{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:10:10Z","timestamp":1782821410677,"version":"3.54.5"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T00:00:00Z","timestamp":1598486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Respiratory failure and thromboembolism are frequent in severe acute respiratory syndrome coronavirus 2\u2013infected 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 135 hospitalized COVID-19 patients were compared with 184 historic controls. Inactive vitamin K\u2013dependent 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>dp-ucMGP was elevated in COVID-19 patients compared with controls (P\u2005&amp;lt;\u2005.001), with even higher dp-ucMGP in patients with poor outcomes (P\u2005&amp;lt;\u2005.001). PIVKA-II was normal in 82.1% of patients. dp-ucMGP was correlated with desmosine (P\u2005&amp;lt;\u2005.001) and with coronary artery (P\u2005=\u2005.002) and thoracic aortic (P\u2005&amp;lt;\u2005.001) calcification scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciaa1258","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T07:11:18Z","timestamp":1598425878000},"page":"e4039-e4046","source":"Crossref","is-referenced-by-count":88,"title":["Reduced Vitamin K Status as a Potentially Modifiable Risk Factor of Severe Coronavirus Disease 2019"],"prefix":"10.1093","volume":"73","author":[{"given":"Anton S M","family":"Dofferhoff","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ianthe","family":"Piscaer","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon J","family":"Schurgers","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot P J","family":"Visser","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jody M W","family":"van den Ouweland","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pim A","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Radiology, University Medical Center 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University, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecile","family":"Maassen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther G A","family":"Karssemeijer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cees","family":"Vermeer","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiel F M","family":"Wouters","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Maastricht 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