Lymphocyte Inhibition Mechanisms and Immune Checkpoints in COVID-19: Insights into Prognostic Markers and Disease Severity

COVID-19 中的淋巴细胞抑制机制和免疫检查点:对预后标志物和疾病严重程度的洞察

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作者:Martina Schniederova, Anna Bobcakova, Marian Grendar, Adam Markocsy, Andrej Ceres, Michal Cibulka, Dusan Dobrota, Milos Jesenak

Conclusions

Analysis of the immune response may be useful for monitoring and predicting the course of COVID-19 upon admission. However, it is essential to evaluate complex immune parameters in conjunction with other key clinical and laboratory indicators.

Methods

In this retrospective observational study, we analysed the expression of PD-1 and TIM-3 on CD4+ and CD8+ T cells upon admission and after 7 days of hospitalisation in 770 adult patients. We also evaluated sPD-1 levels in the plasma of 145 patients at different stages of COVID-19 and of 11 control subjects. Molecules were determined using conventional flow cytometry and ELISA and the data were statistically processed.

Results

We observed a significantly higher expression of PD-1 on CD4+ cells in deceased patients than in those with mild-to-moderate disease. All patients with COVID-19 exhibited a significantly higher expression of TIM-3 on both CD4+ and CD8+ T cells compared to controls. After 1 week of hospitalisation, there was no significant change in PD-1 or TIM-3 expression on CD4+ or CD8+ T cells across the studied groups. sPD-1 concentrations were not significantly different between survivors and non-survivors. Plasma sPD-1 levels did not correlate with PD-1 expression on T cells, but a significant correlation was observed between CD4+ PD-1 and CD8+ PD-1. Using machine-learning algorithms, we supported our observations and confirmed immunological variables capable of predicting survival, with AUC = 0.786. Conclusions: Analysis of the immune response may be useful for monitoring and predicting the course of COVID-19 upon admission. However, it is essential to evaluate complex immune parameters in conjunction with other key clinical and laboratory indicators.

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