Values of cytokines in evaluating the severity and prognosis of patients with coronavirus disease 2019_West China Medical Journal

Authors：

JIN Xin , WANG Dong , BAO Tengfei , GU Junjuan , DUAN Yongwei ,  XIE Wen

Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P. R. China;

Corresponding author：

XIE Wen, Email: whxw007@126.com

Keywords：

Coronavirus disease 2019; Cytokines; Risk factors

DOI：

10.7507/1002-0179.202008212

Video：

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Objective To investigate the values of cytokines in evaluating the severity and prognosis of patients with coronavirus disease 2019 (COVID-19). Methods A total of 205 COVID-19 patients in Wuhan Leishenshan Hospital were retrospectively analyzed. According to the severity of the disease, patients were divided into common group (n=117), severe group (n=69) and critical group (n=19). The patients’ basic condition and cytokine related parameters were collected, the differences between the three groups were compared and their values in assessing the severity and prognosis of COVID-19 patients were analyzed. Results There were statistically significant differences in the age, severe acute respiratory syndrome coronavirus 2 nucleic acid test results, interleukin (IL)-6, IL-10, IL-2 receptor, IL-8, and tumor necrosis factor-α among the three groups of patients (P<0.05). Correlation analysis showed that the age, severe acute respiratory syndrome coronavirus 2 nucleic acid test continued to be positive for 20 days, IL-6 level, IL-10 level, IL-2 receptors level, IL-8 level and tumor necrosis factor-α level were related to the classification of COVID-19. The correlation coefficient r_s was 0.354, 0.187, 0.366, 0.327, 0.329, 0.273 and 0.157, respectively (P<0.05). The levels of IL-6, IL-10, IL-2 receptor, IL-8, and tumor necrosis factor-α in dead patients with COVID-19 were higher than those in surviving patients (P<0.05). Multivariate analysis showed that age [odds ratio (OR)=1.034, 95% confidence interval (CI) (1.006, 1.063), P=0.016], IL-6 level [OR=1.030, 95%CI (1.006, 1.055), P=0.015], IL-10 level [OR=1.088, 95%CI (1.003, 1.179), P=0.042] and IL-2 receptor level [OR=1.003, 95%CI (1.001, 1.005), P=0.001] were independent risk factors for common COVID-19 to become severe or critical. Conclusion The levels of cytokines in COVID-19 patients are closely related to the severity and prognosis of the disease.

Citation： JIN Xin, WANG Dong, BAO Tengfei, GU Junjuan, DUAN Yongwei, XIE Wen. Values of cytokines in evaluating the severity and prognosis of patients with coronavirus disease 2019. West China Medical Journal, 2021, 36(11): 1502-1507. doi: 10.7507/1002-0179.202008212 Copy

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18.	张竞文, 胡欣, 金鹏飞. 新型冠状病毒引起的细胞因子风暴及其药物治疗. 中国药学杂志, 2020, 55(5): 333-336.
19.	刘智霖, 马建岭, 董尚娟, 等. 基于 Th17/Treg 免疫失衡探讨新型冠状病毒肺炎的发病及防治. 中国病理生理杂志, 2020, 36(10): 1913-1920.
20.	Gong J, Dong H, Xia QS, et al. Correlation analysis between disease severity and inflammation-related parameters in patients with COVID-19: a retrospective study. BMC Infect Dis, 2020, 20(1): 963.
21.	Shimabukuro-Vornhagen A, Gödel P, Subklewe M, et al. Cytokine release syndrome. J Immunother Cancer, 2018, 6(1): 56.
22.	Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol, 2015, 16(5): 448-457.
23.	Umare V, Pradhan V, Nadkar M, et al. Effect of proinflammatory cytokines (IL-6, TNF-α, and IL-1β) on clinical manifestations in Indian SLE patients. Mediators Inflamm, 2014, 2014: 385297.
24.	Wan S, Yi Q, Fan S, et al. Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). (2020-02-12)[2020-08-21].https://www.medrxiv.org/content/10.1101/2020.02.10.20021832v1.
25.	Liu J, Li S, Liu J, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine, 2020, 55: 102763.
26.	Awasthi S, Wagner T, Venkatakrishnan AJ, et al. Plasma IL-6 levels following corticosteroid therapy as an indicator of ICU length of stay in critically ill COVID-19 patients. Cell Death Discov, 2021, 7(1): 55.
27.	Han H, Ma Q, Li C, et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect, 2020, 9(1): 1123-1130.
28.	Zheng W, Flavell RA. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4T cells. Cell, 1997, 89(4): 587-596.

1. Hui DS, I Azhar E, Madani TA, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - the latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis, 2020, 91: 264-266.
2. Paules CI, Marston HD, Fauci AS. Coronavirus infections-more than just the common cold. JAMA, 2020, 323(8): 707-708.
3. Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature, 2020, 579(7798): 265-269.
4. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet, 2020, 395(10224): 565-574.
5. Cai Y, Hao Z, Gao Y, et al. Coronavirus disease 2019 in the perioperative period of lung resection: a brief report from a single thoracic surgery department in Wuhan, People’s Republic of China. J Thorac Oncol, 2020, 15(6): 1065-1072.
6. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 2020, 395(10223): 507-513.
7. Jin X, Duan Y, Bao T, et al. The values of coagulation function in COVID-19 patients. PLoS One, 2020, 15(10): e0241329.
8. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA, 2020, 323(11): 1061-1069.
9. Chan JF, Kok KH, Zhu Z, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect, 2020, 9(1): 221-236.
10. Tisoncik JR, Korth MJ, Simmons CP, et al. Into the eye of the cytokine storm. Microbiol Mol Biol Rev, 2012, 76(1): 16-32.
11. Behrens EM, Koretzky GA. Review: cytokine storm syndrome: looking toward the precision medicine era. Arthritis Rheumatol, 2017, 69(6): 1135-1143.
12. Arai KI, Lee F, Miyajima A, et al. Cytokines: coordinators of immune and inflammatory responses. Annu Rev Biochem, 1990, 59: 783-836.
13. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020, 395(10223): 497-506.
14. 国家卫生健康委办公厅, 国家中医药管理局办公室. 关于印发新型冠状病毒肺炎诊疗方案(试行第七版)的通知. (2020-03-03)[2020-08-21]. http://www.gov.cn/zhengce/zhengceku/2020-03/04/content_5486705.htm.
15. Guo YR, Cao QD, Hong ZS, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res, 2020, 7(1): 11.
16. Zou X, Chen K, Zou J, et al. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med, 2020, 14(2): 185-192.
17. 明茜, 肖毅. SARS-CoV-2 感染引起细胞因子风暴的诊断及处理. 中国血液流变学杂志, 2020, 30(3): 395-401.
18. 张竞文, 胡欣, 金鹏飞. 新型冠状病毒引起的细胞因子风暴及其药物治疗. 中国药学杂志, 2020, 55(5): 333-336.
19. 刘智霖, 马建岭, 董尚娟, 等. 基于 Th17/Treg 免疫失衡探讨新型冠状病毒肺炎的发病及防治. 中国病理生理杂志, 2020, 36(10): 1913-1920.
20. Gong J, Dong H, Xia QS, et al. Correlation analysis between disease severity and inflammation-related parameters in patients with COVID-19: a retrospective study. BMC Infect Dis, 2020, 20(1): 963.
21. Shimabukuro-Vornhagen A, Gödel P, Subklewe M, et al. Cytokine release syndrome. J Immunother Cancer, 2018, 6(1): 56.
22. Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol, 2015, 16(5): 448-457.
23. Umare V, Pradhan V, Nadkar M, et al. Effect of proinflammatory cytokines (IL-6, TNF-α, and IL-1β) on clinical manifestations in Indian SLE patients. Mediators Inflamm, 2014, 2014: 385297.
24. Wan S, Yi Q, Fan S, et al. Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). (2020-02-12)[2020-08-21].https://www.medrxiv.org/content/10.1101/2020.02.10.20021832v1.
25. Liu J, Li S, Liu J, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine, 2020, 55: 102763.
26. Awasthi S, Wagner T, Venkatakrishnan AJ, et al. Plasma IL-6 levels following corticosteroid therapy as an indicator of ICU length of stay in critically ill COVID-19 patients. Cell Death Discov, 2021, 7(1): 55.
27. Han H, Ma Q, Li C, et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect, 2020, 9(1): 1123-1130.
28. Zheng W, Flavell RA. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4T cells. Cell, 1997, 89(4): 587-596.

West China Medical Journal

Values of cytokines in evaluating the severity and prognosis of patients with coronavirus disease 2019

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