Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19)
Authors: Diao et al.
Journal/ Pre-Print: medRxiv
This study analyses CD4 and CD8 T cell counts and cytokine levels in the blood of 499 patients. They show decreased T cell numbers and increased cytokines (TNFa, IL-10, and IL-6) in the serum of severely affected patients (elderly and ICU patients). There is an inverse correlation between cytokine levels and T cell numbers suggesting that these high cytokine levels may negatively regulate T cell survival or proliferation. In a smaller cohort of 14 patients they show increased PD-1 and TIM-3 on the T cells of ICU patients, indicating exhaustion of the surviving T cells.
- T cell numbers decrease in blood of severe patients below a critical threshold
- IL-6, TNFa, and IL10 are increased in severe patients
- T cells in severe patients have a more “exhausted” phenotype
This research allows us to focus on cytokines of interested associated with severe disease. This study also highlights the need to understand what is happening to the T cell compartment in severe patients and whether there is a corresponding increase in another leukocyte population, e.g. neutrophils. The study also suggests that anti-inflammatory or anti-viral drugs such as Tocilizumab or Remdesivir may have therapeutic potential to treat severely affected patients in the clinic.
FACS of blood
Methods to detect cytokine concentrations is unclear
Strengths and weaknesses of the paper:
Strengths include a large number of patients (499) for T cell and cytokine analysis.
Clinical data allowed patients to be stratified by severity.
Weaknesses the authors suggest causation based on the inverse correlation between cytokine and T cell numbers which is not justified, although the data appears to be robust.
Numbers for “exhaustion” phenotype are small. PD-1 and TIM-3 may also be upregulated on stimulated cells so we cannot necessarily conclude the T cells are exhausted. Thus, a much more extensive phenotypic charecterisation would be required to conclude that the T cells are truly exhausted.
All samples are from the blood so likely miss the critically important immune processes occurring in the tissue, particularly the lung.
Controls were not apparently tested for absence of infection. Some may have been asymptomatic which would confound the results.