PB0073 - Matrix metalloproteinases are associated with poor prognosis in hospitalized patients with COVID-19

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

María Marcos-Jubilar, MD, PhD

Clinica Universidad de Navarra
Pamplona, Navarra, Spain

Co-Author(s)

MP

María Panizo

Hematology Service
Clínica Universidad de Navarra
Pamplona, Navarra, Spain
AA

Ana Alfonso-Piérola

Hematology Service
Clinica Universidad de Navarra
Pamplona, Navarra, Spain
Josune Orbe, PhD

Researcher
Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra
Pamplona, Navarra, Spain
FA

Felix Alegre

Internal Medicine Department
Clínica Universidad de Navarra
Pamplona, Navarra, Spain
AA

Allan Argueta

Pathology Department
Clínica Universidad de Navarra
Pamplona, Navarra, Spain
RT

Rita Troyas

Faculty of Medicine
Universidad de Navarra
Pamplona, Navarra, Spain
JD

Jose Luis Del Pozo

Infectious Diseases Division
Clínica Universidad de Navarra
Pamplona, Navarra, Spain
ML

Maria Dolores Lozano

Pathology Department
Clínica Universidad de Navarra
Pamplona, Navarra, Spain
JP

Jose Antonio Páramo

Hematology Service
Clínica Universidad de Navarra
Pamplona, Navarra, Spain
RL

Ramón Lecumberri

Hematology Service
Clínica Universidad de Navarra
Pamplona, Navarra, Spain

Background: Patients with SARS-CoV-2 infection have highly variable presentations, from asymptomatic disease to severe bilateral pneumonia. Hyperinflammatory host response leads to lung and endothelial severe injury. Matrix-metalloproteinases (MMPs) and their inhibitors (TIMPs), involved in tissue degradation and remodeling, are dysregulated in inflammatory processes and could play a role in the pathophysiology of COVID-19.

Aims: To evaluate the association of MMPs/TIMPs with SARS-CoV-2 infection evolution and its role as prognosis biomarkers.

Methods: Retrospective study of SARS-CoV-2 patients that required hospitalization between March and December 2020. Upon admission, plasma sample were collected. We measured MMPs (1, 2, 7, 9 and 10) with MAP Human MMP panel 2 (Luminex) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) with ELISA kit for TIMP-1 (R&D Systems). The primary outcome was all-cause death during hospitalization. Secondary endpoint included a composite of death, requirement of mechanical ventilation or intensive care unit (ICU) admission and venous/arterial thrombosis.

Results: We included 151 patients (mean age 62±14 years). Overall, 9.9% patients died during hospitalization, 17.9% required transfer to the ICU and 7.9% developed a thrombotic event, despite the use of antithrombotic therapy in 99% of the patients. Statistically significant but weak positive correlations (R < 0.4 in all cases) between MMPs/TIMP-1 and inflammatory biomarkers such as neutrophil count, CRP, Ferritin or IL-6 were stablished. In the multivariate analysis, MMP-10 was associated with the risk of death (odds ratio 6.05; 95% confidence interval, 1.80-20.36; p=0.004). Both, MMP-10 and TIMP-1 levels were independently associated with worse combined outcome (OR (95%CI) were 3.32 (1.41-7.83) and 4.38 (1.22 – 15.76) respectively). These OR were higher than those obtained for D-Dimer (OR 2.41 (95%CI: 1.05-5.57)).

Conclusion(s): Baseline MMP-10 and TIMP-1 levels are predictors of unfavorable outcome in hospitalized COVID-19 patients. Future studies should focus their use as potential therapeutic targets.