Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/56538 |
Resumo: | Universidade de Brasília. Programa de Pós-Graduação em Ciências Médicas. Brasília, DF, Brazil. |
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Jardim-Santos, Gabriela ProfírioSchulte, Heidi LuiseKurizky, Patricia ShuGomes, Ciro MartinsNóbrega, Otávio TolêdoGois, Eliana Teles deCarvalho, Maíra Rocha Machado deMartins, Francielle PulccinelliNicola, André MoraesAlbuquerque, Cleandro Pires deEspindola, Laila SalmenNaves, Luciana AnsaneliSoares, Alexandre Anderson de Sousa MunhozAlbuquerque, PatríciaFontes, WagnerAmaral, Laurence Rodrigues doGomes, Matheus de SouzaBertarini, Pedro Luiz LimaBrito-de-Sousa, Joaquim PedroAzevedo, Ana Carolina CampiPascoal, Vanessa Peruhype MagalhãesCarvalho, Andrea Teixeira deValim, ValériaMartins Filho, Olindo AssisMota, Licia Maria Henrique da2023-01-20T17:12:45Z2023-01-20T17:12:45Z2022JARDIM-SANTO, Gabriela Profírio et al. Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients. Front Immunol. V. 13, 1004023, 2022. doi: 10.3389/fimmu.2022.1004023.1664-3224https://www.arca.fiocruz.br/handle/icict/56538engFrontiers Research FoundationUnbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patientsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade de Brasília. Programa de Pós-Graduação em Ciências Médicas. Brasília, DF, Brazil.Universidade de Brasília. Programa de Pós-Graduação em Ciências Médicas. Brasília, DF, Brazil.Universidade de Brasília. Programa de Pós-Graduação em Ciências Médicas. Brasília, DF, Brazil/Universidade de Brasília. Hospital Universitário de Brasília. Serviço de Dermatologia. Brasília, DF, BrazilUniversidade de Brasília. Programa de Pós-Graduação em Ciências Médicas. Brasília, DF, Brazil/Universidade de Brasília. Hospital Universitário de Brasília. Serviço de Dermatologia. Brasília, DF, Brazil/Universidade de Brasília. Programa de Pós-Graduação em Patologia Molecular. Brasília, DF, Brazil.Universidade de Brasília. Programa de Pós-Graduação em Ciências Médicas. Brasília, DF, Brazil.Universidade de Brasília. Programa de Pós-Graduação em Ciências Médicas. Brasília, DF, Brazil/Hospital Regional do Gama. Unidade de Clínica Médica. Brasília, DF, Brazil.Universidade de Brasília. Programa de Pós-Graduação em Ciências Médicas. Brasília, DF, Brazil/Hospital Regional da Asa Norte. Unidade de Clínica Médica. Brasília, DF, Brazil.Universidade de Brasília. Programa de Pós-Graduação em Ciências Médicas. Brasília, DF, Brazil/Hospital Regional da Asa Norte. Unidade de Clínica Médica. Brasília, DF, Brazil.Universidade de Brasília. Faculdade de Medicina. Brasília, DF, Brazil.Universidade de Brasília. Programa de Pós-Graduação em Ciências Médicas. Brasília, DF, Brazil/Universidade de Brasília. Hospital Universitário de Brasília. Brasília, DF, Brazil.Universidade de Brasília. Programa de Pós-Graduação em Ciências Médicas. Brasília, DF, Brazil.Universidade de Brasília. Hospital Universitário de Brasília. Brasília, DF, Brazil/Universidade de Brasília. Programa de Pós-Graduação em Ciências da Saúde. Brasília, DF, Brazil.Universidade de Brasília. Programa de Pós-Graduação em Ciências Médicas. Brasília, DF, Brazil.Universidade de Brasília. Faculdade UnB Ceilândia. Brasília, DF, Brazil.Universidade de Brasília. Instituto de Ciências Biológicas. Departamento de Biologia Celular. Laboratório de Bioquímica e Química de Proteínas. Brasília, DF, Brazil.Universidade Federal de Uberlândia. Laboratório de Bioinformática e Análises Moleculares. Patos de Minas, MG, Brazil/Universidade Federal de Uberlândia. Faculdade de Engenharia Elétrica. Laboratório de Tecnologias Urbanas e Rurais. Patos de Minas, MG, Brazil.Universidade Federal de Uberlândia. Laboratório de Bioinformática e Análises Moleculares. Patos de Minas, MG, Brazil/Universidade Federal de Uberlândia. Faculdade de Engenharia Elétrica. Laboratório de Tecnologias Urbanas e Rurais. Patos de Minas, MG, Brazil.Universidade Federal de Uberlândia. Laboratório de Bioinformática e Análises Moleculares. Patos de Minas, MG, Brazil/Universidade Federal de Uberlândia. Faculdade de Engenharia Elétrica. Laboratório de Tecnologias Urbanas e Rurais. Patos de Minas, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.Universidade Federal do Espírito Santo. Hospital Universitário Cassiano Antônio Moraes. Programa de Pós-Graduação em Saúde Coletiva. Vitória, ES, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.Universidade de Brasília. Programa de Pós-Graduação em Ciências Médicas. Brasília, DF, Brazil/Universidade de Brasília. Hospital Universitário de Brasília. Brasília, DF, Brazil.The present study applied distinct models of descriptive analysis to explore the integrative networks and the kinetic timeline of serum soluble mediators to select a set of systemic biomarkers applicable for the clinical management of COVID-19 patients. For this purpose, a total of 246 participants (82 COVID-19 and 164 healthy controls - HC) were enrolled in a prospective observational study. Serum soluble mediators were quantified by high-throughput microbeads array on hospital admission (D0) and at consecutive timepoints (D1-6 and D7-20). The results reinforce that the COVID-19 group exhibited a massive storm of serum soluble mediators. While increased levels of CCL3 and G-CSF were associated with the favorable prognosis of non-mechanical ventilation (nMV) or discharge, high levels of CXCL10 and IL-6 were observed in patients progressing to mechanical ventilation (MV) or death. At the time of admission, COVID-19 patients presented a complex and robust serum soluble mediator network, with a higher number of strong correlations involving IFN-γ, IL-1Ra and IL-9 observed in patients progressing to MV or death. Multivariate regression analysis demonstrates the ability of serum soluble mediators to cluster COVID-19 from HC. Ascendant fold change signatures and the kinetic timeline analysis further confirmed that the pairs "CCL3 and G-CSF" and "CXCL10 and IL-6" were associated with favorable or poor prognosis, respectively. A selected set of systemic mediators (IL-6, IFN-γ, IL-1Ra, IL-13, PDGF and IL-7) were identified as putative laboratory markers, applicable as complementary records for the clinical management of patients with severe COVID-19.COVID-19biomarkerschemokinescytokinesimmune responsekineticsserum soluble mediatorsinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/56538/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALUnbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients.pdfUnbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients.pdfapplication/pdf8834488https://www.arca.fiocruz.br/bitstream/icict/56538/2/Unbalanced%20networks%20and%20disturbed%20kinetics%20of%20serum%20soluble%20mediators%20associated%20with%20distinct%20disease%20outcomes%20in%20severe%20COVID-19%20patients.pdf99bd5ba05c73c50cc617143a9a3aa42dMD52icict/565382023-01-20 14:12:46.492oai:www.arca.fiocruz.br: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ório 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dc.title.en_US.fl_str_mv |
Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients |
title |
Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients |
spellingShingle |
Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients Jardim-Santos, Gabriela Profírio COVID-19 biomarkers chemokines cytokines immune response kinetics serum soluble mediators |
title_short |
Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients |
title_full |
Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients |
title_fullStr |
Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients |
title_full_unstemmed |
Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients |
title_sort |
Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients |
author |
Jardim-Santos, Gabriela Profírio |
author_facet |
Jardim-Santos, Gabriela Profírio Schulte, Heidi Luise Kurizky, Patricia Shu Gomes, Ciro Martins Nóbrega, Otávio Tolêdo Gois, Eliana Teles de Carvalho, Maíra Rocha Machado de Martins, Francielle Pulccinelli Nicola, André Moraes Albuquerque, Cleandro Pires de Espindola, Laila Salmen Naves, Luciana Ansaneli Soares, Alexandre Anderson de Sousa Munhoz Albuquerque, Patrícia Fontes, Wagner Amaral, Laurence Rodrigues do Gomes, Matheus de Souza Bertarini, Pedro Luiz Lima Brito-de-Sousa, Joaquim Pedro Azevedo, Ana Carolina Campi Pascoal, Vanessa Peruhype Magalhães Carvalho, Andrea Teixeira de Valim, Valéria Martins Filho, Olindo Assis Mota, Licia Maria Henrique da |
author_role |
author |
author2 |
Schulte, Heidi Luise Kurizky, Patricia Shu Gomes, Ciro Martins Nóbrega, Otávio Tolêdo Gois, Eliana Teles de Carvalho, Maíra Rocha Machado de Martins, Francielle Pulccinelli Nicola, André Moraes Albuquerque, Cleandro Pires de Espindola, Laila Salmen Naves, Luciana Ansaneli Soares, Alexandre Anderson de Sousa Munhoz Albuquerque, Patrícia Fontes, Wagner Amaral, Laurence Rodrigues do Gomes, Matheus de Souza Bertarini, Pedro Luiz Lima Brito-de-Sousa, Joaquim Pedro Azevedo, Ana Carolina Campi Pascoal, Vanessa Peruhype Magalhães Carvalho, Andrea Teixeira de Valim, Valéria Martins Filho, Olindo Assis Mota, Licia Maria Henrique da |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Jardim-Santos, Gabriela Profírio Schulte, Heidi Luise Kurizky, Patricia Shu Gomes, Ciro Martins Nóbrega, Otávio Tolêdo Gois, Eliana Teles de Carvalho, Maíra Rocha Machado de Martins, Francielle Pulccinelli Nicola, André Moraes Albuquerque, Cleandro Pires de Espindola, Laila Salmen Naves, Luciana Ansaneli Soares, Alexandre Anderson de Sousa Munhoz Albuquerque, Patrícia Fontes, Wagner Amaral, Laurence Rodrigues do Gomes, Matheus de Souza Bertarini, Pedro Luiz Lima Brito-de-Sousa, Joaquim Pedro Azevedo, Ana Carolina Campi Pascoal, Vanessa Peruhype Magalhães Carvalho, Andrea Teixeira de Valim, Valéria Martins Filho, Olindo Assis Mota, Licia Maria Henrique da |
dc.subject.en.en_US.fl_str_mv |
COVID-19 biomarkers chemokines cytokines immune response kinetics serum soluble mediators |
topic |
COVID-19 biomarkers chemokines cytokines immune response kinetics serum soluble mediators |
description |
Universidade de Brasília. Programa de Pós-Graduação em Ciências Médicas. Brasília, DF, Brazil. |
publishDate |
2022 |
dc.date.issued.fl_str_mv |
2022 |
dc.date.accessioned.fl_str_mv |
2023-01-20T17:12:45Z |
dc.date.available.fl_str_mv |
2023-01-20T17:12:45Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
JARDIM-SANTO, Gabriela Profírio et al. Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients. Front Immunol. V. 13, 1004023, 2022. doi: 10.3389/fimmu.2022.1004023. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/56538 |
dc.identifier.issn.en_US.fl_str_mv |
1664-3224 |
identifier_str_mv |
JARDIM-SANTO, Gabriela Profírio et al. Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients. Front Immunol. V. 13, 1004023, 2022. doi: 10.3389/fimmu.2022.1004023. 1664-3224 |
url |
https://www.arca.fiocruz.br/handle/icict/56538 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Frontiers Research Foundation |
publisher.none.fl_str_mv |
Frontiers Research Foundation |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
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Fundação Oswaldo Cruz (FIOCRUZ) |
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FIOCRUZ |
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FIOCRUZ |
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Repositório Institucional da FIOCRUZ (ARCA) |
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Repositório Institucional da FIOCRUZ (ARCA) |
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