Elevated plasma levels of selective cytokines in COVID-19 patients reflect viral load and lung injury

Yingxia Liu; Cong Zhang; Fengming Huang; Yang Yang; Fuxiang Wang; Jing Yuan; Zheng Zhang; Yuhao Qin; Xiaoyun Li; Dandan Zhao; Shunwang Li; Shuguang Tan; Zhaoqin Wang; Jinxiu Li; Chenguang Shen; Jianming Li; Ling Peng; Weibo Wu; Mengli Cao; Li Xing; Zhixiang Xu; Li Chen; Congzhao Zhou; William J Liu; Lei Liu; Chengyu Jiang

doi:10.1093/nsr/nwaa037

Elevated plasma levels of selective cytokines in COVID-19 patients reflect viral load and lung injury

Natl Sci Rev. 2020 Jun;7(6):1003-1011. doi: 10.1093/nsr/nwaa037. Epub 2020 Mar 9.

Authors

Yingxia Liu¹, Cong Zhang², Fengming Huang³, Yang Yang¹, Fuxiang Wang¹, Jing Yuan¹, Zheng Zhang¹, Yuhao Qin³, Xiaoyun Li³, Dandan Zhao³, Shunwang Li³, Shuguang Tan⁴, Zhaoqin Wang¹, Jinxiu Li¹, Chenguang Shen¹, Jianming Li¹, Ling Peng¹, Weibo Wu¹, Mengli Cao¹, Li Xing¹, Zhixiang Xu¹, Li Chen¹, Congzhao Zhou², William J Liu⁴, Lei Liu¹, Chengyu Jiang³

Affiliations

¹ Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen 518112, China.
² Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
³ The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry, Peking Union Medical College, Beijing 100005, China.
⁴ The NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.

Abstract

A recent outbreak of pneumonia in Wuhan, China was found to be caused by a 2019 novel coronavirus (2019-nCoV or SARS-CoV-2 or HCoV-19). We previously reported the clinical features of 12 patients with 2019-nCoV infections in Shenzhen, China. To further understand the pathogenesis of COVID-19 and find better ways to monitor and treat the disease caused by 2019-nCoV, we measured the levels of 48 cytokines in the blood plasma of those 12 COVID-19 patients. Thirty-eight out of the 48 measured cytokines in the plasma of 2019-nCoV-infected patients were significantly elevated compared to healthy individuals. Seventeen cytokines were linked to 2019-nCoV loads. Fifteen cytokines, namely M-CSF, IL-10, IFN-α2, IL-17, IL-4, IP-10, IL-7, IL-1ra, G-CSF, IL-12, IFN-γ, IL-1α, IL-2, HGF and PDGF-BB, were strongly associated with the lung-injury Murray score and could be used to predict the disease severity of 2019-nCoV infections by calculating the area under the curve of the receiver-operating characteristics. Our results suggest that 2019-nCoV infections trigger extensive changes in a wide array of cytokines, some of which could be potential biomarkers of disease severity of 2019-nCoV infections. These findings will likely improve our understanding of the immunopathologic mechanisms of this emerging disease. Our results also suggest that modulators of cytokine responses may play a therapeutic role in combating the disease once the functions of these elevated cytokines have been characterized.

Keywords: 2019-nCoV; COVID-19; IL-17; IP-10; cytokine storm.