Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients.

OBJECTIVE: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. METHODS: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1ß, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. RESULTS: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1ß. CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. TRIAL REGISTRATION NUMBERS: RBR-8jyhxh.

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.