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

Overview

Journal Vaccines (Basel)

Date 2024 Jun 27

PMID 38932408

Authors

Cristina Martin-Martin

Estefania Salgado Del Riego

Jose R Vidal Castineira

Maria Soledad Zapico-Gonzalez

Mercedes Rodriguez-Perez

Viviana Corte-Iglesias

Maria Laura Saiz

Paula Diaz-Bulnes

Dolores Escudero

Beatriz Suarez-Alvarez

Carlos Lopez-Larrea

Affiliations

Soon will be listed here.

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.

References

Saini S, Hersby D, Tamhane T, Povlsen H, Amaya Hernandez S, Nielsen M . SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 T cell activation in COVID-19 patients. Sci Immunol. 2021; 6(58). PMC: 8139428. DOI: 10.1126/sciimmunol.abf7550. View

Bert N, Tan A, Kunasegaran K, Tham C, Hafezi M, Chia A . SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature. 2020; 584(7821):457-462. DOI: 10.1038/s41586-020-2550-z. View

Grifoni A, Weiskopf D, Ramirez S, Mateus J, Dan J, Rydyznski Moderbacher C . Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell. 2020; 181(7):1489-1501.e15. PMC: 7237901. DOI: 10.1016/j.cell.2020.05.015. View

Roltgen K, Nielsen S, Silva O, Younes S, Zaslavsky M, Costales C . Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination. Cell. 2022; 185(6):1025-1040.e14. PMC: 8786601. DOI: 10.1016/j.cell.2022.01.018. View

Long Q, Liu B, Deng H, Wu G, Deng K, Chen Y . Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020; 26(6):845-848. DOI: 10.1038/s41591-020-0897-1. View

Shahbaz S, Xu L, Sligl W, Osman M, Bozorgmehr N, Mashhouri S . The Quality of SARS-CoV-2-Specific T Cell Functions Differs in Patients with Mild/Moderate versus Severe Disease, and T Cells Expressing Coinhibitory Receptors Are Highly Activated. J Immunol. 2021; 207(4):1099-1111. DOI: 10.4049/jimmunol.2100446. View

Ruan Q, Yang K, Wang W, Jiang L, Song J . Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020; 46(5):846-848. PMC: 7080116. DOI: 10.1007/s00134-020-05991-x. View

Phetsouphanh C, Zaunders J, Kelleher A . Detecting Antigen-Specific T Cell Responses: From Bulk Populations to Single Cells. Int J Mol Sci. 2015; 16(8):18878-93. PMC: 4581277. DOI: 10.3390/ijms160818878. View

Sureshchandra S, Lewis S, Doratt B, Jankeel A, Ibraim I, Messaoudi I . Single-cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine. JCI Insight. 2021; 6(24). PMC: 8783687. DOI: 10.1172/jci.insight.153201. View

10.

Del Riego E, Saiz M, Corte-Iglesias V, Leoz Gordillo B, Martin-Martin C, Rodriguez-Perez M . Divergent SARS-CoV-2-specific T cell responses in intensive care unit workers following mRNA COVID-19 vaccination. Front Immunol. 2022; 13:942192. PMC: 9582956. DOI: 10.3389/fimmu.2022.942192. View

11.

Takahashi T, Ellingson M, Wong P, Israelow B, Lucas C, Klein J . Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature. 2020; 588(7837):315-320. PMC: 7725931. DOI: 10.1038/s41586-020-2700-3. View

12.

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y . Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020; 395(10223):507-513. PMC: 7135076. DOI: 10.1016/S0140-6736(20)30211-7. View

13.

Neidleman J, Luo X, George A, McGregor M, Yang J, Yun C . Distinctive features of SARS-CoV-2-specific T cells predict recovery from severe COVID-19. Cell Rep. 2021; 36(3):109414. PMC: 8238659. DOI: 10.1016/j.celrep.2021.109414. View

14.

Sekine T, Perez-Potti A, Rivera-Ballesteros O, Stralin K, Gorin J, Olsson A . Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19. Cell. 2020; 183(1):158-168.e14. PMC: 7427556. DOI: 10.1016/j.cell.2020.08.017. View

15.

Kuhlmann C, Mayer C, Claassen M, Maponga T, Burgers W, Keeton R . Breakthrough infections with SARS-CoV-2 omicron despite mRNA vaccine booster dose. Lancet. 2022; 399(10325):625-626. PMC: 8765759. DOI: 10.1016/S0140-6736(22)00090-3. View

16.

Rha M, Shin E . Activation or exhaustion of CD8 T cells in patients with COVID-19. Cell Mol Immunol. 2021; 18(10):2325-2333. PMC: 8374113. DOI: 10.1038/s41423-021-00750-4. View

17.

Kundura L, Cezar R, Andre S, Campos-Mora M, Lozano C, Vincent T . Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID. Front Immunol. 2022; 13:1029006. PMC: 9630742. DOI: 10.3389/fimmu.2022.1029006. View

18.

Yang G, Wang J, Sun P, Qin J, Yang X, Chen D . SARS-CoV-2 epitope-specific T cells: Immunity response feature, TCR repertoire characteristics and cross-reactivity. Front Immunol. 2023; 14:1146196. PMC: 10036809. DOI: 10.3389/fimmu.2023.1146196. View

19.

Alwan N . Track COVID-19 sickness, not just positive tests and deaths. Nature. 2020; 584(7820):170. DOI: 10.1038/d41586-020-02335-z. View

20.

Ji N, Forsthuber T . ELISPOT Techniques. Methods Mol Biol. 2014; 1304:63-71. DOI: 10.1007/7651_2014_111. View