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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Safety and Outcomes Associated with the Pharmacological Inhibition of the Kinin-Kallikrein System in Severe COVID-19

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Mansour, Eli [1] ; Palma, Andre C. [1] ; Ulaf, Raisa G. [1] ; Ribeiro, Luciana C. [1] ; Bernardes, Ana Flavia [1] ; Nunes, Thyago A. [1] ; Agrela, V, Marcus ; Bombassaro, Bruna [2] ; Monfort-Pires, Milena [2] ; Camargo, Rafael L. [2] ; Araujo, Eliana P. [2, 3] ; Brunetti, Natalia S. [4] ; Farias, Alessandro S. [4] ; Falcao, Antonio Luis E. [5] ; Santos, Thiago Martins [6] ; Trabasso, Plinio [6] ; Dertkigil, Rachel P. [7] ; Dertkigil, Sergio S. [7] ; Moretti, Maria Luiza [6] ; Velloso, Licio A. [6, 2]
Total Authors: 20
Affiliation:
[1] Univ Estadual Campinas, Sch Med Sci, Dept Internal Med, BR-13083887 Campinas, SP - Brazil
[2] Univ Estadual Campinas, Obes & Comorbid Res Ctr, BR-13083864 Campinas, SP - Brazil
[3] Univ Estadual Campinas, Sch Nursing, BR-13083887 Campinas, SP - Brazil
[4] Univ Estadual Campinas, Inst Biol, Dept Genet Microbiol & Immunol, Autoimmune Res Lab, BR-13083862 Campinas, SP - Brazil
[5] Univ Estadual Campinas, Sch Med Sci, Dept Surg, BR-13083887 Campinas, SP - Brazil
[6] Agrela, Marcus, V, Univ Estadual Campinas, Sch Med Sci, Dept Internal Med, BR-13083887 Campinas, SP - Brazil
[7] Univ Estadual Campinas, Sch Med Sci, Dept Radiol, BR-13083887 Campinas, SP - Brazil
Total Affiliations: 7
Document type: Journal article
Source: Viruses-Basel; v. 13, n. 2 FEB 2021.
Web of Science Citations: 0
Abstract

Background: Coronavirus disease 19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O-2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin-converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to the accumulation of bradykinin. Methods: In this case control study, we tested two pharmacological inhibitors of the kinin-kallikrein system that are currently approved for the treatment of hereditary angioedema, icatibant, and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Results: Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in changes in time to clinical improvement. However, both compounds were safe and promoted the significant improvement of lung computed tomography scores and increased blood eosinophils, which are indicators of disease recovery. Conclusions: In this small cohort, we found evidence for safety and a beneficial role of pharmacological inhibition of the kinin-kallikrein system in two markers that indicate improved disease recovery. (AU)

FAPESP's process: 20/04522-5 - Clinical trial for bradykinin inhibition in hospitalized adults with COVID-19 grave
Grantee:Licio Augusto Velloso
Support type: Regular Research Grants
FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
Grantee:Licio Augusto Velloso
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC