Heparanase‐1 and MMPs in Covid‐19 and non‐Covid‐19 pneumonia

Together with the ACE2 protein, heparan sulfate present at the level of the glycocalyx in the lung epithelia is considered a cellular “co‐receptor” for the viral spike protein that allows severe acute respiratory syndrome coronavirus 2 (SARS‐CoV) to infect cells. An increase in the amount and activity of heparanase‐1 (HPSE), the only enzyme capable of degrading the heparan sulfate (HS) chains of the glycocalyx and of the extracellular matrix, has been described in the plasma of patients affected by coronavirus disease 2019 (Covid‐19). Furthermore, the activity of matrix metalloproteases, or MMPs, has been related to matrix degradation, oxidative stress, and inflammation in Covid‐19 patients. In this study, we enrolled 26 Covid‐19 patients and 15 controls with diagnosis of non‐SARS‐CoV‐2‐related pneumonia. We evaluated the expression and activity of HPSE and the expression of MMPs in their serum together with other clinical markers of disease and inflammation. Results proved that HPSE expression and activity serum levels were significantly increased, whereas MMP2 and 9 were decreased in Covid‐19 versus non‐Covid‐19 pneumonia patients. In addition, IL‐6 levels were higher, whereas platelet and white blood cells were lower in Covid‐19 with respect to non‐Covid‐19 pneumonia. Moreover, MMP9 but not HPSE (expression and activity) levels were increased in Covid‐19 pneumonia patients with ongoing lung alteration over time. In summary, the present findings indicate that HPSE and MMPs are differentially regulated in Covid‐19 and non‐Covid‐19 pneumonia.