The molecular basis of the wide clinical heterogeneity of Coronavirus disease 2019 (COVID-19) is still unknown. Matrix metalloproteinases (MMPs) may have a role in the lung damage and regeneration that occur in severe patients. We studied serum MMP3 and MMP9 as potential biomarkers of COVID-19 severity, in 108 hospitalized patients with different World Health Organization (WHO) severity stage and in 48 controls. At hospital admission, serum MMP3 was increased in COVID-19 patients with a significant trend along the progression of the WHO stage, while serum levels of MMP9 were significantly increased in COVID-19 patients with no correlation with disease severity. At 1 week from hospitalization, MMP3 was reduced, suggesting an early pathogenic role of the protein in lung inflammation, while MMP9 levels were further increased, indicating a late role of the protein in the inflammatory process, specifically during the repairing phase. Furthermore, serum MMP9 was positively correlated with serum interleukin-6, myeloperoxidase, and circulating neutrophils and monocytes number. In conclusion, serum MMP3 may help to early predict the severity of COVID-19 and both proteins, MMP3 and MMP9, may contribute to define severe COVID-19 patients that may benefit from a targeted therapy on MMPs.
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