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Early IL-1 receptor blockade in severe inflammatory respiratory failure complicating COVID-19.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Aug 11; Vol. 117 (32), pp. 18951-18953. Date of Electronic Publication: 2020 Jul 22. - Publication Year :
- 2020
-
Abstract
- 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 <superscript>-1</superscript> 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.<br />Competing Interests: The authors declare no competing interest.<br /> (Copyright © 2020 the Author(s). Published by PNAS.)
- Subjects :
- Aged
Anti-Inflammatory Agents administration & dosage
COVID-19
Case-Control Studies
Coronavirus Infections complications
Female
Humans
Immunologic Factors administration & dosage
Injections, Intravenous
Interleukin 1 Receptor Antagonist Protein administration & dosage
Male
Middle Aged
Pandemics
Pneumonia, Viral complications
Pneumonia, Viral etiology
Respiratory Insufficiency etiology
Anti-Inflammatory Agents therapeutic use
Coronavirus Infections drug therapy
Immunologic Factors therapeutic use
Interleukin 1 Receptor Antagonist Protein therapeutic use
Pneumonia, Viral drug therapy
Respiratory Insufficiency drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 117
- Issue :
- 32
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 32699149
- Full Text :
- https://doi.org/10.1073/pnas.2009017117