HYPERTENSION AND COVID-19: THE POSSIBLE ROLE OF METALLOPROTEINASE-9 IN COVID-19 PATHOPHYSIOLOGY

Objective: The pathophysiological mechanism of acute lung injury in COVID-19 includes a cascade of local and systemic responses with activation of several proinflammatory cytokines, including metalloproteinases. The aim of this study is investigate the role of matrix metalloproteinase-9 (MMP-9) in plasma from patients with severe COVID-19 hospitalized in a Brazilian ICU Design and method: The study was designed to analyze the MMP-9 plasmatic in COVID-19 severe infection. Epidemiological data and blood samples were obtained from 42 subjects hospitalized in the ICU with clinically SARS-CoV-2 infection con firmed by RT-PCR (COVID), and 15 healthy subjects (Control). Zymography methods obtained the MMP-9 plasma activity. Continuous variables are shown by mean±STDV and analyzed by the Mann-Whitney test. Categorical variables were compared by the Chi-squared test. The MMMP-9 activity is shown in the log of normalized and analyzed by unpaired T-test. Two-way ANOVA was used to analyze subgroups divided by gender, age greater or less than the median 60.4-year-old, hypertensive or normotensive, non-obese or obese Results: The COVID and Control groups did not differ signi ficantly by age (62.6±13vs.57.6±12.2 years old, p=0.097) and BMI (30.3±6.1vs.29.33±5.7 kg/m2, p=0.338). The COVID group has fewer women than the Control group (28.6%vs.80%, p=0.0008). The COVID subjects with hypertension were 42% vs.67% in the Control group (p=0,2), and diabetes was similar in both groups The hospital stay in the COVID group was 14.5±11.5 days and the hospitalization death rate was 32.5% The COVID-19 group has shown an increase in MMP-9 activity compared with the Control group (0.38±0.072 UA;95%CI=0.23-0.52,p<0.0001). The MMP-9 activity increasing was independent of gender (p=0.45), age (p=0.93), BMI (p=0.3) or hypertension (p=0.6) and dependent of the COVID-19 infection (p<0.0001). Therefore, our data are showing that the COVID-19 infection was responsible for MMP-9 improvement in plasma of severe COVID-19 infection (p<0.0001) while all different analyses consistently showed a signi ficant effect of COVID-19 infection (p<0.0001) Conclusions: There is a signi ficant increase in the MMP-9 plasmatic activity in severe COVID-19 patients independently of sex, age, obesity, and hypertension Therefore, MMP-9 may be a potential new target for acute lung injury therapy in patients with COVID-19.