Abstract Background & Aims : Previous results from observational, interventional studies and in vitro experiments suggest that certain micronutrients possess anti-viral and immunomodulatory activities. In particular, it has been hypothesized that zinc, selenium, copper and vitamin K 1 have strong potential for prophylaxis and treatment of COVID-19. We aimed to test whether genetically predicted Zn, Se, Cu or vitamin K 1 levels have a causal effect on COVID-19 related outcomes, including risk of infection, hospitalization and critical illness. Methods : We employed a two-sample Mendelian Randomization (MR) analysis. Our genetic variants derived from European-ancestry GWAS reflected circulating levels of Zn, Cu, Se in red blood cells as well as Se and vitamin K 1 in serum/plasma. For the COVID-19 outcome GWAS, we used infection, hospitalization or critical illness. Our inverse-variance weighted (IVW) MR analysis was complemented by sensitivity analyses including a more liberal selection of variants at a genome-wide sub-significant threshold, MR-Egger and weighted median/mode tests. Results : Circulating micronutrient levels show limited evidence of association with COVID-19 infection, with the odds ratio [OR] ranging from 0.97 (95% CI: 0.87–1.08, p -value = 0.55) for zinc to 1.07 (95% CI: 1.00–1.14, p -value = 0.06)—i.e., no beneficial effect for copper was observed per 1 SD increase in exposure. Similarly minimal evidence was obtained for the hospitalization and critical illness outcomes with OR from 0.98 (95% CI: 0.87–1.09, p -value = 0.66) for vitamin K 1 to 1.07 (95% CI: 0.88–1.29, p -value = 0.49) for copper, and from 0.93 (95% CI: 0.72–1.19, p -value = 0.55) for vitamin K 1 to 1.21 (95% CI: 0.79–1.86, p -value = 0.39) for zinc, respectively. Conclusions : This study does not provide evidence that supplementation with zinc, selenium, copper or vitamin K 1 can prevent SARS-CoV-2 infection, critical illness or hospitalization for COVID-19.
【저자키워드】 COVID-19, SARS-CoV-2, Zinc, mendelian randomization, Selenium, copper, vitamin K1, 【초록키워드】 Treatment, Zinc, Critical illness, Micronutrient, Hospitalization, SARS-COV-2 infection, Infection, outcome, variants, Anti-viral, Prophylaxis, outcomes, COVID-19 infection, sensitivity analysis, Selenium, Vitamin, Genetic variant, GWAS, red blood cells, copper, vitamin K, threshold, Critical, red blood cell, association, Evidence, Analysis, Odds ratio, risk of infection, evidence of, treatment of COVID-19, 95% CI, P -value, Sensitivity analyses, serum/plasma, circulating, aims, immunomodulatory activities, MR-Egger, Prevent, Result, predicted, reflected, increase in, was obtained, in vitro experiment, inverse-variance weighted, IVW, liberal, selection of variant, with COVID-19, 【제목키워드】 Zinc, Selenium, copper, Effect,