Background and importanceMany patients with moderate–severe COVID-19 develop immune dysregulation characterised by marked activation of innate immunity, elevation of acute phase reactants and release of proinflammatory cytokines (eg, interleukin 1 (IL-1) and IL-6), thus creating a hyperinflammatory state Aim and objectivesTo determine the feasibility and safety of fighting hyperinflammation in patients with refractory moderate–severe COVID-19 by using a 3 day course of low dose subcutaneous anakinra Material and methodsA prospective study was conducted in two hospitals in Spain, from 1 April to 8 May 2020, of nine hospitalised patients refractory to standard-of-care treatment with laboratory confirmed SARS-CoV-2 infection, a clinical course of at least 5 days, radiological pneumonia and moderate–severe COVID-19 according to clinical/analytical criteria Patients received a daily subcutaneous dose of anakinra 100 mg for 3 consecutive days The primary outcome was radiological improvement 72 hours after the first administration, together with appropriate clinical and analytical changes according to a combined set of response criteria Secondary outcomes included incidence of serious adverse events, mortality, need for invasive ventilation at days 3 and 14, and days of hospitalisation ResultsAll patients (aged 48–88 years) had bilateral pneumonia and received hydroxychloroquine;7 received azithromycin, 5 ceftriaxone, 3 cyclosporine, 2 lopinavir/ritonavir, 1 interferon and 6 corticosteroids Anakinra was introduced between 1 and 17 days (median 8 days) after admission Six patients reached the primary outcome at day 3 An improvement in the chest X-ray at day 3 was observed in 7 of the 9 patients, and no radiological worsening was recorded in the 2 other patients Median SpO2 at baseline was 92% (IQR 88–95), with a significant improvement of 97% (IQR 96–98) (p=0 007) at day 3 Significant differences were also observed in various laboratory parameters between days 0 and 3 No serious adverse events were observed On days 3 and 14, no patient had died and none required invasive ventilation One patient died after 21 days of hospitalisation;the remaining 8 were discharged (length of stay 6–45 days) Conclusion and relevanceIn this study of patients with refractory moderate–severe COVID-19, a 3 day course of low dose subcutaneous anakinra was effective and safe, resulting in radiological, clinical and analytical improvement in most cases These observations require further evaluation in clinical trials References and/or acknowledgementsConflict of interestNo conflict of interest
4CPS-314 3 day course of low dose subcutaneous anakinra in patients with refractory moderate–severe COVID-19: a proof-of-concept study