Matrix metalloproteinases are associated with severity of disease among COVID‐19 patients: A possible pharmacological target

Abstract

AbstractCOVID‐19 is a devastating disease and imbalanced matrix metalloproteinase (MMP) activity may contribute to its pathophysiology. This exploratory study examined whether increased circulating concentrations of MMP‐2 and MMP‐9, and their endogenous inhibitors, the tissue inhibitors of MMP (TIMP)‐1, TIMP‐2, TIMP‐3 and TIMP‐4 are persistently found in patients 2 weeks after their recovery from severe or critical COVID‐19 as compared with those in healthy controls. Subjects who had severe (n = 26) or critical (n = 25) PCR‐confirmed COVID‐19 and healthy controls (n = 21) had blood samples drawn 2 weeks after recovery and serum MMP‐2, MMP‐9, TIMP‐1, TIMP‐2, TIMP‐3 and TIMP‐4 were determined using two Human Luminex® Discovery Assays. Circulating MMP activity was also determined by gel zymography. Patients who had severe or critical COVID‐19 had increased circulating MMP‐9 and MMP‐2 concentrations, with increased MMP‐9/TIMP‐1 and MMP‐2/TIMP‐2 ratios indicating increased MMP activity, confirmed by gel zymography (all p < 0.05). Higher circulating MMP‐9 (but not MMP‐2) concentrations were found in critical versus severe COVID‐19 (p < 0.05). We found increased circulating MMP‐9 and MMP‐2 concentrations and activity many days after recovery from the acute disease, with MMP‐9 levels associated with disease severity. These biochemical alterations suggest that MMP‐2 and MMP‐9 may be important pharmacological targets in COVID‐19.