Th1 cytokine endotype discriminates and predicts severe complications in COVID-19

Area of Science:

• Immunology
• Virology
• Public Health

Background:

• Severe and critical coronavirus disease 2019 (COVID-19) treatment remains a public health priority.
• Previous research identified distinct Th1 cytokines in severe COVID-19 pathophysiology.
• Understanding immune responses is crucial for managing severe COVID-19.

Purpose of the Study:

• To investigate the association between Th1/Th2 cytokine/chemokine endotypes and cell-mediated immunity in COVID-19 patients.
• To classify COVID-19 cases into severity clusters based on inflammatory markers for prognostic reference.
• To explore the relationship between identified endotypes and clinical outcomes.

Main Methods:

• Multiplex immunophenotyping of peripheral blood mononuclear cells.
• Single-cell RNA sequencing (scRNA-Seq) analysis.
• Analysis of serum cytokine profiles, systemic inflammatory markers, and clinical features.
• Clustering of COVID-19 cases based on identified markers.

Main Results:

• Four clusters of increasing COVID-19 severity (I-IV) were identified based on serum cytokines and inflammatory markers.
• Cluster III (severe/critical) showed decreased CCL17 and increased IL-6, C-reactive protein (CRP), CXCL9, IL-18, and IL-10.
• Cluster II (mild/moderate) exhibited predominant CXCL9 and IL-18, with relatively low IL-6 and CRP, potentially influenced by early anti-inflammatory treatment.
• A decrease in effector T cells with signs of T cell exhaustion was observed in Cluster III.

Conclusions:

• Specific inflammatory marker profiles define distinct endotypes in COVID-19 patients.
• These endotypes correlate with disease severity and clinical outcomes.
• Endotype clustering provides a prognostic reference for targeted treatment strategies in severe COVID-19.