Impaired T-cell and antibody immunity after COVID-19 infection in chronically immunosuppressed transplant recipients

  1. Chethan Ashokkumar
  2. Vinayak Rohan
  3. Alexander H Kroemer
  4. Sohail Rao
  5. George Mazariegos
  6. Brandon W Higgs
  7. Satish Nadig
  8. Jose Almeda
  9. Harmeet Dhani
  10. Khalid Khan
  11. Nada Yazigi
  12. Udeme Ekong
  13. Stuart Kaufman
  14. Monica M Betancourt-Garcia
  15. Kavitha Mukund
  16. Pradeep Sethi
  17. Shikhar Mehrotra
  18. Kyle Soltys
  19. Manasi S Singh
  20. Geoffrey Bond
  21. Ajai Khanna
  22. Mylarappa Ningappa
  23. Brianna Spishock
  24. Elizabeth Sindhi
  25. Neha Atale
  26. Maggie Saunders
  27. Prabhakar Baliga
  28. Thomas Fishbein
  29. Shankar Subramaniam
  30. Rakesh Sindhi

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Abstract

Assessment of T-cell immunity to the COVID-19 coronavirus requires reliable assays and is of great interest, given the uncertain longevity of the antibody response. Some recent reports have used immunodominant spike (S) antigenic peptides and anti-CD28 co-stimulation in varying combinations to assess T-cell immunity to SARS-CoV-2. These assays may cause T-cell hyperstimulation and could overestimate antiviral immunity in chronically immunosuppressed transplant recipients, who are predisposed to infections and vaccination failures. Here, we evaluate CD154-expressing T-cells induced by unselected S antigenic peptides in 204 subjects-103 COVID-19 patients and 101 healthy unexposed subjects. Subjects included 72 transplanted and 130 non-transplanted subjects. S-reactive CD154+T-cells co-express and can thus substitute for IFNγ (n=3). Assay reproducibility in a variety of conditions was acceptable with coefficient of variation of 2-10.6%. S-reactive CD154+T-cell frequencies were a) higher in 42 healthy unexposed transplant recipients who were sampled pre-pandemic, compared with 59 healthy non-transplanted subjects (p=0.02), b) lower in Tr COVID-19 patients compared with healthy transplant patients (p<0.0001), c) lower in Tr patients with severe COVID-19 (p<0.0001), or COVID-19 requiring hospitalization (p<0.05), compared with healthy Tr recipients. S-reactive T-cells were not significantly different between the various COVID-19 disease categories in NT recipients. Among transplant recipients with COVID-19, cytomegalovirus co-infection occurred in 34%; further, CMV-specific T-cells (p<0.001) and incidence of anti-receptor-binding-domain IgG (p=0.011) were lower compared with non-transplanted COVID-19 patients. Healthy unexposed transplant recipients exhibit pre-existing T-cell immunity to SARS-CoV-2. COVID-19 infection leads to impaired T-cell and antibody responses to SARS-CoV-2 and increased risk of CMV co-infection in transplant recipients.

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  1. ScreenIT

    SciScore for 10.1101/2021.05.03.442371: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The culture medium contained fluorochrome-labeled antibody to CD154 (catalog #563886, BD Biosciences, San Jose, CA).
    CD154
    suggested: (BD Biosciences Cat# 563886, RRID:AB_2738466)
    Cells were acquired on the FACS-Canto II flow cytometer with blue, red and violet lasers after addition of fluorochrome labeled antibodies to CD3, CD4, CD8, and CD19 and the viability dye 7-aminoactinomycin-D (catalog #s 340662, 641407, 340692, 341103, 559925, respectively, BD Biosciences, San Jose, CA).
    CD3
    suggested: (Fitzgerald Industries International Cat# 61R-CD3gHUAPCC7, RRID:AB_1283251)
    CD4
    suggested: (BioLegend Cat# 391503, RRID:AB_2721611)
    CD8
    suggested: (BioLegend Cat# 391503, RRID:AB_2721611)
    CD19
    suggested: (BD Biosciences Cat# 341103, RRID:AB_400224)
    Precoated wells were incubated with diluted samples for 2 hours, followed by anti-human IgG (Fab specific) HRP labeled secondary antibody 1:3000 in PBS-T containing 1% milk for 1 hour.
    anti-human IgG
    suggested: None

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 25. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • 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 10.1101/2021.05.03.442371v1 on bioRxiv