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

Frontiers in Immunology

Immunology

Chantal Reusken¹  Lenneke E. M. Haas²  Sanne van der Wal³  Michiel Heron³  Bing J. Thio³  Steven F. T. Thijsen³  Hendrik Gremmels⁴  Wouter L. Smit⁴  Lidewij W. Rümke⁴  Danya Muilwijk⁵  Jeffrey M. Beekman⁵  Ailko Bossink⁶  Gijs J. M. Limonard⁶  Yvonne M. G. van Os⁷  Monique Nijhuis⁸  Annemarie M. J. Wensing⁸ 

[1] Centre for Infectious Disease Control, WHO Reference Laboratory for COVID-19, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands;Department of Intensive Care, Diakonessenhuis Utrecht, Utrecht, Netherlands;Department of Medical Microbiology and Immunology, Diakonessenhuis Utrecht, Utrecht, Netherlands;Department of Medical Microbiology and Immunology, Diakonessenhuis Utrecht, Utrecht, Netherlands;Virology, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands;Department of Pediatric Pulmonology, Wilhelmina Children’s Hospital, University Medical Center, Utrecht University, Utrecht, Netherlands;Regenerative Medicine Center Utrecht, University Medical Center, Utrecht University, Utrecht, Netherlands;Department of Pulmonary Diseases, Diakonessenhuis Utrecht, Utrecht, Netherlands;Occupational Health Office, Department of Human Resources, University Medical Center Utrecht, Utrecht, Netherlands;Virology, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands;

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

DOI  :  10.3389/fimmu.2023.1046639

 received in 2022-09-16, accepted in 2023-03-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Rümke, Smit, Bossink, Limonard, Muilwijk, Haas, Reusken, van der Wal, Thio, van Os, Gremmels, Beekman, Nijhuis, Wensing, Heron and Thijsen