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

Biomolecules. 2023 Jun 26;13(7):1040. doi: 10.3390/biom13071040.

Abstract

Background: 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. Methods: 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. Results: At the baseline, compared to HD (n = 53), COVID-19 patients (n = 129) showed higher plasma levels of MMP-9 (p < 0.0001) and TIMP-1 (p < 0.0001) and the higher plasma activity of MMP-2 (p < 0.0001) and MMP-9 (p < 0.0001). In the ARDS group, higher plasma levels of MMP-9 (p = 0.0339) and TIMP-1 (p = 0.0044) and the plasma activity of MMP-2 (p = 0.0258) and MMP-9 (p = 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, p = 0.0160) was observed. At the T post, a reduction in plasma levels of TIMP-1 (p < 0.0001), whereas an increase in the plasma levels of MMP-9 was observed (p = 0.0088). Conclusions: 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.

Keywords: ELISA; MMP-2; MMP-9; PASC; computed tomography; matrix metalloproteinases; post-acute sequelae of SARS-CoV-2 infection; pulmonary fibrosis; sCD14; sCD163; zymography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19*
  • Humans
  • Matrix Metalloproteinase 1
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Tissue Inhibitor of Metalloproteinase-1*
  • Tissue Inhibitor of Metalloproteinase-2

Substances

  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 2
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 1

Grants and funding

This research was funded by the Ministero dell’Università e della Ricerca (MUR)-Bando FIRS 2020, grant number FISR2020IP_01914.