The compromised expression of ENPP1, ENPP2, ENPP3, and NT5E (CD73) in the peripheral blood of COVID-19 patients shown here, negatively correlates to plasma levels of the inflammatory marker CRP and the neutrophil-to-lymphocyte ratio, supporting the hypothesis of a direct contribution of the purinergic metabolism to the pathogenesis of the disease. This evidence concerns the gene ENPP2 and COVID-19.