Early IL-1 receptor blockade in severe inflammatory respiratory failure complicating COVID-19

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.

Unique inflammatory profile is associated with higher SARS-CoV-2 acute respiratory distress syndrome (ARDS) mortality

“…Moreover, a single nucleotide polymorphism (SNP) leading to higher plasma IL1RA levels is associated with reduced ARDS susceptibility 37 . These data suggest that IL1RA elevation represents a feature of COVID19-induced respiratory failure that differs from non-COVID19 ARDS, and the potential pharmacologic modulation of IL1ra has been recently suggested for COVID19 patients 38,39 .…”

Neurobiochemical Cross-talk Between COVID-19 and Alzheimer’s Disease

“…IL-1 had been noticed to be significantly higher in the COVID-19 patients during disease onset and entire range of disease progression [27,28]. Anakinra, a recombinant IL-1 receptor antagonist, had been found effective in improving clinical symptoms especially respiratory distress in 72% cases [27,28]. Levels of IL-1 had also been reported to be increased in AD patients [29].…”

The Possible Dual Role of the ACE2 Receptor in Asthma and Coronavirus (SARS-CoV2) Infection

“…A preliminary study by Leng et al showed that transplantation of seven patients from Beijing YouAn Hospital, China, with ACE2-negative mesenchymal stem cells (MSCs) was effective in improving the clinical outcomes of pneumonia, mainly due to immune modulation, with decreased TNF and increased IL-10 (Leng et al, 2020). Other reports have highlighted the usage of anti-TNF (Brito et al, 2020) and anti-IL-1β to regulate inflammation in COVID-19 patients (Cauchois et al, 2020).…”