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Reanalysis of peripheral blood gene expression of IFIH1 rs1990760 variants in critically-ill COVID-19 patients [third-party re-analysis of GSE168400]

ABSTRACT: Peripheral blood gene expression analysis of IFIH1 rs1990760 variants in critically-ill COVID-19 patients

ORGANISM(S): Homo sapiens

PROVIDER: GSE233626 | GEO | 2024/05/22

REPOSITORIES: GEO

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Reanalysis of peripheral blood gene expression of IFIH1 rs1990760 variants in critically-ill COVID-19 patients with and without corticosteroids treatment [third-party re-analysis of GSE177025]

Project description:Peripheral blood gene expression analysis of IFIH1 rs1990760 variants in critically-ill COVID-19 patients with and without corticosteroids treatment

2024-05-22 | GSE233627 | GEO

Peripheral blood gene expression according to IFIH1 rs1990760 variants in critically-ill COVID-19 patients

Project description:Background: Outcomes in patients with severe SARS-CoV-2 infection (COVID-19) are conditioned by viral control and regulation of inflammation. Variants in IFIH1, a gene coding the cytoplasmatic RNA sensor MDA5, regulate the response to viral infections. Methods: Patients admitted to an intensive care unit (ICU) with documented COVID-19 were prospectively included and IFIH1 rs1990760 genotypes determined. Peripheral blood gene expression, cell populations and immune mediators were measured during the first day after ICU admission before steroid therapy. Peripheral blood mononuclear cells from healthy volunteers were exposed ex-vivo to an MDA5 agonist and dexamethasone, and changes in gene expression assessed. ICU discharge and hospital death were modelled using rs1990760 variants and dexamethasone therapy as factors. Findings: 237 patients were studied. Patients with the IFIH1 rs1990760 TT variant showed a decrease in expression of inflammation-related pathways, an anti-inflammatory cell profile and a decrease in pro-inflammatory mediators. Cells with TT variant exposed to an MDA5 agonist ex-vivo showed an increase in FOXO3 and IL6 when dexamethasone was added. All patients with the TT variant not treated with steroids (n=14) survived their ICU stay (HR 2.49 95% confidence interval 1.29 – 4.79). Dexamethasone therapy in this subgroup (N=50) delayed ICU discharge and increased hospital mortality (HR 2.19, 95% confidence interval 1.01 – 4.87) and serum IL-6 concentrations. Interpretation: COVID-19 ICU patients with the IFIH1 rs1990760 TT variant show an ameliorated inflammatory response that results in better outcomes than CC/CT variants. Dexamethasone can reverse this anti-inflammatory phenotype, worsening the outcome. Funding: Instituto de Salud Carlos III.

2021-07-03 | GSE168400 | GEO

Transcriptomic clustering of critically-ill COVID-19 patients [Day 4 RNAseq]

Project description:Infections caused by SARS-CoV-2 may cause a severe disease, termed COVID-19, with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms, and their modulation is the only therapeutic strategy that has shown a mortality benefit. Herein, we used peripheral blood transcriptomes of critically-ill COVID-19 patients obtained at admission in an Intensive Care Unit, to identify two clusters that, in spite of no major clinical differences, have different gene expression profiles that reveal different underlying pathogenetic mechanisms and ultimately have different ICU outcome. A transcriptomic signature was used to identify these clusters in an external validation cohort, yielding a similar result. These results illustrate the potential of transcriptomic profiles to identify patient endotypes and point to relevant pathogenetic mechanisms in COVID-19.

2023-04-29 | GSE206264 | GEO

Transcriptomic clustering of critically-ill COVID-19 patients [Day 1-RNA-Seq]

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Transcriptomic clustering of critically-ill COVID-19 patients

Project description:This SuperSeries is composed of the SubSeries listed below.

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Peripheral blood gene expression according to IFIH1 rs1990760 variants in critically-ill COVID-19 patients

Project description:Peripheral blood gene expression according to IFIH1 rs1990760 variants in critically-ill COVID-19 patients

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People critically ill with COVID-19 exhibit peripheral immune profiles predictive of mortality and reflective of SARS-CoV-2 lung viral burden

Project description:There remains an urgent need to delinate immune cell states that contribute to mortality in critially ill COVID-19 patients. To better understand determinants of mortality, we performed high dimensional profiling of blood and respiratory samples from critially ill COVID-19 patients. Single-cell RNAseq based characterization of peripheral immune states reveal distinct expression profiles that were predictive of COVID-19 mortality. Temporal analysis revealed a that persistently elevated levels of inflammatory monocyte signatures and persistent interferon signaling preceeded concerted upregulation of inflammatory cytokines. Interrogation of lower respiratory tract saples revelaed that infected myeliod cells upregulated CXCL10, and elevated levels of CXCL10 in plasma were associated with a high risk of death. Overall, our data suggest a pivotal role for myeloid cell states in severe COVID-19 and may faciliate discovery of new diagnostics and therapeutics.

2021-12-08 | GSE180578 | GEO

Transcriptomic clustering of critically-ill COVID-19 patients [miRNA-Seq]

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