Early IL-1 receptor blockade in severe inflammatory respiratory failure complicating COVID-19
Raphaël Cauchois, Marie Koubi, D. Delarbre, Cécile Manet, Julien Carvelli, Valéry Blasco, R Jean, Louis Fouché, Charléric Bornet, Vanessa Pauly, K. Mazodier, Vincent Pestre, Pierre‐André Jarrot, Charles A. Dinarello, Gilles Kaplanski
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 −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.