TIM-3 as a potential exhaustion marker in CD4⁺ T cells of COVID-19 patients

Background: COVID-19 causes a range of clinical symptoms from mild to critical and can be life-threatening. Up to now, it has led to many deaths. We aimed to evaluate exhausted markers on CD4⁺ T cells of COVID-19 patients.

Methods: In this study, we evaluated 44 patients with confirmed COVID-19 disease and 16 healthy individuals. Patients were divided into moderate/severe and critical groups. Peripheral blood mononuclear cells (PBMCs) were isolated and stained by anti-human CD39, PD-1, TIM-3, and anti-human CD4. The percentage of each CD4⁺ subpopulation was calculated by flow cytometry. Furthermore, we collected clinical information and laboratory data of both control and patient groups.

Results: We detected overexpression of TIM-3 on CD4⁺ T cells in both critical and moderate/severe patients than in healthy individuals (HIs; p < .01 and p < .0001, respectively). CD4⁺ TIM-3⁺ CD39⁺ lymphocytes were significantly higher in the critical patients than in HI (p < .05). Both Patient groups showed lymphopenia in comparison with HI, but CD4⁺ lymphocytes did not show any significant difference between study subjects. The increased amount of C-reactive protein, erythrocyte sedimentation rate, creatinine, blood urea nitrogen, and neutrophil count was observed in patients compared to HI.

Conclusion: T cell exhaustion occurs during COVID-19 disease and TIM-3 is the most important exhausted marker on CD4⁺ T cells.