tetano
Editor, Senior Moderator
Front Immunol
. 2023 Jan 20;13:1043219.
doi: 10.3389/fimmu.2022.1043219. eCollection 2022.
Blood transcriptome responses in patients correlate with severity of COVID-19 disease
Ya Wang[SUP] 1 2 3 [/SUP], Klaus Schughart[SUP] 4 5 [/SUP], Tiana Maria Pelaia[SUP] 1 [/SUP], Tracy Chew[SUP] 6 [/SUP], Karan Kim[SUP] 2 [/SUP], Thomas Karvunidis[SUP] 7 [/SUP], Ben Knippenberg[SUP] 8 [/SUP], Sally Teoh[SUP] 1 [/SUP], Amy L Phu[SUP] 9 10 [/SUP], Kirsty R Short[SUP] 11 [/SUP], Jonathan Iredell[SUP] 12 13 14 15 [/SUP], Irani Thevarajan[SUP] 16 17 [/SUP], Jennifer Audsley[SUP] 16 17 [/SUP], Stephen Macdonald[SUP] 18 19 20 [/SUP], Jonathon Burcham[SUP] 21 [/SUP], Anthony McLean[SUP] 1 3 [/SUP]; PREDICT-19 consortium; Benjamin Tang[SUP] 1 2 [/SUP], Maryam Shojaei[SUP] 1 2 3 [/SUP]
Collaborators, Affiliations
Abstract
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.
Keywords: RNA sequencing; SARS-CoV-2; WGCNA; deconvolution; host immune response.
. 2023 Jan 20;13:1043219.
doi: 10.3389/fimmu.2022.1043219. eCollection 2022.
Blood transcriptome responses in patients correlate with severity of COVID-19 disease
Ya Wang[SUP] 1 2 3 [/SUP], Klaus Schughart[SUP] 4 5 [/SUP], Tiana Maria Pelaia[SUP] 1 [/SUP], Tracy Chew[SUP] 6 [/SUP], Karan Kim[SUP] 2 [/SUP], Thomas Karvunidis[SUP] 7 [/SUP], Ben Knippenberg[SUP] 8 [/SUP], Sally Teoh[SUP] 1 [/SUP], Amy L Phu[SUP] 9 10 [/SUP], Kirsty R Short[SUP] 11 [/SUP], Jonathan Iredell[SUP] 12 13 14 15 [/SUP], Irani Thevarajan[SUP] 16 17 [/SUP], Jennifer Audsley[SUP] 16 17 [/SUP], Stephen Macdonald[SUP] 18 19 20 [/SUP], Jonathon Burcham[SUP] 21 [/SUP], Anthony McLean[SUP] 1 3 [/SUP]; PREDICT-19 consortium; Benjamin Tang[SUP] 1 2 [/SUP], Maryam Shojaei[SUP] 1 2 3 [/SUP]
Collaborators, Affiliations
- PMID: 36741372
- PMCID: PMC9896980
- DOI: 10.3389/fimmu.2022.1043219
Abstract
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.
Keywords: RNA sequencing; SARS-CoV-2; WGCNA; deconvolution; host immune response.