Evaluation of the mechanisms of hemostatic activation in COVID-19 and their modulation by bradykinin inhibitors

• Grant number: 20/05985-9
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2020
• End date: November 30, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Erich Vinicius de Paula
• Grantee: Erich Vinicius de Paula
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Fabio Trindade Maranhão Costa ; Fernanda Loureiro de Andrade Orsi ; Joyce Maria Annichino-Bizzacchi ; Licio Augusto Velloso
• Associated research grant: 16/14172-6 - Investigation of the pathophysiological aspects and novel therapeutic approaches for thromboembolic disorders, AP.TEM

Abstract

Severe forms of COVID-19 are characterized by intense inflammation associated with significant increase in biomarkers of hemostasis activation. According to the concept of immunothrombosis, hemostasis and inflammation are intimately connected elements of the host response to pathogens. Based on this model, when regulated, local activation of hemostasis contributes to pathogen eradication, but when deregulated or with loss of localization, it can lead to secondary damage, such as the formation of thrombi in the microcirculation. Interestingly, the activation of hemostasis during inflammation is apparently mediated by different pathways that those activated in response to breaches in endothelial line causing post-traumatic bleeding, and involves elements such as the expression of tissue factor in monocytes and microparticles, the activation of intrinsic pathways by DNA released from neutrophil extracellular traps, among others. In addition, endothelial barrier disruption, which also contributes to the host's response to injury by mediating diapedesis, can become a secondary mechanism of injury, by promoting changes in the alveolar-capillary barrier or even to the activation of hemostasis. In this project, we will evaluate a panel of laboratory parameters linked to the activation of hemostasis and to the regulation of endothelial barrier integrity in patients with COVID-19 enrolled in a clinical study aimed to evaluate the effect of bradykinin inhibitors on the clinical course of this disease. The panel will be performed at different time-points (admission, days +4, +12 and +28), and the allocation by treatment groups will allow us to assess these parameters in patients on supportive treatment, or under use of bradykinin inhibitors, which have the potential to modulate both the crosstalk between inflammation and the intrinsic coagulation pathway, and the regulation of endothelial barrier integrity. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MORAES, CARLA ROBERTA PEACHAZEPI; BORBA-JUNIOR, IVANIO TEIXEIRA; DE LIMA, FRANCIELE; SILVA, JESSICA RIBEIRO ALVES; BOMBASSARO, BRUNA; PALMA, ANDRE C.; MANSOUR, ELI; VELLOSO, LICIO AUGUSTO; ORSI, FERNANDA ANDRADE; COSTA, FABIO TRINDADE MARANHAO; et al. Association of Ang/Tie2 pathway mediators with endothelial barrier integrity and disease severity in COVID-19. FRONTIERS IN PHYSIOLOGY, v. 14, p. 8-pg., 2023-02-21. (20/05985-9)

DE PAULA, ERICH VINICIUS; MARTINS, MARCIO SOUZA; BORTOLUZO DE LORENZO, ANA LUISA; LINO DUARTE, BRUNO KOSA; REZENDE, SUELY MEIRELES; COSTA, FERNANDO FERREIRA. The landscape of hematology research in Brazil: an analysis of data from citation databases. Hematology, Transfusion and Cell Therapy, v. 45, p. 11-pg., 2023-07-01. (19/18886-1, 20/05985-9)

DE LIMA, FRANCIELE; HOUNKPE, BIDOSSESSI WILFRIED; PEACHAZEPI DE MORAES, CARLA ROBERTA; BORBA, IVANIO TEIXEIRA; COSTA, FERNANDO FERREIRA; DE PAULA, ERICH, V. Safety and feasibility of the gene transfer of hemopexin for conditions with increased free heme. Experimental Biology and Medicine, v. N/A, p. 9-pg., 2023-07-15. (20/05985-9)

BORBA-JUNIOR, IVANIO TEIXEIRA; LIMA, FRANCIELE; SIDARTA-OLIVEIRA, DAVI; MORAES, CARLA ROBERTA PEACHAZEPI; ANNICHINO-BIZZACCHI, JOYCE M.; BOMBASSARO, BRUNA; PALMA, ANDRE C.; MARANHAO COSTA, FABIO TRINDADE; MORETTI, MARIA LUIZA; MANSOUR, ELI; et al. Podoplanin and CLEC-2 levels in patients with COVID-19. RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS, v. 7, n. 5, p. 9-pg., 2023-07-01. (16/14172-6, 20/05369-6, 20/05985-9)

HENDERSON, MICHAEL W.; LIMA, FRANCIELE; PEACHAZEPI MORAES, CARLA ROBERTA; ILICH, ANTON; HUBER, STEPHANY CARES; BARBOSA, MAYCK SILVA; SANTOS, IRENE; PALMA, ANDRE C.; NUNES, THYAGO ALVES; ULAF, RAISA GUSSO; et al. Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19. BLOOD ADVANCES, v. 6, n. 11, p. 11-pg., 2022-06-06. (16/14172-6, 20/05985-9)

DE LIMA, FRANCIELE; MORAES, CARLA ROBERTA PEACHAZEPI; BARBOSA, MAYCK SILVA; BOMBASSARO, BRUNA; PALMA, ANDRE C.; DERTKIGIL, SERGIO SAN JUAN; MORETTI, MARIA LUIZA; ORSI, FERNANDA ANDRADE; ANNICHINO-BIZZACCHI, JOYCE M.; MANSOUR, ELI; et al. Association of heme-oxygenase 1, hemopexin, and heme levels with markers of disease severity in COVID-19. Experimental Biology and Medicine, v. N/A, p. 8-pg., 2023-02-05. (16/14172-6, 20/05985-9)