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 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.
Keywords: COVID-19; elastic fibers; factor II; matrix Gla protein; vitamin K.
【저자키워드】 COVID-19, vitamin K, Matrix Gla Protein, elastic fibers, factor II, 【초록키워드】 coronavirus disease, Coronavirus disease 2019, coronavirus, Respiratory failure, thrombosis, severe COVID-19, severity, Proteins, outcome, severe acute respiratory syndrome Coronavirus, Computed tomography, Severe acute respiratory syndrome, Protein, Patient, Thromboembolism, Control, Vitamin, Coagulation factors, Degradation, respiratory, vitamin K, elastic fiber, patients, prothrombin, protein S, COVID-19 patients, elastic fibers, hospitalized COVID-19 patient, Anticoagulant, Thoracic, COVID-19 patient, Coronary artery, coagulation factor, endothelial, acute respiratory syndrome, Activation, Vascular, These data, thromboembolic disease, calcification, arterial, fiber, controls, desmosine, procoagulant, PROTECT, was measured, remained, required, elevated, activated, correlated, activate, implicated, accelerated, were measured, MGP, procoagulant factor, was related, 【제목키워드】 Vitamin, Factor, status,