| Autor: |
Nikolaos Markou, Chryssa Pourzitaki, Haralampos Milionis, Elli Kouriannidi, Eleni Stefanatou, Nikolaos K. Gatselis, Apostolos Komnos, Vasiliki Dimakopoulou, George Nikolaidis, George N Dalekos, Mihai G. Netea, Antonia Koutsoukou, Georgia Damoraki, Georgios Papathanakos, Maria Saridaki, Karolina Akinosoglou, Ioannis Koutsodimitropoulos, Vasilios Koulouras, Evangelia Neou, Vassileios Zoumpos, Evangelos J. Giamarellos-Bourboulis, Jesper Eugen-Olsen, Nikolaos Vechlidis, Eleni Karakike, Aikaterini Ioakeimidou, Stamatios Chalvatzis, Christina Avgoustou, Eleni Gkeka, Elisabeth Paramythiotou, Antigone Kotsaki, George Dimopoulos, Nikoletta Rovina |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
RationaleMacrophage activation syndrome (MAS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19.ObjectiveTo investigate the outcome of personalized immunotherapy in critical COVID-19.MethodsIn this open-label prospective trial, 102 patients with SOFA (sequential organ failure assessment) score ≥2 or ARDS by SARS-CoV-2 were screened for MAS (ferritin more than 4420 ng/ml) and CID (ferritin ≤4420 ng/ml and low expression of HLA-DR on CD14-monocytes). Patients with MAS and CID with increased aminotransferases were assigned to intravenous anakinra; those with CID and normal aminotransferases to tocilizumab. The primary outcome was at least 25% decrease of SOFA score and/or 50% increase of respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28; serum biomarkers and cytokine production by mononuclear cells were secondary endpoints.Measurements and Main ResultsThe primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (odds ratio 3.11; 95% CIs 1.29-7.73; P: 0.011). No differences were found in mortality and in SOFA score changes. By day 4, ferritin was decreased among anakinra-treated patients; interleukin (IL)-6, soluble urokinase plasminogen activator receptor (suPAR) and the expression of HLA-DR were increased among tocilizumab-treated patients. Anakinra increased capacity of mononuclear cells to produce IL-6. Survivors by day 28 who received anakinra were distributed to scales of the WHO clinical progression of lower severity. Greater incidence of secondary infections was found with tocilizumab treatment.ConclusionsBiomarkers may guide favourable anakinra responses in critically ill patients with COVID-19.Trial RegistrationClinicalTrials.gov, NCT04339712 |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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