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, Yani Sim, An Bracke, Michelle De Bruyn, Emilie De Hert, Gwendolyn Vliegen, An Hotterbeekx, Alexandra Vujkovic, Lida van Petersen, Fien H R De Winter, Isabel Brosius, Caroline Theunissen, Sabrina van Ierssel, Maartje van Frankenhuijsen, Erika Vlieghe, Koen Vercauteren, Samir Kumar-Singh, Ingrid De Meester, Dirk Hendriks

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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.

Original languageEnglish
Article number1494
JournalJournal of Clinical Medicine
Volume11
Issue number6
Number of pages11
ISSN2077-0383
DOIs
Publication statusPublished - 2022

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