• Giorgio Bozzi, Davide Mangioni, Francesca Minoia, Stefano Aliberti, Giacomo Grasselli, Laura Barbetta, Valeria Castelli, Emanuele Palomba, Laura Alagna, Andrea Lombardi, Riccardo Ungaro, Carlo Agostoni, Marina Baldini, Francesco Blasi, Matteo Cesari, Giorgio Costantino, Anna Ludovica Fracanzani, Nicola Montano, Valter Monzani, Antonio Pesenti, Flora Peyvandi, Marcello Sottocorno, Antonio Muscatello, Giovanni Filocamo, Andrea Gori, and Alessandra Bandera.
• Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Infectious Disease Unit, Milan, Italy.
• J. Allergy Clin. Immunol. 2021 Feb 1; 147 (2): 561-566.e4.

BackgroundImmunomodulants have been proposed to mitigate severe acute respiratory syndrome coronavirus 2-induced cytokine storm, which drives acute respiratory distress syndrome in coronavirus disease 2019 (COVID-19).ObjectiveWe sought to determine efficacy and safety of the association of IL-1 receptor antagonist anakinra plus methylprednisolone in severe COVID-19 pneumonia with hyperinflammation.MethodsA secondary analysis of prospective observational cohort studies was carried out at an Italian tertiary health care facility. COVID-19 patients consecutively hospitalized (February 25, 2020, to March 30, 2020) with hyperinflammation (ferritin ≥1000 ng/mL and/or C-reactive protein >10 mg/dL) and respiratory failure (oxygen therapy from 0.4 FiO2 Venturi mask to invasive mechanical ventilation) were evaluated to investigate the effect of high-dose anakinra plus methylprednisolone on survival. Patients were followed from study inclusion to day 28 or death. Crude and adjusted (sex, age, baseline PaO2:FiO2 ratio, Charlson index, baseline mechanical ventilation, hospitalization to inclusion lapse) risks were calculated (Cox proportional regression model).ResultsA total of 120 COVID-19 patients with hyperinflammation (median age, 62 years; 80.0% males; median PaO2:FiO2 ratio, 151; 32.5% on mechanical ventilation) were evaluated. Of these, 65 were treated with anakinra and methylprednisolone and 55 were untreated historical controls. At 28 days, mortality was 13.9% in treated patients and 35.6% in controls (Kaplan-Meier plots, P = .005). Unadjusted and adjusted risk of death was significantly lower for treated patients compared with controls (hazard ratio, 0.33, 95% CI, 0.15-0.74, P = .007, and HR, 0.18, 95% CI, 0.07-0.50, P = .001, respectively). No significant differences in bloodstream infections or laboratory alterations were registered.ConclusionsTreatment with anakinra plus methylprednisolone may be a valid therapeutic option in COVID-19 patients with hyperinflammation and respiratory failure, also on mechanical ventilation. Randomized controlled trials including the use of either agent alone are needed to confirm these results.Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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