Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia
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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 measuredCOVID-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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- 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
- ORCID
- Meschiari, Marianna
- Gibellini, Lara
- Borella, Rebecca
- Gozzi, Licia
- Iannone, Anna
- Lo Tartaro, Domenico
- Mattioli, Marco
- Paolini, Annamaria
- Menozzi, Marianna
- Milić, Jovana
- Franceschi, Giacomo
- Fantini, Riccardo
- Tonelli, Roberto
- Sita, Marco
- Sarti, Mario
- Trenti, Tommaso
- Brugioni, Lucio
- Facchinetti, Fabio
- Pietrangelo, Antonello
- Clini, Enrico
- Girardis, Massimo
- Guaraldi, Giovanni
- Mussini, Cristina
- Cossarizza, Andrea
- Venue
- Nature Communications
- Published
- 2020-07-06
- Volume
- 11
- Issue
- 1
- Pages
- 3434-3434
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7338513
- 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
- gold
- doi.org
- 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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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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