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

PREDICT-19 Consortium, Ya Wang, Klaus Schughart, Tiana Maria Pelaia, Tracy Chew, Karan Kim, Thomas Karvunidis, Ben Knippenberg, Sally Teoh, Amy L. Phu, Kirsty R. Short, Jonathan Iredell, Irani Thevarajan, Jennifer Audsley, Stephen Macdonald, Jonathon Burcham, Anthony McLean, Benjamin Tang, Maryam Shojaei

Research output: Contribution to journalArticlepeer-review


Background: Coronavirus 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. Aim: Our 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. Results: All 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. Conclusions: Our data revealed discrete gene signatures associated with mild, moderate, and severe COVID-19 identifying valuable candidates for future biomarker discovery.
Original languageEnglish
Article number1043219
JournalFrontiers in Immunology
Publication statusPublished - 20 Jan 2023


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