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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

The relationship between cytokine and neutrophil gene network distinguishes SARS-CoV-2-infected patients by sex and age

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Autor(es):
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Freire, Paula P. [1] ; Marques, Alexandre H. C. [1] ; Baiocchi, Gabriela C. [1] ; Schimke, Lena F. [1] ; Fonseca, Dennyson L. M. [1] ; Salgado, Ranieri C. [1] ; Filgueiras, Igor S. [1] ; Napoleao, Sarah M. S. [1] ; Placa, Desiree R. [2] ; Akashi, Karen T. [2] ; Crespo Hirata, Thiago Dominguez [2] ; El Khawanky, Nadia [3] ; Giil, Lasse M. [4] ; Cabral-Miranda, Gustavo [1] ; Carvalho, Robson F. [5] ; Ferreira, Luis Carlos S. [6] ; Condino-Neto, Antonio [1] ; Nakaya, I, Helder ; Jurisica, Igor [7, 8, 9] ; Ochs, Hans D. [10, 11] ; Saraiva Camara, Niels Olsen [1] ; Calich, Vera Lucia G. [1] ; Cabral-Marques, Otavio [1, 12, 13]
Número total de Autores: 23
Afiliação do(s) autor(es):
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[1] Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, Lineu Prestes Ave 1730, BR-05508 Sao Paulo - Brazil
[2] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo, SP - Brazil
[3] Univ Freiburg, Fac Med, Dept Hematol & Oncol, Freiburg - Germany
[4] Haraldsplass Deaconess Hosp, Dept Internal Med, Bergen - Norway
[5] Sao Paulo State Univ, Inst Biosci, Dept Struct & Funct Biol, Botucatu, SP - Brazil
[6] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Vaccine Dev Lab, Sao Paulo - Brazil
[7] Univ Toronto, Dept Med Biophys, Toronto, ON - Canada
[8] Univ Toronto, Dept Comp Sci, Toronto, ON - Canada
[9] Univ Toronto, Krembil Res Inst, Univ Hlth Network, Toronto, ON - Canada
[10] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 - USA
[11] Seattle Childrens Res Inst, Seattle, WA - USA
[12] Nakaya, Helder, I, Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo, SP - Brazil
[13] Universal Sci Educ & Res Network, Network Immun Infect Malignancy & Autoimmun, Sao Paulo - Brazil
Número total de Afiliações: 13
Tipo de documento: Artigo Científico
Fonte: JCI INSIGHT; v. 6, n. 10 MAY 24 2021.
Citações Web of Science: 0
Resumo

The fact that the COVID-19 fatality rate varies by sex and age is poorly understood. Notably, the outcome of SARS-CoV-2 infections mostly depends on the control of cytokine storm and the increasingly recognized pathological role of uncontrolled neutrophil activation. Here, we used an integrative approach with publicly available RNA-Seq data sets of nasopharyngeal swabs and peripheral blood leukocytes from patients with SARS-CoV-2, according to sex and age. Female and young patients infected by SARS-CoV-2 exhibited a larger number of differentially expressed genes (DEGs) compared with male and elderly patients, indicating a stronger immune modulation. Among them, we found an association between upregulated cytokine/chemokine- and downregulated neutrophil-related DEGs. This was correlated with a closer relationship between female and young subjects, while the relationship between male and elderly patients was closer still. The association between these cytokine/chemokines and neutrophil DEGs is marked by a strongly correlated interferome network. Here, female patients exhibited reduced transcriptional levels of key proinflammatory/neutrophil-related genes, such as CXCL8 receptors (CXCR1 and CXCR2), IL-1 beta, S100A9, ITGAM, and DBNL, compared with male patients. These genes are well known to be protective against inflammatory damage. Therefore, our work suggests specific immune-regulatory pathways associated with sex and age of patients infected with SARS-CoV-2 and provides a possible association between inverse modulation of cytokine/chemokine and neutrophil transcriptional signatures. (AU)

Processo FAPESP: 20/09146-1 - Análise sistêmica e integrativa dos mecanismos moleculares associados à imunorregulação em pacientes com COVID-19
Beneficiário:Paula Paccielli Freire-Barguil
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 20/01688-0 - Análise sistêmica e integrativa da resposta imune às infecções virais por Zika e Dengue
Beneficiário:Otávio Cabral Marques
Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
Processo FAPESP: 17/05264-7 - Metabolismo celular, microbiota e sistema imune: novos paradigmas na fisiopatologia das doenças renais
Beneficiário:Niels Olsen Saraiva Câmara
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 13/50343-1 - Genomic profiling of messenger RNAs and microRNAs in cancer cachexia
Beneficiário:Robson Francisco Carvalho
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 20/07069-0 - Análise sistêmica e integrativa dos mecanismos de exaustão dos linfócitos T de pacientes com COVID-19
Beneficiário:Otávio Cabral Marques
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 20/07972-1 - Análise sistêmica e integrativa dos mecanismos de exaustão dos linfócitos T de pacientes com COVID-19
Beneficiário:Gabriela Crispim Baiocchi
Modalidade de apoio: Bolsas no Brasil - Doutorado Direto