##common.pageHeaderLogo.altText##

Original article

Vol. 151 No. 3738 (2021)

Highly specific and reliable in vitro diagnostic analysis of memory T and B lymphocytes in a Swiss cohort of COVID-19 patients

  • Lester Thoo
  • Pierre I. Gumowski
  • Kevin Kammermann
  • Swelia Nussli
  • Benno Grabscheid
  • Oliver Hausmann
  • Ulrika Axius
  • Werner J. Pichler
  • Daniel Yerly
Cite this as:
Swiss Med Wkly. 2021;151:w30005
Published
13.09.2021

Summary

The SARS-CoV-2 pandemic has claimed many lives and disrupted the quality of life of most individuals. Diagnostic tests not only serve to confirm past exposure but can provide information crucial for guiding healthcare options for patients. Current diagnostic tests for the presence of the SARS-CoV-2 virus or anti-spike protein antibodies do not address the question whether longer lasting cellular immunity is mounted in most individuals. Using an activation marker flow cytometric immunoassay (SARS-CoV-2 lymphocytes analysis), we showed that both CD4+/CD8+ T cell and B cell activation differ between naïve and infected individuals up to 11 months after infection. On the basis of the specificity of this diagnostic tool for detecting both SARS-CoV-2-experienced T and B cells, we propose that this assay could benefit immunocompromised individuals who are unable to mount sustained antibody responses, by determining cellular immunity as possible partial protection, and for studying immune correlates of protection – thereby increasing knowledge of COVID-19 in a wider range of patient groups.

References

  1. Weissleder R, Lee H, Ko J, Pittet MJ. COVID-19 diagnostics in context. Sci Transl Med. 2020 Jun;12(546):1–7. https://doi.org/10.1126/scitranslmed.abc1931
  2. Vandenberg O, Martiny D, Rochas O, van Belkum A, Kozlakidis Z. Considerations for diagnostic COVID-19 tests. Nat Rev Microbiol. 2020; https://doi.org/10.1038/s41579-020-00461-z
  3. Baden, L. R. et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N. Engl. J. Med. NEJMoa2035389 (2020) doi:https://doi.org/10.1056/NEJMoa2035389.
  4. Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al.; C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 Dec;383(27):2603–15. https://doi.org/10.1056/NEJMoa2034577
  5. Sahin U, Muik A, Derhovanessian E, Vogler I, Kranz LM, Vormehr M, et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature. 2020 Oct;586(7830):594–9. https://doi.org/10.1038/s41586-020-2814-7
  6. Corbett KS, Flynn B, Foulds KE, Francica JR, Boyoglu-Barnum S, Werner AP, et al. Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates. N Engl J Med. 2020 Oct;383(16):1544–55. https://doi.org/10.1056/NEJMoa2024671
  7. Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al.; mRNA-1273 Study Group. An mRNA Vaccine against SARS-CoV-2 — preliminary Report. N Engl J Med. 2020 Nov;383(20):1920–31. https://doi.org/10.1056/NEJMoa2022483
  8. Ferretti AP, Kula T, Wang Y, Nguyen DM, Weinheimer A, Dunlap GS, et al. Unbiased Screens Show CD8+ T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein. Immunity. 2020 Nov;53(5):1095–1107.e3. https://doi.org/10.1016/j.immuni.2020.10.006
  9. Farber DL, Yudanin NA, Restifo NP. Human memory T cells: generation, compartmentalization and homeostasis. Nat Rev Immunol. 2014 Jan;14(1):24–35. https://doi.org/10.1038/nri3567
  10. Reynolds CJ, Swadling L, Gibbons JM, Pade C, Jensen MP, Diniz MO, et al.; COVIDsortium investigators; COVIDsortium immune correlates network. Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection. Sci Immunol. 2020 Dec;5(54):eabf3698. https://doi.org/10.1126/sciimmunol.abf3698
  11. Vabret N, Britton GJ, Gruber C, Hegde S, Kim J, Kuksin M, et al.; Sinai Immunology Review Project. Immunology of COVID-19: Current State of the Science. Immunity. 2020 Jun;52(6):910–41. https://doi.org/10.1016/j.immuni.2020.05.002
  12. Mateus, J. et al. Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science (80-.). 370, 89–94 (2020).
  13. Dan JM, Lindestam Arlehamn CS, Weiskopf D, da Silva Antunes R, Havenar-Daughton C, Reiss SM, et al. A Cytokine-Independent Approach To Identify Antigen-Specific Human Germinal Center T Follicular Helper Cells and Rare Antigen-Specific CD4+ T Cells in Blood. J Immunol. 2016 Aug;197(3):983–93. https://doi.org/10.4049/jimmunol.1600318
  14. Reiss S, Baxter AE, Cirelli KM, Dan JM, Morou A, Daigneault A, et al. Comparative analysis of activation induced marker (AIM) assays for sensitive identification of antigen-specific CD4 T cells. PLoS One. 2017 Oct;12(10):e0186998. https://doi.org/10.1371/journal.pone.0186998
  15. Ni L, Ye F, Cheng ML, Feng Y, Deng YQ, Zhao H, et al. Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals. Immunity. 2020 Jun;52(6):971–977.e3. https://doi.org/10.1016/j.immuni.2020.04.023
  16. Todryk SM. T cell memory to vaccination. Vaccines (Basel). 2018 Dec;6(4):1–6. https://doi.org/10.3390/vaccines6040084
  17. Martin MD, Badovinac VP. Defining memory CD8 T cell. Front Immunol. 2018 Nov;9:2692. https://doi.org/10.3389/fimmu.2018.02692
  18. Flaxman A, Ewer KJ. Methods for measuring T-cell memory to vaccination: from mouse to man. Vaccines (Basel). 2018 Jul;6(3):6. https://doi.org/10.3390/vaccines6030043
  19. Macallan DC, Borghans JA, Asquith B. Human T cell memory: A dynamic view. Vaccines (Basel). 2017 Feb;5(1):5. https://doi.org/10.3390/vaccines5010005
  20. Tarke A, Sidney J, Kidd CK, Dan JM, Ramirez SI, Yu ED, et al. Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases. Cell Rep Med. 2021 Feb;2(2):100204. https://doi.org/10.1016/j.xcrm.2021.100204
  21. Papp KA, Haraoui B, Kumar D, Marshall JK, Bissonnette R, Bitton A, et al. Vaccination Guidelines for Patients With Immune-Mediated Disorders on Immunosuppressive Therapies. J Cutan Med Surg. 2019 Jan/Feb;23(1):50–74. https://doi.org/10.1177/1203475418811335
  22. Sudre CH, Murray B, Varsavsky T, Graham MS, Penfold RS, Bowyer RC, et al. Attributes and predictors of long COVID. Nat Med. 2021 Apr;27(4):626–31. https://doi.org/10.1038/s41591-021-01292-y
  23. Alwan NA. Track post-COVID sickness, not just cases and deaths. Nature. 2020;584(7820):170–170. https://doi.org/10.1038/d41586-020-02335-z