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Despite the advances in COVID\u201019 research, it is still crucial to seek a panel of molecular markers that enable accurate stratification of COVID\u201019 patients. Here, we performed a study that combined analysis of blood transcriptome, demographic data, clinical aspects and laboratory findings from 66 participants classified into different degrees of COVID\u201019 severity and healthy subjects. We identified a perturbation in blood\u2010leukocyte transcriptional profile associated with COVID\u201019 aggravation, which was mainly related to processes that disfavoured lymphocyte activation and favoured neutrophil activation. This transcriptional profile stratified patients according to COVID\u201019 severity. Hence, it enabled identification of a turning point in transcriptional dynamics that distinguished disease outcomes and non\u2010hospitalized from hospitalized moderate patients. Central genes of this unique neutrophil signature were <jats:italic>S100A9<\/jats:italic>, <jats:italic>ANXA3<\/jats:italic>, <jats:italic>CEACAM6<\/jats:italic>, <jats:italic>VNN1<\/jats:italic>, <jats:italic>OLFM4<\/jats:italic>, <jats:italic>IL1R2<\/jats:italic>, <jats:italic>TCN1<\/jats:italic> and <jats:italic>CD177<\/jats:italic>. Our study indicates the molecular changes that are linked with the differing clinical aspects presented by humans when suffering from COVID\u201019, which involve neutrophil activation.<\/jats:p>","DOI":"10.1111\/imm.13631","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T03:08:46Z","timestamp":1675652926000},"page":"323-343","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The turning point of <scp>COVID\u201019<\/scp> severity is associated with a unique circulating neutrophil gene signature"],"prefix":"10.1111","volume":"169","author":[{"given":"Carlos A.","family":"Fuzo","sequence":"first","affiliation":[{"name":"Departamento de An\u00e1lises Cl\u00ednicas, Toxicol\u00f3gicas e Bromatol\u00f3gicas, Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto Universidade de S\u00e3o Paulo  Ribeir\u00e3o Preto S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2053-8938","authenticated-orcid":false,"given":"Thais F. 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