High levels of SARS-CoV-2–specific T cells with restricted functionality in severe courses of COVID-19
David Schub, Verena Klemis, Sophie Schneitler, Janine Mihm, Philipp M. Lepper, Heinrike Wilkens, Robert Bals, Hermann Eichler, Barbara C. Gärtner, Sören L. Becker, Urban Sester, Martina Sester, Tina Schmidt
David Schub, Verena Klemis, Sophie Schneitler, Janine Mihm, Philipp M. Lepper, Heinrike Wilkens, Robert Bals, Hermann Eichler, Barbara C. Gärtner, Sören L. Becker, Urban Sester, Martina Sester, Tina Schmidt
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Clinical Research and Public Health COVID-19

High levels of SARS-CoV-2–specific T cells with restricted functionality in severe courses of COVID-19

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.CONCLUSION Given 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.FUNDING The 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

David Schub, Verena Klemis, Sophie Schneitler, Janine Mihm, Philipp M. Lepper, Heinrike Wilkens, Robert Bals, Hermann Eichler, Barbara C. Gärtner, Sören L. Becker, Urban Sester, Martina Sester, Tina Schmidt

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Figure 1

Reduced counts of lymphocytes and lymphocyte subpopulations in patients with severe COVID-19.

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Reduced counts of lymphocytes and lymphocyte subpopulations in patients ...
Absolute cell numbers per microliter whole blood of lymphocytes and lymphocyte subpopulations were calculated in SARS-CoV-2–negative individuals (n = 10), patients with severe COVID-19 (n = 14), and convalescent patients (n = 21) based on flow cytometry and differential blood counts. Flow cytometry data were obtained from all convalescent patients, but 15/36 had to be excluded because no differential blood count was available. Natural killer (NK) cells were defined as CD3−CD16+/CD56+, B cells as CD19+, T cells as CD3+, CD4+ and CD8+ T cells as CD4+CD8− and CD8+CD4− T cells, and regulatory T cells (Tregs) as CD4+CD25hiCD127lo within lymphocytes, respectively. Bars represent medians with IQRs. Differences between the groups were calculated using Kruskal-Wallis test and Dunn’s posttest. **P < 0.01, ***P < 0.001, ****P < 0.0001.