Early IL-1 receptor blockade in severe inflammatory respiratory failure complicating COVID-19
Early IL-1 receptor blockade in severe inflammatory respiratory failure complicating COVID-19
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DOI：
10.1073/pnas.2009017117
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发表时间：
2020-08-11
影响因子：
11.1
通讯作者：
Kaplanski, Gilles
中科院分区：
文献类型：
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作者：
Cauchois, Raphael;Koubi, Marie;Kaplanski, Gilles
在确诊后的第10天左右，与20%的冠状病毒病2019(新冠肺炎)相关的患者一样，与肺炎相关的肺炎演变为严重的氧依赖(2b期)和急性呼吸窘迫综合征(3期)，与系统性炎症相关，通常被称为“细胞因子风暴”。由于白细胞介素1(IL-1)阻断了IL-6和其他促炎细胞因子的产生，我们在新冠肺炎患者的早期使用了IL-1受体拮抗剂Anakinra。我们对来自法国三个不同中心的22名2b期和3期新冠肺炎相关肺炎患者进行了回顾性比较，这些患者表现为急性严重呼吸衰竭和全身炎症，他们要么接受标准护理治疗(10名患者)，要么接受静脉注射Anakinra治疗(12名患者)。治疗开始于300mg.d(-1)，持续5d，然后逐渐减少，剂量较小，超过3d。两个人群在年龄、合并症、临床分期和全身炎症生物标志物升高方面具有可比性。与对照组相比，接受Anakinra治疗的所有患者临床症状均有改善(P<；0.01)，无死亡病例，氧耗量显著减少(P<；0.05)，无创机械通气天数增加(P<；0.06)。根据第3天的发热和C反应蛋白显著下降来判断Anakinra的效果是迅速的。平均总剂量为1,950 mg，没有不良反应和细菌感染。我们的结论是，早期阻断IL-1受体对新冠肺炎患者急性高炎症性呼吸衰竭是有效的。
Around the tenth day after diagnosis, similar to 20% of patients with coronavirus disease 2019 (COVID-19)-associated pneumonia evolve toward severe oxygen dependence (stage 2b) and acute respiratory distress syndrome (stage 3) associated with systemic inflammation often termed a "cytokine storm." Because interleukin-1 (IL-1) blocks the production of IL-6 and other proinflammatory cytokines, we treated COVID-19 patients early in the disease with the IL-1 receptor antagonist, anakinra. We retrospectively compared 22 patients from three different centers in France with stages 2b and 3 COVID-19-associated pneumonia presenting with acute severe respiratory failure and systemic inflammation who received either standard-of-care treatment alone (10 patients) or combined with intravenous anakinra (12 patients). Treatment started at 300 mg.d(-1) for 5 d, then tapered with lower dosing over 3 d. Both populations were comparable for age, comorbidities, clinical stage, and elevated biomarkers of systemic inflammation. All of the patients treated with anakinra improved clinically (P < 0.01), with no deaths, significant decreases in oxygen requirements (P < 0.05), and more days without invasive mechanical ventilation (P < 0.06), compared with the control group. The effect of anakinra was rapid, as judged by significant decrease of fever and C-reactive protein at day 3. A mean total dose of 1,950 mg was infused with no adverse side effects or bacterial infection. We conclude that early blockade of the IL-1 receptor is therapeutic in acute hyperinflammatory respiratory failure in COVID-19 patients.