Vitamin K & D Deficiencies are independently associated with COVID-19 disease severity

Ankita P. Desai; Sahera Dirajlal-Fargo; Jared C. Durieux; Heather Tribout; Danielle Labbato; Grace A. McComsey

doi:10.1093/ofid/ofab408

Vitamin K & D Deficiencies are independently associated with COVID-19 disease severity

Ankita P. Desai, Sahera Dirajlal-Fargo, Jared C. Durieux, Heather Tribout, Danielle Labbato, Grace A. McComsey

Pediatrics

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Background: We investigated the association of vitamin K and vitamin D with coronavirus disease 2019 (COVID-19) outcomes. Methods: Levels of inactive vitamin K-dependent dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP; marker of vitamin K status) and 25-hydroxyvitamin D (25(OH)D; vitamin D status) were measured in plasma samples from participants with confirmed acute COVID-19 and were age- and sex-matched to healthy controls. Unadjusted odds ratios and adjusted odds ratios (AORs) with 95% CIs were computed using cumulative logistic regression. Results: One hundred fifty subjects were included, 100 COVID-19+ and 50 controls. The median age (interquartile range) was 55 (48-63) years, and 50% were females. Thirty-four percent had mild COVID-19 disease, 51% moderate disease, and 15% severe. Dp-ucMGP levels were higher (ie, worse K status) in COVID-19+ vs controls (776.5 ng/mL vs 549.8 ng/mL; P <. 0001) with similar 25(OH)D between groups (25.8 vs 21.9 ng/mL; P =. 09). Participants who were vitamin D deficient (<20 ng/mL) had the worse vitamin K status (dp-ucMGP >780 ng/mL) and experienced the most severe COVID-19 outcomes. In adjusted models, every 1-unit increase in the log2 dp-ucMGP nearly doubled the odds of acute critical disease or death (AOR, 1.84; 95% CI, 1.01-3.45), and every 1-unit decrease in the natural log 25(OH)D was associated with >3 times the likelihood of severe COVID-19 disease (AOR, 0.29; 95% CI, 0.11-0.67). Conclusions: Early in acute COVID-19, both vitamin K and vitamin D deficiency were independently associated with worse COVID-19 disease severity, suggesting a potential synergistic interplay between these 2 vitamins in COVID-19.

Original language	English (US)
Article number	ofab408
Journal	Open Forum Infectious Diseases
Volume	8
Issue number	10
DOIs	https://doi.org/10.1093/ofid/ofab408
State	Published - Oct 1 2021

Funding

This work was supported by funding through University Hospitals Cleveland Medical Center (UHCMC) and the Clinical and Translational Science Collaborative of Cleveland, as well as UL1TR002548 from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health (NIH) and NIH roadmap for Medical Research. Funding supported the enrollment of participants. Findings in the manuscript are solely the responsibility of the authors and do not necessarily represent the official views of UHCMC or the NIH. In addition, the study was partially funded by Kappa Bioscience AS; Kappa Bioscience AS funded the vitamin K and vitamin D assays by directly paying the Maine laboratory. Kappa Bioscience AS has no access to any raw data or any participants' data besides what is described in this manuscript.

Keywords

COVID-19
SARS-CoV-2
Vitamin D
Vitamin K

ASJC Scopus subject areas

Oncology
Clinical Neurology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/ofid/ofab408

Cite this

@article{788a21cfe82a4576b460718355925a14,

title = "Vitamin K & D Deficiencies are independently associated with COVID-19 disease severity",

abstract = "Background: We investigated the association of vitamin K and vitamin D with coronavirus disease 2019 (COVID-19) outcomes. Methods: Levels of inactive vitamin K-dependent dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP; marker of vitamin K status) and 25-hydroxyvitamin D (25(OH)D; vitamin D status) were measured in plasma samples from participants with confirmed acute COVID-19 and were age- and sex-matched to healthy controls. Unadjusted odds ratios and adjusted odds ratios (AORs) with 95% CIs were computed using cumulative logistic regression. Results: One hundred fifty subjects were included, 100 COVID-19+ and 50 controls. The median age (interquartile range) was 55 (48-63) years, and 50% were females. Thirty-four percent had mild COVID-19 disease, 51% moderate disease, and 15% severe. Dp-ucMGP levels were higher (ie, worse K status) in COVID-19+ vs controls (776.5 ng/mL vs 549.8 ng/mL; P <. 0001) with similar 25(OH)D between groups (25.8 vs 21.9 ng/mL; P =. 09). Participants who were vitamin D deficient (<20 ng/mL) had the worse vitamin K status (dp-ucMGP >780 ng/mL) and experienced the most severe COVID-19 outcomes. In adjusted models, every 1-unit increase in the log2 dp-ucMGP nearly doubled the odds of acute critical disease or death (AOR, 1.84; 95% CI, 1.01-3.45), and every 1-unit decrease in the natural log 25(OH)D was associated with >3 times the likelihood of severe COVID-19 disease (AOR, 0.29; 95% CI, 0.11-0.67). Conclusions: Early in acute COVID-19, both vitamin K and vitamin D deficiency were independently associated with worse COVID-19 disease severity, suggesting a potential synergistic interplay between these 2 vitamins in COVID-19.",

keywords = "COVID-19, SARS-CoV-2, Vitamin D, Vitamin K",

author = "Desai, {Ankita P.} and Sahera Dirajlal-Fargo and Durieux, {Jared C.} and Heather Tribout and Danielle Labbato and McComsey, {Grace A.}",

note = "Funding Information: This work was supported by funding through University Hospitals Cleveland Medical Center (UHCMC) and the Clinical and Translational Science Collaborative of Cleveland, as well as UL1TR002548 from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health (NIH) and NIH roadmap for Medical Research. Funding supported the enrollment of participants. Findings in the manuscript are solely the responsibility of the authors and do not necessarily represent the official views of UHCMC or the NIH. In addition, the study was partially funded by Kappa Bioscience AS; Kappa Bioscience AS funded the vitamin K and vitamin D assays by directly paying the Maine laboratory. Kappa Bioscience AS has no access to any raw data or any participants' data besides what is described in this manuscript. Publisher Copyright: {\textcopyright} 2021 The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.",

year = "2021",

month = oct,

day = "1",

doi = "10.1093/ofid/ofab408",

language = "English (US)",

volume = "8",

journal = "Open Forum Infectious Diseases",

issn = "2328-8957",

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TY - JOUR

T1 - Vitamin K & D Deficiencies are independently associated with COVID-19 disease severity

AU - Desai, Ankita P.

AU - Dirajlal-Fargo, Sahera

AU - Durieux, Jared C.

AU - Tribout, Heather

AU - Labbato, Danielle

AU - McComsey, Grace A.

N1 - Funding Information: This work was supported by funding through University Hospitals Cleveland Medical Center (UHCMC) and the Clinical and Translational Science Collaborative of Cleveland, as well as UL1TR002548 from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health (NIH) and NIH roadmap for Medical Research. Funding supported the enrollment of participants. Findings in the manuscript are solely the responsibility of the authors and do not necessarily represent the official views of UHCMC or the NIH. In addition, the study was partially funded by Kappa Bioscience AS; Kappa Bioscience AS funded the vitamin K and vitamin D assays by directly paying the Maine laboratory. Kappa Bioscience AS has no access to any raw data or any participants' data besides what is described in this manuscript. Publisher Copyright: © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

PY - 2021/10/1

Y1 - 2021/10/1

N2 - Background: We investigated the association of vitamin K and vitamin D with coronavirus disease 2019 (COVID-19) outcomes. Methods: Levels of inactive vitamin K-dependent dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP; marker of vitamin K status) and 25-hydroxyvitamin D (25(OH)D; vitamin D status) were measured in plasma samples from participants with confirmed acute COVID-19 and were age- and sex-matched to healthy controls. Unadjusted odds ratios and adjusted odds ratios (AORs) with 95% CIs were computed using cumulative logistic regression. Results: One hundred fifty subjects were included, 100 COVID-19+ and 50 controls. The median age (interquartile range) was 55 (48-63) years, and 50% were females. Thirty-four percent had mild COVID-19 disease, 51% moderate disease, and 15% severe. Dp-ucMGP levels were higher (ie, worse K status) in COVID-19+ vs controls (776.5 ng/mL vs 549.8 ng/mL; P <. 0001) with similar 25(OH)D between groups (25.8 vs 21.9 ng/mL; P =. 09). Participants who were vitamin D deficient (<20 ng/mL) had the worse vitamin K status (dp-ucMGP >780 ng/mL) and experienced the most severe COVID-19 outcomes. In adjusted models, every 1-unit increase in the log2 dp-ucMGP nearly doubled the odds of acute critical disease or death (AOR, 1.84; 95% CI, 1.01-3.45), and every 1-unit decrease in the natural log 25(OH)D was associated with >3 times the likelihood of severe COVID-19 disease (AOR, 0.29; 95% CI, 0.11-0.67). Conclusions: Early in acute COVID-19, both vitamin K and vitamin D deficiency were independently associated with worse COVID-19 disease severity, suggesting a potential synergistic interplay between these 2 vitamins in COVID-19.

AB - Background: We investigated the association of vitamin K and vitamin D with coronavirus disease 2019 (COVID-19) outcomes. Methods: Levels of inactive vitamin K-dependent dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP; marker of vitamin K status) and 25-hydroxyvitamin D (25(OH)D; vitamin D status) were measured in plasma samples from participants with confirmed acute COVID-19 and were age- and sex-matched to healthy controls. Unadjusted odds ratios and adjusted odds ratios (AORs) with 95% CIs were computed using cumulative logistic regression. Results: One hundred fifty subjects were included, 100 COVID-19+ and 50 controls. The median age (interquartile range) was 55 (48-63) years, and 50% were females. Thirty-four percent had mild COVID-19 disease, 51% moderate disease, and 15% severe. Dp-ucMGP levels were higher (ie, worse K status) in COVID-19+ vs controls (776.5 ng/mL vs 549.8 ng/mL; P <. 0001) with similar 25(OH)D between groups (25.8 vs 21.9 ng/mL; P =. 09). Participants who were vitamin D deficient (<20 ng/mL) had the worse vitamin K status (dp-ucMGP >780 ng/mL) and experienced the most severe COVID-19 outcomes. In adjusted models, every 1-unit increase in the log2 dp-ucMGP nearly doubled the odds of acute critical disease or death (AOR, 1.84; 95% CI, 1.01-3.45), and every 1-unit decrease in the natural log 25(OH)D was associated with >3 times the likelihood of severe COVID-19 disease (AOR, 0.29; 95% CI, 0.11-0.67). Conclusions: Early in acute COVID-19, both vitamin K and vitamin D deficiency were independently associated with worse COVID-19 disease severity, suggesting a potential synergistic interplay between these 2 vitamins in COVID-19.

KW - COVID-19

KW - SARS-CoV-2

KW - Vitamin D

KW - Vitamin K

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ER -

Vitamin K & D Deficiencies are independently associated with COVID-19 disease severity

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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