Long-term course of ambulatory patients with COVID-19 initially treated with enoxaparin vs no anticoagulation: final analysis of the OVID (enoxaparin for outpatients with COVID-19) randomized trial

Abstract

Background: Early thromboprophylaxis does not prevent hospital admissions and death among outpatients with symptomatic COVID-19. Its impact on long-term outcomes, including long COVID symptoms and performance status, is unknown.

Objectives: To assess the long-term effects of thromboprophylaxis given at the time of acute COVID-19 in outpatients.

Methods: The OVID (enoxaparin for outpatients with COVID-19) trial randomized outpatients older than 50 years with acute COVID-19 to receive either subcutaneous enoxaparin 40 mg once daily for 14 days or standard of care (no thromboprophylaxis). In this follow-up study, we assessed the 2-year outcomes, including all-cause hospitalization and death, cardiovascular events, long COVID symptoms, and functional limitations based on the Post-COVID-19 Functional Status (PCFS) scale and EuroQol-5 Dimensions-5 Levels scale.

Results: Of 469 potentially eligible patients, 468 survived, of whom 439 (mean age 59 years; 54% men) participated in the Post-OVID study. There was no difference in terms of hospitalization and death (8.3% in the treatment group vs 10% in controls; relative risk, 0.83; 95% CI, 0.5-1.5) and of cardiovascular events between groups. The risk of presenting with long COVID symptoms was similar in the 2 groups (44% in the treatment group vs 47% in the standard of care group), with no difference between groups also concerning individual symptoms. A PCFS grade of 1 to 3, indicating light-to-moderate functional limitation, was recorded in 15% of patients in each group (odds ratio, 0.98; 95% CI, 0.6-1.7). No patients reported severe limitations (PCFS grade 4). Median EuroQol visual analog scale score was 85 on 100 points (IQR, 80-90 for the standard of care group and 75-90 for the enoxaparin group).

Conclusion: Early thromboprophylaxis does not improve long-term, 2-year clinical and functional outcomes among symptomatic ambulatory patients with acute COVID-19.

Keywords: COVID-19; heparin; long COVID; quality of life; thrombosis.

Figure 1

Most common persisting symptoms reported between day 90 and month 24 after SARS-CoV-2 infection.

Figure 2

Distribution of Post–COVID-19 Functional Status (PCFS) scale levels by treatment group. PCFS grading among the enoxaparin group and the control group (no anticoagulation) 24 months after acute COVID-19 disease. PCFS grading classifies patients from 0 (no functional limitations) to 4 (severe functional limitations) and 5 (death).

Figure 3

Distribution of the results of the EuroQol visual analog scale (EQ-VAS) by treatment group. EQ-VAS grading among the enoxaparin group and the control group (no anticoagulation) 24 months after acute COVID-19 disease. EQ-VAS is a standardized instrument for measuring an individual’s self-rated health on a vertical visual analog scale ranging from 0 to 100, where 0 represents the “worst imaginable health state” and 100 represents the “best imaginable health state”.

Figure 4

Dichotomized results of the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) scale by treatment group. EQ-5D-5L grading among the enoxaparin group and the control group (no anticoagulation) 24 months after acute COVID-19 disease. A standardized instrument for measuring generic health status, EQ-5D-5L assesses health in 5 dimensions: mobility, self-care, usual activities, pain, and anxiety. Each dimension has 5 levels of severity, ranging from no impairment to extreme impairment. Since the patients were highly functioning and had few limitations, the results of the scale were dichotomized into “no impairment” (level 1) vs “Any grade of impairment” (levels 2-5).

Figure 5

Correlation between the results of the Post–COVID-19 Functional Status (PCFS) scale and the EuroQol visual analog scale (EQ-VAS). The results of the PCFS and the EQ-VAS were stratified by the language group in which the questionnaires were administered to study participants. Higher degrees of functional impairment (as indicated by PCFS grade) were associated with lower self-perceived health status (EQ-VAS score).