Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)
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Open Access
- 1 May 2020
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
- Vol. 11, 827
- https://doi.org/10.3389/fimmu.2020.00827
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/mu L, respectively, were negatively correlated with patient survival. T cell numbers were negatively correlated to serum IL-6, IL-10, and TNF-alpha concentration, with patients in the disease resolution period showing reduced IL-6, IL-10, and TNF-alpha 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/mu L 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
This publication has 38 references indexed in Scilit:
- Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genomeThe Lancet, 2013
- The acute respiratory distress syndromeJCI Insight, 2012
- Differentiation of Effector CD4 T Cell PopulationsAnnual Review of Immunology, 2010
- The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndromeThe American Journal of Emergency Medicine, 2008
- Update on Avian Influenza A (H5N1) Virus Infection in HumansThe New England Journal of Medicine, 2008
- Interleukin-10 determines viral clearance or persistence in vivoNature Medicine, 2006
- Resolution of a chronic viral infection after interleukin-10 receptor blockadeThe Journal of Experimental Medicine, 2006
- Signals required for programming effector and memory development by CD8+ T cellsImmunological Reviews, 2006
- Role of NF-κB signaling pathway in increased tumor necrosis factor-α-induced apoptosis of lymphocytes in aged humansCell Death & Differentiation, 2005
- An interferon‐γ‐related cytokine storm in SARS patientsJournal of Medical Virology, 2004