Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430079, Hubei, China.
Department of Rheumatology and Immunology, The First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
J Transl Med. 2020 Oct 29;18(1):406. doi: 10.1186/s12967-020-02571-x.
Interleukin-6 (IL-6) was proposed to be associated with the severity of coronavirus disease 2019 (COVID-19). The present study aimed to explore the kinetics of IL-6 levels, validate this association in COVID-19 patients, and report preliminary data on the efficacy of IL-6 receptor blockade.
We conducted a retrospective single-institutional study of 901 consecutive confirmed cases. Serum IL-6 concentrations were tested on admission and/or during hospital stay. Tocilizumab was given to 16 patients with elevated IL-6 concentration.
366 patients were defined as common cases, 411 patients as severe, and 124 patients as critical according to the Chinese guideline on diagnosis and treatment of COVID-19. The median concentration of IL-6 was < 1.5 pg/ml (IQR < 1.50-2.15), 1.85 pg/ml (IQR < 1.50-5.21), and 21.55 pg/ml (IQR 6.47-94.66) for the common, severe, and critical groups respectively (P < 0.001). The follow-up kinetics revealed serum IL-6 remained high in critical patients even when cured. An IL-6 concentration higher than 37.65 pg/ml was predictive of in-hospital death (AUC 0.97 [95% CI 0.95-0.99], P < 0.001) with a sensitivity of 91.7% and a specificity of 95.7%. In the 16 patients who received tocilizumab, IL-6 concentrations were significantly increased after administration, and survival outcome was not significantly different from that of propensity-score matched counterparts (n = 53, P = 0.12).
Serum IL-6 should be included in diagnostic work-up to stratify disease severity, but the benefit of tocilizumab needs further confirmation. Trial registration retrospectively registered.
白细胞介素 6(IL-6)被认为与 2019 年冠状病毒病(COVID-19)的严重程度有关。本研究旨在探讨 IL-6 水平的变化规律,验证其与 COVID-19 患者的相关性,并报告 IL-6 受体阻断的初步疗效数据。
我们进行了一项回顾性的单机构研究,共纳入 901 例连续确诊的 COVID-19 患者。入院时和/或住院期间检测血清 IL-6 浓度。对 IL-6 浓度升高的 16 例患者给予托珠单抗治疗。
根据《COVID-19 诊疗方案》,366 例患者为普通型,411 例为重型,124 例为危重型。IL-6 中位数浓度分别为<1.5 pg/ml(IQR<1.50-2.15)、1.85 pg/ml(IQR<1.50-5.21)和 21.55 pg/ml(IQR 6.47-94.66)(P<0.001)。随访动力学显示,即使治愈,危重型患者的血清 IL-6 仍持续升高。IL-6 浓度高于 37.65 pg/ml 预测住院死亡(AUC 0.97 [95%CI 0.95-0.99],P<0.001),其敏感性为 91.7%,特异性为 95.7%。在接受托珠单抗治疗的 16 例患者中,给药后 IL-6 浓度明显升高,但与倾向性评分匹配的对照组(n=53,P=0.12)的生存结局无显著差异。
血清 IL-6 应纳入诊断性检查,以分层疾病严重程度,但托珠单抗的获益尚需进一步确认。试验注册:回顾性注册。