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

2022; Elsevier BV; Volume: 210; Linguagem: Inglês

10.1016/j.envres.2022.112890

1096-0953

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 Rodrı́guez-Tenreiro, Ana Dacosta-Urbieta, Xabier Bello, Sara Pischedda, María José Currás-Tuala, Sandra Viz-Lasheras, Federico Martinón‐Torres, Antonio Salas, Aguilera Guirao Antonio, J. Álvarez, Antela López Antonio, Barbeito Castiñeiras Gema, Bello Paderne Xabier, Ben García Miriam, Carral García María Victoria, Cebey López Miriam, Amparo Coira, Conde Pájaro Mónica, Costa Alcalde José Javier, María José Currás-Tuala, Ana Dacosta-Urbieta, 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, Alberto Gómez‐Carballa, José Gómez Rial, González Barcala Francisco Javier, Guerra Liñares Beatriz, Leboráns Iglesias Pilar, Lence Massa Beatriz, López Franco Montserrat, López Lago Ana, Federico Martinón‐Torres, Antonio Salas, 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, Sara Pischedda, Manuel Portela‐Romero, Pose Reino Antonio, Prada Hervella Gloria María, Queiro Verdes Teresa, Redondo Collazo Lorenzo, Regueiro Casuso Patricia, Rey García Susana, R. Sara, Riveiro Blanco Vanessa, Irene Rivero‐Calle, Rivero Velasco Carmen, Rodríguez Núñez Nuria, Carmen Rodrı́guez-Tenreiro, 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, Bastón-Rey iria, Calviño-Suárez Cristina,

Respiratory viral infections research

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.