Impaired SARS-CoV-2 specific T-cell response in patients with severe COVID-19

Lidewij W. Rümke; Wouter L. Smit; Ailko Bossink; Gijs J.M. Limonard; Danya Muilwijk; Lenneke E.M. Haas; Chantal Reusken; Sanne van der Wal; Bing J. Thio; Yvonne M.G. van Os; Hendrik Gremmels; Jeffrey M. Beekman; Monique Nijhuis; Annemarie M.J. Wensing; Michiel Heron; Steven F.T. Thijsen

doi:10.3389/fimmu.2023.1046639

Impaired SARS-CoV-2 specific T-cell response in patients with severe COVID-19

Lidewij W. Rümke, Wouter L. Smit, Ailko Bossink, Gijs J.M. Limonard, Danya Muilwijk, Lenneke E.M. Haas, Chantal Reusken, Sanne van der Wal, Bing J. Thio, Yvonne M.G. van Os, Hendrik Gremmels, Jeffrey M. Beekman, Monique Nijhuis, Annemarie M.J. Wensing, Michiel Heron^*, Steven F.T. Thijsen

^*Corresponding author for this work

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Abstract

Cellular immune responses are of pivotal importance to understand SARS-CoV-2 pathogenicity. Using an enzyme-linked immunosorbent spot (ELISpot) interferon-γ release assay with wild-type spike, membrane and nucleocapsid peptide pools, we longitudinally characterized functional SARS-CoV-2 specific T-cell responses in a cohort of patients with mild, moderate and severe COVID-19. All patients were included before emergence of the Omicron (B.1.1.529) variant. Our most important finding was an impaired development of early IFN-γ-secreting virus-specific T-cells in severe patients compared to patients with moderate disease, indicating that absence of virus-specific cellular responses in the acute phase may act as a prognostic factor for severe disease. Remarkably, in addition to reactivity against the spike protein, a substantial proportion of the SARS-CoV-2 specific T-cell response was directed against the conserved membrane protein. This may be relevant for diagnostics and vaccine design, especially considering new variants with heavily mutated spike proteins. Our data further strengthen the hypothesis that dysregulated adaptive immunity plays a central role in COVID-19 immunopathogenesis.

Original language	English
Article number	1046639
Number of pages	9
Journal	Frontiers in Immunology
Volume	14
DOIs	https://doi.org/10.3389/fimmu.2023.1046639
Publication status	Published - Apr 2023

Keywords

COVID-19 ELISpot IFN-γ release assay
membrane protein
nucleocapsid protein
SARS-CoV-2
spike protein
T-cell immunity

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Rümke, L. W., Smit, W. L., Bossink, A., Limonard, G. J. M., Muilwijk, D., Haas, L. E. M., Reusken, C., van der Wal, S., Thio, B. J., van Os, Y. M. G., Gremmels, H., Beekman, J. M., Nijhuis, M., Wensing, A. M. J., Heron, M., & Thijsen, S. F. T. (2023). Impaired SARS-CoV-2 specific T-cell response in patients with severe COVID-19. Frontiers in Immunology, 14, Article 1046639. https://doi.org/10.3389/fimmu.2023.1046639

@article{ef4541c3d2dc4f50929123ff09d9a379,

title = "Impaired SARS-CoV-2 specific T-cell response in patients with severe COVID-19",

abstract = "Cellular immune responses are of pivotal importance to understand SARS-CoV-2 pathogenicity. Using an enzyme-linked immunosorbent spot (ELISpot) interferon-γ release assay with wild-type spike, membrane and nucleocapsid peptide pools, we longitudinally characterized functional SARS-CoV-2 specific T-cell responses in a cohort of patients with mild, moderate and severe COVID-19. All patients were included before emergence of the Omicron (B.1.1.529) variant. Our most important finding was an impaired development of early IFN-γ-secreting virus-specific T-cells in severe patients compared to patients with moderate disease, indicating that absence of virus-specific cellular responses in the acute phase may act as a prognostic factor for severe disease. Remarkably, in addition to reactivity against the spike protein, a substantial proportion of the SARS-CoV-2 specific T-cell response was directed against the conserved membrane protein. This may be relevant for diagnostics and vaccine design, especially considering new variants with heavily mutated spike proteins. Our data further strengthen the hypothesis that dysregulated adaptive immunity plays a central role in COVID-19 immunopathogenesis.",

keywords = "COVID-19 ELISpot IFN-γ release assay, membrane protein, nucleocapsid protein, SARS-CoV-2, spike protein, T-cell immunity",

author = "R{\"u}mke, {Lidewij W.} and Smit, {Wouter L.} and Ailko Bossink and Limonard, {Gijs J.M.} and Danya Muilwijk and Haas, {Lenneke E.M.} and Chantal Reusken and {van der Wal}, Sanne and Thio, {Bing J.} and {van Os}, {Yvonne M.G.} and Hendrik Gremmels and Beekman, {Jeffrey M.} and Monique Nijhuis and Wensing, {Annemarie M.J.} and Michiel Heron and Thijsen, {Steven F.T.}",

note = "Funding Information: This collaboration project is co-funded by Health~Holland (LSHM2008), ZonMw (114025009), the Cornelis Visser Foundation and the Diakonessenhuis Hospital. Publisher Copyright: Copyright {\textcopyright} 2023 R{\"u}mke, Smit, Bossink, Limonard, Muilwijk, Haas, Reusken, van der Wal, Thio, van Os, Gremmels, Beekman, Nijhuis, Wensing, Heron and Thijsen.",

year = "2023",

month = apr,

doi = "10.3389/fimmu.2023.1046639",

language = "English",

volume = "14",

journal = "Frontiers in Immunology",

issn = "1664-3224",

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}

Rümke, LW, Smit, WL, Bossink, A, Limonard, GJM, Muilwijk, D, Haas, LEM, Reusken, C, van der Wal, S, Thio, BJ, van Os, YMG, Gremmels, H, Beekman, JM , Nijhuis, M , Wensing, AMJ, Heron, M & Thijsen, SFT 2023, 'Impaired SARS-CoV-2 specific T-cell response in patients with severe COVID-19', Frontiers in Immunology, vol. 14, 1046639. https://doi.org/10.3389/fimmu.2023.1046639

TY - JOUR

T1 - Impaired SARS-CoV-2 specific T-cell response in patients with severe COVID-19

AU - Rümke, Lidewij W.

AU - Smit, Wouter L.

AU - Bossink, Ailko

AU - Limonard, Gijs J.M.

AU - Muilwijk, Danya

AU - Haas, Lenneke E.M.

AU - Reusken, Chantal

AU - van der Wal, Sanne

AU - Thio, Bing J.

AU - van Os, Yvonne M.G.

AU - Gremmels, Hendrik

AU - Beekman, Jeffrey M.

AU - Nijhuis, Monique

AU - Wensing, Annemarie M.J.

AU - Heron, Michiel

AU - Thijsen, Steven F.T.

N1 - Funding Information: This collaboration project is co-funded by Health~Holland (LSHM2008), ZonMw (114025009), the Cornelis Visser Foundation and the Diakonessenhuis Hospital. Publisher Copyright: Copyright © 2023 Rümke, Smit, Bossink, Limonard, Muilwijk, Haas, Reusken, van der Wal, Thio, van Os, Gremmels, Beekman, Nijhuis, Wensing, Heron and Thijsen.

PY - 2023/4

Y1 - 2023/4

N2 - Cellular immune responses are of pivotal importance to understand SARS-CoV-2 pathogenicity. Using an enzyme-linked immunosorbent spot (ELISpot) interferon-γ release assay with wild-type spike, membrane and nucleocapsid peptide pools, we longitudinally characterized functional SARS-CoV-2 specific T-cell responses in a cohort of patients with mild, moderate and severe COVID-19. All patients were included before emergence of the Omicron (B.1.1.529) variant. Our most important finding was an impaired development of early IFN-γ-secreting virus-specific T-cells in severe patients compared to patients with moderate disease, indicating that absence of virus-specific cellular responses in the acute phase may act as a prognostic factor for severe disease. Remarkably, in addition to reactivity against the spike protein, a substantial proportion of the SARS-CoV-2 specific T-cell response was directed against the conserved membrane protein. This may be relevant for diagnostics and vaccine design, especially considering new variants with heavily mutated spike proteins. Our data further strengthen the hypothesis that dysregulated adaptive immunity plays a central role in COVID-19 immunopathogenesis.

AB - Cellular immune responses are of pivotal importance to understand SARS-CoV-2 pathogenicity. Using an enzyme-linked immunosorbent spot (ELISpot) interferon-γ release assay with wild-type spike, membrane and nucleocapsid peptide pools, we longitudinally characterized functional SARS-CoV-2 specific T-cell responses in a cohort of patients with mild, moderate and severe COVID-19. All patients were included before emergence of the Omicron (B.1.1.529) variant. Our most important finding was an impaired development of early IFN-γ-secreting virus-specific T-cells in severe patients compared to patients with moderate disease, indicating that absence of virus-specific cellular responses in the acute phase may act as a prognostic factor for severe disease. Remarkably, in addition to reactivity against the spike protein, a substantial proportion of the SARS-CoV-2 specific T-cell response was directed against the conserved membrane protein. This may be relevant for diagnostics and vaccine design, especially considering new variants with heavily mutated spike proteins. Our data further strengthen the hypothesis that dysregulated adaptive immunity plays a central role in COVID-19 immunopathogenesis.

KW - COVID-19 ELISpot IFN-γ release assay

KW - membrane protein

KW - nucleocapsid protein

KW - SARS-CoV-2

KW - spike protein

KW - T-cell immunity

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U2 - 10.3389/fimmu.2023.1046639

DO - 10.3389/fimmu.2023.1046639

M3 - Article

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AN - SCOPUS:85158126659

SN - 1664-3224

VL - 14

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 1046639

ER -

Impaired SARS-CoV-2 specific T-cell response in patients with severe COVID-19

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