Freire, Paula P.Marques, Alexandre H. C.Baiocchi, Gabriela C.Schimke, Lena F.Fonseca, Dennyson L. M.Salgado, Ranieri C.Filgueiras, Igor S.Napoleao, Sarah M. S.Placa, Desiree R.Akashi, Karen T.Crespo Hirata, Thiago DominguezEl Khawanky, NadiaGiil, Lasse M.Cabral-Miranda, GustavoCarvalho, Robson F. [UNESP]Ferreira, Luis Carlos S.Condino-Neto, AntonioNakaya, HelderJurisica, IgorOchs, Hans D.Saraiva Camara, Niels OlsenCalich, Vera Lucia G.Cabral-Marques, Otavio2021-06-252021-06-252021-05-24Jci Insight. Ann Arbor: Amer Soc Clinical Investigation Inc, v. 6, n. 10, 17 p., 2021.http://hdl.handle.net/11449/210433The 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.17engArtigo10.1172/jci.insight.147535WOS:000653507400023