 risk and outcomes, and to explore potential causal effects. We used logistic regression to identify associations between different vitamin D variables (25-hydroxyvitamin D concentration (25-OHD), ambient UVB and genetically-predicted 25-OHD concentrations) and COVID-19 (risk of infection, hospitalisation and death) in 495,780 participants from UK Biobank. We subsequently performed a Mendelian Randomisation (MR) study to test if there was any causal effect. In total, 1,746 COVID-19 cases and 399 COVID-19 deaths occurred between March and June 2020. We found significant inverse associations between COVID-19 infection and 25-OHD in univariable models, but these associations were non-significant after adjustment for confounders. Ambient UVB was strongly and inversely associated with hospitalization and death. Although the main MR analysis showed that genetically-predicted vitamin D levels were not causally associated with COVID-19 risk, MR sensitivity analysis using weighted mode method indicated a potential causal effect (OR=0.72, 95% CI:0.53-0.98; P=0.041). In conclusion, our study found suggestive evidence of association between vitamin D and the risk or severity of COVID-19 but further studies are needed.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
E.T. is supported by a Cancer Research UK Career Development Fellowship (C31250/A22804).
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
UK Biobank has approval from the North West Multi-Centre Research Ethics Committee (11/NW/0382) and obtained written informed consent from all participants prior to the study. Data used in this study were obtained from UK Biobank under an approved data request application (application ID: 10775).
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Data Availability
Details of genotyping and quality control of UK biobank available at: http://biobank.ndph.ox.ac.uk/crystal/docs/genotyping_qc.pdf
Details of genotype imputation of UK biobank available at: http://www.ukbiobank.ac.uk/wpcontent/uploads/2014/04/imputation%20documentation%20May2015.pdf
Participants description of UK biobank available at: https://www.biorxiv.org/content/biorxiv/early/2017/07/20/166298.full.pdf
Abbreviations
- 25-OHD
- 25-hydroxyvitamin D;
- BMI
- body mass index;
- COVID-19
- Corona Virus Disease 2019;
- IQR
- interquartile range;
- MR
- Mendelian Randomisation;
- OR
- Odds Ratio;
- SD
- Standard Deviation;
- UVB
- ultraviolet radiation b;
- vitD
- vitamin D;
- wGRS
- weighted genetic risk score.