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.
COVID-19 is a rapidly spreading pandemic increasing the burden on medical facilities. Symptoms vary from mild fever to ARDS complicating diagnosis, prognosis, and monitoring. Hence it is vital to ascertain a patient's condition in a timely manner.
When assessing a patient with COVID-19 infection, biomarkers can be useful to clinicians in starting treatment and may help improve prognosis and outcomes.
To date, being in the infant stages of understanding the pathology of this infectious disease, there are few biomarkers to predict the severity of the disease or mortality. Biomarkers can be used as an adjunct in clinical practice to guide treatment and admission to intensive care unit. By doing so, they may improve prognosis and minimize the mortality rates.
Matrix metalloproteinases and, namely, gelatinases (MMP-2 and MMP-9) that degrade type IV collagen, a main constituent of basement membranes, play an important role in pathologic pulmonary processes. The role of gelatinases is essential for the remodeling of basement membranes observed during various pulmonary inflammatory diseases. Recent findings suggest that MMP-2 and MMP-9 play an important role in the pathophysiology of tissue damage.
To date, it¿s possible to evaluated MMP-2, MMP-9 and their inhibitors levels in biological fluids by immunoenzymatic assays (ELISA) which are highly specific and sensitive for measurement of latent gelatinases. Otherwise, the evaluation of the MMP-2 and MMP-9 activity could be performed by zymography which distinguishes between active and latent enzyme or in biological fluids. Finally, MMP-2, MMP-9 and their relative inhibitors mRNA expression in peripheral blood mononuclear cells (PBMCs) by quantitative polymerase chain reaction (qPCR) could be useful to understand completely the regulation process for MMP-2 and MMP-9 activity.
In this study, MMP-2, MMP-9 and their relative inhibitors will be longitudinally in order to define modifications during COVID-19 pneumonia.
The aim of the present study was to assess the role of MMP-9 and MMP-2 and their natural inhibitors (TIMP-1 and TIMP-2, respectively) in the pathogenesis and the clinical course of COVID-19 compared to healthy donors and stratifying patients according to the severity of the disease. Moreover, among patients with COVID-19 a longitudinal evaluation will be performed and after three months from the recovery will be evaluated too.
The comparison between patients with COVID-19 and healthy donors as well as between patients with severe and non-severe COVID-19 pneumonia could give a deeper insight in the role of MMP-2 and MMP-9 and their natural inhibitors as predictive tools for severe COVID-19 onset. Finally, the longitudinal evaluation could be contributed to clarify the immune pathogenesis of COVID-19 by comparing clinical features to gelatinases and their inhibitors results.
This approach will be intended to identify biomarkers of disease progression, which will be helpful for clinical management in patients with COVID-19, improving safety profile. Moreover, may help in designing the appropriate new therapeutic options against current coronavirus.
Finally, the comparison between the expression of CD147 on monocytes of peripheral whole blood and MMPs and TIMPs results could be useful to understand completely the regulation process for MMP-2 and MMP-9 activity.
Results of this study may allow to assess whether MMPs and TIMPs might be used as biomarkers of disease progression and lang fibrosis, respectively.