Preemptive interleukin-6 blockade in patients with COVID-19.
Preemptive interleukin-6 blockade in patients with COVID-19.
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DOI：
10.1038/s41598-020-74001-3
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发表时间：
2020-10-08
影响因子：
4.6
通讯作者：
Masiá M
中科院分区：
文献类型：
--
作者：
Guillén L;Padilla S;Fernández M;Agulló V;García JA;Telenti G;García-Abellán J;Botella Á;Gutiérrez F;Masiá M
过度的白细胞介素-6信号传导是导致COVID-19临床表现中涉及的细胞因子释放综合征的关键因素。初步结果表明，tocilizumab，一种人源化单克隆抗白细胞介素-6受体抗体，可能对重症患者有益，但没有关于疾病早期阶段的数据。一个预期的阻断白细胞介素-6可能假设防止灾难性的后果，明显的细胞因子风暴。我们评估了在COVID-19住院患者中早期给予托珠单抗，并确定了结局预测因素。符合预定标准的初始序贯器官衰竭评估（SOFA）评分< 3的患者接受托珠单抗治疗。收集系列血浆生物标志物和鼻咽拭子。在193名因COVID-19入院的患者中，64名符合入选标准。托珠单抗治疗后，49例（76.6%）患者早期获得良好反应。调整后的反应预测因子为性别、SOFA评分、中性粒细胞/淋巴细胞比率、Charlson合并症指数和收缩压。在第4周，56.1%的应答者和30%的无应答者从鼻咽清除了SARS-CoV-2。根据托珠单抗应答和最终住院结局的不同，白细胞介素-6、C反应蛋白、中性粒细胞/淋巴细胞比率、NT-ProBNP、D-二聚体和心肌肌钙蛋白-I的时间曲线也不同。未观察到死亡或疾病复发。在大多数患者中，托珠单抗的预先治疗是安全的，并与良好的结局相关。生物学和临床标志物预测结果。
Excessive interleukin-6 signaling is a key factor contributing to the cytokine release syndrome implicated in clinical manifestations of COVID-19. Preliminary results suggest that tocilizumab, a humanized monoclonal anti-interleukin-6 receptor antibody, may be beneficial in severely ill patients, but no data are available on earlier stages of disease. An anticipated blockade of interleukin-6 might hypothetically prevent the catastrophic consequences of the overt cytokine storm. We evaluated early-given tocilizumab in patients hospitalized with COVID-19, and identified outcome predictors. Consecutive patients with initial Sequential-Organ-Failure-Assessment (SOFA) score < 3 fulfilling pre-defined criteria were treated with tocilizumab. Serial plasma biomarkers and nasopharyngeal swabs were collected. Of 193 patients admitted with COVID-19, 64 met the inclusion criteria. After tocilizumab, 49 (76.6%) had an early favorable response. Adjusted predictors of response were gender, SOFA score, neutrophil/lymphocyte ratio, Charlson comorbidity index and systolic blood pressure. At week-4, 56.1% of responders and 30% of non-responders had cleared the SARS-CoV-2 from nasopharynx. Temporal profiles of interleukin-6, C-reactive protein, neutrophil/lymphocyte ratio, NT-ProBNP, D-dimer, and cardiac-troponin-I differed according to tocilizumab response and discriminated final in-hospital outcome. No deaths or disease recurrences were observed. Preemptive therapy with tocilizumab was safe and associated with favorable outcomes in most patients. Biological and clinical markers predicted outcomes.
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影响因子：
28.2
作者：
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通讯作者：
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作者：
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通讯作者：
Rodriguez LL
影响因子：
2.2
作者：
Wattrang, E;Jessett, DM;Hannant, D
通讯作者：
Hannant, D