Immunogenicity of COVID-19 Tozinameran Vaccination in Patients on Chronic Dialysis

  1. Eva Schrezenmeier
  2. Leon Bergfeld
  3. David Hillus
  4. Joerg-Detlev Lippert
  5. Ulrike Weber
  6. Pinkus Tober-Lau
  7. Irmgard Landgraf
  8. Tatjana Schwarz
  9. Kai Kappert
  10. Ana-Luisa Stefanski
  11. Arne Sattler
  12. Katja Kotsch
  13. Thomas Dörner
  14. Leif Erik Sander
  15. Klemens Budde
  16. Fabian Halleck
  17. Florian Kurth
  18. Victor Max Corman
  19. Mira Choi

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Abstract

Patients with kidney failure have notoriously weak responses to common vaccines. Thus, immunogenicity of novel SARS-CoV-2 vaccines might be impaired in this group. To determine immunogenicity of SARS-CoV-2 vaccination in patients with chronic dialysis, we analyzed the humoral and T-cell response after two doses of mRNA vaccine Tozinameran (BNT162b2 BioNTech/Pfizer). This observational study included 43 patients on dialysis before vaccination with two doses of Tozinameran 21 days apart. Overall, 36 patients completed the observation period until three weeks after the second dose and 32 patients were further analyzed at week 10. Serum samples were analyzed by SARS-CoV-2 specific IgG and IgA antibodies ~1, ~3–4 and ~10 weeks after the second vaccination. In addition, SARS-CoV-2-specific T-cell responses were assessed at ~3–4 weeks by an interferon-gamma release assay (IGRA). Antibody and T cell outcomes at this timepoint were compared to a group of 44 elderly patients not on dialysis, after immunization with Tozinameran. Median age of patients on chronic dialysis was 74.0 years (IQR 66.0, 82.0). The proportion of males was higher (69.4%) than females. Only 20/36 patients (55.6%, 95%CI: 38.29–71.67) developed SARS-CoV-2-IgG antibodies at the first sampling, whereas 32/36 patients (88.9%, 95%CI: 73.00–96.38) demonstrated IgG detection at the second sampling. In a longitudinal follow-up at ~10 weeks after the second dose, the proportion of dialysis patients reactive for anti-SARS-CoV-2-IgG decreased to 27/32 (84.37%, 95%CI: 66.46–94.10) The proportion of anti-SARS-CoV-2 S1 IgA decreased from 33/36 (91.67%; 95%CI: 76.41–97.82) at weeks 3–4 down to 19/32 (59.38; 95%CI: 40.79–75.78). Compared to a cohort of vaccinees with similar age but not on chronic dialysis seroconversion rates and antibody titers were significantly lower. SARS-CoV-2-specific T-cell responses 3 weeks after second vaccination were detected in 21/31 vaccinated dialysis patients (67.7%, 95%CI: 48.53–82.68) compared to 42/44 (93.3%, 95%CI: 76.49–98.84) in controls of similar age. Patients on dialysis demonstrate a delayed, but robust immune response three to four weeks after the second dose, which indicates effective vaccination of this vulnerable group. However, the lower immunogenicity of Tozinameran in these patients needs further attention to develop potential countermeasures such as an additional booster vaccination.

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  1. Version published to 10.3389/fimmu.2021.690698
  2. ScreenIT

    SciScore for 10.1101/2021.03.31.21254683: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serum samples of vaccinated dialysis patients (Table 1, Supplement for cohort details) were analyzed for anti-SARS-CoV-2 antibodies ∼1 and ∼3-4 weeks after the second dose by anti-SARS-CoV-2-S1 IgG/IgA ELISA (Euroimmun, Lübeck, Germany).
    anti-SARS-CoV-2
    suggested: None
    anti-SARS-CoV-2-S1 IgG/IgA
    suggested: None
    Potential neutralizing antibodies were tested by a surrogate virus neutralization test (sNT, cPass, Medac, Wedel, Germany) [6].
    sNT, cPass, Medac, Wedel, Germany) [6
    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: We detected the following sentences addressing limitations in the study:
    Of note, in our dialysis cohort, three patients developed COVID-19 after first vaccination, of whom one died of COVID-19, underlining the need for ongoing non-pharmaceutical intervention after vaccinations, especially in these patients Limitations of our studies include the small cohort size and the use of only one mRNA vaccine. Therefore, further risk factors contributing to a negative immune response remain to be defined. Prospective studies with other vaccines against COVID-19, e.g., viral vector–based vaccines, will help to elucidate the efficacy of different vaccines in these patients. Moreover, antibody titer persistence in patients on dialysis might differ from otherwise healthy persons, which should be addressed in longitudinal observations.

    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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.03.31.21254683v1 on medRxiv