Increased circulating level of interleukin-6 and CD8+ T cell exhaustion are associated with progression of COVID-19
Penghui Yang, Yibo Ding, Zhe Xu, Rui Pu, Ping Li, Yan Jin, Jiluo Liu, Fanping Meng, Lei Huang, Lei Shi, Tianjun Jiang, Enqiang Qin, Min Zhao, Dawei Zhang, Peng Zhao, Lingxiang Yu, Zhao-Hai Wang, Zhixian Hong, Zhaohui Xiao, Qing Xi, De-Xi Zhao, Peng Yu, Caizhong Zhu, Zhu Chen, Shaogeng Zhang, JI Jun-sheng, Fu‐Sheng Wang, Guangwen Cao
Abstract
Abstract Background Coronavirus disease 2019 (COVID-19) is pandemic. It is critical to identify COVID-19 patients who are most likely to develop a severe disease. This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression. Methods Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing, China from December 27, 2019 to March 12, 2020 were enrolled in this study and followed-up to March 16, 2020. Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by the χ 2 test or the Fisher exact test (categorical variables) and independent group t test or Mann–Whitney U test (continuous variables). The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19. Results The mean incubation was 8.67 (95% confidence interval, 6.78–10.56) days. Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38 (9.86–12.90) days. Compared to pneumonia-free patients, pneumonia patients were 16.5 years older and had higher frequencies of having hypertension, fever, and cough and higher circulating levels of neutrophil proportion, interleukin-6, low count (< 190/µl) of CD8 + T cells, and neutrophil/lymphocyte ratio. Thirteen patients deteriorated during hospitalization. Cox regression analysis indicated that older age and higher serum levels of interleukin-6, C-reactive protein, procalcitonin, and lactate at admission significantly predicted the progression of COVID-19. During hospitalization, circulating counts of T lymphocytes, CD4 + T cells, and CD8 + T cells were lower, whereas neutrophil proportion, neutrophil/lymphocyte ratio, and the circulating levels of interleukin-6, C-reactive protein, and procalcitonin were higher, in pneumonia patients than in pneumonia-free patients. CD8 + lymphocyte count in pneumonia patients did not recover when discharged. Conclusions Older age and higher levels of C-reactive protein, procalcitionin, interleukin-6, and lactate might predict COVID-19 progression. T lymphocyte, especially CD8 + cell-mediated immunity is critical in recovery of COVID-19. This study may help in predicting disease progression and designing immunotherapy for COVID-19.