Early identification of COVID-19 cytokine storm and treatment with anakinra or tocilizumab
Annette Langer-Gould, Jessica B Smith, Edlin G Gonzales, Rhina D Castillo, Judith Garza Figueroa, Anusha Ramanathan, Bonnie H Li, Michael K Gould
International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.07.081
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 scoreadjusted 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.
Author contributions Annette Langer-Gould conceptualized and designed the study, collected and interpreted the data, drafted and revised the manuscript for intellectual content, had full access to all the data in the study, and takes responsibility for the integrity of the data and the accuracy of the data analyses. Jessica B. Smith collected, analyzed, and interpreted the data and revised the manuscript for content. Edlin G. Gonzales collected the data and revised the manuscript for content. Rhina D. Castillo conceptualized and designed the study and revised the manuscript for content. Judith G. Figueroa conceptualized and designed the study and revised the manuscript for content. Anusha Ramanathan conceptualized and designed the study and revised the manuscript for content. Bonnie H. Li analyzed and interpreted the data and revised the manuscript for content. Michael K. Gould conceptualized and designed the study and revised the manuscript for content.
Conflicts of interests Annette Langer-Gould currently serves as a voting member on the California Technology Assessment Forum, a core program of the Institute for Clinical and Economic Review (ICER). She has received sponsored and reimbursed travel from ICER. Michael K. Gould has received research support through his employer from Medial EarlySign to develop computer models of lung cancer risk and royalties from UpToDate to co-author topics on lung cancer diagnosis and staging. Jessica B. Smith, Edlin G. Gonzales, Rhina D...
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doi:10.1016/S0140-6736(20)30566-3DOI record:
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