The turning point of COVID-19 severity is associated with a unique circulating neutrophil gene signature

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Fuzo, Carlos A. ; Fraga-Silva, Thais F. C. ; Maruyama, Sandra R. ; Bastos, Victor A. F. ; Rogerio, Luana A. ; Takamiya, Nayore T. ; da Silva-Neto, Pedro V. ; Pimentel, Vinicius E. ; Toro, Diana M. ; Perez, Malena M. ; de Carvalho, Jonatan C. S. ; Carmona-Garcia, Ingryd ; Oliveira, Camilla N. S. ; Degiovani, Augusto M. ; Ostini, Fatima M. ; Constant, Leticia F. ; de Amorim, Alessandro P. ; Vilar, Fernando C. ; Feitosa, Marley R. ; Parra, Rogerio S. ; da Rocha, Jose J. R. ; Feres, Omar ; Gaspar, Gilberto G. ; Viana, Angelina L. ; Fernandes, Ana P. M. ; Santos, Isabel K. F. M. ; Russo, Elisa M. S. ; Cardoso, Cristina R. B. ; Sorgi, Carlos A. ; Faccioli, Lucia H. ; Bonato, Vania L. D. ; Dias-Baruffi, Marcelo ; ImmunoCOVID study grp

• Document type: Journal article
• Source: IMMUNOLOGY; v. 169, n. 3, p. 21-pg., 2023-03-08.

Abstract

COVID-19 has a broad spectrum of clinical manifestations associated with the host immune response heterogeneity. Despite the advances in COVID-19 research, it is still crucial to seek a panel of molecular markers that enable accurate stratification of COVID-19 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-19 severity and healthy subjects. We identified a perturbation in blood-leukocyte transcriptional profile associated with COVID-19 aggravation, which was mainly related to processes that disfavoured lymphocyte activation and favoured neutrophil activation. This transcriptional profile stratified patients according to COVID-19 severity. Hence, it enabled identification of a turning point in transcriptional dynamics that distinguished disease outcomes and non-hospitalized from hospitalized moderate patients. Central genes of this unique neutrophil signature were S100A9, ANXA3, CEACAM6, VNN1, OLFM4, IL1R2, TCN1 and CD177. Our study indicates the molecular changes that are linked with the differing clinical aspects presented by humans when suffering from COVID-19, which involve neutrophil activation. (AU)

• FAPESP's process: 15/00658-1 - New functional aspects of eicosanoids
• Grantee: Lúcia Helena Faccioli
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 21/04590-3 - Exploratory analysis of functional lipidomics in the COVID-19 pathophysiology: molecular targets, metabolism and biochemical reprogramming due to hypoxia
• Grantee: Carlos Arterio Sorgi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/08534-8 - Lipidomic analysis using high-resolution mass spectrometry for molecular profile determination in plasma of patients infected with SARS-CoV-2
• Grantee: Malena Martínez Pérez
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/05207-6 - Prospective evaluation of lipid mediators production on the immune response against COVID-19: search for biomarkers and new therapeutic targets in the evolution of the disease
• Grantee: Lúcia Helena Faccioli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/09881-6 - Role of TLR2 and TLR9-dependent signalling in epithelial or dendritic cells in lung inflammation during allergen reexposure and pneumococcal infection
• Grantee: Thais Fernanda de Campos Fraga da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/07125-6 - New functional aspects of eicosanoids
• Grantee: Lúcia Helena Faccioli
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/05270-0 - Role of human airway epithelial cell death in the inflammation caused by 2019-nCoV and confirmation by transcriptional analysis of infected patients
• Grantee: Vânia Luiza Deperon Bonato
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/16328-6 - Visceral Leishmaniasis: genomics approaches for integrated molecular analysis of host and parasite.
• Grantee: Sandra Regina Costa Maruyama
• Support Opportunities: Scholarships in Brazil - Young Researchers