Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes.
Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes.
复制标题
DOI：
10.1016/s2213-2600(20)30404-5
复制
发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Deutschman CS
中科院分区：
文献类型：
--
作者：
Leisman DE;Ronner L;Pinotti R;Taylor MD;Sinha P;Calfee CS;Hirayama AV;Mastroiani F;Turtle CJ;Harhay MO;Legrand M;Deutschman CS
对COVID-19患者中所谓的细胞因子风暴的描述促使人们考虑抗细胞因子疗法，特别是白细胞介素-6拮抗剂。然而，尚未报告COVID-19与其他与细胞因子浓度升高相关的危重疾病的直接系统性比较。在本次快速审查中，我们报告了对2019年11月1日至2020年4月14日期间发表或发布的COVID-19研究的系统性综述和荟萃分析结果，其中记录了严重或危重疾病患者的白细胞介素-6浓度。最终纳入了25项COVID-19研究（n=1245例患者）。对照组包括4项试验，分别涉及败血症（n=5320）、细胞因子释放综合征（n=72）和与COVID-19无关的急性呼吸窘迫综合征（n=2767）。在重度或危重COVID-19患者中，汇总平均血清白细胞介素-6浓度为36.7 pg/mL（95% CI 21.6 - 62.3 pg/mL; I2= 57.7%）。细胞因子释放综合征患者的平均白细胞介素6浓度高出近100倍（3110·5 pg/mL，632·3-15 302·9 pg/mL; p<0·0001），脓毒症患者高27倍（983·6 pg/mL，550·1-1758·4 pg/mL; p<0·0001），与COVID-19无关的急性呼吸窘迫综合征患者高12倍（460 pg/mL，216·3-978·7 pg/mL; p<0·0001）。我们的研究结果质疑细胞因子风暴在COVID-19诱导的器官功能障碍中的作用。关于COVID-19的免疫特征以及抗细胞因子和免疫调节治疗在该疾病患者中的潜在作用，仍存在许多问题。
The description of a so-called cytokine storm in patients with COVID-19 has prompted consideration of anti-cytokine therapies, particularly interleukin-6 antagonists. However, direct systematic comparisons of COVID-19 with other critical illnesses associated with elevated cytokine concentrations have not been reported. In this Rapid Review, we report the results of a systematic review and meta-analysis of COVID-19 studies published or posted as preprints between Nov 1, 2019, and April 14, 2020, in which interleukin-6 concentrations in patients with severe or critical disease were recorded. 25 COVID-19 studies (n=1245 patients) were ultimately included. Comparator groups included four trials each in sepsis (n=5320), cytokine release syndrome (n=72), and acute respiratory distress syndrome unrelated to COVID-19 (n=2767). In patients with severe or critical COVID-19, the pooled mean serum interleukin-6 concentration was 36·7 pg/mL (95% CI 21·6–62·3 pg/mL; I2=57·7%). Mean interleukin-6 concentrations were nearly 100 times higher in patients with cytokine release syndrome (3110·5 pg/mL, 632·3–15 302·9 pg/mL; p<0·0001), 27 times higher in patients with sepsis (983·6 pg/mL, 550·1–1758·4 pg/mL; p<0·0001), and 12 times higher in patients with acute respiratory distress syndrome unrelated to COVID-19 (460 pg/mL, 216·3–978·7 pg/mL; p<0·0001). Our findings question the role of a cytokine storm in COVID-19-induced organ dysfunction. Many questions remain about the immune features of COVID-19 and the potential role of anti-cytokine and immune-modulating treatments in patients with the disease.