An inflammatory cytokine signature predicts COVID-19 severity and survival
An inflammatory cytokine signature predicts COVID-19 severity and survival
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DOI：
10.1101/2020.05.28.20115758
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发表时间：
2020-08-24
期刊：
影响因子：
82.9
通讯作者：
Gnjatic, Sacha
中科院分区：
文献类型：
--
作者：
Del Valle, Diane Marie;Kim-Schulze, Seunghee;Gnjatic, Sacha
入院时血清IL-6和TNF-α水平的升高是两组COVID-19患者临床预后的独立和重要的预测因素。多项研究表明，严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的高炎症反应是疾病严重程度和死亡的主要原因。然而，严重缺乏病原性炎症的预测生物标记物来帮助指导靶向免疫途径。我们实施了一种快速的多重细胞因子检测方法来检测住院的2019年冠状病毒病患者(新冠肺炎)的血清IL-6、IL-8、肿瘤坏死因子-α和IL-1β的水平。对1484例患者进行入院后41d(中位数8d)的随访，收集临床资料、实验室检查结果和患者转归。我们发现入院时血清IL-6、IL-8和肿瘤坏死因子-α水平升高是患者生存的独立预测因子(P<；0.0001，P=0.0205和P=0.0140)。值得注意的是，当根据疾病严重程度、常见的实验室炎症标志物、低氧和其他生命体征、人口统计学和一系列合并症进行调整时，血清IL-6和TNF-α水平仍然是疾病严重程度和死亡的独立和重要预测因素。这些发现在第二组患者(n=231)中得到了验证。我们建议，在新冠肺炎患者的管理和治疗中应考虑血清IL-6和肿瘤坏死因子-α的水平，以对前瞻性临床试验进行分层，指导资源分配，并提供治疗方案。
Elevated levels of serum IL-6 and TNF-alpha at the time of hospitalization are independent and significant predictors of clinical outcome in two cohorts of patients with COVID-19.Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-alpha and IL-1 beta in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-alpha levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001,P = 0.0205 andP = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-alpha serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-alpha levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options.