We demonstrated, for the first time, that the enzymatic activity and levels of MMP-2 and MMP-8 increased significantly in the lung microenvironment of intubated patients with COVID-19, and this MMP-axis was associated with infiltration of lung neutrophils, oxidative stress and release of sTREM-1 and sHLA-G, important mediators for the regulation of immune response. This evidence concerns the gene MMP2 and COVID-19.