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Cytokine release syndrome in COVID-19: a major mechanism of morbidity and mortality.

Authors
  • Que, Yifan1
  • Hu, Chao2
  • Wan, Kun3
  • Hu, Peng1
  • Wang, Runsheng1
  • Luo, Jiang2
  • Li, Tianzhi2
  • Ping, Rongyu4
  • Hu, Qinyong5
  • Sun, Yu6
  • Wu, Xudong7
  • Tu, Lei8
  • Du, Yingzhen1
  • Chang, Christopher9, 10
  • Xu, Guogang2
  • 1 Department of Respiratory Medicine, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China. , (China)
  • 2 The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China. , (China)
  • 3 Medical Supplies Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China. , (China)
  • 4 Department of Neurology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China. , (China)
  • 5 Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China. , (China)
  • 6 Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. , (China)
  • 7 Department of Cell Biology, Tianjin Medical University, Tianjin, China. , (China)
  • 8 Division of Gastroenterology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China. , (China)
  • 9 Division of Pediatric Immunology, Allergy and Rheumatology, Joe DiMaggio Children's Hospital, Hollywood, Florida, USA.
  • 10 Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis , Davis, California, USA.
Type
Published Article
Journal
International Reviews of Immunology
Publisher
Informa UK (Taylor & Francis)
Publication Date
Feb 22, 2021
Pages
1–14
Identifiers
DOI: 10.1080/08830185.2021.1884248
PMID: 33616462
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) erupted in Hubei Province of China in December 2019 and has become a pandemic. Severe COVID-19 patients who suffer from acute respiratory distress syndrome (ARDS) and multi-organ dysfunction have high mortality. Several studies have shown that this is closely related to the cytokine release syndrome (CRS), often loosely referred to as cytokine storm. IL-6 is one of the key factors and its level is positively correlated with the severity of the disease. The molecular mechanisms for CRS in COVID-19 are related to the effects of the S-protein and N-protein of the virus and its ability to trigger NF-κB activation by disabling the inhibitory component IκB. This leads to activation of immune cells and the secretion of proinflammatory cytokines such as IL-6 and TNF-α. Other mechanisms related to IL-6 include its interaction with GM-CSF and interferon responses. The pivotal role of IL-6 makes it a target for therapeutic agents and studies on tocilizumab are already ongoing. Other possible targets of treating CRS in COVID-19 include IL-1β and TNF-α. Recently, reports of a CRS like illness called multisystem inflammatory syndrome in children (MIS-C) in children have surfaced, with a variable presentation which in some cases resembles Kawasaki disease. It is likely that the immunological derangement and cytokine release occurring in COVID-19 cases is variable, or on a spectrum, that can potentially be governed by genetic factors. Currently, there are no approved biological modulators for the treatment of COVID-19, but the urgency of the pandemic has led to numerous clinical trials worldwide. Ultimately, there is great promise that an anti-inflammatory modulator targeting a cytokine storm effect may prove to be very beneficial in reducing morbidity and mortality in COVID-19 patients.

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