Vitamin K & D Deficiency Are Independently Associated With Covid-19 Disease Severity

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

BACKGROUND: We investigated the status of vitamin K and vitamin D and association to 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 levels (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 (UOR) and adjusted odds ratios (AOR) with 95% confidence intervals (CI) were computed using cumulative logistic regression. RESULTS: 150 subjects were included, 100 COVID-19+ and 50 controls. Median agewas 55 (IQR: 48, 63), 50% were females. 34% had mild COVID-19 disease, 51% moderate disease, and 15% severe. Dp-ucMGP levels were higher (i.e. worse K status) in COVID-19+ vs controls (776.5 ng/mL vs 549.8 ng/mL, p <0.0001) with similar 25(OH)D between groups (25.8 vs 21.9 ng/mL, p=0.09). Participants who were vitamin D deficient (<20ng/mL) had the worse vitamin K status (dp-ucMGP >780ng/mL) and experienced the most severe COVID-19 outcomes. In adjusted models, every one-unit increase in the log2 dp-ucMGP nearly doubled the odds of acute critical disease or death [AOR 95%CI: 1.84 (1.01, 3.45)] and every one-unit decrease in the natural log 25(OH)D was associated with more than three times the likelihood of COVID-19 disease severity [AOR 95%CI: 0.29 (0.11, 0.67)]. CONCLUSION: 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 two vitamins in COVID-19.