ADA2 activity showed a strong positive correlation with M2-associated factors, and flow cytometry confirmed the presence of CD206<sup>+</sup>CD86<sup>+</sup> hybrid macrophages.<h4>Conclusions</h4>Overall, our findings suggest that ADA2 regulates macrophage plasticity in COVID-19, promoting M1/M2 hybrid polarization and contributing to immune dysregulation. This evidence concerns the gene MRC1 and COVID-19.