Scientific Reports (Jul 2022)

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,
  • Jose Gómez-Rial,
  • Carmen Rivero-Velasco,
  • Nuria Rodríguez-Núñez,
  • Gema Barbeito-Castiñeiras,
  • Hugo Pérez-Freixo,
  • Manuel Barreiro-de Acosta,
  • Aubrey J. Cunnington,
  • Jethro A. Herberg,
  • Victoria J. Wright,
  • Alberto Gómez-Carballa,
  • Antonio Salas,
  • Michael Levin,
  • Federico Martinon-Torres,
  • Myrsini Kaforou,
  • PERFORM consortium,
  • GEN-COVID (www.gencovid.eu) study group

DOI
https://doi.org/10.1038/s41598-022-15547-2
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 14

Abstract

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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.