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.
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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'
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' <jats:sec>\n'
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' <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'
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