A multi-tissue study of immune gene expression profiling highlights the key role of the nasal epithelium in COVID-19 severity

Autor:	Alberto Gómez-Carballa, Irene Rivero-Calle, Jacobo Pardo-Seco, José Gómez-Rial, Carmen Rivero-Velasco, Nuria Rodríguez-Núñez, Gema Barbeito-Castiñeiras, Hugo Pérez-Freixo, Miriam Cebey-López, Ruth Barral-Arca, Carmen Rodriguez-Tenreiro, Ana Dacosta-Urbieta, Xabier Bello, Sara Pischedda, María José Currás-Tuala, Sandra Viz-Lasheras, Federico Martinón-Torres, Antonio Salas, Aguilera Guirao Antonio, Álvarez Escudero Julián, Antela López Antonio, Barbeito Castiñeiras Gema, Bello Paderne Xabier, Ben García Miriam, Carral García María Victoria, Cebey López Miriam, Coira Nieto Amparo, Conde Pájaro Mónica, Costa Alcalde José Javier, Currás Tuala María José, Dacosta Urbieta Ana Isabel, Díaz Esteban Blanca, Domínguez Santalla María Jesús, Fernández Pérez Cristina, Fernández Villaverde Juan, Galbán Rodríguez Cristóbal, García Allut José Luis, García Vicente Luisa, Giráldez Vázquez Elena, Gómez Carballa Alberto, Gómez Rial José, González Barcala Francisco Javier, Guerra Liñares Beatriz, Leboráns Iglesias Pilar, Lence Massa Beatriz, López Franco Montserrat, López Lago Ana, Martinón-Torres Federico, Navarro De la Cruz Daniel, Núñez Masid Eloína, Ortolá Devesa Juan Bautista, Pardo Seco Jacobo, Pazo Núñez María, Pérez del Molino Bernal Marisa, Pérez Freixo Hugo, Piñeiro Rodríguez Lidia, Pischedda Sara, Portela Romero Manuel, Pose Reino Antonio, Prada Hervella Gloria María, Queiro Verdes Teresa, Redondo Collazo Lorenzo, Regueiro Casuso Patricia, Rey García Susana, Rey Vázquez Sara, Riveiro Blanco Vanessa, Rivero Calle Irene, Rivero Velasco Carmen, Rodríguez Núñez Nuria, Rodríguez-Tenreiro Sánchez Carmen, Saborido Paz Eva, Sadiki Orayyou José Miguel, Saito Villanueva Carla, Serén Fernández Sonia, Souto Sanmartín Pablo, Taboada Muñiz Manuel, Trastoy Pena Rocío, Treviño Castellano Mercedes, Valdés Cuadrado Luis, Varela García Pablo, Vilas Iglesias María Soledad, Viz Lasheras Sandra, Ferreiro-Iglesias Rocio, null Bastón-Rey iria, Calviño-Suárez Cristina
Přispěvatelé:	Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría
Rok vydání:	2022
Předmět:	SARS-CoV-2 Gene Expression Profiling COVID-19 Multi-tissue COVID-19 severity Biochemistry Antiviral Agents Immunity Innate Co-expression analysis Nasal Mucosa Pathways analysis Humans Gene expression Immune response Differential expression analysis Biomarkers General Environmental Science
Zdroj:	Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela instname
Popis:	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 This study received support from Instituto de Salud Carlos III (ISCIII): GePEM (PI16/01478/Cofinanciado FEDER; A.S.), DIAVIR (DTS19/00049/Cofinanciado FEDER, A.S.), Resvi-Omics (PI19/01039/Cofinanciado FEDER, A.S.), ReSVinext (PI16/01569/Cofinanciado FEDER, F.M.T.), Enterogen (PI19/01090/Cofinanciado FEDER, F.M.T.); Agencia Gallega para la Gestión del Conocimiento en Salud (ACIS): BI-BACVIR (PRIS-3, A.S.), and CovidPhy (SA 304 C, A.S.); Agencia Gallega de Innovación (GAIN): Grupos con Potencial de Crecimiento (IN607B 2020/08, A.S.), GEN-COVID (IN845D 2020/23, F.M.T.); Framework Partnership Agreement between the Consellería de Sanidad de la XUNTA de Galicia and GENVIP-IDIS - 2021–2024 (SERGAS-IDIS march 2021); and consorcio Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CB21/06/00103; F.M.T.). We also thank Aida Freire Valls from Nanostring for her support SI
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::427c4de362232d0274d669ae55c5be5a http://hdl.handle.net/10347/29019 Zobrazit plný text záznamu