Reduced Vitamin K Status as a Potentially Modifiable Risk Factor of Severe Coronavirus Disease 2019
Dofferhoff, Anton S.M.; Piscaer, Ianthe; Schurgers, Leon J.; Visser, Margot P.J.; van den Ouweland, Jody M.W.; de Jong, Pim A.; Gosens, Reinoud; Hackeng, Tilman M.; van Daal, Henny; Lux, Petra; Maassen, Cecile; Karssemeijer, Esther G.A.; Vermeer, Cees; Wouters, Emiel F.M.; Kistemaker, Loes E.M.; Walk, Jona; Janssen, Rob
(2021) Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, volume 73, issue 11, pp. e4039 - e4046
(Article)
Abstract
BACKGROUND: Respiratory failure and thromboembolism are frequent in severe acute respiratory syndrome coronavirus 2-infected patients. Vitamin K activates both hepatic coagulation factors and extrahepatic endothelial anticoagulant protein S, required for thrombosis prevention. In times of vitamin K insufficiency, hepatic procoagulant factors are preferentially activated over extrahepatic proteins. Vitamin K also
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activates matrix Gla protein (MGP), which protects against pulmonary and vascular elastic fiber damage. We hypothesized that vitamin K may be implicated in coronavirus disease 2019 (COVID-19), linking pulmonary and thromboembolic disease. METHODS: A total of 135 hospitalized COVID-19 patients were compared with 184 historic controls. Inactive vitamin K-dependent MGP (desphospho-uncarboxylated [dp-uc] MGP) and prothrombin (PIVKA-II) were measured inversely related to extrahepatic and hepatic vitamin K status, respectively. Desmosine was measured to quantify the rate of elastic fiber degradation. Arterial calcification severity was assessed using computed tomography. RESULTS: dp-ucMGP was elevated in COVID-19 patients compared with controls (P < .001), with even higher dp-ucMGP in patients with poor outcomes (P < .001). PIVKA-II was normal in 82.1% of patients. dp-ucMGP was correlated with desmosine (P < .001) and with coronary artery (P = .002) and thoracic aortic (P < .001) calcification scores. CONCLUSIONS: dp-ucMGP was severely increased in COVID-19 patients, indicating extrahepatic vitamin K insufficiency, which was related to poor outcome; hepatic procoagulant factor II remained unaffected. These data suggest pneumonia-induced extrahepatic vitamin K depletion leading to accelerated elastic fiber damage and thrombosis in severe COVID-19 due to impaired activation of MGP and endothelial protein S, respectively.
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Keywords: COVID-19, elastic fibers, factor II, matrix Gla protein, vitamin K, SARS-CoV-2, Humans, Risk Factors, Biomarkers, Vitamin K 1/analogs & derivatives, Microbiology (medical), Infectious Diseases, Journal Article
ISSN: 1058-4838
Publisher: Oxford University Press
Note: Publisher Copyright: © 2020 The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
(Peer reviewed)