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.

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