Clinical characterization and risk factors associated with cytokine release syndrome induced by COVID-19 and chimeric antigen receptor T-cell therapy

Hong, Ruoxi; Zhao, Houli; Wang, Yiyun; Chen, Yu; Cai, Hongliu; Hu, Yongxian; Wei, Guoqing; Huang, He

doi:10.1038/s41409-020-01060-5

Cited by 29 publications

(16 citation statements)

References 42 publications

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“… 110 Our group also compared the clinical characteristics and risk factors associated with severe CRS induced by COVID-19 and CAR-T-cell therapy. 187 We found a significantly higher incidence of grade 4 CRS in the COVID-19 group than in the CAR-T-cell therapy group. In addition, COVID-19 group showed increased TNF-α level and decreased IL-2, IL-6, IL-10, and IFN-γ levels.…”

Section: Cutting-edge Technologies In Crs-related Studiesmentioning

confidence: 55%

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

Shao

Zhang

et al. 2021

Sig Transduct Target Ther

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Cytokine release syndrome (CRS) embodies a mixture of clinical manifestations, including elevated circulating cytokine levels, acute systemic inflammatory symptoms and secondary organ dysfunction, which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza, SARS-CoV and COVID-19, immunotherapy of tumor, after chimeric antigen receptor T (CAR-T) therapy, and in monogenic disorders and autoimmune diseases. Particularly, severe CRS is a very significant and life-threatening complication, which is clinically characterized by persistent high fever, hyperinflammation, and severe organ dysfunction. However, CRS is a double-edged sword, which may be both helpful in controlling tumors/viruses/infections and harmful to the host. Although a high incidence and high levels of cytokines are features of CRS, the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain unclear. In the present review, we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of CRS. Considering that CRS is the major adverse event in human diseases and intervention therapy, our review delineates the characteristics, kinetics, signaling pathways, and potential mechanisms of CRS, which shows its clinical relevance for achieving both favorable efficacy and low toxicity.

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Section: Cutting-edge Technologies In Crs-related Studiesmentioning

confidence: 55%

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

Shao

Zhang

et al. 2021

Sig Transduct Target Ther

Self Cite

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“…IFN-γ, which was upregulated by FSS in the present work, is known to further exacerbate autoimmune diseases, such as multiple sclerosis [ 45 , 46 ]. Severe cytokine release syndrome by CAR T cell therapy and COVID-19 have also been shown to occur more frequently in hypertensive patients [ 47 ]. The results of this study and the correlation between hypertension and autoimmune diseases suggest that inhibition of Piezo1 and other mechanosensitive ion channels in T cells may hold therapeutic potential for autoimmune diseases and cytokine release syndromes.…”

Section: Discussionmentioning

confidence: 99%

Fluid shear stress enhances T cell activation through Piezo1

et al. 2022

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Background T cell activation is a mechanical process as much as it is a biochemical process. In this study, we used a cone-and-plate viscometer system to treat Jurkat and primary human T cells with fluid shear stress (FSS) to enhance the activation of the T cells through mechanical means. Results The FSS treatment of T cells in combination with soluble and bead-bound CD3/CD28 antibodies increased the activation of signaling proteins essential for T cell activation, such as zeta-chain-associated protein kinase-70 (ZAP70), nuclear factor of activated T cells (NFAT), nuclear factor kappa B (NF-κB), and AP-1 (activator protein 1). The FSS treatment also enhanced the expression of the cytokines tumor necrosis factor alpha (TNF-α), interleukin 2 (IL-2), and interferon gamma (IFN-γ), which are necessary for sustained T cell activation and function. The enhanced activation of T cells by FSS was calcium dependent. The calcium signaling was controlled by the mechanosensitive ion channel Piezo1, as GsMTx-4 and Piezo1 knockout reduced ZAP70 phosphorylation by FSS. Conclusions These results demonstrate an intriguing new dynamic to T cell activation, as the circulatory system consists of different magnitudes of FSS and could have a proinflammatory role in T cell function. The results also identify a potential pathophysiological relationship between T cell activation and FSS, as hypertension is a disease characterized by abnormal blood flow and is correlated with multiple autoimmune diseases.

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“…Patients with severe COVID-19 have symptoms of systemic hyperinflammation, with increased plasma concentrations of pro-inflammatory cytokines, including interleukin (IL)-6, IL-10, granulocyte-colony stimulating factor, monocyte chemoattractant protein 1, macrophage inflammatory protein-1α, and tumor necrosis factor (TNF)-α. [ 13 ],[ 14 ],[ 15 ] New evidence on T-cell immunopathology in patients with COVID-19 was reported by Diao et al . Their data point to significant T-cytopenia in circulating CD4+ and CD8+ T cells in patients with confirmed COVID-19.…”

Section: Brief Summary Of the Virological Pathological And Immunologi...mentioning

confidence: 99%

Potential Adverse Effects of Coronavirus Disease 2019 on the Cardiovascular System

Wang¹,

You²,

Liu³

2021

Cardiology Plus

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Coronavirus disease 2019 (COVID-19) has spread, at an unprecedented speed and scale, into a global pandemic, infecting more than 29 million cases worldwide across 215 countries and territories and killing more than 930,000 individuals. There is evidence that preexisting cardiac disease can render individuals vulnerable. A large number of patients with COVID-19 present with preexisting cardiovascular disease or develop new-onset cardiac dysfunction during the course of the illness. Therefore, particular attention should be given to cardiovascular protection during COVID-19 treatment. This review highlights recent advances in our understanding of the interaction between COVID-19 and the cardiovascular system, with special attention to the virological, pathological, and immunological characteristics of COVID-19, acute myocardial injury, myocarditis, arrhythmias, coronary artery disease, heart function, and the possible mechanisms.

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Clinical characterization and risk factors associated with cytokine release syndrome induced by COVID-19 and chimeric antigen receptor T-cell therapy

Cited by 29 publications

References 42 publications

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

Fluid shear stress enhances T cell activation through Piezo1

Potential Adverse Effects of Coronavirus Disease 2019 on the Cardiovascular System

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