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Longitudinal Profiling of Cytokines and Chemokines in COVID-19 Reveals Inhibitory Mediators IL-1Ra and IL-10 Are Associated with Disease Severity While Elevated RANTES Is an Early Predictor of Mild Disease

21 Pages Posted: 29 Apr 2020

See all articles by Yan Zhao

Yan Zhao

Capital Medical University - Beijing Youan Hospital

Ling Qin

Capital Medical University - Beijing Youan Hospital

Ping Zhang

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

Kang Li

Capital Medical University - Beijing Youan Hospital

Lianchun Liang

Capital Medical University - Beijing Youan Hospital

Jianping Sun

Capital Medical University - Beijing Youan Hospital

Bin Xu

Capital Medical University - Beijing Youan Hospital

Yanchao Dai

Capital Medical University - Beijing Youan Hospital

Xuemei Li

Capital Medical University - Beijing Youan Hospital

Chi Zhang

Capital Medical University - Beijing Youan Hospital

Yanchun Peng

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

Yingmei Feng

Capital Medical University - Beijing Institute of Hepatology; Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer

Prod Ang Li

Capital Medical University - Beijing Youan Hospital

Zhongjie Hu

Capital Medical University - Beijing Youan Hospital

Haiping Xiang

Capital Medical University - Beijing Youan Hospital

Graham Ogg

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

Ling-Pei Ho

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

Andrew McMichael

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

Ronghua Jin

Capital Medical University - Beijing Institute of Hepatology; Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer

Julian C. Knight

University of Oxford - Wellcome Trust Centre for Human Genetics

Tao Dong

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

Yonghong Zhang

Capital Medical University - Beijing Youan Hospital

More...

Abstract

Background: Identifying immune correlates of COVID-19 disease severity is an urgent need for clinical management, vaccine evaluation and drug development. Here we present a temporal analysis of key immune mediators, cytokine and chemokines in blood of hospitalised COVID-19 patients from serial sampling and follow up over four weeks.

Methods: A total of 71 patients with laboratory-confirmed COVID-19 admitted to Beijing You’an hospital in China with either mild (53 patients) or severe disease (18 patients) were enrolled with 18 healthy volunteers. We measured 34 immune mediators, cytokines and chemokines in peripheral blood every 4-7 days over one month per patient using a bio-plex multiplex immunoassay.

Findings: We found that the chemokine RANTES(CCL5) was significantly elevated, from an early stage of the infection, in patients with mild but not severe disease. We also found that early production of inhibitory mediators including IL-10 and IL-1RA were significantly associated with disease severity. The majority of cytokines that are known to be associated with the cytokine storm in virus infections such as IL-6 and IFN-gamma were only significantly elevated in the late stage of severe COVID-19 illness. TNF- alpha and GM-CSF showed no significant differences between severe and mild cases.

Interpretations: Together our data strongly suggest a classical cytokine storm may not be the major cause of severe COVID illness. Early intervention to reduce IL-10 and IL-1Ra mediated inhibition or to increase expression of CCL5 may prevent patients from developing severe illness. Our data also suggest that measurement of levels of CCL5, as well as IL-1Ra, IL-10 in blood individually and in combination might be useful prognostic bio-markers to guide treatment strategies.

Funding Statement: This work was supported by the Beijing Natural Science Foundation (7191004 and 7202069), Beijing Municipal Science & Technology Commission (Z171100001017078), Beijing municipal administration of hospitals (DFL20181701 and ZYLX201711), Beijing Key Laboratory (BZ0373), and Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS), China (grant number: 2018-I2M-2-002); TD is supported by Medical Research Council (MRC), UK (MR/L018942/1 and MRC Human Immunology Unit Core) and Nuffield Department of Medicine, Oxford University. JCK is supported by a Wellcome Trust Investigator Award (204969/Z/16/Z), JCK, LPH and GO are in part supported by the NIHR Oxford Biomedical Research Centre.

Declaration of Interests: All authors declare no competing interests.

Ethics Approval Statement: The study was approved by the Institutional Review Board of Beijing Youan Hospital. Written informed consent was obtained from all patients.

Keywords: COVID-19; cytokine; RANTES/CCL5, IL1Ra, IL-10

Suggested Citation

Zhao, Yan and Qin, Ling and Zhang, Ping and Li, Kang and Liang, Lianchun and Sun, Jianping and Xu, Bin and Dai, Yanchao and Li, Xuemei and Zhang, Chi and Peng, Yanchun and Feng, Yingmei and Li, Prod Ang and Hu, Zhongjie and Xiang, Haiping and Ogg, Graham and Ho, Ling-Pei and McMichael, Andrew and Jin, Ronghua and Knight, Julian C. and Dong, Tao and Zhang, Yonghong, Longitudinal Profiling of Cytokines and Chemokines in COVID-19 Reveals Inhibitory Mediators IL-1Ra and IL-10 Are Associated with Disease Severity While Elevated RANTES Is an Early Predictor of Mild Disease (4/14/2020). Available at SSRN: https://ssrn.com/abstract=3576836

Yan Zhao

Capital Medical University - Beijing Youan Hospital

China

Ling Qin

Capital Medical University - Beijing Youan Hospital

China

Ping Zhang

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

United Kingdom

Kang Li

Capital Medical University - Beijing Youan Hospital

China

Lianchun Liang

Capital Medical University - Beijing Youan Hospital

China

Jianping Sun

Capital Medical University - Beijing Youan Hospital

China

Bin Xu

Capital Medical University - Beijing Youan Hospital

China

Yanchao Dai

Capital Medical University - Beijing Youan Hospital

China

Xuemei Li

Capital Medical University - Beijing Youan Hospital

China

Chi Zhang

Capital Medical University - Beijing Youan Hospital

China

Yanchun Peng

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

United Kingdom

Yingmei Feng

Capital Medical University - Beijing Institute of Hepatology ( email )

Beijing, 100069
China

Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer ( email )

Beijing
China

Prod Ang Li

Capital Medical University - Beijing Youan Hospital

China

Zhongjie Hu

Capital Medical University - Beijing Youan Hospital

China

Haiping Xiang

Capital Medical University - Beijing Youan Hospital

China

Graham Ogg

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

United Kingdom

Ling-Pei Ho

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

United Kingdom

Andrew McMichael

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

United Kingdom

Ronghua Jin

Capital Medical University - Beijing Institute of Hepatology ( email )

Beijing, 100069
China

Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer ( email )

Beijing
China

Julian C. Knight

University of Oxford - Wellcome Trust Centre for Human Genetics

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

Tao Dong (Contact Author)

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI) ( email )

United Kingdom

Yonghong Zhang

Capital Medical University - Beijing Youan Hospital ( email )

China

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