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, MD Grace A Mccomsey
Open Forum Infectious Diseases, doi:10.1093/ofid/ofab408
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.
Supplementary Data Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.
References
Anastasi, Ialongo, Labriola, Vitamin K deficiency and COVID-19, Scand J Clin Lab Invest
Dofferhoff, Piscaer, Schurgers, Reduced vitamin K status as a potentially modifiable risk factor of severe COVID-19, Clin Infect Dis
Eckard, 'riordan, Rosebush, Vitamin D supplementation decreases immune activation and exhaustion in HIV-1-infected youth, Antivir Ther
Fain, Kapuku, Paulson, Inactive matrix Gla protein, arterial stiffness, and endothelial function in African American hemodialysis patients, Am J Hypertens
Holick, Vitamin D deficiency, N Engl J Med
Jamilloux, Henry, Belot, Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions, Autoimmun Rev
Jespersen, Møllehave, Thuesen, Uncarboxylated matrix Glaprotein: a biomarker of vitamin K status and cardiovascular risk, Clin Biochem
Liu, Zhang, Xu, The anti-inflammatory effects of vitamin D in tumorigenesis, Int J Mol Sci
Martineau, Jolliffe, Hooper, Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data, BMJ
Meltzer, Best, Zhang, Association of vitamin D status and other clinical characteristics with COVID-19 test results, JAMA Netw Open
Ohsaki, Shirakawa, Hiwatashi, Vitamin K suppresses lipopolysaccharide-induced inflammation in the rat, Biosci Biotechnol Biochem
Ohsaki, Shirakawa, Miura, Vitamin K suppresses the lipopolysaccharide-induced expression of inflammatory cytokines in cultured macrophage-like cells via the inhibition of the activation of nuclear factor κB through the repression of IKKα/β phosphorylation, J Nutr Biochem
Ozaki, Zhang, Mizuta, Menatetrenone, a vitamin K2 analogue, inhibits hepatocellular carcinoma cell growth by suppressing cyclin D1 expression through inhibition of nuclear factor kappaB activation, Clin Cancer Res
Pan, Maresz, Lee, Inhibition of TNF-α, IL-1α, and IL-1β by pretreatment of human monocyte-derived macrophages with menaquinone-7 and cell activation with TLR agonists in vitro, J Med Food
Panagiotou, Tee, Ihsan, Low serum 25-hydroxyvitamin D (25[OH] D) levels in patients hospitalized with COVID-19 are associated with greater disease severity, Clin Endocrinol (Oxf)
Piscaer, Van Den Ouweland, Vermeersch, Low vitamin K status is associated with increased elastin degradation in chronic obstructive pulmonary disease, J Clin Med
Prietl, Treiber, Pieber, Amrein, Vitamin D and immune function, Nutrients
Reddi, Henderson, Meghji, Interleukin 6 production by lipopolysaccharide-stimulated human fibroblasts is potently inhibited by naphthoquinone (vitamin K) compounds, Cytokine
Schurgers, Vermeer, Differential lipoprotein transport pathways of K-vitamins in healthy subjects, Biochim Biophys Acta
Shen, Bimali, Faramawi, Orloff, Consumption of vitamin K and vitamin A are associated with reduced risk of developing emphysema: NHANES 2007-2016, Front Nutr
Simes, Viegas, Araujo, Marreiros, Vitamin K as a diet supplement with impact in human health: current evidence in age-related diseases, Nutrients
Suleiman, Négrier, Boukerche, Protein S: a multifunctional anticoagulant vitamin K-dependent protein at the crossroads of coagulation, inflammation, angiogenesis, and cancer, Crit Rev Oncol Hematol
Van Ballegooijen, Beulens, Kieneker, Combined low vitamin D and K status amplifies mortality risk: a prospective study, Eur J Nutr
Wiersinga, Rhodes, Cheng, Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review, JAMA
Xia, Matsuhashi, Hamajima, The role of PKC isoforms in the inhibition of NF-κB activation by vitamin K2 in human hepatocellular carcinoma cells, J Nutr Biochem
Yancy, COVID-19 and African Americans, JAMA
Zabetakis, Lordan, Norton, Tsoupras, COVID-19: the inflammation link and the role of nutrition in potential mitigation, Nutrients
Zhang, Lee, Ang, Risk factors for severe disease and efficacy of treatment in patients infected with COVID-19: a systematic review, metaanalysis, and meta-regression analysis, Clin Infect Dis
Zwakenberg, Burgess, Sluijs, EPIC-CVD consortium. Circulating phylloquinone, inactive matrix Gla protein and coronary heart disease risk: a two-sample Mendelian randomization study, Clin Nutr
DOI record:
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"abstract": "<jats:title>Abstract</jats:title>\n <jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>We investigated the association of vitamin K and vitamin D with coronavirus disease 2019 (COVID-19) outcomes.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>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 &lt; .0001) with similar 25(OH)D between groups (25.8 vs 21.9 ng/mL; P = .09). Participants who were vitamin D deficient (&lt;20 ng/mL) had the worse vitamin K status (dp-ucMGP &gt;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 &gt;3 times the likelihood of severe COVID-19 disease (AOR, 0.29; 95% CI, 0.11–0.67).</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec>",
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