Characterisation of the blood RNA host response underpinning severity in COVID-19 patients
Authors: Jackson Heather , Rivero Calle Irene , Broderick Claire , Habgood-Coote Dominic , D’Souza Giselle , Nichols Samuel , Vito Ortensia , Gómez-Rial Jose , Rivero-Velasco Carmen , Rodríguez-Núñez Nuria , Barbeito-Castiñeiras Gema , Pérez-Freixo Hugo , Barreiro-de Acosta Manuel , Cunnington Aubrey J. , Herberg Jethro A. , Wright Victoria J. , Gómez-Carballa Alberto , Salas Antonio , Levin Michael , Martinon-Torres Federico , Kaforou Myrsini ,   PERFORM consortium, Jackson Heather , Calle Irene Rivero , Habgood-Coote Dominic , D’Souza Giselle , Nichols Samuel , Gómez-Rial Jose , Cunnington Aubrey J. , Herberg Jethro A. , Wright Victoria J. , Gómez-Carballa Alberto , Salas Antonio , Levin Michael , Martinon-Torres Federico , Kaforou Myrsini ,   GEN-COVID (www.gencovid.eu) study group, Antonio Aguilera Guirao , Julián Álvarez Escudero , Antonio Antela López , Gema Barbeito Castiñeiras , Xabier Bello Paderne , Miriam Ben García , María Victoria Carral García , Miriam Cebey López , Amparo Coira Nieto , Mónica Conde Pájaro , José Javier Costa Alcalde , María José Currás Tuala , Ana Isabel Dacosta Urbieta , Blanca Díaz Esteban , María Jesús Domínguez Santalla , Cristina Fernández Pérez , Juan Fernández Villaverde , Cristóbal Galbán Rodríguez , José Luis García Allut , Luisa García Vicente , Elena Giráldez Vázquez , Alberto Gómez Carballa , José Gómez Rial , Francisco Javier González Barcala , Beatriz Guerra Liñares , Pilar Leboráns Iglesias , Beatriz Lence Massa , Marta Lendoiro Fuentes , Montserrat López Franco , Ana López Lago , Federico Martinón-Torres , De la Cruz Daniel Navarro , Eloína Núñez Masid , Juan Bautista Ortolá Devesa , Jacobo Pardo Seco , María Pazo Núñez , del Molino Bernal Marisa Pérez , Hugo Pérez Freixo , Lidia Piñeiro Rodríguez , Sara Pischedda , Manuel Portela Romero , Antonio Pose Reino , Gloria María Prada Hervella , Teresa Queiro Verdes , Lorenzo Redondo Collazo , Patricia Regueiro Casuso , Susana Rey García , Sara Rey Vázquez , Vanessa Riveiro Blanco , Irene Rivero Calle , Carmen Rivero Velasco , Nuria Rodríguez Núñez , Carmen Rodríguez-Tenreiro Sánchez , Eva Saborido Paz , José Miguel Sadiki Orayyou , Carla Saito Villanueva , Sonia Serén Fernández , Pablo Souto Sanmartín , Manuel Taboada Muñiz , Rocío Trastoy Pena , Mercedes Treviño Castellano , Luis Valdés Cuadrado , Pablo Varela García , Soledad Vilas Iglesias María , Sandra Viz Lasheras , Rocio Ferreiro-Iglesias , Iria Bastón-Rey , Cristina Calviño-Suárez 
Published: July 2022

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.