Cited by 1,094COVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 ResearchRespiratory Support and Mechanisms

Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies

Open access
Tang, Yujun, Liu, Jiajia, Zhang, Dingyi, Xu, Zhenghao, Ji, Jinjun, Wen, Chengping·2020·Frontiers in Immunology

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the pathogen that causes coronavirus disease 2019 (COVID-19). As of 25 May 2020, the outbreak of COVID-19 has caused 347,192 deaths around the world. The current evidence showed that severely ill patients tend to have a high concentration of pro-inflammatory cytokines, such as interleukin (IL)-6, compared to those who are moderately ill. The high level of cytokines also indicates a poor prognosis in COVID-19. Besides, excessive infiltration of pro-inflammatory cells, mainly involving macrophages and T-helper 17 cells, has been found in lung tissues of patients with COVID-19 by postmortem examination. Recently, increasing studies indicate that the "cytokine storm" may contribute to the mortality of COVID-19. Here, we summarize the clinical and pathologic features of the cytokine storm in COVID-19. Our review shows that SARS-Cov-2 selectively induces a high level of IL-6 and results in the exhaustion of lymphocytes. The current evidence indicates that tocilizumab, an IL-6 inhibitor, is relatively effective and safe. Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, and antimalarial agents could be potentially useful and reliable approaches to counteract cytokine storm in COVID-19 patients.

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  • Many treatments have been developed around the hyperinflammatory state seen in severe cases.

    “A starting point for many therapeutic strategies has been the hyperinflammatory state in severe disease (Tang et al., 2020; Wang et al., 2020a).”

    From COVID-19 and the human innate immune system (2021) · cites this paper as Tang et al., 2020

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  1. [11]Zhong-yong C Wei-bin Y Qiang W Guo-lin L Clinical significance of serum hs-CRP, IL-6, and PCT in diagnosis and prognosis of patients with COVID-19. Drugs Clin. (2020) 35: 417– 20. 10.7501/j.issn.1674-5515.2020.03.005 · DOI
  2. [12]Guohua L Ling L Min H Haibiao L Peifeng K Zishao Z Value of various inflammatory markers combined with lymphocyte subsets on clinical diagnosis of different clinical types of COVID-19. J Chong Med Univ. (2020). 10.13406/j.cnki.cyxb.002465. [Epub ahead of print]. · DOI
  3. [42]Zilong L Ruyuan H Wenyang J Tao F Qing G Clinical characteristics and immune function analysis of COVID-19. Med J Wuhan Univ. (2020) 41: 529– 32. 10.14188/j.1671-8852.2020.0126 · DOI
  4. [43]Jing X Ming-feng H Feng-de Z Ting Z Lei M Clinical manifestations and sero-immunological characteristics of 155 patients with COVID-19. Chin J Nosocomiol. (2020) 30: 2261– 5. 10.11816/cn.ni.2020-200577 · DOI
  5. [63]Firestein GS Budd R Gabriel SE McInnes IB O'Dell JR Kelley's Textbook of Rheumatology E-Book. Amsterdam: Elsevier Health Sciences (2012).
  6. [93]Xiaolin T Aiguo L Zhiyuan Z Jun D Xiaoguang C Chuanjin H Clinical observation on 16 cases of infectious atypical pneumonia treated by traditional Chinese Medicine. J Tradition Chin Med. (2003) 44: 506– 7. 10.13288/j.11-2166/r.2003.07.020 · DOI
  7. [94]Tan W Li S Yiyang C Yakun F Wei Y Xiaozheng D Clinical efficacy analysis of 50 cases of corona virus disease 2019 in traditional Chinese medicine. Jilin J Chin Med. (2020) 40: 281– 5. 10.13463/j.cnki.jlzyy.2020.03.001 · DOI
  8. [95]Kai-tao Y Ming-yu L Xin L Ji-han H Hong-bin C Retrospective clinical analysis on treatment of novel coronavirus-infected pneumonia with traditional chinese medicine Lianhua Qingwen. Chin J Exp Tradition Med Formul. (2020) 26: 8– 12. 10.13422/j.cnki.syfjx.20201099 · DOI
  9. [96]Wen-guang X Chang-qing A Chan-juan Z Ji-xian Z Min H Yu W Clinical study on 34 novel coronavirus pneumoniae treated with integrated traditional Chinese and Western Medicine. J Tradition Chin Med. (2020) 61: 375– 82. 10.13288/j.11-2166/r.2020.05.002 · DOI

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Sorted by citations

Authors
Tang, Y., Liu, J., Zhang, D., Xu, Z., Ji, J., & Wen, C.
Affiliations
Zhejiang Chinese Medical University (CN)
Corresponding author
  • Ji, Jinjun
  • Wen, Chengping
Venue
Frontiers in Immunology
Published
2020-07-10
Volume
11
Pages
1708-1708
ISSN
1664-3224 (ISSN-L)
OpenAlex
W3041667892
Cited by
1,094
References
133
Citations by year
2026: 28 · 2025: 52 · 2024: 96 · 2023: 166 · 2022: 334 · 2021: 353 · 2020: 65
FWCI
10.84
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Natural Science Foundation of Zhejiang Province
Topics
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
Keywords
cytokine storm, COVID-19 pandemic, SARS-CoV-2, interleukin-6, inflammatory cytokines, lymphocyte exhaustion, tocilizumab, IL-6 inhibitors, corticosteroids, PD-1/PD-L1 inhibitors, intravenous immunoglobulin, antimalarial drugs, macrophages, Th17 cells, lung pathology, mortality
MeSH terms
Betacoronavirus, Artesunate, COVID-19, SARS-CoV-2, Interleukin-6 Inhibitors, Adrenal Cortex Hormones, Animals, Antimalarials, Hemoperfusion, Humans, Hydroxychloroquine, Pneumonia, Viral, Interleukin-6, Immunoglobulins, Intravenous, Coronavirus Infections, Mice, Pandemics, Programmed Cell Death 1 Receptor, Antibodies, Monoclonal, Humanized

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