Longitudinal COVID-19 profiling associates IL-1RA and IL-10 with disease severity and RANTES with mild disease
Yan Zhao, … , Tao Dong, Yonghong Zhang
Yan Zhao, … , Tao Dong, Yonghong Zhang
Published June 5, 2020
Citation Information: JCI Insight. 2020;5(13):e139834. https://doi.org/10.1172/jci.insight.139834.
View: Text | PDF
Research Article COVID-19

Longitudinal COVID-19 profiling associates IL-1RA and IL-10 with disease severity and RANTES with mild disease

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, cytokines, and chemokines in blood of hospitalized COVID-19 patients from serial sampling and follow-up over 4 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 (18 patients) disease were enrolled with 18 healthy volunteers. We measured 34 immune mediators, cytokines, and chemokines in peripheral blood every 4–7 days over 1 month per patient using a bioplex multiplex immunoassay. RESULTS. 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, and a combination of CCL5, IL-1 receptor antagonist (IL-1RA), and IL-10 at week 1 may predict patient outcomes. The majority of cytokines that are known to be associated with the cytokine storm in virus infections such as IL-6 and IFN-γ were only significantly elevated in the late stage of severe COVID-19 illness. TNF-α and GM-CSF showed no significant differences between severe and mild cases. CONCLUSION. Together, our data suggest that early intervention 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 and IL-10 in blood individually and in combination, might be useful prognostic biomarkers to guide treatment strategies.

Authors

Yan Zhao, Ling Qin, Ping Zhang, Kang Li, Lianchun Liang, Jianping Sun, Bin Xu, Yanchao Dai, Xuemei Li, Chi Zhang, Yanchun Peng, Yingmei Feng, Ang Li, Zhongjie Hu, Haiping Xiang, Graham Ogg, Ling-Pei Ho, Andrew McMichael, Ronghua Jin, Julian C. Knight, Tao Dong, Yonghong Zhang

×

Figure 3

Inhibitory cytokines IL-1RA and IL-10 are significantly elevated in severe cases at early stage of infection.

Options: View larger image (or click on image) Download as PowerPoint
Inhibitory cytokines IL-1RA and IL-10 are significantly elevated in seve...
(A and B) The values of IL-1RA (A) and IL-10 (B) in severe and mild infection patients and healthy control were compared with each other. Two-tailed Student’s t test was used to compare parametric continuous data (evaluated with Kolmogorov-Smirnov test), and nonparametric t test (Mann-Whitney U test) was used when data were not normally distributed. The differences between each group were presented with a P value in the table under the diagram. The values of IL-1RA (A) and IL-10 (B) in healthy controls and COVID-19 infection patients in weeks 1–4 of onset of symptoms are presented in scatter diagrams, in which health control was represented with black circles, mild patients with blue squares, and severe with red triangles. The dynamics of IL-1RA (A) and IL-10 (B) were presented with red lines in severe patients and blue lines in mild patients.