Characterisation of the blood RNA host response underpinning severity in COVID-19 patients

Journal article

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.H.J. receives support from the Wellcome Trust (4-Year PhD programme, grant number 215214/Z/19/Z). M.K. acknowledges support from the Wellcome Trust (Sir Henry Wellcome Fellowship grant number 206508/Z/17/Z) and the Medical Research Foundation (MRF-160-0008-ELP-KAFO-C0801). C.B. receives support from NIHR Imperial BRC (Imperial 4i Fellowship grant number RDA02). S.N., G.S., D.H-C., J.A.H., A.J.C., M.K., M.L., I.C.R., F.M-T., V.W., O.V. acknowledge funding for the EUCLIDS and PERFORM studies, funded by the European Union, grant numbers 668303 and 279185. J.A.H., M.L. and M.K. acknowledge support from the NIHR Imperial BRC. F.M-T. has received support for the present work from the Instituto de Salud Carlos III (Proyecto de Investigacion en Salud, Accion Estrategica en Salud): Fondo de Investigacion Sanitaria (FIS; PI070069/PI1000540/PI1601569/PI1901090) del plan nacional de I + D + I and `fondos FEDER' and Proyectos GaIN Rescata-Covid_ IN845D 2020/23 (GAIN, Xunta de Galicia)

Authors: Jackson, H; Rivero Calle, I; Broderick, C; Habgood-Coote, D; D’Souza, G

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Scientific Reports
• Volume: 12
• Issue: 1
• Pages: 12216-12216
• Article number: 12216
• Publication date: 2022-07-17
• DOI: 10.1038/s41598-022-15547-2
• EISSN: 2045-2322
• ISSN: 2045-2322
• Language: English
• Keywords: Immunology; Immune system; Immune dysregulation; Disease; Transcriptome; Medicine; Whole blood; Internal medicine; Biology; Infectious disease (medical specialty); Asymptomatic; Gene; Genetics; Coronavirus disease 2019 (COVID-19); Gene expression; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)