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

Autor(es):Mostrar menos -

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]}

Afiliação do(s) autor(es):Mostrar menos -

^[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

• 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)

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