tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2020 Jul 22;202009017.
doi: 10.1073/pnas.2009017117. Online ahead of print.
Early IL-1 receptor blockade in severe inflammatory respiratory failure complicating COVID-19
Rapha?l Cauchois[SUP] 1 [/SUP], Marie Koubi[SUP] 1 [/SUP], David Delarbre[SUP] 2 [/SUP], C?cile Manet[SUP] 3 [/SUP], Julien Carvelli[SUP] 4 [/SUP], Valery Benjamin Blasco[SUP] 5 [/SUP], Rodolphe Jean[SUP] 1 [/SUP], Louis Fouche[SUP] 6 [/SUP], Charleric Bornet[SUP] 7 [/SUP], Vanessa Pauly[SUP] 8 [/SUP], Karin Mazodier[SUP] 1 [/SUP], Vincent Pestre[SUP] 3 [/SUP], Pierre-Andr? Jarrot[SUP] 1 [/SUP], Charles A Dinarello[SUP] 9 [/SUP], Gilles Kaplanski[SUP] 10 [/SUP]
Affiliations
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[SUP]-1[/SUP] 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.
Keywords: COVID-19; anakinra; interleukin-1; pneumonia.
. 2020 Jul 22;202009017.
doi: 10.1073/pnas.2009017117. Online ahead of print.
Early IL-1 receptor blockade in severe inflammatory respiratory failure complicating COVID-19
Rapha?l Cauchois[SUP] 1 [/SUP], Marie Koubi[SUP] 1 [/SUP], David Delarbre[SUP] 2 [/SUP], C?cile Manet[SUP] 3 [/SUP], Julien Carvelli[SUP] 4 [/SUP], Valery Benjamin Blasco[SUP] 5 [/SUP], Rodolphe Jean[SUP] 1 [/SUP], Louis Fouche[SUP] 6 [/SUP], Charleric Bornet[SUP] 7 [/SUP], Vanessa Pauly[SUP] 8 [/SUP], Karin Mazodier[SUP] 1 [/SUP], Vincent Pestre[SUP] 3 [/SUP], Pierre-Andr? Jarrot[SUP] 1 [/SUP], Charles A Dinarello[SUP] 9 [/SUP], Gilles Kaplanski[SUP] 10 [/SUP]
Affiliations
- PMID: 32699149
- DOI: 10.1073/pnas.2009017117
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[SUP]-1[/SUP] 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.
Keywords: COVID-19; anakinra; interleukin-1; pneumonia.