MMP-9 metalloproteinase and its regulator are not associated with mid-term CT residual abnormalities in patients with COVID-19 pneumonia

Abstract

Background: COVID-19 patients may have residual pulmonary alterations after the acute disease, with fibrotic-like alterations. Since metalloproteinases (MMP) and their regulators may be involved in inflammation and abnormal repair processing, we aimed to investigate the correlations between MMP-9, a tissue inhibitor of metalloproteinases (TIMP-1) and chest CT abnormalities in acute phase and mid-term follow-up.

Methods: COVID-19 patients with plasma analyses and CT scans performed at acute onset and 3 months after discharge (T post) were evaluated. MMP-9, TIMP-1, and MMP-9/TIMP-1 ratio were analyzed. CT extents of COVID-19 pneumonia and fibrotic-like alterations were visually scored (score range 0-25). Spearman rank correlation analysis (p-value <.05) was computed between acute and mid-term plasma analyses and CT scores.

Results: 39 patients were enrolled. At hospital admission, MMP-9, TIMP-1, and MMP-9/TIMP-1 had a median of 240.5 ng/mL, 258.8 ng/mL, and 0.9. The median CT global and fibrotic-like scores were 9 and 6. At T post, MMP-9 and TIMP-1 were not statistically different (p-value <.05). There was a reduction of CT global score (p-value = .00007). A significant correlation was found between MMP-9 and CT global score at hospital admission (ρ = 0.456, p-value = .003) and between MMP-9/TIMP-1 ratio and CT global score at hospital admission (ρ = 0.406, p-value = .009). No other significant correlations were found between plasma enzymes and CT alterations, both in acute and mid-term follow-up.

Conclusion: MMP-9 plasma levels and MMP-9/TIMP-1 ratio correlate with lung involvement during the acute phase. None of the levels of MMP-9, TIMP-1, and MMP-9/TIMP-1 ratio may be adopted as predictors of residual pulmonary alterations in mid-term follow-up.

Keywords: COVID-19; ELISA; MMP-9; TIMP-1; computed tomography; matrix metalloproteinases.

Figure 1.

Chest CT findings of COVID-19 pneumonia. Patient 1 (a; b): extensive area of ground-glass opacity in the right upper lobe with a small inner area of consolidation (black arrow) and crazy paving (white arrow) at hospital admission, global CT score of 4 (a); complete resolution after 3 months (b). Patient 2 (c; d): bilateral areas of ground-glass opacities at hospital admission, global CT score of 12 (c); residual abnormalities, mainly sustained by ground-glass opacity, global CT score of 11, and a consolidation with architectural distortions and a bronchial dilation (white arrow), configuring a fibrotic-like appearance (d).

Figure 2.

Scatter plots of correlations between MMP-9 and MMP-9/TIMP-1 ratio with CT global score at hospital admission. MMP-9: matrix metalloproteinase-9; TIMP-1: tissue inhibitor of metalloproteinase-1.