Serological Response to Three, Four and Five Doses of SARS-CoV-2 Vaccine in Kidney Transplant Recipients

  1. Bilgin Osmanodja
  2. Simon Ronicke
  3. Klemens Budde
  4. Annika Jens
  5. Charlotte Hammett
  6. Nadine Koch
  7. Evelyn Seelow
  8. Johannes Waiser
  9. Bianca Zukunft
  10. Friederike Bachmann
  11. Mira Choi
  12. Ulrike Weber
  13. Bettina Eberspächer
  14. Jörg Hofmann
  15. Fritz Grunow
  16. Michael Mikhailov
  17. Lutz Liefeldt
  18. Kai-Uwe Eckardt
  19. Fabian Halleck
  20. Eva Schrezenmeier

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Abstract

Mortality from COVID-19 among kidney transplant recipients (KTR) is high, and their response to three vaccinations against SARS-CoV-2 is strongly impaired. We retrospectively analyzed the serological response of up to five doses of the SARS-CoV-2 vaccine in KTR from 27 December 2020 until 31 December 2021. Particularly, the influence of the different dose adjustment regimens for mycophenolic acid (MPA) on serological response to fourth vaccination was analyzed. In total, 4277 vaccinations against SARS-CoV-2 in 1478 patients were analyzed. Serological response was 19.5% after 1203 basic immunizations, and increased to 29.4%, 55.6%, and 57.5% in response to 603 third, 250 fourth, and 40 fifth vaccinations, resulting in a cumulative response rate of 88.7%. In patients with calcineurin inhibitor and MPA maintenance immunosuppression, pausing MPA and adding 5 mg prednisolone equivalent before the fourth vaccination increased the serological response rate to 75% in comparison to the no dose adjustment (52%) or dose reduction (46%). Belatacept-treated patients had a response rate of 8.7% (4/46) after three vaccinations and 12.5% (3/25) after four vaccinations. Except for belatacept-treated patients, repeated SARS-CoV-2 vaccination of up to five times effectively induces serological response in kidney transplant recipients. It can be enhanced by pausing MPA at the time of vaccination.

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  1. Version published to 10.3390/jcm11092565
  2. ScreenIT

    SciScore for 10.1101/2022.03.23.22270017: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All patients provided written and informed consent into off-label use for vaccine doses four and five.
    IRB: The ethics committee of Charité – Universitätsmedizin Berlin approved this study (EA1/030/22).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    We used an anti-SARS-CoV-2 enzyme-linked immunosorbent assays (ELISA) for the detection of IgG antibodies against the S1 domain of the SARS-CoV-2 spike (S) protein in serum according to the instructions of the manufacturer (Anti-SARS-CoV-2-ELISA (IgG),
    anti-SARS-CoV-2
    suggested: None
    Anti-SARS-CoV-2-ELISA ( IgG
    suggested: None
    Comparison of mycophenolic acid (MPA) dose adjustment regimens: Due to the important role of MPA with regard to the response to immunization, different approaches for MPA dose adjustment before fourth SARS-CoV-2 immunization were followed at our institution according to the patients’ individual risk factors such as previous rejection episodes, anti-HLA antibodies, previous response to SARS-CoV-2 immunization, and based on the physicians’ and patients’ shared-decision making.
    anti-HLA
    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:
    Limitations arise from the study’s retrospective design. While serological measurements were routinely performed at our institution, there was a considerable number of vaccinations that were not preceded or followed by serological measurements (Figure 1). Consequently, a patient-based approach was discarded in favor of a vaccination-based evaluation, introducing a risk of selection bias. However, our approach allows to account for the incompleteness of the data and to optimize the number of examinable vaccinations. Intraindividual changes of titers between or after vaccinations were not represented with this approach, whereas protection after vaccination will evolve and might effectively decrease over time. With regard to the effects of MPA dose adjustment around the fourth vaccination, the retrospective assignment to treatment groups limits the validity of the results because groups were not fully matched and confounding factors could have influenced the group assignment. Nevertheless, comparison of the major potential influencing factors was provided to account for these risks. Finally, while this study focuses on vaccine-induced humoral response as correlate of protection from disease, there are other contributors to immunity such as T cell response that may influence the degree of protection. In conclusion, repeated vaccination against SARS-CoV-2 of up to five times effectively induces humoral serological response in kidney transplant recipients. Serological response can ...

    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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  3. Version published to 10.1101/2022.03.23.22270017v1 on medRxiv