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

Infect Dis Poverty. 2020 Nov 25;9(1):161. doi: 10.1186/s40249-020-00780-6.

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 χ2 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.

Keywords: CD8+ T cell exhaustion; COVID-19; Interleukin-6; Progression; Prospective case series.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • CD8-Positive T-Lymphocytes / pathology*
  • COVID-19 / diagnosis
  • COVID-19 / epidemiology
  • COVID-19 / pathology*
  • Child
  • Child, Preschool
  • China / epidemiology
  • Disease Progression
  • Female
  • Hospitalization
  • Humans
  • Interleukin-6 / blood*
  • Leukocyte Count
  • Male
  • Middle Aged
  • Neutrophils / pathology
  • Pneumonia, Viral / diagnosis
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / pathology
  • Risk Factors
  • SARS-CoV-2
  • Young Adult

Substances

  • IL6 protein, human
  • Interleukin-6