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. A team led by researchers at the Imperial College London performed whole blood RNA Sequencing of individuals with varying degrees of COVID-19 severity. They 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, these researchers show how immunomodulatory treatments commonly administered to COVID-19 patients greatly alter the transcriptome. These 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.
A schematic summarising the number of patients analysed,
the main analysis steps, and the key findings
The numbers in brackets following mild, moderate, and severe are the WHO severity scores that make up these classifications.
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; PERFORM consortium; GEN-COVID (www.gencovid.eu) study group. (2022) Characterisation of the blood RNA host response underpinning severity in COVID-19 patients. Sci Rep 12(1):12216. [article]
