A multi-tissue study of immune gene expression profiling highlights the key role of the nasal epithelium in COVID-19 severity
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Título: | A multi-tissue study of immune gene expression profiling highlights the key role of the nasal epithelium in COVID-19 severity |
Autor/a: | Gómez Carballa, Alberto Rivero Calle, Irene Pardo Seco, Jacobo José Gómez Rial, José Rivero Velasco, Carmen Rodríguez Núñez, Nuria Barbeito Castiñeiras, Gema Perez Freixo, Hugo Cebey López, Miriam Barral Arca, Ruth Rodríguez-Tenreiro Sánchez, Carmen Dacosta Urbieta, Ana Isabel Bello, Xabier Pischedda, Sara Currás Tuala, María José Viz Lasheras, Sandra Martinón Torres, Federico Salas Ellacuriaga, Antonio Gen Covid Study Group |
Centro/Departamento: | Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría |
Palabras chave: | COVID-19 severity | Gene expression | Immune response | Pathways analysis | Multi-tissue | Differential expression analysis | Co-expression analysis | SARS-CoV-2 | |
Data: | 2022 |
Editor: | Elsevier |
Cita bibliográfica: | Environmental Research 210 (2022) 112890 |
Resumo: | Coronavirus Disease-19 (COVID-19) symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unravelling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences. We carried out a multi-tissue (nasal, buccal and blood; n = 156) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls through the nCounter technology. Mild and asymptomatic cases showed a powerful innate antiviral response in nasal epithelium, characterized by activation of interferon (IFN) pathway and downstream cascades, successfully controlling the infection at local level. In contrast, weak macrophage/monocyte driven innate antiviral response and lack of IFN signalling activity were present in severe cases. Consequently, oral mucosa from severe patients showed signals of viral activity, cell arresting and viral dissemination to the lower respiratory tract, which ultimately could explain the exacerbated innate immune response and impaired adaptative immune responses observed at systemic level. Results from saliva transcriptome suggest that the buccal cavity might play a key role in SARS-CoV-2 infection and dissemination in patients with worse prognosis. Co-expression network analysis adds further support to these findings, by detecting modules specifically correlated with severity involved in the abovementioned biological routes; this analysis also provides new candidate genes that might be tested as biomarkers in future studies. We also found tissue specific severity-related signatures mainly represented by genes involved in the innate immune system and cytokine/chemokine signalling. Local immune response could be key to determine the course of the systemic response and thus COVID-19 severity. Our findings provide a framework to investigate severity host gene biomarkers and pathways that might be relevant to diagnosis, prognosis, and therapy |
Versión do editor: | https://doi.org/10.1016/j.envres.2022.112890 |
URI: | http://hdl.handle.net/10347/29019 |
DOI: | 10.1016/j.envres.2022.112890 |
E-ISSN: | 0013-9351 |
Dereitos: | © 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/) Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
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