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Cytokine storm and translating IL-6 biology into effective treatments for COVID-19

《医学前沿(英文)》 doi: 10.1007/s11684-023-1044-4

摘要: As of May 3, 2023, the coronavirus disease 2019 (COVID-19) pandemic has resulted in more than 760 million confirmed cases and over 6.9 million deaths. Several patients have developed pneumonia, which can deteriorate into acute respiratory distress syndrome. The primary etiology may be attributed to cytokine storm, which is triggered by the excessive release of proinflammatory cytokines and subsequently leads to immune dysregulation. Considering that high levels of interleukin-6 (IL-6) have been detected in several highly pathogenic coronavirus-infected diseases, such as severe acute respiratory syndrome in 2002, the Middle East respiratory syndrome in 2012, and COVID-19, the IL-6 pathway has emerged as a key in the pathogenesis of this hyperinflammatory state. Thus, we review the history of cytokine storm and the process of targeting IL-6 signaling to elucidate the pivotal role played by tocilizumab in combating COVID-19.

关键词: SARS-CoV-2     COVID-19     cytokine storm     interleukin-6     tocilizumab    

Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter

Dongsheng Wang, Binqing Fu, Zhen Peng, Dongliang Yang, Mingfeng Han, Min Li, Yun Yang, Tianjun Yang, Liangye Sun, Wei Li, Wei Shi, Xin Yao, Yan Ma, Fei Xu, Xiaojing Wang, Jun Chen, Daqing Xia, Yubei Sun, Lin Dong, Jumei Wang, Xiaoyu Zhu, Min Zhang, Yonggang Zhou, Aijun Pan, Xiaowen Hu, Xiaodong Mei, Haiming Wei, Xiaoling Xu

《医学前沿(英文)》 2021年 第15卷 第3期   页码 486-494 doi: 10.1007/s11684-020-0824-3

摘要: Tocilizumab has been reported to attenuate the “cytokine storm” in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI −7.19%–21.23%, = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 ( = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI −99.17% to −17.50%, = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.

关键词: tocilizumab     coronavirus disease 2019 (COVID-19)     cytokine storm    

Management of cytokine release syndrome related to CAR-T cell therapy

Hongli Chen, Fangxia Wang, Pengyu Zhang, Yilin Zhang, Yinxia Chen, Xiaohu Fan, Xingmei Cao, Jie Liu, Yun Yang, Baiyan Wang, Bo Lei, Liufang Gu, Ju Bai, Lili Wei, Ruili Zhang, Qiuchuan Zhuang, Wanggang Zhang, Wanhong Zhao, Aili He

《医学前沿(英文)》 2019年 第13卷 第5期   页码 610-617 doi: 10.1007/s11684-019-0714-8

摘要: Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5–10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.

关键词: chimeric antigen receptor T cell     cytokine release syndrome     tocilizumab    

标题 作者 时间 类型 操作

Cytokine storm and translating IL-6 biology into effective treatments for COVID-19

期刊论文

Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter

Dongsheng Wang, Binqing Fu, Zhen Peng, Dongliang Yang, Mingfeng Han, Min Li, Yun Yang, Tianjun Yang, Liangye Sun, Wei Li, Wei Shi, Xin Yao, Yan Ma, Fei Xu, Xiaojing Wang, Jun Chen, Daqing Xia, Yubei Sun, Lin Dong, Jumei Wang, Xiaoyu Zhu, Min Zhang, Yonggang Zhou, Aijun Pan, Xiaowen Hu, Xiaodong Mei, Haiming Wei, Xiaoling Xu

期刊论文

Management of cytokine release syndrome related to CAR-T cell therapy

Hongli Chen, Fangxia Wang, Pengyu Zhang, Yilin Zhang, Yinxia Chen, Xiaohu Fan, Xingmei Cao, Jie Liu, Yun Yang, Baiyan Wang, Bo Lei, Liufang Gu, Ju Bai, Lili Wei, Ruili Zhang, Qiuchuan Zhuang, Wanggang Zhang, Wanhong Zhao, Aili He

期刊论文