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1.
PLoS One ; 16(5): e0251966, 2021.
Article in English | MEDLINE | ID: covidwho-1236594

ABSTRACT

OBJECTIVE: The aim of this study was to assess the incidence of deep vein thrombosis (DVT) of the lower limbs, using serial compression ultrasound (CUS) surveillance, in acutely ill patients with COVID-19 pneumonia admitted to a non-ICU setting. METHODS: Multicenter, prospective study of patients with COVID-19 pneumonia admitted to Internal Medicine units. All patients were screened for DVT of the lower limbs with serial CUS. Anticoagulation was defined as: low dose (enoxaparin 20-40 mg/day or fondaparinux 1.5-2.5 mg/day); intermediate dose (enoxaparin 60-80 mg/day); high dose (enoxaparin 120-160 mg or fondaparinux 5-10 mg/day or oral anticoagulation). The primary end-point of the study was the diagnosis of DVT by CUS. RESULTS: Over a two-month period, 227 consecutive patients with moderate-severe COVID-19 pneumonia were enrolled. The incidence of DVT was 13.7% (6.2% proximal, 7.5% distal), mostly asymptomatic. All patients received anticoagulation (enoxaparin 95.6%) at the following doses: low 57.3%, intermediate 22.9%, high 19.8%. Patients with and without DVT had similar characteristics, and no difference in anticoagulant regimen was observed. DVT patients were older (mean 77±9.6 vs 71±13.1 years; p = 0.042) and had higher peak D-dimer levels (5403 vs 1723 ng/mL; p = 0.004). At ROC analysis peak D-dimer level >2000 ng/mL (AUC 0.703; 95% CI 0.572-0.834; p = 0.004) was the most accurate cut-off value able to predict DVT (RR 3.74; 95%CI 1.27-10, p = 0.016). CONCLUSIONS: The incidence of DVT in acutely ill patients with COVID-19 pneumonia is relevant. A surveillance protocol by serial CUS of the lower limbs is useful to timely identify DVT that would go otherwise largely undetected.


Subject(s)
COVID-19/diagnostic imaging , Venous Thrombosis/epidemiology , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , COVID-19/complications , Enoxaparin/therapeutic use , Female , Fondaparinux/therapeutic use , Humans , Incidence , Lower Extremity/blood supply , Male , Middle Aged , Ultrasonography , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/drug therapy , Venous Thrombosis/etiology
2.
Leukemia ; 35(4): 1121-1133, 2021 04.
Article in English | MEDLINE | ID: covidwho-725732

ABSTRACT

Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus high-flow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.


Subject(s)
COVID-19 Drug Treatment , COVID-19/virology , Compassionate Use Trials , Janus Kinase 1/antagonists & inhibitors , Janus Kinase 2/antagonists & inhibitors , Janus Kinase Inhibitors/therapeutic use , SARS-CoV-2/drug effects , Aged , Aged, 80 and over , Biomarkers , COVID-19/diagnosis , COVID-19/metabolism , Combined Modality Therapy , Comorbidity , Female , Humans , Janus Kinase Inhibitors/pharmacology , Male , Middle Aged , Nitriles , Prospective Studies , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Pyrimidines , Severity of Illness Index , Treatment Outcome , Viral Load
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