The Safety and Immunogenicity of the BNT162b2 mRNA COVID-19 Vaccine in Japanese Patients after Allogeneic Stem Cell Transplantation

  1. Marika Watanabe
  2. Kimikazu Yakushijin
  3. Yohei Funakoshi
  4. Goh Ohji
  5. Wataru Hojo
  6. Hironori Sakai
  7. Miki Saeki
  8. Yuri Hirakawa
  9. Sakuya Matsumoto
  10. Rina Sakai
  11. Shigeki Nagao
  12. Akihito Kitao
  13. Yoshiharu Miyata
  14. Taiji Koyama
  15. Yasuyuki Saito
  16. Shinichiro Kawamoto
  17. Mitsuhiro Ito
  18. Tohru Murayama
  19. Hiroshi Matsuoka
  20. Hironobu Minami

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Abstract

Patients who have undergone hematopoietic stem cell transplantation (HSCT) for hematological disease experience high mortality when infected by coronavirus disease 2019 (COVID-19). However, the safety and efficacy of the COVID-19 vaccine in HSCT patients remain to be investigated. We prospectively evaluated the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine (Pfizer BioNTech) in 25 Japanese allogeneic HSCT patients in comparison with 19 healthy volunteers. While anti-S1 antibody titers in almost all healthy volunteers after the second dose were higher than the cut-off value reported previously, levels in HSCT patients after the second dose were diverse. Nineteen patients (76%) had seroconversion of anti-S1 IgG. The median optical density of antibody levels in HSCT patients with low IgG levels (<600 mg/dL), steroid treatment, or low lymphocytes (<1000/μL) was significantly lower than that in the other HSCT patients. There were no serious adverse events (>Grade 3) and no new development or exacerbation of graft-versus-host disease after vaccination. We concluded that the BNT162b2 mRNA vaccine is safe and effective in Japanese allogeneic HSCT patients.

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  1. Version published to 10.3390/vaccines10020158
  2. ScreenIT

    SciScore for 10.1101/2021.12.28.21268477: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All patients who were at least three months after transplantation and who gave written informed consent to participate in the study between March 2021 and August 2021 were included.
    IRB: This study was approved by the Kobe University Hospital Ethics Committee (No. B2056714) and was conducted in accordance with the Declaration of Helsinki.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibody titers against S1 were measured using the QuaResearch COVID-19 Human IgM IgG ELISA kit (Spike Protein-S1) (Cellspect, Inc., RCOEL961S1, Iwate, Japan).
    S1
    suggested: None
    Based on the previous report11, the optimal optical density (O.D.) cut-off value of anti-S1 IgG antibody for seroconversion was determined as 0.26.
    anti-S1 IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    All statistical tests were two-sided, and were performed using STATA (version 17.0; Stata Corp, TX) and EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria) 12 at P < 0.05 as level of significance.
    STATA
    suggested: (Stata, RRID:SCR_012763)

    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:
    Several limitations of our study warrant mention. First, the cohort was too small to allow multivariate analyses. Second, as the disease status in our cohort was stable, safety and immunogenicity in patients with relapse or receiving high-dose steroids for acute or chronic GVHD are uncertain. Third, the precise titer border line providing clinical protection for COVID-19 remains unclear. However, we believe that many Japanese HSCT patients would have gained sufficient immunity, as did the healthy volunteers. To our knowledge, this study is the first prospective observational study on the safety and immunogenicity of BNT162b2 in Japanese patients who received allogeneic HSCT. Most HSCT patients obtained certain immunogenicity without severe adverse events, whereas patients taking steroids or with low lymphocyte counts did not yield sufficient antibody titers. Further investigation to confirm our findings are needed, and long-term monitoring of antibody levels is warranted.

    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 10.1101/2021.12.28.21268477v1 on medRxiv