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MMP-2 and MMP-9 levels in plasma are altered and associated with mortality in COVID-19 patients - 18/09/21

Doi : 10.1016/j.biopha.2021.112067 
Carolina D`Avila-Mesquita a, Ariel E.S. Couto a, Ligia C.B. Campos a, Tauana F. Vasconcelos b, Jessyca Michelon-Barbosa a, Carlos A.C. Corsi a, Fabiola Mestriner a, Bruno C. Petroski-Moraes b, Maria J. Garbellini-Diab a, Daniel M.S. Couto a, Maria C. Jordani a, Denise Ferro c, Lourenço Sbragia d, Edwaldo E. Joviliano a, Paulo R. Evora c, Rodrigo de Carvalho Santana e, Olindo Assis Martins-Filho f, Katarzyna Polonis g, Mayra G. Menegueti h, Mauricio S. Ribeiro a, Maria Auxiliadora-Martins b, Christiane Becari a,
a Division of Vascular and Endovascular Surgery, Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil 
b Division of Intensive Care, Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil 
c Division of Cardiac Surgery, Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil 
d Division of Pediatrics Surgery, Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil 
e Division of Infectious Diseases, Department of Clinical Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil 
f René Rachou Institute, Oswaldo Cruz Foundation, FIOCRUZ-Minas, Brazil 
g Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA 
h Ribeirão Preto Nurse Medical School, University of São Paulo, Ribeirão Preto, Brazil 

Correspondence to: Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São PauloRibeirão PretoSPBrazil.

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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.

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Graphical Abstract




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Highlights

Metalloproteinase-2 (MMP-2) levels were lower and metalloproteinases-9 (MMP-9) levels were higher in COVID-19 patients.
MMP-9 levels in COVID-19 were not affected by hypertension, obesity, corticosteroid treatment or acute kidney disease.
MMP-2 levels were increased in hypertensive COVID-19 patients, but were unaffected by obesity and acute kidney disease.
MMP-2 and MMP-9 levels correlated with in-hospital death, suggesting possible pathophysiologic and prognostic roles.
MMPs levels were associated with COVID-19 mortality and were better predictors of COVID-19 mortality than SAPS3 and SOFA scores at hospital admission.

El texto completo de este artículo está disponible en PDF.

Abbreviations : ACEi, ACE, ACE2, AKI, Ang, ARB, COVID-19, iRAAs, MMPs, MMP-9, MMP-2, RAS, SARS-CoV-2, SAPS3, SOFA

Keywords : SARS-COV2 infection, COVID-19 pathophysiology, Metalloproteinases, MMP-2, MMP-9


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© 2021  The Authors. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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