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High levels of SARS-CoV-2-specific T cells with restricted functionality in severe courses of COVID-19.
JCI Insight. 2020 10 15; 5(20)JI

Abstract

BACKGROUND

Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) differ in the severity of disease. We hypothesized that characteristics of SARS-CoV-2-specific immunity correlate with disease severity.

METHODS

In this study, SARS-CoV-2-specific T cells and antibodies were characterized in uninfected controls and patients with different coronavirus disease 2019 (COVID-19) disease severity. SARS-CoV-2-specific T cells were flow cytometrically quantified after stimulation with SARS-CoV-2 peptide pools and analyzed for expression of cytokines (IFN-γ, IL-2, and TNF-α) and markers for activation, proliferation, and functional anergy. SARS-CoV-2-specific IgG and IgA antibodies were quantified using ELISA. Moreover, global characteristics of lymphocyte subpopulations were compared between patient groups and uninfected controls.

RESULTS

Despite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2-specific T cells as compared with convalescent individuals. SARS-CoV-2-specific CD4+ T cells dominated over CD8+ T cells and closely correlated with the number of plasmablasts and SARS-CoV-2-specific IgA and IgG levels. Unlike in convalescent patients, SARS-CoV-2-specific T cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4+ and CD8+ T cells in general.CONCLUSIONGiven the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered characteristics may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung.FUNDINGThe study was supported by institutional funds to MS and in part by grants of Saarland University, the State of Saarland, and the Rolf M. Schwiete Stiftung.

Authors+Show Affiliations

Department of Transplant and Infection Immunology.Department of Transplant and Infection Immunology.Institute of Medical Microbiology and Hygiene.Department of Internal Medicine IV.Department of Internal Medicine V, and.Department of Internal Medicine V, and.Department of Internal Medicine V, and.Institute of Clinical Hemostaseology and Transfusion Medicine, Saarland University, Homburg, Germany.Institute of Medical Microbiology and Hygiene.Institute of Medical Microbiology and Hygiene.Department of Internal Medicine IV.Department of Transplant and Infection Immunology.Department of Transplant and Infection Immunology.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32937615

Citation

Schub, David, et al. "High Levels of SARS-CoV-2-specific T Cells With Restricted Functionality in Severe Courses of COVID-19." JCI Insight, vol. 5, no. 20, 2020.
Schub D, Klemis V, Schneitler S, et al. High levels of SARS-CoV-2-specific T cells with restricted functionality in severe courses of COVID-19. JCI Insight. 2020;5(20).
Schub, D., Klemis, V., Schneitler, S., Mihm, J., Lepper, P. M., Wilkens, H., Bals, R., Eichler, H., Gärtner, B. C., Becker, S. L., Sester, U., Sester, M., & Schmidt, T. (2020). High levels of SARS-CoV-2-specific T cells with restricted functionality in severe courses of COVID-19. JCI Insight, 5(20). https://doi.org/10.1172/jci.insight.142167
Schub D, et al. High Levels of SARS-CoV-2-specific T Cells With Restricted Functionality in Severe Courses of COVID-19. JCI Insight. 2020 10 15;5(20) PubMed PMID: 32937615.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High levels of SARS-CoV-2-specific T cells with restricted functionality in severe courses of COVID-19. AU - Schub,David, AU - Klemis,Verena, AU - Schneitler,Sophie, AU - Mihm,Janine, AU - Lepper,Philipp M, AU - Wilkens,Heinrike, AU - Bals,Robert, AU - Eichler,Hermann, AU - Gärtner,Barbara C, AU - Becker,Sören L, AU - Sester,Urban, AU - Sester,Martina, AU - Schmidt,Tina, Y1 - 2020/10/15/ PY - 2020/07/13/received PY - 2020/09/16/accepted PY - 2020/9/17/pubmed PY - 2020/10/29/medline PY - 2020/9/16/entrez KW - COVID-19 KW - Cellular immune response KW - Immunoglobulins KW - T cells JF - JCI insight JO - JCI Insight VL - 5 IS - 20 N2 - BACKGROUNDPatients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) differ in the severity of disease. We hypothesized that characteristics of SARS-CoV-2-specific immunity correlate with disease severity.METHODSIn this study, SARS-CoV-2-specific T cells and antibodies were characterized in uninfected controls and patients with different coronavirus disease 2019 (COVID-19) disease severity. SARS-CoV-2-specific T cells were flow cytometrically quantified after stimulation with SARS-CoV-2 peptide pools and analyzed for expression of cytokines (IFN-γ, IL-2, and TNF-α) and markers for activation, proliferation, and functional anergy. SARS-CoV-2-specific IgG and IgA antibodies were quantified using ELISA. Moreover, global characteristics of lymphocyte subpopulations were compared between patient groups and uninfected controls.RESULTSDespite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2-specific T cells as compared with convalescent individuals. SARS-CoV-2-specific CD4+ T cells dominated over CD8+ T cells and closely correlated with the number of plasmablasts and SARS-CoV-2-specific IgA and IgG levels. Unlike in convalescent patients, SARS-CoV-2-specific T cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4+ and CD8+ T cells in general.CONCLUSIONGiven the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered characteristics may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung.FUNDINGThe study was supported by institutional funds to MS and in part by grants of Saarland University, the State of Saarland, and the Rolf M. Schwiete Stiftung. SN - 2379-3708 UR - https://www.unboundmedicine.com/medline/citation/32937615/High_levels_of_SARS_CoV_2_specific_T_cells_with_restricted_functionality_in_severe_courses_of_COVID_19_ L2 - https://doi.org/10.1172/jci.insight.142167 DB - PRIME DP - Unbound Medicine ER -