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. 2020 May 1:11:827.
doi: 10.3389/fimmu.2020.00827. eCollection 2020.

Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)

Bo Diao  1 , Chenhui Wang  2 , Yingjun Tan  1 , Xiewan Chen  3 , Ying Liu  4 , Lifen Ning  5 , Li Chen  1 , Min Li  1 , Yueping Liu  1 , Gang Wang  1 , Zilin Yuan  1 , Zeqing Feng  2 , Yi Zhang  2 , Yuzhang Wu  2 , Yongwen Chen  2
Affiliations

Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)

Bo Diao et al. Front Immunol. .

Abstract

Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. Methods: We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. In addition, the expression of T cell exhaustion markers were measured in 14 COVID-19 cases. Results: The number of total T cells, CD4+ and CD8+ T cells were dramatically reduced in COVID-19 patients, especially in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8+ T cells or CD4+ T cells lower than 800, 300, or 400/μL, respectively, were negatively correlated with patient survival. T cell numbers were negatively correlated to 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. T cells from COVID-19 patients had significantly higher levels of the exhausted marker PD-1. Increasing PD-1 and Tim-3 expression on T cells was seen as patients progressed from prodromal to overtly symptomatic stages. Conclusions: T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients with total T cells 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.

Keywords: COVID-19; SARS- CoV-2; T cell exhaustion; T cell reduction; cytokine strom.

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Figures

Figure 1
Figure 1
Reduced T cell numbers in COVID-19 patients. (A) Demographics of T cells in patients; (B) T cell numbers in different groups; (C) T cell numbers in patients of different ages; (D) T cell count in Non-ICU care patients with different clinical outcomes. **p < 0.01 and ****p < 0.0001.
Figure 2
Figure 2
Cytokines and relative T cell numbers in COVID-19 patients. (A) Cytokine levels in different groups; (B) Relationship between T cell numbers and cytokine levels; (C) Dynamic profiles of cytokine levels and T cell numbers in Non-ICU care patients. *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.
Figure 3
Figure 3
Exhaustion of T cells in COVID-19 patients. (A,B) PD-1 expression on T cells in different groups; (C,D) Dynamic profile of PD-1 and TIM-3 expression on T cells in 3 patients. NS: not significant, *p < 0.05, **p < 0.01.
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