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 F. Vasconcelos, Jessyca Michelon-Barbosa, Carlos A.C. Corsi, Fabiola Mestriner, Bruno C. Petroski-Moraes, Maria J. Garbellini-Diab, Daniel M.S. Couto, Maria C. Jordani, Denise Ferro, Lourenço Sbragia, Edwaldo E. Joviliano, Paulo R. Evora, Rodrigo de Carvalho Santana, Olindo Assis Martins-Filho, Katarzyna Polonis, Mayra G. Menegueti, Mauricio S. RibeiroMaria Auxiliadora-Martins, Christiane Becari

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


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.

Original languageEnglish
Article number112067
JournalBiomedicine and Pharmacotherapy
StatePublished - Oct 2021


  • COVID-19 pathophysiology
  • MMP-2
  • MMP-9
  • Metalloproteinases
  • SARS-COV2 infection


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