Severe COVID-19 patients could have an exacerbate inflammatory response to SARS-CoV-2 with an over production of many 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 the gelatinases MMP-2 and MMP-9, both directly and indirectly.
Several studies have found elevated serum MMP-2 and MMP-9 levels in many chronic inflammatory conditions including chronic obstructive pulmonary disease.
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 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.
Moreover, sCD163 and sCD14 known as monocyte/macrophage activation marker will be evaluated too. Plasma MMP-2, MMP-9, TIMP-1, TIMP-2, sCD163 and sCD14 levels of will be evaluated by enzyme-linked immunosorbent assay (ELISA) while MMP-2 and MMP-9 activity will be assessed by zymography in plasma samples. Finally, gelatinases and their inhibitors mRNA expression will be evaluated through quantitative real time PCR (qPCR) in peripheral blood mononuclear cells (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 and their natural inhibitors in patients with COVID-19 could be a novel disease marker as well as a therapeutic target.
