Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)
Open accessPublished version of a preprint
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/μL, 300/μL, or 400/μL, respectively, are negatively correlated with patient survival. T cell numbers are negatively correlated to serum IL-6, IL-10 and TNF-α concentration, with patients in decline period showing reduced IL-6, IL-10 and TNF-α concentrations and restored T cell counts. T cells from COVID-19 patients have 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 aggressive intervention even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.
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In a cohort of 522 COVID-19 patients, lymphopenia was strongly associated with age in addition to disease severity, with patients older than 60 having the lowest total blood T cell numbers.
“One cohort of 522 COVID-19 patients revealed a strong association between lymphopenia and age in addition to the association between lymphopenia and disease severity, such that patients older than 60 years had the lowest total number of T cells in their blood139.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [139]
Lymphopenia correlates with serum levels of IL-6, IL-10, and TNFα.
“Lymphopenia does correlate with serum levels of IL-6, IL-10, and TNFα139,140”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [139]
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- Authors
- Diao, B., Wang, C., Tan, Y., Chen, X., Liu, Y., Ning, L., Chen, L., Li, M., Liu, Y., Wang, G., Yuan, Z., Feng, Z., Zhang, Y., Wu, Y., & Chen, Y.
- Affiliations
- General Hospital of Central Theater Command (CN)
- Army Medical University (CN)
- Wuhan University of Science and Technology (CN)
- Corresponding author
- Wu, Yuzhang
- Chen, Yongwen
- ORCID
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2020-05-01
- Volume
- 11
- Pages
- 827-827
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC7205903
- OpenAlex
- W3023991776
- Cited by
- 2,475
- References
- 40
- Citations by year
- 2026: 46 · 2025: 125 · 2024: 199 · 2023: 310 · 2022: 493 · 2021: 725 · 2020: 574 · 2019: 1 · 2013: 1
- FWCI
- 68.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (8177169, 81361120400, 81471862, 91442203)
- National Key Research and Development Program of China (2016YFA0502204)
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- COVID-19 pandemic, SARS-CoV-2, T cell depletion, T cell exhaustion, PD-1, TIM-3, CD4+ T cells, CD8+ T cells, serum cytokines, interleukin-6, IL-10, TNF-α, intensive care unit, patient survival, prognostic factors
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Humans, Pneumonia, Viral, T-Lymphocytes, Cytokines, Coronavirus Infections, Lymphocyte Count, Pandemics
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