Lower Serologic Response to COVID-19 mRNA Vaccine in Patients With Inflammatory Bowel Diseases Treated With Anti-TNFα

  1. Hadar Edelman-Klapper
  2. Eran Zittan
  3. Ariella Bar-Gil Shitrit
  4. Keren Masha Rabinowitz
  5. Idan Goren
  6. Irit Avni-Biron
  7. Jacob E. Ollech
  8. Lev Lichtenstein
  9. Hagar Banai-Eran
  10. Henit Yanai
  11. Yifat Snir
  12. Maor H. Pauker
  13. Adi Friedenberg
  14. Adva Levy-Barda
  15. Arie Segal
  16. Yelena Broitman
  17. Eran Maoz
  18. Baruch Ovadia
  19. Maya Aharoni Golan
  20. Eyal Shachar
  21. Shomron Ben-Horin
  22. Tsachi-Tsadok Perets
  23. Haim Ben Zvi
  24. Rami Eliakim
  25. Revital Barkan
  26. Sophy Goren
  27. Michal Navon
  28. Noy Krugliak
  29. Michal Werbner
  30. Joel Alter
  31. Moshe Dessau
  32. Meital Gal-Tanamy
  33. Natalia T. Freund
  34. Dani Cohen
  35. Iris Dotan

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Abstract

No abstract available

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  1. Version published to 10.1053/j.gastro.2021.10.029
  2. ScreenIT

    SciScore for 10.1101/2021.08.22.21262263: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All participants signed an informed consent form before any study procedure.
    Sex as a biological variablePatients with past COVID-19 infection proved by SARS-CoV-2 polymerase-chain-reaction test and pregnant women were excluded.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Anti-TNFα drug levels and anti-TNFα antibodies were measured.
    anti-TNFα
    suggested: (Beckman Coulter Cat# IM3279U, RRID:AB_2892136)
    Outcomes: The primary endpoint was seropositivity rate and magnitude of the immune response (levels of binding IgG antibodies to SARS-CoV-2 spike (S) antigen and neutralizing and inhibitory antibodies functionality) following BNT162b2 in patients with IBD with or without anti-TNFα treatment, or HC, at V3.
    binding IgG
    suggested: None
    anti-TNFα treatment ,
    suggested: None
    Anti-TNFα drug and anti-drug antibody levels were assessed for adalimumab (ADA and ADA-Abs) and infliximab (IFX and IFX-Abs) using Lisa-Tracker ELISA in accordance with manufacturer’s instructions (Theradiag, Beaubourg, France).
    anti-drug
    suggested: None
    Anti-S antibody concentrations are expressed as geometric mean concentrations (GMCs) with 95% confidence intervals (CI).
    Anti-S
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Preparation of SARS-CoV-2-spike pseudoparticles and neutralization assay: To generate SARS-CoV-2 pseudo typed vesicular stomatitis virus (VSV) particles, human embryonic kidney (HEK)-293T cells were grown to 70% confluence in Dulbecco’s modified eagle medium (DMEM) supplemented in 10% fetal bovine serum (FBS), 1% L-glutamine, and 1% penicillin streptavidin.
    HEK)-293T
    suggested: None
    HEK-293 cells stably expressing human ACE2 were cultured in DMEM (Biological Industries, Beit Haemek, Israel) supplemented in 10% FBS, 1% L-glutamine, and 1% penicillin streptavidin.
    HEK-293
    suggested: None
    Recombinant DNA
    SentencesResources
    Cells were transfected with pCMV3 plasmid encoding the SARS-CoV-2 S protein with C-terminal, 19 residues truncation (pCMV3-SARS-CoV-2-SΔ19) using polyethylenimine (PEI).
    pCMV3
    suggested: RRID:Addgene_161029)
    pCMV3-SARS-CoV-2-SΔ19
    suggested: None
    Software and Algorithms
    SentencesResources
    SARS-CoV-2 IgG II quantitative testing was performed using the Abbott architect i2000sr platform in accordance with manufacturer’s instructions23.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Statistical Analysis: Data were collected in secured web-based platform (REDCap) and analyzed using SPSS version 27 (IBM, New York, United States).
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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 include difference in gender ratio between IBD and HC groups at baseline, the relatively young age of participants (although this reflects typical IBD populations) and the use of only one vaccine type. Evaluation of vaccine efficacy is limited, as infection rate in Israel during the study period was low. Finally, observation was limited to 4 weeks after the second vaccine. To conclude, our study provides prospective, controlled evidence for the efficacy and safety of the COVID-19 BNT162b2 vaccine in patients with IBD stratified according to therapy. We demonstrate the dynamics of development of functional immune response and the factors causing impairment, specifically anti-TNFα therapy and older age. The lack of correlation with timing of anti-TNFα therapy or drug levels, enables important clinical guidance to patients and their caregivers. As immune response longevity in this group may be limited, vaccine booster dose should be considered. Long(er) term outcomes and the mechanism of decreased immune responses should be evaluated.

    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

    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 10.1101/2021.08.22.21262263v1 on medRxiv