Upregulation of PD-1 Expression and High sPD-L1 Levels Associated with COVID-19 Severity.

COVID-19 has several mechanisms that can lead to lymphocyte depletion/exhaustion. The checkpoint inhibitor molecule programmed death protein 1 (PD-1) and its programmed death-ligand 1 (PDL-1) play an important role in inhibiting cellular activity as well as the depletion of these cells. In this study, we evaluated PD-1 expression in TCD4+, TCD8+, and CD19+ lymphocytes from SARS-CoV-2-infected patients. A decreased frequency of total lymphocytes and an increased PD-1 expression in TCD4+ and CD19+ lymphocytes were verified in severe/critical COVID-19 patients. In addition, we found a decreased frequency of total monocytes with an increased PD-1 expression on CD14+ monocytes in severe/critical patients in association with the time of infection. Moreover, we observed an increase in sPD-L1 circulant levels associated with the severity of the disease. Overall, these data indicate an important role of the PD-1/PDL-1 axis in COVID-19 and may provide a severity-associated biomarker and therapeutic target during SARS-CoV-2 infection.