The diagnosis of COVID-19 infection was based on results from polymerase chain reaction testing for SARS-CoV-2 using nasal swabs. Patients were grouped according to whether a positive result was obtained (the COVID-19 group) or whether two negative results were obtained (the control group).

Clinical and laboratory data were recorded for all enrolled patients via electronic medical records. The variables included age, sex, comorbidities, time from symptoms to the development of respiratory failure, reason for ICU admission, mechanical ventilation settings, use of sedatives and neuromuscular blocker agents, need for prone positioning, extracorporeal membrane oxygenation therapy, and renal replacement therapy. Disease severity was scored using the Simplified Acute Physiology Score 3 (SAPS 3) [12]. The anticoagulation protocol for patients with COVID-19 was enoxaparin 1 mg/kg subcutaneous once a day, unless there was renal insufficiency. Patients without COVID-19 received either enoxaparin 1 mg/kg subcutaneous once a day or unfractionated heparin 5000 IU subcutaneous three times a day. For all other patients the standard anticoagulation protocol is 15000UI of low molecular heparin daily. Patients with chronic anticoagulation therapy were excluded and we recorded both the higher dose of anticoagulation throughout the hospital stay and the reason for therapeutic anticoagulation.

Ultrasonography scans were performed as scheduled on days 3, 7, and 14, even after patients were discharged from the ICU to the ward, while they were still at the hospital. The researchers in charge of the scans (JASP, PS and ACTO) were senior physicians who are considered experts in point-of-care ultrasonography. Researchers performing the scans were aware of the COVID-19 status of the patients as soon as results from polymerase chain reaction testing for SARS-CoV-2 using nasal swabs were available and the patients without COVID-19 were transferred to non-COVID ICUs. The ultrasound images were acquired using the Sonosite M-turbo system (Fujifilm Sonosite, Bothell, WA, USA) or the Philips Innosight system (Philips, Eindhoven, Netherlands) with a linear probe (5–10 MHz). Ultrasonography scans were performed as planned even after ICU discharge, while patients were still at the hospital. The patient was placed in the supine position and the bilateral common femoral, femoral, and popliteal veins were examined using B-mode. The attending physicians in charge of patient care were informed of the scan results, and any subsequent decisions regarding anticoagulation or further investigation were at their discretion. All patients were followed until hospital discharge or death (last follow-up September 4, 2020).

Blood samples were obtained for testing to determine plasma D-dimer, platelet, and fibrinogen concentrations at admission, day 3, day 7, and day 14. D-dimer testing was performed via latex agglutination and elevated concentrations were defined as  > 0.5 ng/mL. Platelets were quantified via automated cell count and the normal range was defined as 150–400 × 103/µL. Fibrinogen testing was performed via spectrophotometry and elevated concentrations were defined as  > 400 mg/dL.

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