PB0832 - Targeting endothelial dysfunction when treating convalescent COVID-19 patients from a moderate or severe clinical presentation and the effect on serum biomarkers. A randomized placebo-controlled trial

Background: Endothelial dysfunction is well-recognized to play a central role in COVID-19 patients and can long-persist after the resolution of the acute phase. Targeting the endothelium in the treatment or prevention of COVID-19 severity and complication is of great interest.

Aims: To evaluate the effect of Sulodexide (a glycosaminoglycan-heparin mixture with endothelial affinity) on serum biomarkers when used in patients in a convalescent phase from a moderate or severe clinical COVID-19 presentation.

Methods: This prospective, randomized, placebo-controlled trial, included patients in a convalescent phase from a moderate or severe COVID-19 clinical presentation, with high-risk chronic comorbidities and within 40 days of the initial symptoms. Patients were allocated to either receive an oral 250LRU dose of sulodexide twice a day or a placebo for 8 weeks. Endothelial, inflammatory, and prothrombotic biomarkers were measured using ELISA technique at baseline, week 4, and week 8 plus routine blood work. Comparisons between treatment groups and subgroup analysis were made using the Chi-square test, student t-test, or ANCOVA on the post-baseline value.

Results: A total of 206 patients were recruited (103 in each group), 63% female, mean age of 61 years, and 22 days on average from initial clinical symptoms. 80% of patients received at least one dose of covid-19 vaccine. At week 8, mean serum levels of thrombomodulin (22.3±9.8ng/mL vs 29.5±13.4 ng/mL, p=0.02), vWF (202±114 U/dL vs 268±122 U/dL, p=0.03), IL-6 (10.7±9.8pg/mL vs 15±14.6pg/mL, p< 0.01), d dimer (484.28±362 ngFEU/mL vs 781±998 ngFEU/mL, p< 0.01) and CRP (8.3±8.9 mg/L vs 15.80±19.7 mg/L, p< 0.01) were lower in study group vs placebo. No difference between groups means of p-selectin, fibrinogen, VCAM-1, or ICAM-1 were found.

Conclusion(s): After 8-week of treatment, patients receiving sulodexide showed lower serum levels of biomarkers for endothelial dysfunction. Sulodexide's use could translate into a better clinical outcome, which would need to be confirmed with future studies.