The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes: A Mendelian Randomization Study

Maria K Sobczyk-Barad; Tom R Gaunt

doi:10.3390/nu14020233

The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes: A Mendelian Randomization Study

Maria K Sobczyk-Barad^*, Tom R Gaunt

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

Background & Aims: Previous results from observational, interventional studies and in vitro experiments suggest that certain micronutrients possess anti-viral and im-munomodulatory activities. In particular, it has been hypothesized that zinc, selenium, copper and vitamin K1 have strong potential for prophylaxis and treatment of COVID-19. We aimed to test whether genetically predicted Zn, Se, Cu or vitamin K1 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 K1 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 in-fection, 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 K1 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 K1 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 K1 can prevent SARS-CoV-2 infection, critical illness or hospitalization for COVID-19.

Original language	English
Article number	233
Pages (from-to)	1-17
Number of pages	17
Journal	Nutrients
Volume	14
Issue number	2
DOIs	https://doi.org/10.3390/nu14020233
Publication status	Published - 6 Jan 2022

Bibliographical note

Funding Information:
Conflicts of Interest: TRG receives funding from Biogen for unrelated research.

Funding Information:
Funding: This work was supported by the UK Medical Research Council [mc_uu_00011/4] and carried out in the MRC Integrative Epidemiology Unit.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

COVID-19
SARS-CoV-2
Mendelian randomization
copper
zinc
selenium
Vitamin K

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Reply to Janssen et al. Comment on “Sobczyk, M.K.; Gaunt, T.R. The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes: A Mendelian Randomization Study. Nutrients 2022, 14, 233
Sobczyk-Barad, M. K. & Gaunt, T. R., 7 Mar 2022, In: Nutrients. 14, 5, p. 1-2 2 p., 1113.
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@article{fcde98858dfe47439db0eadf610e21c7,

title = "The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes: A Mendelian Randomization Study",

abstract = "Background & Aims: Previous results from observational, interventional studies and in vitro experiments suggest that certain micronutrients possess anti-viral and im-munomodulatory activities. In particular, it has been hypothesized that zinc, selenium, copper and vitamin K1 have strong potential for prophylaxis and treatment of COVID-19. We aimed to test whether genetically predicted Zn, Se, Cu or vitamin K1 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 K1 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 in-fection, 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 K1 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 K1 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 K1 can prevent SARS-CoV-2 infection, critical illness or hospitalization for COVID-19.",

keywords = "COVID-19, SARS-CoV-2, Mendelian randomization, copper, zinc, selenium, Vitamin K",

author = "Sobczyk-Barad, {Maria K} and Gaunt, {Tom R}",

note = "Funding Information: Conflicts of Interest: TRG receives funding from Biogen for unrelated research. Funding Information: Funding: This work was supported by the UK Medical Research Council [mc_uu_00011/4] and carried out in the MRC Integrative Epidemiology Unit. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

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doi = "10.3390/nu14020233",

language = "English",

volume = "14",

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journal = "Nutrients",

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T1 - The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes

T2 - A Mendelian Randomization Study

AU - Sobczyk-Barad, Maria K

AU - Gaunt, Tom R

N1 - Funding Information: Conflicts of Interest: TRG receives funding from Biogen for unrelated research. Funding Information: Funding: This work was supported by the UK Medical Research Council [mc_uu_00011/4] and carried out in the MRC Integrative Epidemiology Unit. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/1/6

Y1 - 2022/1/6

N2 - Background & Aims: Previous results from observational, interventional studies and in vitro experiments suggest that certain micronutrients possess anti-viral and im-munomodulatory activities. In particular, it has been hypothesized that zinc, selenium, copper and vitamin K1 have strong potential for prophylaxis and treatment of COVID-19. We aimed to test whether genetically predicted Zn, Se, Cu or vitamin K1 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 K1 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 in-fection, 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 K1 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 K1 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 K1 can prevent SARS-CoV-2 infection, critical illness or hospitalization for COVID-19.

AB - Background & Aims: Previous results from observational, interventional studies and in vitro experiments suggest that certain micronutrients possess anti-viral and im-munomodulatory activities. In particular, it has been hypothesized that zinc, selenium, copper and vitamin K1 have strong potential for prophylaxis and treatment of COVID-19. We aimed to test whether genetically predicted Zn, Se, Cu or vitamin K1 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 K1 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 in-fection, 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 K1 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 K1 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 K1 can prevent SARS-CoV-2 infection, critical illness or hospitalization for COVID-19.

KW - COVID-19

KW - SARS-CoV-2

KW - Mendelian randomization

KW - copper

KW - zinc

KW - selenium

KW - Vitamin K

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DO - 10.3390/nu14020233

M3 - Article (Academic Journal)

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JO - Nutrients

JF - Nutrients

SN - 2072-6643

IS - 2

M1 - 233

ER -

The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes: A Mendelian Randomization Study

Abstract

Bibliographical note

Keywords

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Research output

Reply to Janssen et al. Comment on “Sobczyk, M.K.; Gaunt, T.R. The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes: A Mendelian Randomization Study. Nutrients 2022, 14, 233

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