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Clin Infect Dis . Reduced vitamin K status as a potentially modifiable risk factor of severe COVID-19

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  • Clin Infect Dis . Reduced vitamin K status as a potentially modifiable risk factor of severe COVID-19


    Clin Infect Dis


    . 2020 Aug 27;ciaa1258.
    doi: 10.1093/cid/ciaa1258. Online ahead of print.
    Reduced vitamin K status as a potentially modifiable risk factor of severe COVID-19


    Anton S M Dofferhoff 1 , Ianthe Piscaer 2 , Leon J Schurgers 3 , Margot P J Visser 4 , Jody M W van den Ouweland 5 , Pim A de Jong 6 , Reinoud Gosens 7 , Tilman M Hackeng 3 , Henny van Daal 5 , Petra Lux 3 , Cecile Maassen 3 , Esther G A Karssemeijer 1 , Cees Vermeer 3 , Emiel F M Wouters 2 8 , Loes E M Kistemaker 9 , Jona Walk 1 , Rob Janssen 4



    Affiliations

    Abstract

    Background: Respiratory failure and thromboembolism are frequent in SARS-CoV-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 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: 135 hospitalized COVID-19 patients were compared with 184 historical controls. Poor outcome was defined as invasive ventilation and/or death. Inactive vitamin K-dependent MGP (dp-ucMGP) 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 by computed tomography.
    Results: Dp-ucMGP was elevated in COVID-19 patients compared to controls (p<0.001), with even higher dp-ucMGP in patients with poor outcomes (p<0.001). PIVKA-II was normal in 82.1% of patients. Dp-ucMGP was correlated with desmosine (p<0.001), and coronary artery (p=0.002) and thoracic aortic (p<0.001) calcification scores.
    Conclusions: Dp-ucMGP was severely increased in COVID-19 patients, indicating extrahepatic vitamin K insufficiency, which was related to poor outcome while hepatic procoagulant factor II remained unaffected. These data suggest a mechanism of 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. A clinical trial could assess whether vitamin K administration improves COVID-19 outcomes.

    Keywords: COVID-19; elastic fibers; factor II; matrix Gla protein; protein S; vitamin K.

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