MMP-2 and MMP-9 levels in plasma are altered and associated with mortality in COVID-19 patients

D`Avila-Mesquita, Carolina; Couto, Ariel E.S.; Campos, Ligia C.B.; Vasconcelos, Tauana F.; Barbosa, Jessyca M.; Corsi, Carlos A.C.; Mestriner, Fabiola; Moraes, Bruno C.P.; Diab, Maria J.G.; Couto, Daniel M.S.; Jordani, Maria C.; Ferro, Denise; Sbragia-Neto, Lourenço; Joviliano, Edwaldo E.; Evora, Paulo R.; Santana, Rodrigo C.; Martins-Filho, Olindo Assis; Polonis, Katarzyna; Menegueti, Mayra G.; Ribeiro, Mauricio S.; Auxiliadora-Martins, M.; Becari, Christiane

Respiratory symptoms are one of COVID-19 manifestations, and the metalloproteinases (MMPs) have essential roles in the lung physiology. We sought to characterize the plasmatic levels of matrix metalloproteinase-2 and 9 (MMP-2 and MMP-9) in patients with severe COVID-19 and to investigate an association between plasma MMP-2 and MMP-9 levels and clinical outcomes and mortality. MMP-2 and MMP-9 levels in plasma from patients with COVID-19 treated in the ICU (COVID-19 group) and Control patients were measured with the zymography. The study groups were matched for age, sex, hypertension, diabetes, BMI, and obesity profile. MMP-2 levels were lower and MMP-9 levels were higher in a COVID-19 group (p<0.0001) compared to Controls. MMP-9 levels in COVID-19 patients were not affected by comorbidity such as hypertension or obesity. MMP-2 levels were affected by hypertension (p<0.05), but unaffected by obesity status. Notably, hypertensive COVID-19 patients had higher MMP-2 levels compared to the non-hypertensive COVID-19 group, albeit still lower than Controls (p<0.05). No association between MMP-2 and MMP-9 plasmatic levels and corticosteroid treatment or acute kidney injury was found in COVID-19 patients. The survival analysis showed that COVID-19 mortality was associated with increased MMP-2 and MMP-9 levels, age, hypertension, BMI, and MMP-2 and MMP-9 were better predictors of mortality during hospitalization than SAPS3 and SOFA scores at hospital admission. In conclusion, a significant association between MMP-2 and MMP-9 levels and COVID-19 was found. Notably, MMP-2 and MMP-9 levels predicted the risk of in-hospital death suggesting possible pathophysiologic and prognostic roles.