4.6 Article

Increased circulating level of interleukin-6 and CD8+ T cell exhaustion are associated with progression of COVID-19

Journal

INFECTIOUS DISEASES OF POVERTY
Volume 9, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s40249-020-00780-6

Keywords

COVID-19; Progression; Interleukin-6; CD8(+) T cell exhaustion; Prospective case series

Funding

  1. National Natural Science Foundation of China [82041022]
  2. Science and Technology Commission Shanghai Municipality [20JC1410200, 20431900404]
  3. Ministry of Science and Technology of the People's Republic of China [2018ZX10101003-001-003]

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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 chi(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/mu l) 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.

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