Decreased progenitor TCF1 + T-cells correlate with COVID-19 disease severity

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• COVID-19 (Coronavirus disease 2019) is linked to lymphopenia, but T-cell depletion causes are unclear.
• TCF1+ progenitor T-cells are vital for replenishing peripheral T-cells during infections.

Purpose of the Study:

• To investigate T-cell subset changes during COVID-19 progression.
• To focus on the role of TCF1+ progenitor T-cells in COVID-19 pathogenesis.

Main Methods:

• Assessed T-cell subsets (TCF1+, Ki67+, BcL2+, caspase-3+) in mild to severe COVID-19 patients.
• Analyzed TCF1 transcription inhibition by patient sera and IL-12 blocking antibodies.
• Correlated T-cell changes with vitamin D levels in severe cases.

Main Results:

• A significant decline in TCF1+ progenitor T-cells (CD4+, CD8+) was observed with increasing COVID-19 severity.
• This decline affected naive, memory, and effector-memory TCF1+ subsets, with reduced cell division (Ki67) and survival markers (BcL2).
• Severe COVID-19 patients showed increased caspase-3 expression in TCF1- T-cells, and TCF1 transcription was inhibited by patient sera, partially mediated by IL-12.

Conclusions:

• TCF1+ progenitor T-cells play a critical role in maintaining immunity during severe COVID-19.
• Loss of these cells contributes to immune deficiency in severe cases.
• Identified TCF1+, Ki67+, BcL2+, and caspase-3+ as potential biomarkers for COVID-19 severity and immune status.