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

By B. Diao, Chenhui Wang, Yi-ran Tan, Xie-Wan Chen, Ying Liu, Lifen Ning, Li Chen, Min Li, Yueping Liu, Gang Wang and 5 more. Frontiers in Immunology, 2020

2,350 citations recorded by the source corpus.

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.

Subfields: Infectious Diseases, Neurology

View Paper: https://www.semanticscholar.org/paper/525065701dcc1a0c8ee64e22a832343e663da46e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Infectious Diseases

1. Bo Huang
2. Youhai H. Chen
3. Savannah F. Pedersen
4. X. Wan
5. Jinyan Liu
6. Zhixin Zhang
7. Yi Zhang
8. E. Wherry

In Neurology

1. Bo Huang
2. Youhai H. Chen
3. Savannah F. Pedersen
4. X. Wan
5. Jinyan Liu
6. Zhixin Zhang
7. Yi Zhang
8. Y. Ho

Citations in the corpus

• COVID-19: immunopathogenesis and Immunotherapeutics (2020, background): “These observations indicate that B cell activation and proliferation in patients with COVID-19, especially in severe cases, is correlated with poor outcome, which is similar to our study data showing that patients with relatively high B cell levels have poor survival.(26,27)”
• SARS-CoV-2 infection: The role of cytokines in COVID-19 disease (2020, background): “[82] Retrospective study To analyze figures and markers of T-cell exhaustion in”
• Interleukin‐6 in Covid‐19: A systematic review and meta‐analysis (2020, background): “30,31 Four studies were determined to be at high risk of bias, 37,39,41,42 five moderate, 33,35,36,38,40 and one low (Supplementary Figure 1); 34 this was mostly driven by lack of control for confounding and potential inconsistencies in the measurement of the inflammatory mediators under study.”
• Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19 (2020, neutral): “incomplete and sometimes conflicting[3, 11, 12, 13, 14].”
• Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications (2020, background): “T cell exhaustion (12, 13) and increased inhibitory receptor expression on peripheral T cells have also been reported (7, 14), though these inhibitory receptors are also increased after T cell activation (15).”
• Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis (2020, positive): “Persistent viral infections are associated with increased PD-1 expression, a marker of T cell exhaustion (Diao et al., 2020).”
• Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions (2020, positive): “Analyses have shown that all subsets of lymphocytes were decreased, including CD4+ and CD8+ cytotoxic T cells [57, 60] , natural killer (NK) cells, memory and regulatory T cells [61] along with B cells [62] .”
• Immunology of COVID-19: Current State of the Science (2020, positive): “correlated with lung lesions and reflected disease severity (Wang, 2020).”
• SARS-CoV-2: A Storm is Raging. (2020, positive): “Further, the level of IL-6, IL-10 and tumor necrosis factor (TNF)-α inversely correlates with CD4 + and CD8 + T cell count (18), confirming previous animal studies that it is the cytokine storm which dampens adaptive immunity against SARS-CoV infection (17).”