Early identification of COVID-19 cytokine storm and treatment with anakinra or tocilizumab

Int J Infect Dis. 2020 Oct:99:291-297. doi: 10.1016/j.ijid.2020.07.081. Epub 2020 Aug 6.


Objective: To examine outcomes among patients who were treated with the targeted anti-cytokine agents, anakinra or tocilizumab, for COVID-19 -related cytokine storm (COVID19-CS).

Methods: We conducted a retrospective cohort study of all SARS-coV2-RNA-positive patients treated with tocilizumab or anakinra in Kaiser Permanente Southern California. Local experts developed and implemented criteria to define COVID19-CS. All variables were extracted from electronic health records.

Results: At tocilizumab initiation (n = 52), 50 (96.2%) were intubated, and only seven (13.5%) received concomitant corticosteroids. At anakinra initiation (n = 41), 23 (56.1%) were intubated, and all received concomitant corticosteroids. Fewer anakinra-treated patients died (n = 9, 22%) and more were extubated/never intubated (n = 26, 63.4%) compared to tocilizumab-treated patients (n = 24, 46.2% dead, n = 22, 42.3% extubated/never intubated). Patients who died had more severe sepsis and respiratory failure and met COVID-CS laboratory criteria longer (median = 3 days) compared to those extubated/never intubated (median = 1 day). After accounting for differences in disease severity at treatment initiation, this apparent superiority of anakinra over tocilizumab was no longer statistically significant (propensity score-adjusted hazards ratio 0.46, 95% confidence interval 0.18-1.20).

Conclusions: Prompt identification and treatment of COVID19-CS before intubation may be more important than the specific type of anti-inflammatory treatment. Randomized controlled trials of targeted anti-cytokine treatments and corticosteroids should report the duration of cytokine storm in addition to clinical severity at randomization.

Keywords: Anakinra; COVID-19; Corticosteroids; Cytokine storm; Tocilizumab.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use*
  • Aged
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Betacoronavirus / immunology*
  • COVID-19
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / immunology
  • Coronavirus Infections / virology
  • Cytokines / immunology*
  • Early Medical Intervention
  • Female
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use*
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / virology
  • Retrospective Studies
  • SARS-CoV-2
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal, Humanized
  • Cytokines
  • Interleukin 1 Receptor Antagonist Protein
  • tocilizumab