Cited by 789COVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 ResearchT-cell and B-cell Immunology

Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia

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De Biasi, Sara, Meschiari, Marianna, Gibellini, Lara, Bellinazzi, Caterina, Borella, Rebecca, Fidanza, Lucia, Gozzi, Licia, Iannone, Anna +20 more·2020·Nature Communications

Published version of a preprint

Abstract

The immune system of patients infected by SARS-CoV-2 is severely impaired. Detailed investigation of T cells and cytokine production in patients affected by COVID-19 pneumonia are urgently required. Here we show that, compared with healthy controls, COVID-19 patients’ T cell compartment displays several alterations involving naïve, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1 + CD57 + exhausted T cells. Significant alterations exist also in several lineage-specifying transcription factors and chemokine receptors. Terminally differentiated T cells from patients proliferate less than those from healthy controls, whereas their mitochondria functionality is similar in CD4 + T cells from both groups. Patients display significant increases of proinflammatory or anti-inflammatory cytokines, including T helper type-1 and type-2 cytokines, chemokines and galectins; their lymphocytes produce more tumor necrosis factor (TNF), interferon-γ, interleukin (IL)-2 and IL-17, with the last observation implying that blocking IL-17 could provide a novel therapeutic strategy for COVID-19.

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  • Responding CD4+ and CD8+ T cells predominantly produced effector and Th1 cytokines, although Th2 and Th17 cytokines were also detected.

    “predominantly produced effector and Th1 cytokines, although Th2 and Th17 cytokines were also detected [119, 126]”

    From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [126]

    The Results section, “In vitro production of proinflammatory cytokines” (page unavailable), reports that stimulated CD4+ and CD8+ T cells produced IFN-γ, TNF and IL-17, supporting detection of Th1-associated and Th17 cytokines. It does not report detection of Th2 cytokines or establish that effector and Th1 cytokines predominated. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • COVID-19-related VIS may aggravate age-related pathologies via enhanced SASP-mediated inflammation, as demonstrated for cardiovascular diseases and diabetes in preclinical models, and might further deteriorate immune competence by inducing senescence in immune cells.

    “COVID-19-related VIS may also aggravate age-related pathologies via enhanced SASP-mediated inflammation29,169, as demonstrated for cardiovascular diseases and diabetes in preclinical models170, and might further deteriorate immune competence by inducing senescence in immune cells171,172.”

    From COVID-19 and cellular senescence (2023) · cites this paper as [171]

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Research works printed but not linked: 1

  1. [41]Shin HS Immune responses to Middle East Respiratory Syndrome coronavirus during the acute and convalescent phases of human infection Clin. Infect. Dis. 2019 68 984 992 30060038 PMC7108191

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Authors
De Biasi, S., Meschiari, M., Gibellini, L., Bellinazzi, C., Borella, R., Fidanza, L., Gozzi, L., Iannone, A., Lo Tartaro, D., Mattioli, M., Paolini, A., Menozzi, M., Milić, J., Franceschi, G., Fantini, R., Tonelli, R., Sita, M., Sarti, M., Trenti, T., Brugioni, L., Cicchetti, L., Facchinetti, F., Pietrangelo, A., Clini, E., Girardis, M., Guaraldi, G., Mussini, C., & Cossarizza, A.
Affiliations
  • University of Modena and Reggio Emilia (IT)
  • Azienda Ospedaliero-Universitaria di Modena (IT)
Corresponding author
Cossarizza, Andrea
Venue
Nature Communications
Published
2020-07-06
Volume
11
Issue
1
Pages
3434-3434
ISSN
2041-1723 (ISSN-L)
OpenAlex
W3039456903
Cited by
789
References
55
Citations by year
2026: 20 · 2025: 39 · 2024: 67 · 2023: 141 · 2022: 185 · 2021: 257 · 2020: 77 · 2014: 2
FWCI
21.65
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
International Society for Advancement of Cytometry
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 pneumonia, SARS-CoV-2, T cell activation, T cell senescence, T cell exhaustion, PD-1, CD57, Th17 cells, IL-17, cytokine production, chemokine receptors, transcription factors, terminally differentiated T cells, mitochondrial function, regulatory T cells, CD4+ T cells, galectins, TNF-α, interferon-gamma, interleukin-2, IL-17 inhibition
MeSH terms
Betacoronavirus, Cytokine Release Syndrome, COVID-19, SARS-CoV-2, Adult, Aged, Aged, 80 and over, Female, Humans, Immunologic Memory, Italy, Lymphocyte Activation, Male, Middle Aged, Pneumonia, Viral, Biomarkers, CD4-Positive T-Lymphocytes, T-Lymphocyte Subsets, Cytokines, Cellular Senescence, Coronavirus Infections, CD8-Positive T-Lymphocytes, Lymphocyte Count, Th17 Cells, Pandemics

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