Early Identification of COVID-19 Cytokine Storm and Treatment with Anakinra or Tocilizumab

Langer-Gould, Annette; Smith, Jessica B.; Gonzales, Edlin G.; Castillo, Rhina D.; Garza Figueroa, Judith; Ramanathan, Anusha; Li, Bonnie H.; Gould, Michael K.

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 the electronic health record. RESULTS: At tocilizumab initiation (n = 52), 50 (96.2%) were intubated, and only 7 (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 prior to 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 duration of cytokine storm in addition to clinical severity at randomization.