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

https://doi.org/10.1016/j.ijid.2020.07.081Get rights and content
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Highlights

  • Targeted anti-cytokine agents, tocilizumab and anakinra, used to treat COVID-19 related cytokine storm, yield mixed results

  • Early identification of cytokine storm using laboratory abnormalities can detect patients prior to mechanical ventilation

  • Early identification and treatment of cytokine storm with anakinra and corticosteroids led to improved outcomes compared to initiating tocilizumab shortly after mechanical ventilation.

  • Early identification and treatment of cytokine storm may be more important than which anti-inflammatory treatment is chosen

  • Our results provide additional support for the use of corticosteroid treatment of COVID19 cytokine storm

Abstract

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

COVID-19
Cytokine storm
Anakinra
Tocilizumab
Corticosteroids

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