The signal pathways and treatment of cytokine storm in COVID-19

Yang, L., Xie, X., Tu, Z., Fu, J., Xu, D. and Zhou, Y. (2021) The signal pathways and treatment of cytokine storm in COVID-19. Signal Transduction and Targeted Therapy, 6(1), 255. (doi: 10.1038/s41392-021-00679-0) (PMID:34234112) (PMCID:PMC8261820)

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The Coronavirus Disease 2019 (COVID-19) pandemic has become a global crisis and is more devastating than any other previous infectious disease. It has affected a significant proportion of the global population both physically and mentally, and destroyed businesses and societies. Current evidence suggested that immunopathology may be responsible for COVID-19 pathogenesis, including lymphopenia, neutrophilia, dysregulation of monocytes and macrophages, reduced or delayed type I interferon (IFN-I) response, antibody-dependent enhancement, and especially, cytokine storm (CS). The CS is characterized by hyperproduction of an array of pro-inflammatory cytokines and is closely associated with poor prognosis. These excessively secreted pro-inflammatory cytokines initiate different inflammatory signaling pathways via their receptors on immune and tissue cells, resulting in complicated medical symptoms including fever, capillary leak syndrome, disseminated intravascular coagulation, acute respiratory distress syndrome, and multiorgan failure, ultimately leading to death in the most severe cases. Therefore, it is clinically important to understand the initiation and signaling pathways of CS to develop more effective treatment strategies for COVID-19. Herein, we discuss the latest developments in the immunopathological characteristics of COVID-19 and focus on CS including the current research status of the different cytokines involved. We also discuss the induction, function, downstream signaling, and existing and potential interventions for targeting these cytokines or related signal pathways. We believe that a comprehensive understanding of CS in COVID-19 will help to develop better strategies to effectively control immunopathology in this disease and other infectious and inflammatory diseases.

Item Type:Articles
Additional Information:This work was supported by grants from the National Key RandD Program of China (2016YFC1305102 to Y.Z.); National Natural Science Foundation of China (81671561, 81974248 to Y.Z.); the International Joint Laboratory Program of National Children’s Medical Center (EK1125180109 to Y.Z.); Program for Outstanding Medical Academic Leader (2019LJ19 to Y.Z.); Shanghai Municipal Planning Commission of Science and Research Fund (201740065 to Y.Z.). Shanghai Committee of Science and Technology (21140902400 to Y.Z.,21ZR1410000, 19ZR1406400 to J.F.); Versus Arthritis UK (21327 to D.X.); and Shenzhen Science and Technology Peacock Team Project (KQTD20170331145453160).
Glasgow Author(s) Enlighten ID:Xu, Dr Damo
Authors: Yang, L., Xie, X., Tu, Z., Fu, J., Xu, D., and Zhou, Y.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Signal Transduction and Targeted Therapy
Publisher:Springer Nature
ISSN (Online):2059-3635
Published Online:07 July 2021
Copyright Holders:Copyright © The Author(s) 2021
First Published:First published in Signal Transduction and Targeted Therapy 6(1):255
Publisher Policy:Reproduced under a Creative Commons Licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173474Is interleukin-37a important in the pathology and treatment of inflammatory arthritis?Damo XuVersus Arthritis (ARTRESUK)21327III - Immunology - Dr D Xu