Higher Incidence of Deep Venous Thrombosis and Pulmonary Emboli Among Coronavirus Disease 2019 (COVID-19) Positive Patients: A Multisite Healthcare System Experience

Abstract

Background: Patients with novel coronavirus disease-2019 , present a systemic inflammatory response with vascular endothelial damage and an increased risk of thromboembolic complications. Sulodexide can help restore venous and arterial endothelial glycocalyx integrity lost in certain chronic diseases, which can downregulate or limit the response to inflammatory molecules. It has an antithrombotic effect that could help reduce the incidence of thromboembolic complications which can be beneficial in these patients. We hypothesize that sulodexide, instituted in the early symptomatic stages of COVID-19, would improve the clinical outcomes with decreased hospital admission, decrease morbidity, and mortality.Methods: Prospectively, patients were recruited with early clinical symptoms of COVID-19 (shortness of breath, fever, headache, cough, etc), and screened for inclusion criteria, age 40 to 80 years, male or female, and risk of developing a severe presentation of the disease >50% given by the IMSS (Mexican Social Security Institute) COVID-19 health risk calculator. Exclusion criteria were negative COVID-19 test result, chronic use of steroid medication or anticoagulation. Patients were randomized for allocation into control group to received placebo + standard of care, or study group to receive an oral dose of 500 lipase releasing units sulodexide two times per day. The treatment lasted 21 days. A follow-up visit was scheduled via electronic media at 7 days intervals or as needed. Primary end points variables to measure were, days of hospital care, the need for supplemental oxygen, D-dimer, and C-reactive protein serum levels, and mortality rate.Results: A total of 243 patients were randomly assigned to the sulodexide group (n ¼ 124) or the placebo group (n ¼ 119). The demographics and clinical characteristics of the patients were similar in both groups. The symptoms that presented a significant improvement in the sulodexide group were body aches at week 2 (P ¼ .002), malaise/fatigue at week 3 (P ¼ .003), and shortness of breath at week 2 (P ¼ .001) and week3 (P ¼ .031). A total of 37 patients (29%) developed respiratory symptoms that warrant the need for in-home oxygen support in the sulodexide group versus 50 (42%) in the control group (P ¼ .047). A total of 56 patients (24%) required hospital admission, 22 (17.7%) in the sulodexide group and 35 (29.4%) in the placebo group (P ¼ .032), with an average length of stay of 6.4 days in the sulodexide group versus 7.8 control group (P ¼ .211). A total of 3 patients (2.4%) died in the sulodexide group versus 7 (5.8%) in the placebo group (P ¼ .121).Conclusions: Our findings supported the effectiveness of sulodexide in the prevention of a severe clinical progression of COVID-19 when used in the early symptomatic stages compare to the standard of care, reducing the need for hospital care of these patients.