Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome


The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, December 2019, and continuously poses a serious threat to public health. Our previous study has shown that cytokine storm occurred during SARS-CoV-2 infection, while the detailed role of cytokines in the disease severity and progression remained unclear due to the limited case number. In this study, we examined 48 cytokines in the plasma samples from 53 COVID-19 cases, among whom 34 were severe cases, and the others moderate. Results showed that 14 cytokines were significantly elevated upon admission in COVID-19 cases. Moreover, IP-10, MCP-3, and IL-1ra were significantly higher in severe cases, and highly associated with the PaO2/FaO2 and Murray score. Furthermore, the three cytokines were independent predictors for the progression of COVID-19, and the combination of IP-10, MCP-3 and IL-1ra showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations. Serial detection of IP-10, MCP-3 and IL-1ra in 14 severe cases showed that the continuous high levels of these cytokines were associated with disease deterioration and fatal outcome. In conclusion, we report three cytokines that closely associated with disease severity and outcome of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, which suggested novel therapeutic targets and strategy. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the National Natural Science Foundation of China (Grant 81802004) and the National Science and Technology Major Project (Grants 2018ZX10711001, 2017ZX10204401 and 2017ZX10103011), Sanming Project of Medicine in Shenzhen (SZSM201412003, SZSM201512005). ### Author Declarations All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data generated or used during the study have been presented in the submitted article.

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Yang Yang, Shen Chenguang, Li Jinxiu, Yuan Jing, Yang Minghui, Wang Fuxiang, Li Guobao, Li Yanjie, Xing Li, Peng Ling, Wei Jinli, Cao Mengli, Zheng Haixia, Wu Weibo, Zou Rongrong, Li Delin, Xu Zhixiang, Wang Haiyan, Zhang Mingxia, Zhang Zheng, Liu Lei, Liu Yingxia. (2020). Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome. Cold Spring Harbor Laboratory Press