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 2020More...
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
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