• Laura Pasin, Giulio Cavalli, Paolo Navalesi, Nicolò Sella, Giovanni Landoni, Andrey G Yavorovskiy, Valery V Likhvantsev, Alberto Zangrillo, Lorenzo Dagna, and Giacomo Monti.
• Institute of Anesthesia and Intensive Care, Azienda Ospedaliera Universitaria di Padova, Padova (Italy).
• Eur. J. Intern. Med. 2021 Apr 1; 86: 344034-40.

IntroductionSevere COVID-19 cases have a detrimental hyper-inflammatory host response and different cytokine-blocking biologic agents were explored to improve outcomes. Anakinra blocks the activity of both IL-1α and IL‑1β and is approved for different autoinflammatory disorders, but it is used off-label for conditions characterized by an excess of cytokine production. Several studies on anakinra in COVID-19 patients reported positive effects. We performed a meta-analysis of all published evidence on the use of anakinra in COVID19 to investigate its effect on survival and need for mechanical ventilation.MethodsWe searched for any study performed on adult patients with acute hypoxemic failure related to 2019-nCoV infection, receiving anakinra versus any comparator. Primary endpoint was mortality at the longest available follow-up. Adverse effects, need for mechanical ventilation and discharge at home with no limitations were also analysed.ResultsFour observational studies involving 184 patients were included. Overall mortality of patients treated with anakinra was significantly lower than mortality in the control group (95% CI 0.14-0.48, p<0.0001). Moreover, patients treated with anakinra had a significantly lower risk of need for mechanical ventilation than controls (95% CI 0.250.74, p=0.002). No difference in adverse events and discharge at home with no limitations was observed. The Trial Sequential Analysis z-cumulative line reached the monitoring boundary for benefit and the required sample size.ConclusionsAdministration of anakinra in COVID-19 patients was safe and might be associated with reductions in both mortality and need for mechanical ventilation. Randomized clinical trials are warranted to confirm these findings.Copyright © 2021. Published by Elsevier B.V.

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