Respiratory Impairment Predicts Response to IL-1 and IL-6 Blockade in COVID-19 Patients With Severe Pneumonia and Hyper-Inflammation.
Respiratory Impairment Predicts Response to IL-1 and IL-6 Blockade in COVID-19 Patients With Severe Pneumonia and Hyper-Inflammation.
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DOI：
10.3389/fimmu.2021.675678
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发表时间：
2021
影响因子：
7.3
通讯作者：
Dagna L
中科院分区：
文献类型：
--
作者：
Della-Torre E;Lanzillotta M;Campochiaro C;Cavalli G;De Luca G;Tomelleri A;Boffini N;De Lorenzo R;Ruggeri A;Rovere-Querini P;Castagna A;Landoni G;Tresoldi M;Ciceri F;Zangrillo A;Dagna L
抑制不适应性炎症被认为是治疗严重冠状病毒病-19(新冠肺炎)的基本策略，但现有的关于促炎细胞因子的选择性抑制剂的研究并未提供明确的证据表明生存优势。延迟给药通常被认为是治疗失败的主要原因，但新冠肺炎患者开始抗细胞因子治疗的最佳时机从未明确确定。为更好地发挥白介素1和白介素6对新冠肺炎的阻断作用，寻找治疗机会之窗。对接受Anakinra、tocilizumab、sarilumab或标准护理治疗的严重高度炎症新冠肺炎患者的可用最长随访期的存活率进行了评估，这些治疗根据治疗开始时的呼吸损害进行分层。107例接受生物制剂治疗的患者和103例接受标准护理治疗的当代患者进行了研究。经过平均106d的随访(范围3-186d)，在PaO2/FiO2≥为100毫米汞柱的患者开始接受生物制剂治疗时，其存活率显著高于标准疗法(p<；0.001)。在PaO2/FiO2为100毫米汞柱的患者中，Anakinra也降低了死亡率(p=0.04)。在严重呼吸衰竭确诊之前开始IL-1和IL-6阻断治疗更有可能为高度炎症的新冠肺炎患者提供生存优势。
Restraining maladaptive inflammation is considered a rationale strategy to treat severe coronavirus disease-19 (COVID-19) but available studies with selective inhibitors of pro-inflammatory cytokines have not provided unequivocal evidence of survival advantage. Late administration is commonly regarded as a major cause of treatment failure but the optimal timing for anti-cytokine therapy initiation in COVID-19 patients has never been clearly established. To identify a window of therapeutic opportunity for maximizing the efficacy of interleukin (IL)-1 and IL-6 blockade in COVID-19. Survival at the longest available follow-up was assessed in severe hyper-inflamed COVID-19 patients treated with anakinra, tocilizumab, sarilumab, or standard of care, stratified according to respiratory impairment at the time of treatment initiation. 107 patients treated with biologics and 103 contemporary patients treated with standard of care were studied. After a median of 106 days of follow-up (range 3-186), treatment with biologics was associated with a significantly higher survival rate compared to standard therapy when initiated in patients with a PaO2/FiO2 ≥ 100 mmHg (p < 0.001). Anakinra reduced mortality also in patients with PaO2/FiO2 < 100 mmHg (p = 0.04). IL-1 and IL-6 blocking therapies are more likely to provide survival advantage in hyper-inflamed COVID-19 patients when initiated before the establishment of severe respiratory failure.
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DOI：
10.1016/j.jaci.2021.01.024
发表时间：
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期刊：
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Hermine, Olivier;Mariette, Xavier;Ravaud, Philippe
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影响因子：
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Cavalli G;Larcher A;Tomelleri A;Campochiaro C;Della-Torre E;De Luca G;Farina N;Boffini N;Ruggeri A;Poli A;Scarpellini P;Rovere-Querini P;Tresoldi M;Salonia A;Montorsi F;Landoni G;Castagna A;Ciceri F;Zangrillo A;Dagna L
通讯作者：
Dagna L