Alterations in CD39/CD73 axis of T cells associated with COVID-19 severity

Abstract

Purinergic signaling modulates immune function and is involved in the immunopathogenesis of several viral infections. This study aimed to investigate alterations in purinergic pathways in coronavirus disease 2019 (COVID-19) patients. Mild and severe COVID-19 patients had lower extracellular adenosine triphosphate and adenosine levels, and higher cytokines than healthy controls. Mild COVID-19 patients presented lower frequencies of CD4+CD25+CD39+ (activated/memory regulatory T cell [mTreg]) and increased frequencies of high-differentiated (CD27−CD28−) CD8+ T cells compared with healthy controls. Severe COVID-19 patients also showed higher frequencies of CD4+CD39+, CD4+CD25−CD39+ (memory T effector cell), and high-differentiated CD8+ T cells (CD27−CD28−), and diminished frequencies of CD4+CD73+, CD4+CD25+CD39+ mTreg cell, CD8+CD73+, and low-differentiated CD8+ T cells (CD27+CD28+) in the blood in relation to mild COVID-19 patients and controls. Moreover, severe COVID-19 patients presented higher expression of PD-1 on low-differentiated CD8+ T cells. Both severe and mild COVID-19 patients presented higher frequencies of CD4+Annexin-V+ and CD8+Annexin-V+ T cells, indicating increased T-cell apoptosis. Plasma samples collected from severe COVID-19 patients were able to decrease the expression of CD73 on CD4+ and CD8+ T cells of a healthy donor. Interestingly, the in vitro incubation of peripheral blood mononuclear cell from severe COVID-19 patients with adenosine reduced the nuclear factor-κB activation in T cells and monocytes. Together, these data add new knowledge to the COVID-19 immunopathology through purinergic regulation.