tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Ianthe Piscaer[SUP] 2 [/SUP], Leon J Schurgers[SUP] 3 [/SUP], Margot P J Visser[SUP] 4 [/SUP], Jody M W van den Ouweland[SUP] 5 [/SUP], Pim A de Jong[SUP] 6 [/SUP], Reinoud Gosens[SUP] 7 [/SUP], Tilman M Hackeng[SUP] 3 [/SUP], Henny van Daal[SUP] 5 [/SUP], Petra Lux[SUP] 3 [/SUP], Cecile Maassen[SUP] 3 [/SUP], Esther G A Karssemeijer[SUP] 1 [/SUP], Cees Vermeer[SUP] 3 [/SUP], Emiel F M Wouters[SUP] 2 8 [/SUP], Loes E M Kistemaker[SUP] 9 [/SUP], Jona Walk[SUP] 1 [/SUP], Rob Janssen[SUP] 4 [/SUP]
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.
. 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[SUP] 1 [/SUP], Ianthe Piscaer[SUP] 2 [/SUP], Leon J Schurgers[SUP] 3 [/SUP], Margot P J Visser[SUP] 4 [/SUP], Jody M W van den Ouweland[SUP] 5 [/SUP], Pim A de Jong[SUP] 6 [/SUP], Reinoud Gosens[SUP] 7 [/SUP], Tilman M Hackeng[SUP] 3 [/SUP], Henny van Daal[SUP] 5 [/SUP], Petra Lux[SUP] 3 [/SUP], Cecile Maassen[SUP] 3 [/SUP], Esther G A Karssemeijer[SUP] 1 [/SUP], Cees Vermeer[SUP] 3 [/SUP], Emiel F M Wouters[SUP] 2 8 [/SUP], Loes E M Kistemaker[SUP] 9 [/SUP], Jona Walk[SUP] 1 [/SUP], Rob Janssen[SUP] 4 [/SUP]
Affiliations
- PMID: 32852539
- DOI: 10.1093/cid/ciaa1258
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.