Systemic multi-omics analysis reveals interferon response heterogeneity and links lipid metabolism to immune alterations in severe COVID-19 - PubMed

4 hours ago

Interferons are crucial for antiviral defense, but dysregulation can cause inflammation and immune dysfunction in COVID-19.
Hospitalized COVID-19 patients were stratified into low, moderate, and high ISG score clusters based on interferon-stimulated gene expression.
High ISG patients showed increased inflammation and innate immune cell expansion, but severe cases within this group had distinct metabolic disruptions.
Severe cases exhibited reduced levels of phospholipids, sphingolipids, and TCA cycle intermediates, indicating impaired lipid and mitochondrial metabolism.
Plasma from severe high ISG patients attenuated neutrophil and monocyte activation, suggesting functional immune suppression despite high ISG levels.
Certain metabolites like branched-chain lipids and tryptophan-derived compounds were positively correlated with immune activation markers.
Type-I interferon neutralization was detected in some patients but did not fully explain ISG heterogeneity or disease severity.
High ISG expression in COVID-19 is linked to systemic inflammation, but severe cases show metabolic constraints and reduced immune responsiveness, highlighting an immune-metabolic axis.

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