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Reduced Vitamin K Status as a Potentially Modifiable Risk Factor of Severe Coronavirus Disease 2019

Dofferhoff et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa1258, ISRCTN86049077
Aug 2020  
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Retrospective 135 hospitalized COVID-19 patients showing low vitamin K status was associated with poor outcomes, elastic fiber degradation, and thrombosis risk. Dp-ucMGP, an inverse marker of extrahepatic vitamin K status, was severely elevated in COVID-19 patients compared to controls and was even higher in patients with poor outcomes (invasive ventilation and/or death). The authors propose that pneumonia-induced extrahepatic vitamin K depletion leads to impaired activation of matrix Gla protein (MGP) and endothelial protein S, resulting in accelerated elastic fiber damage and thrombosis in severe COVID-19. The study used a historical control group, limiting confidence in the results.
Dofferhoff et al., 27 Aug 2020, retrospective, Netherlands, peer-reviewed, mean age 19.0, 17 authors, trial ISRCTN86049077. Contact:
This PaperVitamin KAll
Reduced vitamin K status as a potentially modifiable risk factor of severe COVID-19
Anton S M Dofferhoff, M.D Ianthe Piscaer, M.D Leon J Schurgers, PhD Margot P J Visser, M.D Jody M W Van Den Ouweland, Pim A De Jong, M.D Reinoud Gosens, Ph.D Tilman M Hackeng, Ph.D Henny Van Daal, Petra Lux, Cecile Maassen, Esther G A Karssemeijer, Emiel F M Wouters, Loes E M Kistemaker, Ph.D Jona Walk, M.D Rob Janssen
Indirectly quantified extrahepatic vitamin K status is severely reduced in COVID-19 patients. Data suggest pneumonia-induced vitamin K depletion leading to accelerated elastic fiber damage and thrombosis risk due to impaired vitamin K-dependent activation of MGP and endothelial protein S, respectively.
Authors' contributions RJ developed the theory. ASMD, RJ and LJS designed the study. LJS, PL and CM were responsible for the dp-ucMGP and PIVKA-II; and JMWO and HD for the DES measurements. PAJ performed the CT analyses. HD, EGAK, CV, MPJV and JW analyzed the data, and IP performed the statistical analysis. IP, JW and RJ wrote the first draft of the manuscript. ASMD, LJS, JMWO, PAJ, TMH, RG, LEMK, and EFMW critically revised the manuscript. Conflict of interest statements LJS reports consultancy fee from Immunodiagnostic systems and grants from NattoPharma. JMWO and RJ are owners of and RJ is owner of Emphysema Solutions BV. RJ discloses application of a patent on vitamin K in COVID-19 for prognostic and therapeutic purposes. ASMD, IP, JW, MPJV, TMH, PAJ, RG, PL, HD, CM, EGAK, LEMK, CV, and EFMW declare no competing interests. Cardiac or cardiovascular disease (%) 17
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