Study Shows Reduced T-Cell Counts, Functional Exhaustion in Patients with COVID-19

In a study of patients with coronavirus disease 2019 (COVID-19) in China, researchers found that T-cell counts were significantly reduced in patients with COVID-19 and surviving T-cells seemed to be functionally exhausted as well.¹

These findings, published in Frontiers in Immunology, suggested that patients with COVID-19 who do not require intensive care unit (ICU) admission with total T-cell counts lower than 800/μL may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.

"We should pay more attention to T-cell counts and their function, rather than respiratory function of patients," study author Yongwen Chen, PhD, of the Third Military Medical University in China, said in a press release,² adding that "more urgent, early intervention may be required in patients with low T lymphocyte counts."

Researchers retrospectively reviewed the counts of T-cells and serum cytokine concentration from the data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. Additionally, the expression of T-cell exhaustion markers was measured in 14 cases of COVID-19. 

Overall, the number of total T cells, CD4⁺, and CD8⁺ T-cells were found to be significantly reduced in patients with COVID-19, especially in patients requiring ICU care. Moreover, counts of total T-cells, CD8⁺ T-cells or CD4⁺ T-cells lower than 800, 300, or 400/μL, respectively, were negatively associated with patient survival. T-cell numbers were also negatively associated with serum IL-6, IL-10, and TNF-α concentration, with patients in the disease resolution period showing reduced IL-6, IL-10, and TNF-α concentrations and restored T-cell counts.

Even further, T-cells from COVID-19 patients had significantly higher levels of the exhausted marker PD-1. In addition, PD-1 and Tim-3 expression on T-cells was increasingly observed as patients progressed from prodromal to overtly symptomatic stages.

“T-cell exhaustion is a state of T-cell dysfunction that arises during many chronic infections and cancer. It is defined by poor effector function, sustained expression of inhibitory receptors, and a transcriptional state distinct from that of functional effector or memory T-cells,” the authors wrote. “We demonstrate here that COVID-19 patients have very high levels of serum IL-10 following SARS-CoV-2 infection, while also displaying high levels of the PD-1 and Tim-3 exhaustion markers on their T cells, suggesting that IL-10 might be mechanistically responsible. The application of potent antiviral treatments to prevent the progression to T cell exhaustion in susceptible patients may thus be critical to their recovery.”

The authors indicated that tocilizumab (Actemra) is an existing drug that may be effective in treating patients, however it still needs to be investigated further in the context of COVID-19. Antiviral treatments, such as remdesivir, may also prevent the progression of T-cell exhaustion, but all future treatments will require further study.

According to Chen, future research should focus on finding finer subpopulations of T-cells in order to determine their vulnerability and effect in disease, along with identifying drugs that recover T-cell numbers and improve function.

References:

1. Diao B, Wang C, Tan Y, et al. Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). Frontiers in Immunology. doi:10.3389/fimmu.2020.00827.

2. Cytokine storms and T cell counts may offer clues on how to treat COVID-19 [news release]. Frontiers. Published May 1, 2020. eurekalert.org/pub_releases/2020-05/f-csa042320.php. Accessed May 5, 2020.