Immune checkpoint molecules as predictive markers of COVID-19 severity: A comprehensive univariable and multivariable analysis.

Immune dysregulation plays a key role in the deterioration of COVID-19. This study evaluated immune checkpoint molecules (ICMs) as markers of disease severity. Immunophenotyping of 525 hospitalised patients with moderate (n=464) and severe (n=61) COVID-19 was performed at admission and analysed alongside clinical, laboratory, and imaging data. The strongest correlations with severe outcomes and mortality were found for CD200R+CD3+ T and CD19+ B cells. Significant differences in PD-1+ and PD-L1+ lymphocyte subsets were observed between severity groups. Machine learning (SHAP) confirmed that ICM expression was at least as predictive as conventional risk factors. These findings suggest that markers of immune exhaustion, especially PD-1, PD-L1, and CD200R, may help predict COVID-19 severity. Further research is needed to determine whether targeting immune checkpoints could improve outcomes.