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The SARS-COV-2 T-Cell Immunity is Directed Against the Spike, Membrane, and Nucleocapsid Protein and Associated with COVID 19 Severity

27 Pages Posted: 21 May 2020 Sneak Peek Status: Under Review

See all articles by Constantin Thieme

Constantin Thieme

Charité –Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin

Moritz Anft

Center for Translational Medicineand Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum

Krystallenia Paniskaki

Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen

Arturo Blázquez Navarro

Charité –Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin

Adrian Doevelaar

Center for Translational Medicineand Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum

Felix S. Seibert

Center for Translational Medicineand Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum

Bodo Hölzer

Center for Translational Medicineand Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum

Margarethe Justine Konik

Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen

Thorsten Brenner

Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen

Clemens Tempfer

Department of Gynecology and Obstetrics, MarienHospital Herne, University Hospital of the Ruhr-University Bochum

Carsten Watzl

Department of Immunology, Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund (IfADo)

Sebastian Dolff

affiliation not provided to SSRN

Ulf Dittmer

University of Duisburg-Essen - Institute for Virology

Oliver Witzke

University of Duisburg-Essen - Department of Infectious Diseases

Timm H. Westhoff

Center for Translational Medicineand Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum

Ulrik Stervbo

Center for Translational Medicineand Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum

Toralf Roch

affiliation not provided to SSRN

Nina Babel

Ruhr University of Bochum - Medical Clinic I

More...

Abstract

Identification of immunogenic targets of SARS-CoV-2 is crucial for monitoring of antiviral immunity and vaccine design. Currently, mainly anti-spike (S)-protein adaptive immunity is investigated. However, also the nucleocapsid (N)- and membrane (M)-proteins should be considered as diagnostic and prophylactic targets.The aim of our study was to explore and compare the immunogenicity of SARS-CoV-2 S-, M- and N-proteins in context of different COVID-19 manifestations. Analyzing a cohort of COVID-19 patients with moderate, severe, and critical disease severity, we show that overlapping peptide pools (OPP) of all three proteins can activate SARS-CoV-2-reactive T-cells with a stronger response of CD4 + compared to CD8 + T-cells. Although interindividual variations for the three proteins were observed, M‑protein induced the highest frequencies of CD4 + T-cells, suggesting its relevance as diagnostic and vaccination target. Importantly, patients with critical COVID-19 demonstrated the strongest T-cell response, including the highest frequencies of cytokine-producing bi- and trifunctional T-cells, for all three proteins. Although the higher magnitude and superior functionality of SARS-CoV-2-reactive T-cells in critical patients can also be a result of a stronger immunogenicity provided by severe infection, it disproves the hypothesis of insufficient SARS-CoV-2-reactive immunity in critical COVID-19. To this end, activation of effector T-cells with differentiated memory phenotype found in our study could cause hyper-reactive response in critical cases leading to immunopathogenesis.Conclusively, since the S-, M-, and N-proteins induce T-cell responses with individual differences, all three proteins should be evaluated for diagnostics and therapeutic strategies to avoid underestimation of cellular immunity and to deepen our understanding of COVID-19 immunity.

Funding: This work was supported by grants of Mercator Foundation, the BMBF e:KID (01ZX1612A), and BMBF NoChro (FKZ 13GW0338B).

Declaration of Interest: Missing

Ethical Statement: We feel deep gratitude to the patients who donated their blood samples and clinical data for this project.

Suggested Citation

Thieme, Constantin and Anft, Moritz and Paniskaki, Krystallenia and Blázquez Navarro, Arturo and Doevelaar, Adrian and Seibert, Felix S. and Hölzer, Bodo and Konik, Margarethe Justine and Brenner, Thorsten and Tempfer, Clemens and Watzl, Carsten and Dolff, Sebastian and Dittmer, Ulf and Witzke, Oliver and Westhoff, Timm H. and Stervbo, Ulrik and Roch, Toralf and Babel, Nina, The SARS-COV-2 T-Cell Immunity is Directed Against the Spike, Membrane, and Nucleocapsid Protein and Associated with COVID 19 Severity. IMMUNITY-D-20-00623. Available at SSRN: https://ssrn.com/abstract=3606763 or http://dx.doi.org/10.2139/ssrn.3606763
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Constantin Thieme

Charité –Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin ( email )

Charitéplatz 1
Berlin, 10117
Germany

Moritz Anft

Center for Translational Medicineand Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum ( email )

Universitätsstraße 150
Bochum, NRW 44780
Germany

Krystallenia Paniskaki

Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen ( email )

Lotharstrasse 1
Duisburg, 47048
Germany

Arturo Blázquez Navarro

Charité –Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin ( email )

Germany

Adrian Doevelaar

Center for Translational Medicineand Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum ( email )

Universitätsstraße 150
Bochum, NRW 44780
Germany

Felix S. Seibert

Center for Translational Medicineand Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum ( email )

Universitätsstraße 150
Bochum, NRW 44780
Germany

Bodo Hölzer

Center for Translational Medicineand Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum ( email )

Universitätsstraße 150
Bochum, NRW 44780
Germany

Margarethe Justine Konik

Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen ( email )

Lotharstrasse 1
Duisburg, 47048
Germany

Thorsten Brenner

Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen ( email )

Lotharstrasse 1
Duisburg, 47048
Germany

Clemens Tempfer

Department of Gynecology and Obstetrics, MarienHospital Herne, University Hospital of the Ruhr-University Bochum ( email )

Universitätsstraße 150
Bochum, NRW 44780
Germany

Carsten Watzl

Department of Immunology, Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund (IfADo) ( email )

Emil-Figge-Straße 50
Dortmund, 44227
Germany

Sebastian Dolff

affiliation not provided to SSRN

No Address Available

Ulf Dittmer

University of Duisburg-Essen - Institute for Virology ( email )

Hufelandstraße 55
45147 Essen
Germany

Oliver Witzke

University of Duisburg-Essen - Department of Infectious Diseases

Essen, 45147
Germany

Timm H. Westhoff

Center for Translational Medicineand Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum ( email )

Universitätsstraße 150
Bochum, NRW 44780
Germany

Ulrik Stervbo

Center for Translational Medicineand Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum ( email )

Universitätsstraße 150
Bochum, NRW 44780
Germany

Toralf Roch

affiliation not provided to SSRN

No Address Available

Nina Babel (Contact Author)

Ruhr University of Bochum - Medical Clinic I

Germany

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