Background Interleukin-1 plays a pivotal role in the inflammatory response during cytokine storm syndromes . Objective To analyse the efficacy and safety of early anti-inflammatory treatment (AIT) with i.v anakinra with or without glucocorticoids (GC) in COVID19 pneumonia. Methods We performed a retrospective single-centre cohort study on patients admitted for COVID19 pneumonia from February 26th to April 29th, 2020 to assess the efficacy of early AIT with i.v. Anakinra (100mg every 8 hours for 3 days, with tapering) alone or in combination with GC (i.v. methylprednisolone, 1-2 mg/kg daily, with tapering). Standard of care (SOC) treatment was: hydroxychloroquine and/or azithromycin with or without antivirals and anticoagulants. Late rescue AIT with anakinra or tocilizumab was also evaluated. Treatment effect on Overall Survival (OS) was assessed by a Propensity Score adjusted Cox model. Results 128 patients were analyzed; 63 received early AIT (30 anakinra, 33 anakinra and CG) at admission; 65 patients (44 with SOC, 21 SOC plus late rescue AIT) did not and were used as controls. After adjusting for all the unbalanced baseline covariates, early AIT reduced the hazard of mortality by 74% (adjusted HR=0.26, p<0.001). The effect was similar in patients receiving anakinra alone (adjusted HR=0.28, p=0.04) and anakinra plus GC (adjusted HR=0.33, p=0.07). Late rescue treatment did not show a significant advantage over SOC alone (adjusted HR=0.82, p=0.70). Conclusions This study suggests, on a larger series of patients with COVID-19 pneumonia, the potential efficacy and safety of the early use of high doses of i.v. anakinra with or without GC.

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Background Recurrent pericarditis (RP) is a complication (15–30%) of acute pericarditis with an unknown etiology. Treatment regimen consists of a combination of non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine, with the addition of corticosteroids in resistant or intolerant cases. In the last decade anakinra was shown as an effective treatment in patients with colchicine resistant and steroid-dependent RP, initially in anecdotal reports in children and more recently in a randomized trial. Canakinumab is a monoclonal antibody selectively blocking IL-1β and its use is only anecdotally reported to treat pericarditis. We report two pediatric patients with refractory recurrent pericarditis, who presented an optimal response to anakinra treatment but prompt relapse after switch to canakinumab. Case presentation The first patient is a girl with Recurrent Pericarditis started in April 2015, after heart surgery. NSAIDs and oral steroids were started, with prompt relapse after steroid suspension. The child showed a steroid-dependent RP; anakinra was therefore started with excellent response, but discontinued after 2 weeks for local reactions. In July 2016 therapy with canakinumab was started. She experienced four relapses during canakinumab therapy despite dosage increase and steroid treatment. In January 2018 a procedure of desensitization from anakinra was performed, successfully. Anakinra as monotherapy is currently ongoing, without any sign of flare. The second patient is a girl with an idiopathic RP, who showed an initial benefit from NSAIDs and colchicine. However, 10 days after the first episode a relapse occurred and therapy with anakinra was established. Two months later, while being in complete remission, anakinra was replaced with canakinumab due to patient’s poor compliance to daily injections. She experienced a relapse requiring steroids 10 days after the first canakinumab injection. Anakinra was subsequently re-started with complete remission, persisting after 24 months follow-up. Conclusions We describe two cases of failure of the treatment with anti-IL-1β monoclonal antibodies in steroid- dependent idiopathic RP. This anecdotal and preliminary observation suggests a different efficacy of the two IL-1 blockers in the management of RP and support a possible pivotal role of IL-1α in the pathogenesis of this condition.