Characterisation of the blood RNA host response underpinning severity in COVID-19 patients
Jackson H., Rivero Calle I., Broderick C., Habgood-Coote D., D’Souza G., Nichols S., Vito O., Gómez-Rial J., Rivero-Velasco C., Rodríguez-Núñez N., Barbeito-Castiñeiras G., Pérez-Freixo H., Barreiro-de Acosta M., Cunnington AJ., Herberg JA., Wright VJ., Gómez-Carballa A., Salas A., Levin M., Martinon-Torres F., Kaforou M., Jackson H., Calle IR., Habgood-Coote D., D’Souza G., Nichols S., Gómez-Rial J., Cunnington AJ., Herberg JA., Wright VJ., Gómez-Carballa A., Salas A., Levin M., Martinon-Torres F., Kaforou M., Antonio AG., Julián ÁE., Antonio AL., Gema BC., Xabier BP., Miriam BG., María Victoria CG., Miriam CL., Amparo CN., Mónica CP., José Javier CA., María José CT., Ana Isabel DU., Blanca DE., María Jesús DS., Cristina FP., Juan FV., Cristóbal GR., José Luis GA., Luisa GV., Elena GV., Alberto GC., José GR., Francisco Javier GB., Beatriz GL., Pilar LI., Beatriz LM., Marta LF., Montserrat LF., Ana LL., Federico M-T., De la Cruz Daniel N., Eloína NM., Juan Bautista OD., Jacobo PS., María PN., del Molino Bernal Marisa P., Hugo PF., Lidia PR., Sara P., Manuel PR., Antonio PR., Gloria María PH., Teresa QV., Lorenzo RC., Patricia RC., Susana RG., Sara RV., Vanessa RB., Irene RC., Carmen RV., Nuria RN., Carmen R-TS., Eva SP., José Miguel SO., Carla SV., Sonia SF., Pablo SS., Manuel TM., Rocío TP., Mercedes TC., Luis VC., Pablo VG., Soledad VIM., Sandra VL., Rocio F-I., Iria B-R., Cristina C-S.
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.