The potential role of IL-6 in monitoring severe case of coronavirus disease 2019

Liu, Tao; Zhang, Jieying; Yang, Yuhui; Ma, Hong; Li, Zhengyu; Zhang, Jiaoyue; Cheng, Ji; Zhang, Xiaoyun; Zhao, Yuliang; Xia, Zihan; Zhang, Liling; Wu, Gang; Yi, Jianhua

doi:10.1101/2020.03.01.20029769

Cited by 116 publications

(122 citation statements)

References 23 publications

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“…Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL6, IL7, IL10, GSCF, IP10, MCP1, MIP1A, TNFα, lactate dehydrogenase (LDH), ferritin and D-dimer. The number of lymphocytes was significantly reduced and C-reactive protein (CRP) was significantly increased in severe cases [10][11][12][13]. During the submission of this paper, several publications have also reported the analysis of antibody responses to N protein, S protein, and receptor-binding domain (RBD) on S protein in COVID-19 patients [14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 95%

Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients

Sun

Feng

et al. 2020

Emerging Microbes & Infections

474

449

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The emerging COVID-19 caused by SARS-CoV-2 infection poses severe challenges to global public health. Serum antibody testing is becoming one of the critical methods for the diagnosis of COVID-19 patients. We investigated IgM and IgG responses against SARS-CoV-2 nucleocapsid (N) and spike (S) protein after symptom onset in the intensive care unit (ICU) and non-ICU patients. 130 blood samples from 38 COVID-19 patients were collected. The levels of IgM and IgG specific to N and S protein were detected by ELISA. A series of blood samples were collected along the disease course from the same patient, including 11 ICU patients and 27 non-ICU patients for longitudinal analysis. N and S specific IgM and IgG (N-IgM, N-IgG, S-IgM, S-IgG) in non-ICU patients increased after symptom onset. N-IgM and S-IgM in some non-ICU patients reached a peak in the second week, while N-IgG and S-IgG continued to increase in the third week. The combined detection of N and S specific IgM and IgG could identify up to 75% of SARS-CoV-2 infected patients in the first week. S-IgG was significantly higher in non-ICU patients than in ICU patients in the third week. In contrast, N-IgG was significantly higher in ICU patients than in non-ICU patients. The increase of S-IgG positively correlated with the decrease of C-reactive protein (CRP) in non-ICU patients. N and S specific IgM and IgG increased gradually after symptom onset and can be used for detection of SARS-CoV-2 infection. Analysis of the dynamics of S-IgG may help to predict prognosis.

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Section: Introductionmentioning

confidence: 95%

Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients

Sun

Feng

et al. 2020

Emerging Microbes & Infections

474

449

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“…One potential therapeutic target is the IL-6 signaling pathway. IL-6 levels diverge profoundly between survivors and nonsurvivors in the third week after symptom onset and predict COVID-19 severity and in-hospital mortality (1, 8,11). Tocilizumab and sarilumab, monoclonal antibodies targeting the IL-6 receptor, and siltuximab, a chimeric antibody targeting IL-6, are currently being investigated for the treatment of patients with COVID-19-CSS (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23).…”

Section: Treating Cytokine Storm In Covid-19mentioning

confidence: 99%

“…Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists Maximilian F. Konig, 1,2,3,4,5 Mike Powell, 6 Verena Staedtke, 7 Ren-Yuan Bai, 8 David L. Thomas, 9 Nicole Fischer, 5 Sakibul Huq, 8 Adham M. Khalafallah, 8 Allison Koenecke, 10 Ruoxuan Xiong, 11 Brett Mensh, 12 Nickolas Papadopoulos, 1,2,3 Kenneth W. Kinzler, 1,2,3 Bert Vogelstein, 1,2,3 Joshua T. Vogelstein,6 Susan Athey, 13 Shibin Zhou, 1,2,3 and Chetan Bettegowda 1,2,3,8 1 Ludwig Center, 2 Lustgarten Laboratory, and 3 Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland, USA. 4 Division of Rheumatology, 5 Johns Hopkins University (JHU) School of Medicine, Baltimore, Maryland, USA.…”

mentioning

confidence: 99%

Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists

Konig

Powell²,

Staedtke³

et al. 2020

Journal of Clinical Investigation

115

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“…).Overall, elevations in IL-6 levels amongst patients with COVID-19 were identified in all included studies [33][34][35][36][37][38][39][40][41][42]. Multiple studies specifically identified higher levels of IL-6 amongst patients with more severe (complicated) disease.33,37-40 Descriptions of other inflammatory markers, including IL2R and ferritin, are contained in the Supplementary Appendix.…”

mentioning

confidence: 99%

Interleukin-6 in COVID-19: A Systematic Review and Meta-Analysis

Coomes

Haghbayan

2020

Preprint

241

251

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medRxiv preprint ABSTRACT Purpose -Coronaviruses may activate dysregulated host immune responses. As exploratory studies have suggested that interleukin-6 (IL-6) levels are elevated in cases of complicated COVID-19 and that the anti-IL-6 biologic tocilizumab may be beneficial, we undertook a systematic review and meta-analysis to assess the evidence in this field.Methods -We systematically searched MEDLINE and EMBASE for studies investigating the immunological response in COVID-19 or its treatment with tocilizumab; additional grey literature searches were undertaken. Meta-analysis was undertaken using random effects models.Results -Eight published studies, three pre-prints, and five registered trials were eligible. Metaanalysis of mean IL-6 concentrations demonstrated 2.9-fold higher levels in patients with complicated COVID-19 compared with patients with non-complicated disease (six studies; n=1302; 95%CI, 1.17-7.19; I2=100%). A single non-randomized, single-arm study assessed tocilizumab in patients with severe COVID-19, demonstrating decreased oxygen requirements, resolution of radiographic abnormalities, and clinical improvement. No adverse events or deaths were observed.Conclusions -In patients with COVID-19, IL-6 levels are significantly elevated and associated with adverse clinical outcomes. While inhibition of IL-6 with tocilizumab appears to be efficacious and safe in preliminary investigation, the results of several ongoing clinical trials should be awaited to better define the role of tocilizumab in COVID-19 prior to routine clinical application.

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The potential role of IL-6 in monitoring severe case of coronavirus disease 2019

Cited by 116 publications

References 23 publications

Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients

Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients

Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists

Interleukin-6 in COVID-19: A Systematic Review and Meta-Analysis

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