Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: An observational cohort study

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Background: Immunomodulants 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). Objective: We sought to determine efficacy and safety of the association of IL-1 receptor antagonist anakinra plus methylprednisolone in severe COVID-19 pneumonia with hyperinflammation. Methods: A 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). Results: A 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. Conclusions: Treatment 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.

Original languageEnglish
Pages (from-to)561-566.e4
JournalJournal of Allergy and Clinical Immunology
Issue number2
Publication statusPublished - Feb 2021


  • anakinra
  • anti–IL-1
  • corticosteroids
  • COVID-19
  • hyperinflammation
  • immunomodulation
  • mechanical ventilation
  • methylprednisolone
  • respiratory failure
  • SARS-CoV-2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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