Use of canakinumab and remdesivir in moderate-severe COVID-19 patients: A retrospective analysis.

Objectives: The dysregulated immune response occurring upon COVID-19 infection can lead to tissue damage and organ failure. Different therapeutic strategies are needed to cope with the current and future outspread of COVID-19, including antiviral and anti-inflammatory agents. We describe the outcome of hospitalized patients treated with canakinumab and remdesivir plus the standard of care therapy. Methods: This observational study describes the outcome of the combination of canakinumab (450 mg for patients ≥40 and <60 kg, 600 mg for those ≥60 and <80 kg, or 750 mg for patients ≥80 kg) and 200 mg remdesivir intravenous infusion, plus standard of care (SOC), in 17 moderate-to-severe COVID-19 patients hospitalized in the "Annunziata" Hospital, Cosenza, Italy, between August and November 2021. Hematological markers, biochemical, and hemogasanalysis values at baseline versus day 7 of combination treatment were compared by paired t test after checking for normal distribution and correcting for multiple comparison. Results: The median age of patients was 64 years (range: 39-85), and the median hospitalization time (calculated on the 16 patients that were not transferred to intensive care unit) was of 12.5 days (range: 7-35 days); 15/17 patients (88%) did not experience complications. After 7 days of combination therapy, all the inflammatory parameters were significantly reduced with the exception of procalcitonin; moreover, hematological prognostic markers such neutrophil-to-lymphocyte ratio, CRP-to-lymphocyte ratio, and derived neutrophil-to-lymphocyte ratio reduced. Overall, 16/17 patients (94%) recovered after 14 days. Conclusions: Canakinumab and remdesivir treatment, in addition to SOC, in the early stage of moderate-to-severe COVID-19 showed promising outcomes in terms of safety and effectiveness potentially leading to a reduction in inflammatory and hematological prognostic markers after 7 days of treatment.

Subcutaneous tocilizumab treatment in patients with severe COVID-19-related cytokine release syndrome: An observational cohort study.

BACKGROUND: Patients with severe coronavirus disease 2019 (COVID-19) have elevated levels of acute phase reactants and inflammatory cytokines, including interleukin-6, indicative of cytokine release syndrome (CRS). The interleukin-6 receptor inhibitor tocilizumab is used for the treatment of chimeric antigen receptor T-cell therapy-induced CRS. METHODS: Patients aged 18 years or older with laboratory-confirmed COVID-19 admitted to the Annunziata Hospital in Cosenza, Italy, through March 7, 2020, who received at least one dose of tocilizumab 162 mg subcutaneously for the treatment of COVID-19-related CRS in addition to standard care were included in this retrospective observational study. The primary observation was the incidence of grade 4 CRS after tocilizumab treatment. Chest computed tomography (CT) scans were evaluated to investigate lung manifestations. FINDINGS: Twelve patients were included; all had fever, cough, and fatigue at presentation, and all had at least one comorbidity (hypertension, six patients; diabetes, five patients; chronic obstructive lung disease, four patients). Seven patients received high-flow nasal cannula oxygen therapy and five received non-invasive mechanical ventilation for lung complications of COVID-19. No incidence of grade 4 CRS was observed within 1 week of tocilizumab administration in all 12 patients (100%) and within 2 days of tocilizumab administration in 5 patients (42%). The predominant pattern on chest CT scans at presentation was ground-glass opacity, air bronchograms, smooth or irregular interlobular or septal thickening, and thickening of the adjacent pleura. Follow-up CT scans 7 to 10 days after tocilizumab treatment showed improvement of lung manifestations in all patients. No adverse events or new safety concerns attributable to tocilizumab were reported. INTERPRETATION: Tocilizumab administered subcutaneously to patients with COVID-19 and CRS is a promising treatment for reduction in disease activity and improvement in lung function. The effect of tocilizumab should be confirmed in a randomised controlled trial.

[Combined diagnostic approach to venous thromboembolism with multidetector computed tomography]. / Approccio combinato alla malattia tromboembolica venosa con tomografia computerizzata multistrato.

BACKGROUND: Multidetector computed tomography (CT) improves scan length and spatial resolution. The availability of a single test that allows a comprehensive evaluation of the chest and pulmonary arteries, of the deep venous system of the abdomen and legs and the hemodynamic impact of pulmonary emboli on the right heart could be a new and effective strategy for patients with venous thromboembolic disease. We assess a combined study protocol on venous thromboembolic disease by multidetector CT. METHODS: Twenty-four patients with confirmed acute pulmonary embolism, in stable clinical conditions, underwent multidetector CT. After antecubital intravenous infusion of 120 ml of contrast medium at a rate of 4 ml/s followed by 30 ml of saline solution a CT of the chest was performed using 4 x 1 mm collimation, pitch 1.5 and 500 ms rotation time of the X-ray tube; the start delay was checked for each single patient. Indirect CT venography study was acquired 150s after starting the infusion using a 5 mm section width from the diaphragm to the popliteal zone. We evaluated: 1) the presence of intraluminal filling defects in the pulmonary arteries and in the deep venous system from the inferior vena cava to the popliteal veins, and 2) the presence of right ventricular dilation with a right ventricle/left ventricle (RV/LV) ratio > 1. The patients with CT diagnosis of deep vein thrombosis (DVT) and and RV/LV ratio > 1 underwent venous compressive ultrasound and/or echocardiography. RESULTS: Pulmonary embolism was detected in 12% in the main arteries and in 66, 87 and 20% in the lobar, segmental and subsegmental arteries respectively. DVT was found in 14/24 (58%) patients with pulmonary embolism involving the ileo-femoral district in 14% of the whole group. Thirteen patients (54%) showed a volumetric prevalence of the right ventricle on the left ventricle. CT data in the presence of DVT and an RV/LV ratio > 1 was confirmed at ultrasonography. CONCLUSIONS: Multidetector CT allows to obtain rapidly and in one examination useful information about the source and pulmonary involvement of venous thromboembolic disease and about the hemodynamic impact on the right heart.