COVID-19 pneumonia is characterized by diffuse alveolar damage and infiltration of monocytes, macrophages, and lymphocytes in pulmonary interstitium, which blocks alveolar gas exchange and induces ARDS. Patients with severe COVID-19 have high inflammatory response to SARS-CoV-2 with overproduction of inflammatory cytokines, known as macrophage activation syndrome (MAS) or cytokine storm. Activated inflammatory macrophages play a crucial role in matrix destruction by producing matrix metalloproteinases (MMPs), such as MMP-2 and MMP-9.
Several studies have found elevated serum MMP-2 and MMP-9 levels in many chronic inflammatory conditions including chronic obstructive pulmonary disease. Nevertheless, these MMPs are strictly regulated by their specific inhibitor of metalloproteinases (TIMPs), which controls its proteolytic activity.
SARS-CoV-2 invades host cells via two receptors: angiotensin-converting enzyme 2 (ACE2) and CD147. The overexpression of CD147 enhances the release and the activation of MMPs and the invasive potential during the differentiation of monocyte into macrophages. The aim of this study is to evaluate in Covid-19 the imbalance between MMP-2 and MMP-9 and their inhibitors (TIMP-2 and TIMP-1, respectively) that may cause excessive degradation of tissue, a condition that is often related to chronic inflammatory diseases.
Plasma MMP-2, MMP-9, TIMP-1 and TIMP-2 levels of will be evaluated by ELISA while MMP-2 and MMP-9 activity will be assessed by zymography. Gelatinases and their inhibitors mRNA expression will be evaluated through quantitative real time PCR (qPCR) in PBMCs. Moreover, by flow cytometry analysis the expression of CD147 on monocytes will be evaluated and the results will be compared to MMPs and TIMPs results
The evaluation of balance between gelatinases (MMP-2 and MMP-9) and their natural inhibitors (TIMP-1 and TIMP-2) in patients with COVID-19 could be a novel disease marker as well as a therapeutic target.
