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Assessing Predictive Value of SARS-CoV-2 Epitope-Specific CD8⁺ T-Cell Response in Patients with Severe Symptoms.

ABSTRACT: Specific T cell responses against SARS-CoV-2 provided an overview of acquired immunity during the pandemic. Anti-SARS-CoV-2 immunity determines the severity of acute illness, but also might be related to the possible persistence of symptoms (long COVID). We retrospectively analyzed ex vivo longitudinal CD8⁺ T cell responses in 26 COVID-19 patients diagnosed with severe disease, initially (1 month) and long-term (10 months), and in a cohort of 32 vaccinated healthcare workers without previous SARS-CoV-2 infection. We used peptide-human leukocyte antigen (pHLA) dextramers recognizing 26 SARS-CoV-2-derived epitopes of viral and other non-structural proteins. Most patients responded to at least one of the peptides studied, mainly derived from non-structural ORF1ab proteins. After 10 months follow-up, CD8⁺ T cell responses were maintained at long term and reaction against certain epitopes (A*01:01-ORF1ab1637) was still detected and functional, showing a memory-like phenotype (CD127+ PD-1+). The total number of SARS-CoV-2-specific CD8⁺ T cells was significantly associated with protection against long COVID in these patients. Compared with vaccination, infected patients showed a less effective immune response to spike protein-derived peptides restricted by HLA. So, the A*01:01-S865 and A*24:02-S1208 dextramers were only recognized in vaccinated individuals. We conclude that initial SARS-CoV-2-specific CD8⁺ T cell response could be used as a marker to understand the evolution of severe disease and post-acute sequelae after SARS-CoV-2 infection.

SUBMITTER: Martin-Martin C

PROVIDER: S-EPMC11209605 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature

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Assessing Predictive Value of SARS-CoV-2 Epitope-Specific CD8<sup>+</sup> T-Cell Response in Patients with Severe Symptoms.

Martín-Martín Cristina C Del Riego Estefanía Salgado ES Castiñeira Jose R Vidal JRV Zapico-Gonzalez Maria Soledad MS Rodríguez-Pérez Mercedes M Corte-Iglesias Viviana V Saiz Maria Laura ML Diaz-Bulnes Paula P Escudero Dolores D Suárez-Alvarez Beatriz B López-Larrea Carlos C

Vaccines 20240618 6

Specific T cell responses against SARS-CoV-2 provided an overview of acquired immunity during the pandemic. Anti-SARS-CoV-2 immunity determines the severity of acute illness, but also might be related to the possible persistence of symptoms (long COVID). We retrospectively analyzed ex vivo longitudinal CD8<sup>+</sup> T cell responses in 26 COVID-19 patients diagnosed with severe disease, initially (1 month) and long-term (10 months), and in a cohort of 32 vaccinated healthcare workers without p ...[more]

PMID: 38932408

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Project description:IntroductionThe coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the critical importance of understanding protective long-lasting immune responses. This study investigates the epitope specificity, T cell receptor (TCR) usage, and phenotypic changes in SARS-CoV-2-specfic CD8+ and CD4+ T cells over time in convalescent individuals with COVID-19.MethodsPeripheral blood mononuclear cells (PBMCs) were collected from 28 unvaccinated individuals with primary SARS-CoV-2 infection (6 identified as the D614G variant, clade 20C) and analyzed up to 12 months post-symptom onset. Antigen-specific CD8+ and CD4+ T cells were analyzed using flow cytometry and single-cell RNA sequencing (scRNAseq) using specific dextramer and antibody reagents. TCR clonotypes and activation markers were characterized to explore T cell dynamics.ResultsSARS-CoV-2-specific CD8+ T cells exhibited waning frequencies long-term, transitioning from memory-like to a naïve-like state. scRNAseq revealed specificity against both spike and non-spike antigens with increased CD95 and CD127 expression over time, indicating that naïve-like T cells may represent stem cell memory T cells, which are multipotent and self-renewing, likely important for long-lived immunity. TCR clonal expansion was observed mainly in memory T cells, with overlapping TCR beta chain (TRB)-complementary determining region 3 (CDR3) sequences between participants, suggesting shared public TCR epitope-specific repertoires against SARS-CoV-2. Further, unique spike-specific CD4+ T cells with high CD95 and CD127 expression were identified, which may play a crucial role in long-term protection.DiscussionThis study highlights epitope-specificity heterogeneity, with some immunodominant responses, and suggests a potential role for long-lived SARS-CoV-2-specific T cell immunity. Shared TCR repertoires offers insights into cross-reactive and protective T cell clones, providing valuable information for optimizing vaccine strategies against emerging SARS-CoV-2 variants. The findings underscore the critical role of cellular immunity in long-term protection against SARS-CoV-2 and emphasizes the importance of understanding T cell dynamics.

Dataset Information

Assessing Predictive Value of SARS-CoV-2 Epitope-Specific CD8⁺ T-Cell Response in Patients with Severe Symptoms.

Publications

Assessing Predictive Value of SARS-CoV-2 Epitope-Specific CD8<sup>+</sup> T-Cell Response in Patients with Severe Symptoms.

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Dataset Information

Assessing Predictive Value of SARS-CoV-2 Epitope-Specific CD8+ T-Cell Response in Patients with Severe Symptoms.

Publications

Assessing Predictive Value of SARS-CoV-2 Epitope-Specific CD8<sup>+</sup> T-Cell Response in Patients with Severe Symptoms.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Assessing Predictive Value of SARS-CoV-2 Epitope-Specific CD8⁺ T-Cell Response in Patients with Severe Symptoms.