An observational and Mendelian randomisation study on vitamin D and COVID-19 risk in UK Biobank

Authors: Li, Xue ;

van Geffen, Jos;

van Weele, Michiel;

Zhang, Xiaomeng;

He, Yazhou;

Meng, Xiangrui;

Timofeeva, Maria;

Campbell, Harry;

Dunlop, Malcolm G.;

Zgaga, Lina;

Theodoratou, Evropi

Source: Li , X , van Geffen , J , van Weele , M , Zhang , X , He , Y , Meng , X , Timofeeva , M , Campbell , H , Dunlop , M , Zgaga , L & Theodoratou , E 2021 , ' An observational and Mendelian randomisation study on vitamin D and COVID-19 risk in UK Biobank ' , Scientific Reports , vol. 11 , no. 1 , pp. 18262 . https://doi.org/10.1038/s41598-021-97679-5

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Abstract

A growing body of evidence suggests that vitamin D deficiency 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. We used logistic regression to identify associations between vitamin D variables and COVID-19 (risk of infection, hospitalisation and death) in 417,342 participants from UK Biobank. We subsequently performed a Mendelian Randomisation (MR) study to look for evidence of a causal effect. In total, 1746 COVID-19 cases (399 deaths) were registered between March and June 2020. We found no significant associations between COVID-19 infection risk and measured 25-OHD levels after adjusted for covariates, but this finding is limited by the fact that the vitamin D levels were measured on average 11 years before the pandemic. Ambient UVB was strongly and inversely associated with COVID-19 hospitalization and death overall and consistently after stratification by BMI and ethnicity. We also observed an interaction that suggested greater protective effect of genetically-predicted vitamin D levels when ambient UVB radiation is stronger. The main MR analysis did not show that genetically-predicted vitamin D levels are causally associated with COVID-19 risk (OR = 0.77, 95% CI 0.55-1.11, P = 0.160), but MR sensitivity analyses indicated a potential causal effect (weighted mode MR: OR = 0.72, 95% CI 0.55-0.95, P = 0.021; weighted median MR: OR = 0.61, 95% CI 0.42-0.92, P = 0.016). Analysis of MR-PRESSO did not find outliers for any instrumental variables and suggested a potential causal effect (OR = 0.80, 95% CI 0.66-0.98, p-val = 0.030). In conclusion, the effect of vitamin D levels on the risk or severity of COVID-19 remains controversial, further studies are needed to validate vitamin D supplementation as a means of protecting against worsened COVID-19.

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Li, X., van Geffen, J., van Weele, M., Zhang, X., He, Y., Meng, X., Timofeeva, M., Campbell, H., Dunlop, M., Zgaga, L. & Theodoratou, E. 2021, 'An observational and Mendelian randomisation study on vitamin D and COVID-19 risk in UK Biobank'Li, X , van Geffen , J , van Weele , M , Zhang , X , He , Y , Meng , X , Timofeeva , M , Campbell , H , Dunlop , M , Zgaga , L & Theodoratou , E 2021 , ' An observational and Mendelian randomisation study on vitamin D and COVID-19 risk in UK Biobank ' , Scientific Reports , vol. 11 , no. 1 , pp. 18262 . https://doi.org/10.1038/s41598-021-97679-5. https://publichealthscotland.scot/id/45109

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