Early identification of COVID-19 cytokine storm and treatment with anakinra or tocilizumab
Early identification of COVID-19 cytokine storm and treatment with anakinra or tocilizumab
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DOI：
10.1016/j.ijid.2020.07.081
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发表时间：
2020-10-01
影响因子：
8.4
通讯作者：
Gould, Michael K.
中科院分区：
文献类型：
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作者：
Langer-Gould, Annette;Smith, Jessica B.;Gould, Michael K.
目的：为了检查使用靶向抗细胞因子药物阿那白滞素或托珠单抗治疗COVID-19相关细胞因子风暴（COVID-19-CS）的患者的结局，方法：我们在Kaiser Permanente Southern加州对所有SARS-coV 2-RNA阳性患者进行了回顾性队列研究。当地专家制定并实施了COVID 19-CS的定义标准。所有变量提取自电子健康records.Results：在托珠单抗启动（n = 52），50（96.2%）插管，只有7（13.5%）接受伴随皮质类固醇。在阿那白滞素启动时（n = 41），23例（56.1%）插管，所有患者均接受伴随皮质类固醇治疗。与托珠单抗治疗患者（n = 24，46.2%死亡，n = 22，42.3%拔管/从未插管）相比，阿那白滞素治疗患者死亡较少（n = 9，22%），拔管/从未插管较多（n = 26，63.4%）。与拔管/从未插管的患者（中位数= 1天）相比，死亡的患者具有更严重的败血症和呼吸衰竭，并且满足COVID-CS实验室标准的时间更长（中位数= 3天）。在考虑到治疗开始时疾病严重程度的差异后，阿那白滞素对托珠单抗的这种明显优势不再具有统计学显著性（倾向评分调整的风险比为0.46，95%置信区间为0.18-1.20）。结论：在插管前及时识别和治疗COVID 19-CS可能比特定类型的抗炎治疗更重要。靶向抗细胞因子治疗和皮质类固醇的随机对照试验应报告细胞因子风暴的持续时间以及随机化时的临床严重程度。(C)2020年南加州永久医疗集团。由爱思唯尔有限公司代表国际传染病学会出版。
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. (C) 2020 Southern California Permanente Medical Group. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.