Durability of SARS-CoV-2-specific T cell responses at 12-months post-infection

  1. Zhongyan Lu
  2. Eric D. Laing
  3. Jarina Pena-Damata
  4. Katherine Pohida
  5. Marana S. Tso
  6. Emily C. Samuels
  7. Nusrat J. Epsi
  8. Batsukh Dorjbal
  9. Camille Lake
  10. Stephanie A. Richard
  11. Ryan C. Maves
  12. David A. Lindholm
  13. Julia Rozman
  14. Caroline English
  15. Nikhil Huprikar
  16. Katrin Mende
  17. Rhonda E. Colombo
  18. Christopher J. Colombo
  19. Christopher C. Broder
  20. Anuradha Ganesan
  21. Charlotte A. Lanteri
  22. Brian K. Agan
  23. David Tribble
  24. Mark P. Simons
  25. Clifton L. Dalgard
  26. Paul W. Blair
  27. Josh Chenoweth
  28. Simon D. Pollett
  29. Andrew L. Snow
  30. Timothy H. Burgess
  31. Allison M.W. Malloy
  32. the EPICC COVID-19 Cohort Study Group

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Abstract

Background

Characterizing the longevity and quality of cellular immune responses to SARS-CoV-2 is critical to understanding immunologic approaches to protection against COVID-19. Prior studies suggest SARS-CoV-2-specific T cells are present in peripheral blood 10 months after infection. Further analysis of the function, durability, and diversity of the cellular response long after natural infection, over a wider range of ages and disease phenotypes, is needed to further identify preventative and therapeutic interventions.

Methods

We identified participants in our multi-site longitudinal, prospective cohort study 12-months post SARS-CoV-2 infection representing a range of disease severity. We investigated the function, phenotypes, and frequency of T cells specific for SARS-CoV-2 using intracellular cytokine staining and spectral flow cytometry. In parallel, the magnitude of SARS-CoV-2-specific antibodies was compared.

Results

SARS-CoV-2-specific antibodies and T cells were detected at 12-months post-infection. Severity of acute illness was associated with higher frequencies of SARS-CoV-2-specific CD4 T cells and antibodies at 12-months. In contrast, polyfunctional and cytotoxic T cells responsive to SARS-CoV-2 were identified in participants over a wide spectrum of disease severity.

Conclusions

Our data show that SARS-CoV-2 infection induces polyfunctional memory T cells detectable at 12-months post-infection, with higher frequency noted in those who originally experienced severe disease.

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  1. ScreenIT

    SciScore for 10.1101/2021.08.11.455984: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The protocol was approved by the Uniformed Services University Institutional Review Board (IDCRP-085), and all subjects or their legally authorized representative provided informed consent to participate.
    Consent: The protocol was approved by the Uniformed Services University Institutional Review Board (IDCRP-085), and all subjects or their legally authorized representative provided informed consent to participate.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Ten minutes after addition of the peptide pools, CD107a antibody (BioLegend, CA) was added.
    CD107a
    suggested: None
    Software and Algorithms
    SentencesResources
    All cytometric data were analyzed using FlowJo software (BD Biosciences, CA).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    A final wash was performed after 45 minutes of incubation, and antigen-antibody complexes were analyzed on BioPlex 200 multiplexing systems (Bio-Rad) for IgG binding, and median fluorescence intensity (MFI) values were reported for specificity to SARS-CoV-2 S and N protein.
    BioPlex
    suggested: (BioPlex, RRID:SCR_016144)
    Statistical analysis: Data were analyzed using GraphPad Prism 9 (GraphPad Software Inc, CA).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations to our study include the challenge of obtaining biological samples at 12-months PSO prior to vaccination in our MHS cohort, which had timely and reliable access to vaccines. Fifty percent of individuals in our cohort were vaccinated prior to a 12-month draw (Table 1). For these individuals we did not include their S-specific T cell or antibody responses, but did include their N, M and E humoral or cellular responses since these are not components of the mRNA-based vaccines (the vaccines primarily available to our study population). A strength of our cohort is that study participants are followed within the MHS and their epidemiologic, clinical and COVID-19 testing records, and vaccination status are maintained primarily from electronic health record. In addition, sera were analyzed longitudinally to avoid re-infected participants for 12-months T cell analysis. In summary, our data show that both SARS-CoV-2 humoral and cellular responses are measurable 12-months PSO in individuals across a spectrum of disease phenotypes. The magnitude of the CD4 T cell and antibody responses more closely correlated with acute disease severity. Importantly, the memory phenotype and polyfunctional response of the SARS-CoV-2 specific T cells did not differ by disease severity. The breadth of T cell epitope recognition by these memory T cells may provide more durable protection against emerging SARS-CoV-2 variants.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  2. Version published to 10.1101/2021.08.11.455984v1 on bioRxiv