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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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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]
Total Authors: 23
Affiliation:
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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
Total Affiliations: 13
Document type: Journal article
Source: JCI INSIGHT; v. 6, n. 10 MAY 24 2021.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 20/09146-1 - Systemic and integrative analysis of molecular mechanisms associated with immunoregulation in patients with COVID-19
Grantee:Paula Paccielli Freire
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 20/01688-0 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections
Grantee:Otávio Cabral Marques
Support type: Scholarships in Brazil - Young Researchers
FAPESP's process: 17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology
Grantee:Niels Olsen Saraiva Câmara
Support type: Research Projects - Thematic Grants
FAPESP's process: 13/50343-1 - Genomic profiling of messenger RNAs and microRNAs in cancer cachexia
Grantee:Robson Francisco Carvalho
Support type: Regular Research Grants
FAPESP's process: 20/07069-0 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with COVID-19
Grantee:Otávio Cabral Marques
Support type: Regular Research Grants
FAPESP's process: 20/07972-1 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with COVID-19
Grantee:Gabriela Crispim Baiocchi
Support type: Scholarships in Brazil - Doctorate (Direct)