Serological Responses to the First Three Doses of SARS-CoV-2 Vaccination in Inflammatory Bowel Disease: A Prospective Cohort Study

  1. Joshua Quan
  2. Christopher Ma
  3. Remo Panaccione
  4. Lindsay Hracs
  5. Nastaran Sharifi
  6. Michelle Herauf
  7. Ante Markovinović
  8. Stephanie Coward
  9. Joseph W. Windsor
  10. Léa Caplan
  11. Richard J. M. Ingram
  12. Jamil N. Kanji
  13. Graham Tipples
  14. Jessalyn K. Holodinsky
  15. Charles N. Bernstein
  16. Douglas J. Mahoney
  17. Sasha Bernatsky
  18. Eric I. Benchimol
  19. Gilaad G. Kaplan

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Abstract

Individuals with inflammatory bowel disease (IBD) who are immunocompromised may have a reduced serological response to the SARS-CoV-2 vaccine. We investigated serological responses following 1 st , 2 nd , and 3 rd doses of SARS-CoV-2 vaccination in those with IBD.

Methods

A prospective cohort study of persons with IBD ( n = 496) assessed serological response 1–8 weeks after 1 st dose vaccination, 1–8 weeks after 2 nd dose, 8 or more weeks after 2 nd dose, and at least 1 week after 3 rd dose. Seroconversion and geometric mean titer (GMT) with 95% confidence intervals (CI) were assessed for antibodies to the SARS-CoV-2 spike protein. Multivariable linear regression models assessed the adjusted fold change (FC) in antibody levels.

Results

Seroconversion and GMT increased from post-1 st dose to 1–8 weeks post-2 nd dose (81.6%, 1814 AU/mL vs. 98.7%, 9229 AU/mL, p <0.001), decreased after 8 weeks post-2 nd dose (94.9%, 3002 AU/mL, p <0.001), and rebounded post-3 rd dose (99.6%, 14639 AU/mL, p <0.001). Prednisone was the only IBD-related medication associated with diminished antibody response after 3 rd -dose vaccination (FC: 0.07 [95% CI: 0.02, 0.20]). Antibody levels steadily decline following the 2 nd (FC: 0.92 [95% CI: 0.90, 0.94] per week) and 3 rd dose (FC: 0.88 [95% CI: 0.84, 0.92] per week) of the SARS-CoV-2 vaccine.

Conclusion

A three-dose regimen of vaccination to SARS-CoV-2 yields a robust antibody response for those with IBD across all classes of IBD therapies except for prednisone. The decaying antibody levels following the 3 rd dose of the vaccine should be monitored in future studies.

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  1. ScreenIT

    SciScore for 10.1101/2022.03.16.22272440: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All participants provided informed consent, and the study was approved by the University of Calgary’s Conjoint Health Research Ethics Board (REB20-1082).
    IRB: All participants provided informed consent, and the study was approved by the University of Calgary’s Conjoint Health Research Ethics Board (REB20-1082).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Nucleocapsid antibody levels were assessed for serosurveillance of natural infection to SARS-CoV-2 with seroconversion defined as an anti-N antibody concentration of ≥0.7 signal/cutoff index.
    anti-N
    suggested: None
    15 The sensitivity and specificity of the SARS-CoV-2 IgG II Quant assay was 98.1% and 99.6%, respectively.16 Additionally, antibody levels are reported in the World Health Organization binding antibody units (BAU) to allow for comparison across assays.17,18 Serum samples were drawn for assessment of anti-S and anti-N antibodies to SARS-CoV-2 following the 1st, 2nd, and/or 3rd dose of a SARS-CoV-2 vaccine.
    anti-S
    suggested: None
    Mean within-individual differences in antibody concentration were calculated for each subset and stratified by prior infection to SARS-CoV-2.
    SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Antibodies to the RBD of the S1 subunit of the spike protein (anti-S) were assessed using the Abbott Architect SARS-CoV-2 IgG II Quant assay (Abbott, Abbott Park, Illinois, USA).
    Abbott Architect
    suggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Statistics: Statistical analyses were performed using STATA v.
    STATA
    suggested: (Stata, RRID:SCR_012763)
    0 (StataCorp) with a significance threshold of 0.05 and two-sided testing.
    StataCorp
    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 should be considered. Due to a low number of patients with breakthrough COVID-19 infections, we were unable to assess the effectiveness of SARS-CoV-2 vaccination or evaluate whether antibody titres were associated with breakthrough infections. In addition, we did not assess other immune responses to SARS-CoV-2 vaccination, including neutralizing antibodies or T-cell immunity, which may serve as more functional proxies of immune protection over antibody titres.24,29 Due to logistical constraints in data collection during the pandemic, we were unable to obtain samples corresponding to all vaccine doses for all patients, resulting in semi-independent vaccine dose groups. While a community-based recruitment strategy involving all gastroenterologists in the Calgary zone was utilized, population-based sampling was not possible. Further, we did not compare those with IBD to healthy controls; however, a recent serology study performed in the general population within the same jurisdiction and using the same antibody assay demonstrated higher antibodies than our IBD population after 1st and 2nd dose of the vaccine.30 We used the Abbott Architect SARS-CoV-2 IgG II Quant assay, but also converted antibody levels to the World Health Organization BAU/ml (Supplementary Table 4) to support standardization across assays.17,18 Timing and type of vaccination was variable due to changing vaccine availability in Canada. We conducted a sensitivity analysis compari...

    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.

  2. Version published to 10.1101/2022.03.16.22272440v1 on medRxiv