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

Open Forum Infect Dis. 2021 Jul 29;8(10):ofab408. doi: 10.1093/ofid/ofab408. eCollection 2021 Oct.

Authors

Ankita P Desai^{1

2

3}, Sahera Dirajlal-Fargo^{1

2

3}, Jared C Durieux¹, Heather Tribout¹, Danielle Labbato¹, Grace A McComsey^{1

2

3}

Affiliations

¹ University Hospitals Cleveland Medical Center; Cleveland, Ohio, USA.
² Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA.
³ Case Western Reserve University, Cleveland, Ohio, USA.

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.