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Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19
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Abstract
SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. Here, we systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute-phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent-phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits broadly directed and functionally replete memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.
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“This cross-reactivity largely originates from previous exposure to circulating common cold coronaviruses [110-116].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [113]
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“lymphocytes from 20% to 50% of unexposed donors display significant reactivity to SARS-CoV-2 Ag peptide pools (Figure 6).”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [113]
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“A vast majority of responding CD4+ and CD8+ T cells displayed an activated/cycling (CD38+ HLA-DR+ Ki67+ PD-1+) phenotype [113]”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [113]
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In the citing paper
“and SARS-CoV-2-specific memory T cells were detected in convalescent patients, even in exposed individuals who are seronegative.30, 31”
From Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: a randomised, double-blind, placebo-controlled, phase 1 trial (2022) · cites this paper as [31]
In the citing paper
“Virus-specific CD8+ and CD4+ T cells, including CD8+ memory T cells, are present in patients who have recovered from COVID-19 (refs44,45), but their importance in protection against future infection and/or severe disease remain uncertain44,46–48.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [45]
In the citing paper
“By contrast, VAERD has not usually occurred if a TH1 cell-biased CD4+ T cell response is elicited, reflected by increased levels of interferon-γ (IFNγ), IL-2 and tumour necrosis factor (TNF)44–46,49.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [45]
In the citing paper
“Studies of acute and convalescent COVID-19 patients have observed that SARS-CoV-2-specific T cell responses are significantly associated with milder disease (Liao et al., 2020; Rydyznski Moderbacher et al., 2020; Sekine et al., 2020; Zhou et al., 2020b), suggesting that T cell responses may be important for control and resolution of a primary SARS-CoV-2 infection.”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Sekine et al., 2020
In the citing paper
“Overall, circulating SARS-CoV-2-specific CD8+ T cells are less consistently observed than CD4+ T cells (Grifoni et al., 2020; Rydyznski Moderbacher et al., 2020; Sekine et al., 2020).”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Sekine et al., 2020
In the citing paper
“Last, there were initially great concerns about potential immune deviation to Th2 and immunopathogenesis (Peeples, 2020), but SARS-CoV-2-specific CD4+ T cells from patients consistently do not have Th2 characteristics (Grifoni et al., 2020; Rydyznski Moderbacher et al., 2020; Sekine et al., 2020).”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Sekine et al., 2020
In the citing paper
“CD4+ T cell responses to SARS-CoV-2 are more prominent than CD8+ T cell responses (Grifoni et al., 2020; Sekine et al., 2020) and have been associated with control of primary SARS-CoV-2 infection (Rydyznski Moderbacher et al., 2020).”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Sekine et al., 2020
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Metadata
- Authors
- Sekine, T., Perez-Potti, A., Rivera-Ballesteros, O., Strålin, K., Gorin, J.-B., Olsson, A., Llewellyn-Lacey, S., Kamal, H., Bogdanovic, G., Muschiol, S., Wullimann, D. J., Kammann, T., Emgård, J., Parrot, T., Folkesson, E., Akber, M., Berglin, L., Bergsten, H., Brighenti, S., Brownlie, D., Butrym, M., Chambers, B., Chen, P., Jeannin, M. C., Grip, J., Gomez, A. C., Dillner, L., Lozano, I. D., Dzidic, M., Tullberg, M. F., Färnert, A., Glans, H., Haroun-Izquierdo, A., Henriksson, E., Hertwig, L., Kalsum, S., Kokkinou, E., Kvedaraite, E., Loreti, M., Lourda, M., Maleki, K., Malmberg, K.-J., Marquardt, N., Maucourant, C., Michaelsson, J., Mjösberg, J., Moll, K., Muva, J., Mårtensson, J., Nauclér, P., Norrby-Teglund, A., Medina, L. P., Persson, B., Radler, L., Ringqvist, E., Sandberg, J. T., Sohlberg, E., Soini, T., Svensson, M., Tynell, J., Varnaite, R., Kries, A. V., Unge, C., Rooyackers, O., Eriksson, L. I., Henter, J.-I., Sönnerborg, A., Allander, T., Albert, J., Nielsen, M., Klingström, J., Gredmark-Russ, S., Björkström, N. K., Sandberg, J. K., Price, D. A., Ljunggren, H.-G., Aleman, S., & Buggert, M.
- Affiliations
- Karolinska Institutet (SE)
- Karolinska University Hospital (SE)
- National University of General San Martín (AR)
- University Hospital of Wales (GB)
- Corresponding author
- Buggert, Marcus
- ORCID
- Sekine, Takuya
- Strålin, Kristoffer
- Gorin, Jean-Baptiste
- Kamal, Habiba
- Wullimann, David J.
- Kammann, Tobias
- Parrot, Tiphaine
- Folkesson, Elin
- Bergsten, Helena
- Brighenti, Susanna
- Brownlie, Demi
- Butrym, Marta
- Chambers, Benedict
- Chen, Puran
- Grip, Jonathan
- Dillner, Lena
- Dzidic, Majda
- Färnert, Anna
- Glans, Hedvig
- Haroun-Izquierdo, Alvaro
- Hertwig, Laura
- Kalsum, Sadaf
- Kokkinou, Efthymia
- Kvedaraite, Egle
- Maleki, Kimia
- Malmberg, Karl-Johan
- Marquardt, Nicole
- Maucourant, Christopher
- Mjösberg, Jenny
- Mårtensson, Johan
- Nauclér, Pontus
- Ringqvist, Emma
- Sandberg, John Tyler
- Sohlberg, Ebba
- Soini, Tea
- Svensson, Mattias
- Tynell, Janne
- Rooyackers, Olav
- Henter, Jan-Inge
- Sönnerborg, Anders
- Albert, Jan
- Nielsen, Morten
- Klingström, Jonas
- Björkström, Niklas K.
- Sandberg, Johan K.
- Price, David A.
- Ljunggren, Hans-Gustaf
- Aleman, Soo
- Buggert, Marcus
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 183
- Issue
- 1
- Pages
- 158-168.e14
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7427556
- OpenAlex
- W3048775784
- Cited by
- 1,788
- References
- 58
- Citations by year
- 2026: 50 · 2025: 97 · 2024: 150 · 2023: 221 · 2022: 424 · 2021: 624 · 2020: 220
- FWCI
- 48.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- RIUCAM (submittedVersion, cc-by-nc-nd)
- Funders
- Barncancerfonden
- Svenska Sällskapet för Medicinsk Forskning
- Jeanssons Stiftelser
- National Institutes of Health
- Vetenskapsrådet
- Karolinska Institutet
- Cancerfonden
- Åke Wiberg Stiftelse
- Magnus Bergvalls Stiftelse
- Stiftelsen Clas Groschinskys Minnesfond
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- SARS-CoV-2, COVID-19 pandemic, T cell immunity, memory T cells, convalescent patients, asymptomatic infection, mild COVID-19, cytotoxic T lymphocytes, T cell polyfunctionality, family exposure, disease severity
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Adult, Antibodies, Viral, Convalescence, Female, Humans, Immunologic Memory, Male, Middle Aged, Pneumonia, Viral, T-Lymphocytes, Coronavirus Infections, Asymptomatic Infections, Pandemics
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