Characterisation of the blood RNA host response underpinning severity in COVID-19 patients
Heather Jackson, Irene Rivero‐Calle, Claire Broderick, Dominic Habgood-Coote, Giselle D’Souza, Samuel Nichols, Ortensia Vito, José Gómez Rial, Carmen Rivero-Velasco, Nuria Rodríguez‐Núñez, Gema Barbeito‐Castiñeiras, Hugo Pérez-Freixo, Manuel Barreiro‐de Acosta, Aubrey J. Cunnington, Jethro Herberg, Victoria Wright, Alberto Gómez‐Carballa, Antonio Salas, Michael Levin, Federico Martinón‐Torres, Myrsini Kaforou, Heather Jackson, Irene Rivero‐Calle, Dominic Habgood-Coote, Giselle D’Souza, Samuel Nichols, José Gómez Rial, Aubrey J. Cunnington, Jethro Herberg, Victoria Wright, Alberto Gómez‐Carballa, Antonio Salas, Michael Levin, Federico Martinón‐Torres, Myrsini Kaforou, GEN-COVID (www.gencovid.eu) study group, 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, Lendoiro Fuentes Marta, López Franco Montserrat, López Lago Ana, Federico Martinón‐Torres, 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, 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, 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
Abstract
Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups. Increasing COVID-19 severity was characterised by an abundance of inflammatory immune response genes and pathways, including many related to neutrophils and macrophages, in addition to an upregulation of immunoglobulin genes. In this study, for the first time, we show how immunomodulatory treatments commonly administered to COVID-19 patients greatly alter the transcriptome. Our insights into COVID-19 severity reveal the role of immune dysregulation in the progression to severe disease and highlight the need for further research exploring the interplay between SARS-CoV-2 and the inflammatory immune response.