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

• DOI: 10.1016/j.envres.2022.112890
• Publication Date: 2022-02-22T08:24:27Z
• Authors: Alberto Gómez-Car...; Irene Rivero-Calle; Jacobo Pardo-Seco; José Gómez-Rial; Carmen Rivero-Vel...; Nuria Rodríguez-N...; Gema Barbeito-Cas...; Hugo Pérez-Freixo; Miriam Cebey-López; Ruth Barral-Arca; Carmen Rodriguez-...; Ana Dacosta-Urbieta; Xabier Bello; Sara Pischedda; María José Currás...; Sandra Viz-Lasheras; Federico Martinón...; Antonio Salas; Aguilera Guirao A...; Álvarez Escudero ...; Antela López Antonio; Barbeito Castiñei...; Bello Paderne Xabier; Ben García Miriam; Carral García Mar...; Cebey López Miriam; Coira Nieto Amparo; Conde Pájaro Mónica; Costa Alcalde Jos...; Currás Tuala Marí...; Dacosta Urbieta A...; Díaz Esteban Blanca; Domínguez Santall...; Fernández Pérez C...; Fernández Villave...; Galbán Rodríguez ...; García Allut José...; García Vicente Luisa; Giráldez Vázquez ...; Gómez Carballa Al...; Gómez Rial José; González Barcala ...; Guerra Liñares Be...; Leboráns Iglesias...; Lence Massa Beatriz; López Franco Mont...; López Lago Ana; Martinón-Torres F...; Antonio Salas; Navarro De la Cru...; Núñez Masid Eloína; Ortolá Devesa Jua...; Pardo Seco Jacobo; Pazo Núñez María; Pérez del Molino ...; Pérez Freixo Hugo; Piñeiro Rodríguez...; Pischedda Sara; Portela Romero Ma...; Pose Reino Antonio; Prada Hervella Gl...; Queiro Verdes Teresa; Redondo Collazo L...; Regueiro Casuso P...; Rey García Susana; Rey Vázquez Sara; Riveiro Blanco Va...; Rivero Calle Irene; Rivero Velasco Ca...; Rodríguez Núñez N...; Rodríguez-Tenreir...; Saborido Paz Eva; Sadiki Orayyou Jo...; Saito Villanueva ...; Serén Fernández S...; Souto Sanmartín P...; Taboada Muñiz Manuel; Trastoy Pena Rocío; Treviño Castellan...; Valdés Cuadrado Luis; Varela García Pablo; Vilas Iglesias Ma...; Viz Lasheras Sandra; Ferreiro-Iglesias...; Bastón-Rey iria; Calviño-Suárez Cr...
• Keywords: Respiratory tract; SLPI

Coronavirus Disease-19 (COVID-19) symptoms range from mild to severe illness; the cause for this differential response infection remains unknown. Unravelling immune mechanisms acting at different levels of colonization process might be key understand these differences. We carried out a multi-tissue (nasal, buccal and blood; n = 156) gene expression analysis immune-related genes patients affected by COVID-19 severities, healthy controls through nCounter technology. Mild asymptomatic cases showed powerful innate antiviral in nasal epithelium, characterized activation interferon (IFN) pathway downstream cascades, successfully controlling local level. In contrast, weak macrophage/monocyte driven lack IFN signalling activity were present cases. Consequently, oral mucosa signals viral activity, cell arresting dissemination lower respiratory tract, which ultimately could explain exacerbated impaired adaptative responses observed systemic Results saliva transcriptome suggest that cavity play role SARS-CoV-2 with worse prognosis. Co-expression network adds further support findings, detecting modules specifically correlated severity involved abovementioned biological routes; also provides new candidate tested as biomarkers future studies. found tissue specific severity-related signatures mainly represented system cytokine/chemokine signalling. Local determine course thus severity. Our findings provide framework investigate host pathways relevant diagnosis, prognosis, therapy.