Role of human airway epithelial cell death in the inflammation caused by 2019-nCoV and confirmation by transcriptional analysis of infected patients

• Grant number: 20/05270-0
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2020
• End date: April 30, 2022
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Vânia Luiza Deperon Bonato
• Grantee: Vânia Luiza Deperon Bonato
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Cristina Ribeiro de Barros Cardoso ; Fernando Crivelenti Vilar ; Gilberto Gambero Gaspar ; Isabel Kinney Ferreira de Miranda Santos ; José Joaquim Ribeiro da Rocha ; Lúcia Helena Faccioli ; Marcelo Dias Baruffi ; Marley Ribeiro Feitosa ; Omar Feres ; Rogerio Serafim Parra
• Associated research grant: 17/21629-5 - Strategies to study pulmonary inflammation during comorbidities, AP.TEM

Abstract

2019-nCoV infection results in pneumonia marked by intense inflammation. There is still no specific treatment for COVID-19 disease. The fact that 2019-nCoV infection causes intense pathological inflammation shows that surviving the infection is more a matter of tolerating lung damage (damage tolerance) than properly controlling the load viral (pathogen tolerance). New perspectives for the treatment of pneumonia involve host-directed therapies, and should include therapeutic strategies aimed at damage tolerance mechanisms. Lung damage in 2019-nCoV infection involves the destruction of pulmonary alveoli as a result of the death of infected alveolar epithelial cells, and the cytokine storm. Comorbidities, such as chronic lung diseases, obesity, hypertension, cardiovascular diseases, among others, aggravate the infection caused by the new coronavirus. This project has three well-defined objectives: i. to study the role of the death of human alveolar epithelial cells infected by 2019-nCoV, as direct mediators of macrophage activation; ii. analyze the transcriptome of patients with or without comorbidities in order to relate the findings in vivo and in vitro; iii. to establish correlations between transcripts and comorbidities. These objectives are in line with the objectives of the Thematic Project under my coordination, aiming at investigating mechanisms that exacerbate asthma and acute bacterial pneumonia, and diabetes and tuberculosis comorbidity. At the end of the project's development, our purpose will be to list molecular targets to be investigated as pharmacological agonists or antagonists in immunotherapies directed to the host with COVID-19 with or without comorbidities, aiming at tolerance to the damage. This project is a multicentre proposal, which results from the collaboration among FMRP-USP, FCFRP-USP and Hospital São Paulo de Ribeirão Preto, in a collective effort to better understand the immunopathology associated with COVID-19. The peripheral blood samples from patients and individuals from the control group will be shared to carry out different methodologies and the data collected will also be shared, featuring robust research and strengthening links of scientific collaboration. (AU)

Scientific publications

(9)

(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)

DE CAMPOS FRAGA-SILVA, THAIS FERNANDA; MARUYAMA, SANDRA REGINA; SORGI, CARLOS ARTERIO; DE SOUSA RUSSO, ELISA MARIA; MORAIS FERNANDES, ANA PAULA; DE BARROS CARDOSO, CRISTINA RIBEIRO; FACCIOLI, LUCIA HELENA; DIAS-BARUFFI, MARCELO; DEPERON BONATO, VANIA LUIZA. COVID-19: Integrating the Complexity of Systemic and Pulmonary Immunopathology to Identify Biomarkers for Different Outcomes. FRONTIERS IN IMMUNOLOGY, v. 11, JAN 29 2021. (20/05270-0, 17/21629-5, 20/05207-6)

FUZO, CARLOS A.; FRAGA-SILVA, THAIS F. C.; MARUYAMA, SANDRA R.; BASTOS, VICTOR A. F.; ROGERIO, LUANA A.; TAKAMIYA, NAYORE T.; DA SILVA-NETO, PEDRO V.; PIMENTEL, VINICIUS E.; TORO, DIANA M.; PEREZ, MALENA M.; et al. The turning point of COVID-19 severity is associated with a unique circulating neutrophil gene signature. IMMUNOLOGY, v. 169, n. 3, p. 21-pg., 2023-03-08. (15/00658-1, 21/04590-3, 20/08534-8, 20/05207-6, 19/09881-6, 14/07125-6, 20/05270-0, 17/16328-6)

DA SILVA-NETO, PEDRO, V; DO VALLE, VALERIA B.; FUZO, CARLOS A.; FERNANDES, TALITA M.; TORO, DIANA M.; FRAGA-SILVA, THAIS F. C.; BASILE, PATRICIA A.; DE CARVALHO, JONATAN C. S.; PIMENTEL, VINICIUS E.; PEREZ, MALENA M.; et al. Matrix Metalloproteinases on Severe COVID-19 Lung Disease Pathogenesis: Cooperative Actions of MMP-8/MMP-2 Axis on Immune Response through HLA-G Shedding and Oxidative Stress. BIOMOLECULES, v. 12, n. 5, p. 20-pg., 2022-05-01. (14/07125-6, 20/08534-8, 20/05270-0, 14/23946-0, 21/04590-3, 20/05207-6)

FERREIRA DE MIRANDA SANTOS, ISABEL KINNEY; DE BARROS CARDOSO, CRISTINA RIBEIRO. Commentary on "Complement C3 vs C5 inhibition in severe COVID-19: Early clinical findings reveal differential biological efficacy " by DC Mastellos et al.. Clinical Immunology, v. 222, p. 1-pg., 2021-01-16. (20/05270-0)

FERREIRA DE MIRANDA SANTOS, ISABEL KINNEY; DE BARROS CARDOSO, CRISTINA RIBEIRO. Commentary on ``Complement C3 vs C5 inhibition in severe COVID-19: Early clinical findings reveal differential biological efficacy `` by DC Mastellos et al.. Clinical Immunology, v. 222, JAN 2021. (20/05270-0)

POTJE, SIMONE R.; COSTA, TIAGO J.; FRAGA-SILVA, THAIS F. C.; MARTINS, RONALDO B.; BENATTI, MAIRA N.; ALMADO, CARLOS E. L.; DE SA, KEYLA S. G.; BONATO, VANIA L. D.; ARRUDA, EURICO; LOUZADA-JUNIOR, PAULO; et al. Heparin prevents in vitro glycocalyx shedding induced by plasma from COVID-19 patients. Life Sciences, v. 276, JUL 1 2021. (17/25116-2, 16/21239-0, 13/08216-2, 20/05270-0)

DE CARVALHO, JONATAN C. S.; DA SILVA-NETO, PEDRO V.; TORO, DIANA M.; FUZO, CARLOS A.; NARDINI, VIVIANI; PIMENTEL, VINICIUS E.; PEREZ, MALENA M.; FRAGA-SILVA, THAIS F. C.; OLIVEIRA, CAMILLA N. S.; DEGIOVANI, AUGUSTO M.; et al. The Interplay among Glucocorticoid Therapy, Platelet-Activating Factor and Endocannabinoid Release Influences the Inflammatory Response to COVID-19. Viruses-Basel, v. 15, n. 2, p. 22-pg., 2023-02-01. (15/00658-1, 21/04590-3, 20/08534-8, 20/05207-6, 14/07125-6, 22/07287-2, 20/05270-0)

CORDEIRO, JESSICA F. C.; FERNANDES, TALITA M.; TORO, DIANA M.; DA SILVA-NETO, PEDRO, V; PIMENTEL, VINICIUS E.; PEREZ, MALENA M.; DE CARVALHO, JONATAN C. S.; FRAGA-SILVA, THAIS F. C.; OLIVEIRA, CAMILLA N. S.; ARGOLO, JAMILLE G. M.; et al. The Severity of COVID-19 Affects the Plasma Soluble Levels of the Immune Checkpoint HLA-G Molecule. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 17, p. 16-pg., 2022-09-01. (20/05207-6, 20/08534-8, 20/05270-0, 21/04590-3)

FUZO, CARLOS A.; MARTINS, RONALDO B.; FRAGA-SILVA, THAIS F. C.; AMSTALDEN, MARTIN K.; DE LEO, THAIS CANASSA; SOUZA, JULIANO P.; LIMA, THAIS M.; FACCIOLI, LUCIA H.; OKAMOTO, DEBORA NOMA; JULIANO, MARIA APARECIDA; et al. Celastrol: A lead compound that inhibits SARS-CoV-2 replication, the activity of viral and human cysteine proteases, and virus-induced IL-6 secretion. Drug Development Research, v. 83, n. 7, p. 18-pg., 2022-08-21. (20/05270-0)