In total, 651 patients, diagnosed with COVID-19, were enrolled in the study. Only 15 patients were excluded due to admission for less than 24 hours (n=13) and being transferred from another hospital (n=2), with the final sample of 636 patients (Figure 1).
The demographic and baseline characteristics of the sample by the severity group (ICU vs non-ICU) are displayed in Table 1. The mean age was 49 ±16 years and the majority (71%) were male. The mean BMI was 28 ± 6 kg/m2. A small proportion (16.6%, n=106) required ICU admission, 1.9% (n=12) were diagnosed with cancer and 0.94% (n=6) had a history of PE or DVT. The median length of hospitalization in the non-ICU group was 7 days compared to the ICU group (19 days). Compared to the non-ICU group, the ICU group consisted of more males, were older and had more comorbidities. At the end of data collection (July 15, 2020), 7.7% (n=49) participants died, and the rest were discharged. In terms of pharmacological thromboprophylaxis, the majority (90%, n=573), and more than 99% of the ICU group received pharmacological prophylaxis. The most frequently prescribed regimen (59.28%) was enoxaparin 40 mg once daily. Full dose anticoagulation was prescribed for 6.14% of the sample, due to of a pre-existing indication or empirically as part of COVID-19 management (Table 2).
Thrombotic events
VTE
Twelve patients were diagnosed with VTE 1.89% (95% CI, 1.18–3). The rate in the non-ICU group was 0.19% (95% CI, 0.04–0.84) compared to 10.38% (95% CI, 6.45–16.27) in the ICU group. The VTE rate was 21.21 events (95% CI, 11.75–38.31) per 10000 person-days, compared to the ICU group, 83.14 events (95% CI, 46.04–150.13) per 10000 person-days. The cumulative incidence of VTE at 7, 14, and 21 days was 0.47% (95% CI, 0.16 - 1.37), 0.94% (95% CI, 0.43 - 2.04) and 1.26% (95% CI, 0.63 - 2.46) respectively . The cumulative incidence of VTE in the ICU group at 7, 14, and 21 days was 1.89% (95% CI, 0.51 - 6.61), 4.72% (95% CI, 2.03 - 10.57) and 6.6% (95% CI, 3.23 - 13.00). PE with or without DVT were diagnosed in 8 participants, proximal lower extremity DVT in 4, upper extremity DVT in 1 (line related) and 2 portal vein thrombosis. VTE was diagnosed a median of 13 days after admission. The venous thromboembolism, arterial, and bleeding outcomes in ICU and non-ICU patients are displayed in Table 3.
Arterial Events
Fourteen patients were diagnosed with an arterial event with an overall rate of 2.20% (95% CI, 1.43–3.38). The rate in the non-ICU group was 0.94% (95% CI, 0.46–0.1.93) and 8.49% (95% CI, 5.01–14.04) in the ICU group. The arterial event rate was 71.71 events (95% CI, 37.31–137.82) per 10000 person-days. The arterial events rate was 218.34 events (95% CI, 104.09–457.99) per 10000 person-days in the ICU group, and 21.40 (95% CI, 5.35–85.58) in the non-ICU group. The cumulative incidence of arterial events at 7, 14, and 21 days was 1.57% (95% CI, 0.85 - 2.86), 2.04% (95% CI, 1.19 - 3.46) and 2.04% (95% CI, 1.19 - 3.46) respectively. The cumulative incidence of arterial events in the ICU group at 7, 14, and 21 days was 5.66% (95% CI, 2.61 - 11.8), 7.55% (95% CI, 3.87 - 14.19) and 7.55% (95% CI, 3.87 - 14.19). Ten patients developed CVA and 4 patients developed MI.
Composite Events
The overall composite events rate was 2.99% (95% CI, 2.06–4.31). The composite events rate in the non-ICU group was 0.94% (95% CI, 0.46–0.1.93) and 13.21% (95% CI, 8.7–19.54) in the ICU group. The composite events rate was 25.37 events (95% CI, 15.02–42.84) per 10000 person-days. The composite events rate was 85.75 events (95% CI, 48.70–151.01) per 10000 person-days in the ICU group, and 4.85 (95% CI, 1.21–19.41) in the non-ICU group (Table 5). The cumulative incidence of composite events on day 7 was 1.42 (95% CI, 0.74–2.67), day 14 1.89 (95% CI, 1.08–3.27), and day 21, 2.21 (95% CI, 1.31–3.67).
Bleeding
Eleven patients developed bleeding with an overall rate of 1.73% (95% CI, 1.06–2.81). Five were major bleeding and 6 non-major events. The bleeding rate in the non-ICU group was 0.19% (95% CI, 0.04–0.84), and 9.43% (95% CI, 5.72–15.16) in the ICU group. The bleeding rate was 22.62 events (95% CI, 12.17–42.05) per 10000 person-days and 81.97 events (95% CI, 42.65–157.55) per 10000 person-days in the ICU group (Table 5). The cumulative incidence of bleeding at 7, 14, and 21 days was 0.16% (95% CI, 0.02 - 0.88), 0.94% (95% CI, 0.43 - 2.04) and 1.26% (95% CI, 0.63 - 2.46) respectively. The cumulative incidence of bleeding in the ICU group at 7, 14, and 21 days was 0.94% (95% CI, 0.16 - 5.15), 4.72% (95% CI, 2.03 - 10.57) and 6.6% (95% CI, 3.23 - 13.00).
Risk Factors of developing VTE/Composite Events
Of the selected risk factors, the only risk factor that predicted VTE and the composite outcome, was the baseline D-dimer. The baseline D-dimer was a significant risk factor for developing VTE (OR 1.31, 95% CI, 1.084-1.573, p=0.005) and composite events (OR 1.32, 95% CI, 1.126-1.555, p=0.0007).
Mortality
In total, 49 participants died with an overall mortality rate of 7.7%. The rate of mortality in the ICU group was 35.85%, compared to 2.08% in the non-ICU group. The mortality rate was 23.37 deaths (95% CI, 17.66–30.92) per 10000 person-days. The mortality rate was 68.10 deaths (95% CI, 49.55–93.59) per 10000 person-days in the ICU group and 7.15 deaths (95% CI, 3.96–12.91) in the non-ICU group. The participants were more likely to die if they were admitted to ICU (HR 5.0, 95% CI, 2.31–10.83, p=<0.0001), older than 45 years (HR 5.40, 95% CI, 1.60–18.21, p=0.006), had a co-morbidity (HR 1.67, 95% CI, 0.83–3.36, p=0.035), or a composite event (HR 2.30, 95% CI, 1.05–5.0, p=0.035) (Table 4). The participants were 3.5 times more likely to die with the composite events (HR3.5, 95% CI, 1.75-7.24, p=0.0005).