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Tissue Inhibitor of Matrix Metalloproteinases-1 (TIMP-1) and Pulmonary Involvement in COVID-19 Pneumonia

Abstract

The aim of the study was to longitudinally evaluate the association between MMP-2, MMP-9, TIMP-1 and chest radiological findings in COVID-19 patients. COVID-19 patients were evaluated based on their hospital admission (baseline) and three months after hospital discharge (T post) and were stratified into ARDS and non-ARDS groups. As a control group, healthy donors (HD) were enrolled. At the baseline, compared to HD (n = 53), COVID-19 patients (n = 129) showed higher plasma levels of MMP-9 ( < 0.0001) and TIMP-1 ( < 0.0001) and the higher plasma activity of MMP-2 ( < 0.0001) and MMP-9 ( < 0.0001). In the ARDS group, higher plasma levels of MMP-9 ( = 0.0339) and TIMP-1 ( = 0.0044) and the plasma activity of MMP-2 ( = 0.0258) and MMP-9 ( = 0.0021) compared to non-ARDS was observed. A positive correlation between the plasma levels of TIMP-1 and chest computed tomography (CT) score (ρ = 0.2302, = 0.0160) was observed. At the T post, a reduction in plasma levels of TIMP-1 ( < 0.0001), whereas an increase in the plasma levels of MMP-9 was observed ( = 0.0088). The positive correlation between TIMP-1 with chest CT scores highlights its potential use as a marker of fibrotic burden. At T post, the increase in plasma levels of MMP-9 and the reduction in plasma levels of TIMP-1 suggested that inflammation and fibrosis resolution were still ongoing.

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