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

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.