RT Journal Article
T1 A multi-tissue study of immune gene expression profiling highlights the key role of the nasal epithelium in COVID-19 severity
A1 Gómez Carballa, Alberto
A1 Rivero Calle, Irene
A1 Pardo Seco, Jacobo José
A1 Gómez Rial, José
A1 Rivero Velasco, Carmen
A1 Rodríguez Núñez, Nuria
A1 Barbeito Castiñeiras, Gema
A1 Perez Freixo, Hugo
A1 Cebey López, Miriam
A1 Barral Arca, Ruth
A1 Rodríguez-Tenreiro Sánchez, Carmen
A1 Dacosta Urbieta, Ana Isabel
A1 Bello, Xabier
A1 Pischedda, Sara
A1 Currás Tuala, María José
A1 Viz Lasheras, Sandra
A1 Martinón Torres, Federico
A1 Salas Ellacuriaga, Antonio
A1 Gen Covid Study Group, 
K1 COVID-19 severity
K1 Gene expression
K1 Immune response
K1 Pathways analysis
K1 Multi-tissue
K1 Differential expression analysis
K1 Co-expression analysis
K1 SARS-CoV-2
AB 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
PB Elsevier
YR 2022
FD 2022
LK http://hdl.handle.net/10347/29019
UL http://hdl.handle.net/10347/29019
LA eng
NO Environmental Research  210 (2022) 112890
NO 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
DS Minerva
RD 24 abr 2026