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 4

Altered characteristics of global CD4+ and CD8+ T cells in patients with severe COVID-19.

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Altered characteristics of global CD4+ and CD8+ T cells in patients with...
(A) Representative contour plots showing expression of CTLA-4 and PD-1 and intranuclear Ki67 expression of unstimulated total CD4+ and CD8+ T cells from an ICU patient and a convalescent individual. Because cells showed a continuum in the expression of CTLA-4 and PD-1, cell surface expression levels of CTLA-4 and PD-1 were expressed as MFI. Numbers indicate expression levels (MFI) of CTLA-4 and PD-1 and percentage of Ki67+ cells among total CD4+ and CD8+ T cells. (B) Results were compared among SARS-CoV-2–negative individuals (negative, n = 10), patients with severe COVID-19 (ICU, n = 14), and convalescent patients (n = 36). Bars represent medians with IQRs. Differences between the groups were calculated using Kruskal-Wallis test and Dunn’s posttest. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.