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)-α and IL-1β 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-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 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-α 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-α 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.

多项研究表明，严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 引起的过度炎症反应是导致疾病严重和死亡的主要原因。然而，目前严重缺乏有助于指导靶向免疫途径的致病性炎症的预测生物标志物。我们对 2019 年冠状病毒病 (COVID-19) 入院后的住院患者实施了快速多重细胞因子测定，以测量血清白细胞介素 (IL)-6、IL-8、肿瘤坏死因子 (TNF)-α 和 IL-1β纽约西奈卫生系统。患者 ( n = 1,484) 入院后随访至 41 天（中位时间 8 天），收集临床信息、实验室检查结果和患者结局。我们发现住院时高血清 IL-6、IL-8 和 TNF-α 水平是患者生存的强有力且独立的预测因子（分别为P < 0.0001、 P = 0.0205 和P = 0.0140）。值得注意的是，在调整疾病严重程度、常见实验室炎症标志物、缺氧和其他生命体征、人口统计学以及一系列合并症时，IL-6 和 TNF-α 血清水平仍然是疾病严重程度和死亡的独立且重要的预测因子。这些发现在第二组患者中得到了验证（ n = 231）。我们建议在 COVID-19 患者的管理和治疗中应考虑血清 IL-6 和 TNF-α 水平，以对前瞻性临床试验进行分层，指导资源分配并为治疗选择提供信息。