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Proc Natl Acad Sci U S A ; 117(32): 18951-18953, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32699149

RESUMO

Around the tenth day after diagnosis, ∼20% of patients with coronavirus disease 2019 (COVID-19)-associated pneumonia evolve toward severe oxygen dependence (stage 2b) and acute respiratory distress syndrome (stage 3) associated with systemic inflammation often termed a "cytokine storm." Because interleukin-1 (IL-1) blocks the production of IL-6 and other proinflammatory cytokines, we treated COVID-19 patients early in the disease with the IL-1 receptor antagonist, anakinra. We retrospectively compared 22 patients from three different centers in France with stages 2b and 3 COVID-19-associated pneumonia presenting with acute severe respiratory failure and systemic inflammation who received either standard-of-care treatment alone (10 patients) or combined with intravenous anakinra (12 patients). Treatment started at 300 mg⋅d-1 for 5 d, then tapered with lower dosing over 3 d. Both populations were comparable for age, comorbidities, clinical stage, and elevated biomarkers of systemic inflammation. All of the patients treated with anakinra improved clinically (P < 0.01), with no deaths, significant decreases in oxygen requirements (P < 0.05), and more days without invasive mechanical ventilation (P < 0.06), compared with the control group. The effect of anakinra was rapid, as judged by significant decrease of fever and C-reactive protein at day 3. A mean total dose of 1,950 mg was infused with no adverse side effects or bacterial infection. We conclude that early blockade of the IL-1 receptor is therapeutic in acute hyperinflammatory respiratory failure in COVID-19 patients.


Assuntos
Anti-Inflamatórios/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Insuficiência Respiratória/tratamento farmacológico , Idoso , Anti-Inflamatórios/administração & dosagem , COVID-19 , Estudos de Casos e Controles , Infecções por Coronavirus/complicações , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Injeções Intravenosas , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/etiologia , Insuficiência Respiratória/etiologia
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