tetano
Editor, Senior Moderator
J Clin Med
. 2022 Mar 9;11(6):1494.
doi: 10.3390/jcm11061494.
Activation of the Carboxypeptidase U (CPU, TAFIa, CPB2) System in Patients with SARS-CoV-2 Infection Could Contribute to COVID-19 Hypofibrinolytic State and Disease Severity Prognosis
Karen Claesen[SUP] 1 [/SUP], Yani Sim[SUP] 1 [/SUP], An Bracke[SUP] 1 [/SUP], Michelle De Bruyn[SUP] 1 [/SUP], Emilie De Hert[SUP] 1 [/SUP], Gwendolyn Vliegen[SUP] 1 [/SUP], An Hotterbeekx[SUP] 2 [/SUP], Alexandra Vujkovic[SUP] 3 [/SUP], Lida van Petersen[SUP] 4 [/SUP], Fien H R De Winter[SUP] 2 [/SUP], Isabel Brosius[SUP] 4 [/SUP], Caroline Theunissen[SUP] 4 [/SUP], Sabrina van Ierssel[SUP] 5 [/SUP], Maartje van Frankenhuijsen[SUP] 4 [/SUP], Erika Vlieghe[SUP] 5 [/SUP], Koen Vercauteren[SUP] 3 [/SUP], Samir Kumar-Singh[SUP] 2 [/SUP], Ingrid De Meester[SUP] 1 [/SUP], Dirk Hendriks[SUP] 1 [/SUP]
Affiliations
Abstract
Coronavirus disease 2019 (COVID-19) is a viral lower respiratory tract infection caused by the highly transmissible and pathogenic SARS-CoV-2 (severe acute respiratory-syndrome coronavirus-2). Besides respiratory failure, systemic thromboembolic complications are frequent in COVID-19 patients and suggested to be the result of a dysregulation of the hemostatic balance. Although several markers of coagulation and fibrinolysis have been studied extensively, little is known about the effect of SARS-CoV-2 infection on the potent antifibrinolytic enzyme carboxypeptidase U (CPU). Blood was collected longitudinally from 56 hospitalized COVID-19 patients and 32 healthy controls. Procarboxypeptidase U (proCPU) levels and total active and inactivated CPU (CPU+CPUi) antigen levels were measured. At study inclusion (shortly after hospital admission), proCPU levels were significantly lower and CPU+CPUi antigen levels significantly higher in COVID-19 patients compared to controls. Both proCPU and CPU+CPUi antigen levels showed a subsequent progressive increase in these patients. Hereafter, proCPU levels decreased and patients were, at discharge, comparable to the controls. CPU+CPUi antigen levels at discharge were still higher compared to controls. Baseline CPU+CPUi antigen levels (shortly after hospital admission) correlated with disease severity and the duration of hospitalization. In conclusion, CPU generation with concomitant proCPU consumption during early SARS-CoV-2 infection will (at least partly) contribute to the hypofibrinolytic state observed in COVID-19 patients, thus enlarging their risk for thrombosis. Moreover, given the association between CPU+CPUi antigen levels and both disease severity and duration of hospitalization, this parameter may be a potential biomarker with prognostic value in SARS-CoV-2 infection.
Keywords: COVID-19; carboxypeptidase B2; carboxypeptidase U; coronavirus; thrombin-activatable fibrinolysis inhibitor.
. 2022 Mar 9;11(6):1494.
doi: 10.3390/jcm11061494.
Activation of the Carboxypeptidase U (CPU, TAFIa, CPB2) System in Patients with SARS-CoV-2 Infection Could Contribute to COVID-19 Hypofibrinolytic State and Disease Severity Prognosis
Karen Claesen[SUP] 1 [/SUP], Yani Sim[SUP] 1 [/SUP], An Bracke[SUP] 1 [/SUP], Michelle De Bruyn[SUP] 1 [/SUP], Emilie De Hert[SUP] 1 [/SUP], Gwendolyn Vliegen[SUP] 1 [/SUP], An Hotterbeekx[SUP] 2 [/SUP], Alexandra Vujkovic[SUP] 3 [/SUP], Lida van Petersen[SUP] 4 [/SUP], Fien H R De Winter[SUP] 2 [/SUP], Isabel Brosius[SUP] 4 [/SUP], Caroline Theunissen[SUP] 4 [/SUP], Sabrina van Ierssel[SUP] 5 [/SUP], Maartje van Frankenhuijsen[SUP] 4 [/SUP], Erika Vlieghe[SUP] 5 [/SUP], Koen Vercauteren[SUP] 3 [/SUP], Samir Kumar-Singh[SUP] 2 [/SUP], Ingrid De Meester[SUP] 1 [/SUP], Dirk Hendriks[SUP] 1 [/SUP]
Affiliations
- PMID: 35329820
- DOI: 10.3390/jcm11061494
Abstract
Coronavirus disease 2019 (COVID-19) is a viral lower respiratory tract infection caused by the highly transmissible and pathogenic SARS-CoV-2 (severe acute respiratory-syndrome coronavirus-2). Besides respiratory failure, systemic thromboembolic complications are frequent in COVID-19 patients and suggested to be the result of a dysregulation of the hemostatic balance. Although several markers of coagulation and fibrinolysis have been studied extensively, little is known about the effect of SARS-CoV-2 infection on the potent antifibrinolytic enzyme carboxypeptidase U (CPU). Blood was collected longitudinally from 56 hospitalized COVID-19 patients and 32 healthy controls. Procarboxypeptidase U (proCPU) levels and total active and inactivated CPU (CPU+CPUi) antigen levels were measured. At study inclusion (shortly after hospital admission), proCPU levels were significantly lower and CPU+CPUi antigen levels significantly higher in COVID-19 patients compared to controls. Both proCPU and CPU+CPUi antigen levels showed a subsequent progressive increase in these patients. Hereafter, proCPU levels decreased and patients were, at discharge, comparable to the controls. CPU+CPUi antigen levels at discharge were still higher compared to controls. Baseline CPU+CPUi antigen levels (shortly after hospital admission) correlated with disease severity and the duration of hospitalization. In conclusion, CPU generation with concomitant proCPU consumption during early SARS-CoV-2 infection will (at least partly) contribute to the hypofibrinolytic state observed in COVID-19 patients, thus enlarging their risk for thrombosis. Moreover, given the association between CPU+CPUi antigen levels and both disease severity and duration of hospitalization, this parameter may be a potential biomarker with prognostic value in SARS-CoV-2 infection.
Keywords: COVID-19; carboxypeptidase B2; carboxypeptidase U; coronavirus; thrombin-activatable fibrinolysis inhibitor.