ABSTRACT
The aim of this study is to describe the features, the outcomes, and the clinical issues related to Remdesivir administration of a cohort of 220 patients (pts) with COVID-19 hospitalized throughout the last two pandemic waves in Italy. One hundred and nine pts were enrolled from 1 September 2020, to 28 February 2021 (Group A) and 111 from 1 March to 30 September 2021 (Group B). Notably, no differences were reported between the two groups neither in the timing of hospitalization. nor in the timing of Remdesivir administration from symptoms onset. Remarkably, a higher proportion of pts with severe COVID-19 was observed in Group B (25% vs. 10%, p < 0.001). At univariate and multivariate analysis, rather than the timing of Remdesivir administration, age, presence of coexisting conditions, D-dimers, and O2 flow at admission correlated positively to progression to non-invasive ventilation, especially for patients in Group B. However, the rate of admission in the Intensive Care Unit and/or death was comparable in the two groups (7% vs. 4%). Negligible variations in serum GOT, GPT, GGT, and eGFR levels were detected. A mean reduction in heart rate was noticed within the first three days of antiviral treatment (p < 0.001). Low rate of ICU admission, high rate of clinical recovery, and good drug safety were observed in COVID-19 patients treated with Remdesivir during two diverse pandemic waves.
ABSTRACT
BACKGROUND: Many COVID-19 patients develop a hyperinflammatory response which activates blood coagulation and may contribute to the occurrence of thromboembolic complications. Blockade of interleukin-6, a key cytokine in COVID-19 pathogenesis, may improve the hypercoagulable state induced by inflammation. The aim of this study was to evaluate the effects of subcutaneous tocilizumab, a recombinant humanized monoclonal antibody against the interleukin-6 receptor on coagulation parameters. METHODS: Hospitalized adult patients with laboratory-confirmed moderate to critical COVID-19 pneumonia and hyperinflammation, who received a single 324 mg subcutaneous dose of tocilizumab on top of standard of care were enrolled in this analysis. Coagulation parameters were measured before tocilizumab and at day 1, 3, and 7 after treatment. All patients were followed-up for 35 days after admission or until death. RESULTS: 70 patients (mean age 60 years, interquartile range 52-75) were included. Treatment with tocilizumab was associated with a reduction in D-dimer levels (-56%; 95% confidence interval [CI], -68% to -44%), fibrinogen (-48%; 95%CI, -60% to -35%), C-reactive protein (-93%; 95%CI, -99% to -87%), prothrombin time (-4%; 95%CI,-9% to 0.8%), and activated thromboplastin time (-4%; 95%CI,-8.7% to 0.8%), and an increase in platelet count (34%; 95%CI, 23% to 45%). These changes occurred already one day after treatment with sustained reductions throughout day 7. The improvement in coagulation was consistently observed in patients receiving prophylactic or therapeutic dose anticoagulants, and was paralleled by a rapid improvement in respiratory function. CONCLUSIONS: Subcutaneous tocilizumab was associated with significant improvement of blood coagulation parameters independently of thromboprophylaxis dose.