The Association of Low Vitamin K Status with Mortality in a Cohort of 138 Hospitalized Patients with COVID-19
Allan Linneberg, Freja Bach Kampmann, Simone Bastrup Israelsen, Liv Rabøl Andersen, Henrik Løvendahl Jørgensen, Håkon Sandholt, Niklas Rye Jørgensen, Sanne Marie Thysen, Thomas Benfield
Nutrients, doi:10.3390/nu13061985
It has recently been hypothesized that vitamin K could play a role in COVID-19. We aimed to test the hypotheses that low vitamin K status is a common characteristic of patients hospitalized with COVID-19 compared to population controls and that low vitamin K status predicts mortality in COVID-19 patients. In a cohort of 138 COVID-19 patients and 138 population controls, we measured plasma dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP), which reflects the functional vitamin K status in peripheral tissue. Forty-three patients died within 90 days from admission. In patients, levels of dp-ucMGP differed significantly between survivors (mean 877; 95% CI: 778; 995) and non-survivors (mean 1445; 95% CI: 1148; 1820). Furthermore, levels of dp-ucMGP (pmol/L) were considerably higher in patients (mean 1022; 95% CI: 912; 1151) compared to controls (mean 509; 95% CI: 485; 540). Cox regression survival analysis showed that increasing levels of dp-ucMGP (reflecting low vitamin K status) were associated with higher mortality risk (sex-and age-adjusted hazard ratio per doubling of dp-ucMGP was 1.49, 95% CI: 1.03; 2.24). The association attenuated and became statistically insignificant after adjustment for co-morbidities (sex, age, CVD, diabetes, BMI, and eGFR adjusted hazard ratio per doubling of dp-ucMGP was 1.22, 95% CI: 0.82; 1.80). In conclusion, we found that low vitamin K status was associated with mortality in patients with COVID-19 in sex-and age-adjusted analyses, but not in analyses additionally adjusted for co-morbidities. Randomized clinical trials would be needed to clarify a potential role, if any, of vitamin K in the course of COVID-19.
Conflicts of Interest: Benfield reports grants from Novo Nordisk Foundation, grants from Simonsen Foundation, grants and personal fees from GSK, grants and personal fees from Pfizer, personal fees from Boehringer Ingelheim, grants and personal fees from Gilead, personal fees from MSD, grants from Lundbeck Foundation, grants from Kai Hansen Foundation, personal fees from Pentabase A/S, outside the submitted work. Kappa Bioscience AS (https://www.kappabio.com/; accessed on 6 June 2021) contributed with an unrestricted postdoc grant to vitamin K-related epidemiological research at the Center for Clinical Research and Prevention. All other authors have no relevant disclosures. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.
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'abstract': '<jats:p>It has recently been hypothesized that vitamin K could play a role in COVID-19. We '
'aimed to test the hypotheses that low vitamin K status is a common characteristic of patients '
'hospitalized with COVID-19 compared to population controls and that low vitamin K status '
'predicts mortality in COVID-19 patients. In a cohort of 138 COVID-19 patients and 138 '
'population controls, we measured plasma dephosphorylated-uncarboxylated Matrix Gla Protein '
'(dp-ucMGP), which reflects the functional vitamin K status in peripheral tissue. Forty-three '
'patients died within 90 days from admission. In patients, levels of dp-ucMGP differed '
'significantly between survivors (mean 877; 95% CI: 778; 995) and non-survivors (mean 1445; '
'95% CI: 1148; 1820). Furthermore, levels of dp-ucMGP (pmol/L) were considerably higher in '
'patients (mean 1022; 95% CI: 912; 1151) compared to controls (mean 509; 95% CI: 485; 540). '
'Cox regression survival analysis showed that increasing levels of dp-ucMGP (reflecting low '
'vitamin K status) were associated with higher mortality risk (sex- and age-adjusted hazard '
'ratio per doubling of dp-ucMGP was 1.49, 95% CI: 1.03; 2.24). The association attenuated and '
'became statistically insignificant after adjustment for co-morbidities (sex, age, CVD, '
'diabetes, BMI, and eGFR adjusted hazard ratio per doubling of dp-ucMGP was 1.22, 95% CI: '
'0.82; 1.80). In conclusion, we found that low vitamin K status was associated with mortality '
'in patients with COVID-19 in sex- and age-adjusted analyses, but not in analyses additionally '
'adjusted for co-morbidities. Randomized clinical trials would be needed to clarify a '
'potential role, if any, of vitamin K in the course of COVID-19.</jats:p>',
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