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

DOI record: { "DOI": "10.3390/v13020309", "ISSN": [ "1999-4915" ], "URL": "http://dx.doi.org/10.3390/v13020309", "abstract": "<jats:p>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 O2 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.</jats:p>", "alternative-id": [ "v13020309" ], "author": [ { "ORCID": "https://orcid.org/0000-0001-6450-6930", "affiliation": [ { "name": "Department of Internal Medicine, School of Medical Sciences, University of Campinas, 13083-887 Campinas, São Paulo, Brazil" } ], "authenticated-orcid": false, "family": "Mansour", "given": "Eli", "sequence": "first" }, { "ORCID": "https://orcid.org/0000-0001-6823-0847", "affiliation": [ { "name": "Department of Internal Medicine, School of Medical Sciences, University of Campinas, 13083-887 Campinas, São Paulo, Brazil" } ], "authenticated-orcid": false, "family": "Palma", "given": "Andre C.", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-0013-2831", "affiliation": [ { "name": "Department of Internal Medicine, School of Medical Sciences, University of Campinas, 13083-887 Campinas, São Paulo, Brazil" } ], "authenticated-orcid": false, "family": "Ulaf", "given": "Raisa G.", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Internal Medicine, School of Medical Sciences, University of Campinas, 13083-887 Campinas, São Paulo, Brazil" } ], "family": "Ribeiro", "given": "Luciana C.", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Internal Medicine, School of Medical Sciences, University of Campinas, 13083-887 Campinas, São Paulo, Brazil" } ], "family": "Bernardes", "given": "Ana Flavia", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-0202-0550", "affiliation": [ { "name": "Department of Internal Medicine, School of Medical Sciences, University of Campinas, 13083-887 Campinas, São Paulo, Brazil" } ], "authenticated-orcid": false, "family": "Nunes", "given": "Thyago A.", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Internal Medicine, School of Medical Sciences, University of Campinas, 13083-887 Campinas, São Paulo, Brazil" } ], "family": "Agrela", "given": "Marcus V.", "sequence": "additional" }, { "affiliation": [ { "name": "Obesity and Comorbidities Research Center, University of Campinas, 13083-864 Campinas, São Paulo, Brazil" } ], "family": "Bombassaro", "given": "Bruna", "sequence": "additional" }, { "affiliation": [ { "name": "Obesity and Comorbidities Research Center, University of Campinas, 13083-864 Campinas, São Paulo, Brazil" } ], "family": "Monfort-Pires", "given": "Milena", "sequence": "additional" }, { "affiliation": [ { "name": "Obesity and Comorbidities Research Center, University of Campinas, 13083-864 Campinas, São Paulo, Brazil" } ], "family": "Camargo", "given": "Rafael L.", "sequence": "additional" }, { "affiliation": [ { "name": "Obesity and Comorbidities Research Center, University of Campinas, 13083-864 Campinas, São Paulo, Brazil" }, { "name": "School of Nursing, University of Campinas, 13083-887 Campinas, São Paulo, Brazil" } ], "family": "Araujo", "given": "Eliana P.", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-2803-3763", "affiliation": [ { "name": "Autoimmune Research Lab, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, 13083-862 Campinas, São Paulo, Brazil" } ], "authenticated-orcid": false, "family": "Brunetti", "given": "Natalia S.", "sequence": "additional" }, { "affiliation": [ { "name": "Autoimmune Research Lab, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, 13083-862 Campinas, São Paulo, Brazil" } ], "family": "Farias", "given": "Alessandro S.", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Surgery, School of Medical Sciences, University of Campinas, 13083-887 Campinas, São Paulo, Brazil" } ], "family": "Falcão", "given": "Antônio Luís E.", "sequence": "additional" }, { "affiliation": [ { "name": 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