Patients with
COVID-19 predominantly have a
respiratory tract infection and acute lung failure is the most severe complication. While the molecular basis of SARS-CoV-2 immunopathology is still unknown, it is well established that lung
infection is associated with hyper-
inflammation and tissue damage.
Matrix metalloproteinases (
MMPs) contribute to tissue destruction in many pathological situations, and the activity of
MMPs in the lung leads to the release of bioactive mediators with inflammatory properties. We sought to characterize a scenario in which
MMPs could influence the lung pathogenesis of
COVID-19. Although we observed high diversity of
MMPs in lung tissue from
COVID-19 patients by proteomics, we specified the expression and
enzyme activity of MMP-2 in tracheal-aspirate fluid (TAF) samples from intubated
COVID-19 and non-COVID-19 patients. Moreover, the expression of MMP-8 was positively correlated with MMP-2 levels and possible shedding of the immunosuppression mediator sHLA-G and sTREM-1. Together, overexpression of the
MMP-2/
MMP-8 axis, in addition to neutrophil infiltration and products, such as
reactive oxygen species (ROS), increased lipid peroxidation that could promote intensive destruction of lung tissue in severe
COVID-19. Thus, the inhibition of
MMPs can be a novel target and promising treatment strategy in severe
COVID-19.