Regulatory T cell subsets play an age-dependent role in the severity of COVID-19

COVID-19 is a disease characterized by acute respiratory failure that causes a major global healthcare issue. The immune response mechanism of the disease has not been fully defined and still largely unknown. The transcription factor forkhead box P3 (FoxP3) has significant contributions in stabilizing regulatory T cells (Treg) and maintaining their functional immunosuppressive effects. CD25high CD127low FoxP3+ cells can be regarded as the bona fide Tregs. CD39 is considered a marker of highly suppressor Tregs. Here, we aimed to evaluate the role of Treg cell subsets in COVID-19 immunopathogenesis and their relationship with disease severity. 190 COVID-19 patients (juvenile and adults) and 31 volunteers as healthy controls were included in our study. Flow Cytometry analysis was performed with a 10-color monoclonal antibody panel from peripheral blood samples. When evaluating CD4+ CD25high CD127low cell percentages in the adult severe and mild cases, a significant increase was observed compared to the control group. Consistently, a significant increase in severe and mild cases was noted in bona fide Treg cell subset expressing CD39. In juvenile patients, the percentages of CD4+ CD25high CD127low FoxP3 + CD39+ cells were lower in the 0-12 age range compared to the 13-18 age range. To conclude, our study reports significant increases in FoxP3+ CD39+ Treg subsets in adult COVID-19 patients. Interestingly, percentages of Tregs co-expressing FoxP3 and CD39 were positively correlated with increasing age in juvenile patients. Our findings provide a better understanding of the possible role of Tregs in the immune response mechanism in COVID-19 cases.