Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce several vascular endothelial-dependent systemic complications, and sulodexide has pleiotropic actions on the vascular endothelium, which may prove beneficial. We aimed to assess the effect of sulodexide when used within 3 days of coronavirus disease 2019 (COVID-19) clinical onset. We conducted a randomized placebo-controlled outpatient trial. To be included, patients must have been at high risk for severe clinical progression. Participants received sulodexide (oral 1,000 LRU/d) or placebo for 21 days. The primary endpoint was the need for hospital care. Also assessed were patients' need for supplemental oxygen as well as D-dimer and C-reactive protein (CRP) levels, thromboembolic events, major bleeding, and mortality. A total of 243 patients were included in the per-protocol analysis from June 5 to August 30, 2020. Of these, 124 received sulodexide and 119 received a placebo. Only 17.7% of the patients in the sulodexide group required hospitalization, compared with 29.4% in the placebo group (p = 0.03). This benefit persisted in the intention-to-treat analysis (15% in sulodexide group vs. 24% with placebo [p = 0.04]). With sulodexide, fewer patients required supplemental oxygen (30 vs. 42% [p = 0.05]). After 2 weeks, fewer patients had D-dimer levels >500 ng/dL (22 vs. 47% [p < 0.01]), and patients also had lower mean CRP levels (12.5 vs. 17.8 mg/dL [p < 0.01]). There were no between-group differences in thromboembolic events, major bleeding, or mortality. Treatment of COVID-19 patients with sulodexide, when provided within 3 days of clinical onset, improved their clinical outcomes. Although the results should be confirmed, sulodexide could be valuable in an outpatient setting.

In the treatment of venous leg ulcers, vasoactive drugs such as diosmin-hesperidin micronized purified flavonoids (DH) and, more recently, sulodexide (SDX), have been used besides compression therapy and local measures. The purpose of this study was to investigate whether the combined administration of both SDX and DH is better than DH alone in the treatment of venous ulcers. In an open-label, observational, non-parallel trial, 70 patients (90 venous ulcers) were treated with multi-layer bandaging, local measures and DH, 37 patients (50 ulcers) also received SDX, 33 patients (40 ulcers) without SDX were the control group. The evolution of leg ulcers and lipodermatosclerosis was evaluated by computerized imaging measurement. The initial clinical characteristics of both groups were similar. Ulcer size showed a faster reduction in the group receiving SDX (P<0.01). With SDX, all of the ulcers were healed by week 12, in the control group, all ulcers were healed at week 21 (P<0.01 between groups). Lipodermatosclerosis improved in both groups, but it decreased faster in the SDX group. No adverse effects attributed to the medications were seen in either group. The combined administration of SDX and DH was effective in accelerating ulcer healing, controlling pain and improving lipodermatosclerosis.

Introduction: Persistent elevation of biomarkers associated with endothelial dysfunction in convalescent COVID-19 patients has been linked to an increased risk of long-term cardiovascular complications, including long COVID syndrome. Sulodexide, known for its vascular endothelial affinity, has demonstrated pleiotropic protective properties. This study aims to evaluate the impact of sulodexide on serum levels of endothelial dysfunction biomarkers in patients during the convalescent phase of COVID-19. Methods: We conducted a double-blind, single-center, randomized, placebo-controlled trial in Mexico, comparing sulodexide (250 LRU orally, twice daily) with placebo over 8 weeks in adult patients during early COVID-19 convalescence. Differences in serum biomarkers between the groups were analyzed using repeated measures and post hoc tests, with Thrombomodulin (TM) as the primary endpoint. Results: Among 206 analyzed patients (103 in each group), at week 8, the sulodexide group exhibited significantly lower mean levels of Thrombomodulin (TM) (25.2 ± 7.9 ng/mL vs 29.9 ± 14.7 ng/mL, P = .03), von Willebrand Factor (vWF) (232 ± 131 U/dL vs 266 ± 122 U/dL, P = .02) and Interleukin-6 (IL-6) (12.5 ± 13.2 pg/mL vs 16.2 ± 16.5 pg/mL, P = .03) compared to the placebo group. D-dimer and C reactive protein (CRP) in the sulodexide group were also lowered. No significant differences were observed for P-selectin, fibrinogen, VCAM-1, or ICAM-1 levels. Conclusions: Patients in the convalescent phase of COVID-19 who received sulodexide for eight weeks showed a reduction in TM, vWF, D-dimer, CRP, and IL-6 serum levels compared to placebo. These findings suggest a potential protective effect of sulodexide against thromboinflammation and endothelial damage.

Background: Targeting endothelial cells has been suggested for the treatment of patients with COVID-19 and sulodexide has pleiotropic properties within the vascular endothelium that can prove beneficial to the same. We aimed to evaluate the effect of sulodexide when used in the early clinical stages of COVID-19. Methods: We conducted a single-centre, outpatient setting, randomised controlled trial with a parallel-group design in Mexico. Including patients within three days of clinical symptom onset, who were at a high risk of severe clinical progression due to chronic comorbidities. Participants were randomly allocated to receive an oral dose of sulodexide (500 LRU twice a day) or the placebo for 21 days. Primary outcomes were need and length of hospitalisation, need and length of oxygen support. Results: Between June 5 and August 30, 2020, 243 patients were included in the “per-protocol” analysis. One hundred twenty-four of them received sulodexide, while 119 received placeboes. At 21 days follow-up, 22 of 124 patients required hospitalisation in the sulodexide group compared to 35 of 119 in the placebo group [relative risk (RR), 0·6; 95% confidence interval (CI), 0·37-0·96; p=0·03]. Fewer patients required oxygen support in the sulodexide group [37 of 124 vs. 50 of 119; RR, 0·71; 95% CI, 0·5 to 1; p=0·05], and for fewer days (9±7·2 in the sulodexide group vs. 11·5±9·6 in the placebo group; p=0·02). There was no between-group difference concerning the length of hospital stay. Interpretation: Early intervention in COVID-19 patients with sulodexide reduced hospital admissions and oxygen support requirements, although with no significant effect on mortality. This has beneficial implications in the patient well-being, making sulodexide a favourable medication until an effective vaccine or an antiviral becomes available. Funding: Researcher independently initiated, partially funded by Alfasigma, Mexico. Listed in the ISRCTN registry under ID ISRCTN59048638 .

Significant progress has been made in treating Coronavirus disease (COVID) – an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An ominous turn in the pandemic is the evolving public health crisis emanating from persistent SARS-CoV-2 infection and its associated long-term impact. Long COVID or post–COVID syndrome describes protean symptoms that persist at least 3 months after the onset of acute illness and last for at least 2 months in individuals with a history of confirmed SARS-CoV-2 infection. Long COVID has become a public health concern. Millions of infected individuals are now facing chronic multi-organ failures, including neuropsychiatric, cardiovascular, pulmonary, and kidney complications. In general, the cause of long COVID syndrome is unclear but factors such as prolonged activation of immune responses, and viral persistence triggering transcription dysregulation of genes associated with normal thrombotic disease may play a role in cardiovascular complications. Although inflammatory biomarkers are reported in other disorders, it remains unclear whether similar biomarkers are associated with cardiovascular manifestations following COVID. Medications such as sulodexide directed at glycocalyx and coagulation have demonstrated benefits for long COVID in smaller studies. Here, we describe the outcomes of the symposium on the underlying cardiovascular mechanisms of the long COVID.