Profound Treg perturbations correlate with COVID-19 severity

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Severe COVID-19 is characterized by uncontrolled inflammation and immune dysfunction.
• T regulatory cells (Tregs) are crucial for maintaining immune homeostasis.
• The specific role of Tregs in COVID-19 pathology remains poorly understood.

Approach:

• Investigated the hypothesis that Treg perturbations contribute to COVID-19 pathology.
• Utilized cytometric and transcriptomic profiling to analyze Treg phenotype in severe COVID-19 patients.
• Compared Treg characteristics in acute and convalescent severe COVID-19 patients.

Key Points:

• Severe COVID-19 patients exhibited a distinct Treg phenotype with increased proportions and FoxP3 levels, correlating with poor outcomes.
• These Tregs over-expressed suppressive and pro-inflammatory molecules (e.g., IL32), resembling tumor-infiltrating Tregs.
• Altered Treg traits were most pronounced in acute severe disease but persisted in convalescence.

Conclusions:

• Tregs may play a detrimental role in COVID-19 pathogenesis.
• This role could involve suppressing crucial anti-viral T cell responses during severe disease.
• Alternatively, Tregs might exert direct pro-inflammatory effects contributing to COVID-19 severity.