Frontiers in Immunology (Jan 2023)

Blood transcriptome responses in patients correlate with severity of COVID-19 disease

  • Ya Wang,
  • Ya Wang,
  • Ya Wang,
  • Klaus Schughart,
  • Klaus Schughart,
  • Tiana Maria Pelaia,
  • Tracy Chew,
  • Karan Kim,
  • Thomas Karvunidis,
  • Ben Knippenberg,
  • Sally Teoh,
  • Amy L. Phu,
  • Amy L. Phu,
  • Kirsty R. Short,
  • Jonathan Iredell,
  • Jonathan Iredell,
  • Jonathan Iredell,
  • Jonathan Iredell,
  • Irani Thevarajan,
  • Irani Thevarajan,
  • Jennifer Audsley,
  • Jennifer Audsley,
  • Stephen Macdonald,
  • Stephen Macdonald,
  • Stephen Macdonald,
  • Jonathon Burcham,
  • Anthony McLean,
  • Anthony McLean,
  • PREDICT-19 consortium,
  • Benjamin Tang,
  • Benjamin Tang,
  • Maryam Shojaei,
  • Maryam Shojaei,
  • Maryam Shojaei,
  • Alberto Ballestrero,
  • Allan Cripps,
  • Amanda Cox,
  • Amy L Phu,
  • Andrea De Maria,
  • Anthony McLean,
  • Arutha Kulasinghe,
  • Ben Marais,
  • Benjamin Tang,
  • Carl Feng,
  • Damien Chaussabel,
  • Darawan Rinchai,
  • Davide Bedognetti,
  • Gabriele Zoppoli,
  • Gunawan Gunawan,
  • Irani Thevarajan,
  • Jennifer Audsley,
  • John-Sebastian Eden,
  • Jonathan Iredell,
  • Karan Kim,
  • Kirsty Renfree Short,
  • Klaus Schughart,
  • Mandira Chakraborty,
  • Marcela Kralovcova,
  • Marek Nalos,
  • Marko Radic,
  • Martin Matejovic,
  • Maryam Shojaei,
  • Meagan Carney,
  • Michele Bedognetti,
  • Miroslav Prucha,
  • Mohammed Toufiq,
  • Nandan Deshpande,
  • Narasaraju Teluguakula,
  • Nicholas West,
  • Paolo Cremonesi,
  • Philip Britton,
  • Ricardo Garcia Branco,
  • Rodolphe Thiebaut,
  • Rostyslav Bilyy,
  • Sally Teoh,
  • Stephen MacDonald,
  • Tania Sorrell,
  • Thomas Karvunidis,
  • Tiana Maria Pelaia,
  • Tim Kwan,
  • Tracy Chew,
  • Tri Giang Phan,
  • Velma Herwanto,
  • Win Sen Kuan,
  • Ya Wang,
  • Yoann Zerbib

DOI
https://doi.org/10.3389/fimmu.2022.1043219
Journal volume & issue
Vol. 13

Abstract

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BackgroundCoronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infected individuals display a wide spectrum of disease severity, as defined by the World Health Organization (WHO). One of the main factors underlying this heterogeneity is the host immune response, with severe COVID-19 often associated with a hyperinflammatory state.AimOur current study aimed to pinpoint the specific genes and pathways underlying differences in the disease spectrum and outcomes observed, through in-depth analyses of whole blood transcriptomics in a large cohort of COVID-19 participants.ResultsAll WHO severity levels were well represented and mild and severe disease displaying distinct gene expression profiles. WHO severity levels 1-4 were grouped as mild disease, and signatures from these participants were different from those with WHO severity levels 6-9 classified as severe disease. Severity level 5 (moderate cases) presented a unique transitional gene signature between severity levels 2-4 (mild/moderate) and 6-9 (severe) and hence might represent the turning point for better or worse disease outcome. Gene expression changes are very distinct when comparing mild/moderate or severe cases to healthy controls. In particular, we demonstrated the hallmark down-regulation of adaptive immune response pathways and activation of neutrophil pathways in severe compared to mild/moderate cases, as well as activation of blood coagulation pathways.ConclusionsOur data revealed discrete gene signatures associated with mild, moderate, and severe COVID-19 identifying valuable candidates for future biomarker discovery.

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