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HCoV- and SARS-CoV-2 Cross-Reactive T Cells in CVID Patients.
Front Immunol. 2020; 11:607918.FI

Abstract

The inability of patients with CVID to mount specific antibody responses to pathogens has raised concerns on the risk and severity of SARS-CoV-2 infection, but there might be a role for protective T cells in these patients. SARS-CoV-2 reactive T cells have been reported for SARS-CoV-2 unexposed healthy individuals. Until now, there is no data on T cell immunity to SARS-CoV-2 infection in CVID. This study aimed to evaluate reactive T cells to human endemic corona viruses (HCoV) and to study pre-existing SARS-CoV-2 reactive T cells in unexposed CVID patients. We evaluated SARS-CoV-2- and HCoV-229E and -OC43 reactive T cells in response to seven peptide pools, including spike and nucleocapsid (NCAP) proteins, in 11 unexposed CVID, 12 unexposed and 11 post COVID-19 healthy controls (HC). We further characterized reactive T cells by IFNγ, TNFα and IL-2 profiles. SARS-CoV-2 spike-reactive CD4+ T cells were detected in 7 of 11 unexposed CVID patients, albeit with fewer multifunctional (IFNγ/TNFα/IL-2) cells than unexposed HC. CVID patients had no SARS-CoV-2 NCAP reactive CD4+ T cells and less reactive CD8+ cells compared to unexposed HC. We observed a correlation between T cell reactivity against spike of SARS-CoV-2 and HCoVs in unexposed, but not post COVID-19 HC, suggesting cross-reactivity. T cell responses in post COVID-19 HC could be distinguished from unexposed HC by higher frequencies of triple-positive NCAP reactive CD4+ T cells. Taken together, SARS-CoV-2 reactive T cells are detectable in unexposed CVID patients albeit with lower recognition frequencies and polyfunctional potential. Frequencies of triple-functional reactive CD4+ cells might provide a marker to distinguish HCoV cross-reactive from SARS-CoV-2 specific T cell responses. Our data provides evidence, that anti-viral T cell immunity is not relevantly impaired in most CVID patients.

Authors+Show Affiliations

Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. Experimental and Clinical Research Center (ECRC), Charité - Universitätsmedizin Berlin, Berlin, Germany. Berlin Institute of Health (BIH), Berlin, Germany. Berlin Institute of Health Center for Regenerative Therapies (BCRT), Charité University Medicine Berlin, Berlin, Germany.Berlin Institute of Health Center for Regenerative Therapies (BCRT), Charité University Medicine Berlin, Berlin, Germany. Berlin Center for Advanced Therapies (BeCAT), Charité - Universitätsmedizin Berlin, Berlin, Germany.Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, and German Centre for Infection Research (DZIF), Partner Site Charité, Berlin, Germany.Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, and German Centre for Infection Research (DZIF), Partner Site Charité, Berlin, Germany.Institute of Virology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, and German Centre for Infection Research (DZIF), Partner Site Charité, Berlin, Germany.Berlin Institute of Health Center for Regenerative Therapies (BCRT), Charité University Medicine Berlin, Berlin, Germany. Berlin Center for Advanced Therapies (BeCAT), Charité - Universitätsmedizin Berlin, Berlin, Germany.Department of Pediatrics, Kinderklinik München Schwabing, StKM GmbH und Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. Berlin Institute of Health Center for Regenerative Therapies (BCRT), Charité University Medicine Berlin, Berlin, Germany. Berlin Center for Advanced Therapies (BeCAT), Charité - Universitätsmedizin Berlin, Berlin, Germany.Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. Berlin Institute of Health Center for Regenerative Therapies (BCRT), Charité University Medicine Berlin, Berlin, Germany.Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33424856

Citation

Steiner, Sophie, et al. "HCoV- and SARS-CoV-2 Cross-Reactive T Cells in CVID Patients." Frontiers in Immunology, vol. 11, 2020, p. 607918.
Steiner S, Sotzny F, Bauer S, et al. HCoV- and SARS-CoV-2 Cross-Reactive T Cells in CVID Patients. Front Immunol. 2020;11:607918.
Steiner, S., Sotzny, F., Bauer, S., Na, I. K., Schmueck-Henneresse, M., Corman, V. M., Schwarz, T., Drosten, C., Wendering, D. J., Behrends, U., Volk, H. D., Scheibenbogen, C., & Hanitsch, L. G. (2020). HCoV- and SARS-CoV-2 Cross-Reactive T Cells in CVID Patients. Frontiers in Immunology, 11, 607918. https://doi.org/10.3389/fimmu.2020.607918
Steiner S, et al. HCoV- and SARS-CoV-2 Cross-Reactive T Cells in CVID Patients. Front Immunol. 2020;11:607918. PubMed PMID: 33424856.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HCoV- and SARS-CoV-2 Cross-Reactive T Cells in CVID Patients. AU - Steiner,Sophie, AU - Sotzny,Franziska, AU - Bauer,Sandra, AU - Na,Il-Kang, AU - Schmueck-Henneresse,Michael, AU - Corman,Victor M, AU - Schwarz,Tatjana, AU - Drosten,Christian, AU - Wendering,Désirée J, AU - Behrends,Uta, AU - Volk,Hans-Dieter, AU - Scheibenbogen,Carmen, AU - Hanitsch,Leif G, Y1 - 2020/12/23/ PY - 2020/09/18/received PY - 2020/11/20/accepted PY - 2021/1/11/entrez PY - 2021/1/12/pubmed PY - 2021/1/16/medline KW - T cell response KW - common variable immunodeficiency disorder (CVID) KW - coronavirus disease 2019 (COVID-19) KW - human endemic coronavirus 229E (HCoV-229E) KW - human endemic coronavirus OC-43 (HCoV-OC43) KW - primary immunodeficiency (PID) KW - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) SP - 607918 EP - 607918 JF - Frontiers in immunology JO - Front Immunol VL - 11 N2 - The inability of patients with CVID to mount specific antibody responses to pathogens has raised concerns on the risk and severity of SARS-CoV-2 infection, but there might be a role for protective T cells in these patients. SARS-CoV-2 reactive T cells have been reported for SARS-CoV-2 unexposed healthy individuals. Until now, there is no data on T cell immunity to SARS-CoV-2 infection in CVID. This study aimed to evaluate reactive T cells to human endemic corona viruses (HCoV) and to study pre-existing SARS-CoV-2 reactive T cells in unexposed CVID patients. We evaluated SARS-CoV-2- and HCoV-229E and -OC43 reactive T cells in response to seven peptide pools, including spike and nucleocapsid (NCAP) proteins, in 11 unexposed CVID, 12 unexposed and 11 post COVID-19 healthy controls (HC). We further characterized reactive T cells by IFNγ, TNFα and IL-2 profiles. SARS-CoV-2 spike-reactive CD4+ T cells were detected in 7 of 11 unexposed CVID patients, albeit with fewer multifunctional (IFNγ/TNFα/IL-2) cells than unexposed HC. CVID patients had no SARS-CoV-2 NCAP reactive CD4+ T cells and less reactive CD8+ cells compared to unexposed HC. We observed a correlation between T cell reactivity against spike of SARS-CoV-2 and HCoVs in unexposed, but not post COVID-19 HC, suggesting cross-reactivity. T cell responses in post COVID-19 HC could be distinguished from unexposed HC by higher frequencies of triple-positive NCAP reactive CD4+ T cells. Taken together, SARS-CoV-2 reactive T cells are detectable in unexposed CVID patients albeit with lower recognition frequencies and polyfunctional potential. Frequencies of triple-functional reactive CD4+ cells might provide a marker to distinguish HCoV cross-reactive from SARS-CoV-2 specific T cell responses. Our data provides evidence, that anti-viral T cell immunity is not relevantly impaired in most CVID patients. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/33424856/HCoV__and_SARS_CoV_2_Cross_Reactive_T_Cells_in_CVID_Patients_ L2 - https://doi.org/10.3389/fimmu.2020.607918 DB - PRIME DP - Unbound Medicine ER -