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Anakinra for patients with COVID-19: an updated systematic review and meta-analysis

  • Giulio Cavalli1
  • Paolo Navalesi2,3
  • Giovanni Landoni4,5,*,
  • Andrey G. Yavorovskiy6
  • Valery V. Likhvantsev6,7
  • Alberto Zangrillo4,5
  • Lorenzo Dagna1,5
  • Giacomo Monti4,5
  • Laura Pasin2

1Unit of Immunology, Rheumatology, Allergy, and Rare Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy

2Institute of Anesthesia and Intensive Care, Azienda Ospedale-Università di Padova, 35128 Padova, Italy

3Department of Medicine (DIMED), University of Padova, 35128 Padova, Italy

4Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy

5Faculty of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy

6I.M. Sechenov First Moscow State Medical University, Ministry of Public Health of Russia, 119991 Moscow, Russia

7V. Negovsky Reanimatology Research Institute, 107031 Moscow, Russia

DOI: 10.22514/sv.2023.025

Submitted: 18 August 2022 Accepted: 20 October 2022

Online publish date: 13 April 2023

*Corresponding Author(s): Giovanni Landoni E-mail:


Severe COVID-19 patients can develop a maladaptive immune response with hyper-production of cytokines and chemokines which lead to alveolar damage, endothelial activation, coagulopathy and thromboembolic events. We performed a meta-analysis which included any study performed on COVID-19 patients with respiratory hypoxemic failure who received anakinra versus any comparator. Primary endpoint was mortality. Secondary endpoints were intubation rate, superinfection and thromboembolic events. Subgroups analyses included patients in general ward, with hyperinflammation and/or baseline ratio of arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2) >200. Twenty-four studies were included. Mortality in anakinra patients was significantly lower than mortality of controls (19% vs. 28%; p < 0.0001). Anakinra patients had significantly lower risk of intubation (16% vs. 33%; p < 0.001). Mortality reduction was confirmed in general ward settings, in patients with hyperinflammation and with PaO2/FiO2 >200, but not when selecting randomized studies only. A trend towards increased mortality in more severe patients was observed.


Anakinra; COVID-19; SARS-CoV-2; Meta-analysis; Mortality

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Giulio Cavalli,Paolo Navalesi,Giovanni Landoni,Andrey G. Yavorovskiy,Valery V. Likhvantsev,Alberto Zangrillo,Lorenzo Dagna,Giacomo Monti,Laura Pasin. Anakinra for patients with COVID-19: an updated systematic review and meta-analysis. Signa Vitae. 2023.doi:10.22514/sv.2023.025.


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