MMP-2 and MMP-9 levels in plasma are altered and associated with mortality in COVID-19 patients
Carolina D`Avila-Mesquita, Ariel E.S. Couto, Ligia C.B. Campos, Tauana Fernandes Vasconcelos, Jéssyca Michelon-Barbosa, Carlos Alexandre Curylofo Corsi, Fabíola Mestriner, Bruno C. Petroski-Moraes, Maria J. Garbellini-Diab, Daniel Couto, Maria Cecília Jordani, Denise Ferro, Lourenço Sbragia, Edwaldo Édner Joviliano, Paulo Roberto Barbosa Évora, Rodrigo de Carvalho Santana, Olindo Assis Martins‐Filho, Katarzyna Polonis, Mayra Gonçalves Menegueti, Maurício Serra Ribeiro, Maria Auxiliadora‐Martins, Christiane Becari
Abstract
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.