Humoral immune response to COVID‐19 vaccination in diabetes is age‐dependent but independent of type of diabetes and glycaemic control: The prospective COVAC‐DM cohort study

  1. Caren Sourij
  2. Norbert J. Tripolt
  3. Faisal Aziz
  4. Felix Aberer
  5. Patrick Forstner
  6. Anna M. Obermayer
  7. Harald Kojzar
  8. Barbara Kleinhappl
  9. Peter N. Pferschy
  10. Julia K. Mader
  11. Gerhard Cvirn
  12. Nandu Goswami
  13. Nadine Wachsmuth
  14. Max L. Eckstein
  15. Alexander Müller
  16. Farah Abbas
  17. Jacqueline Lenz
  18. Michaela Steinberger
  19. Lisa Knoll
  20. Robert Krause
  21. Martin Stradner
  22. Peter Schlenke
  23. Nazanin Sareban
  24. Barbara Prietl
  25. Susanne Kaser
  26. Othmar Moser
  27. Ivo Steinmetz
  28. Harald Sourij
  29. COVAC‐DM study group

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Abstract

Aims

To investigate the seroconversion following first and second COVID‐19 vaccination in people with type 1 and type 2 diabetes in relation to glycaemic control prior to vaccination and to analyse the response in comparison to individuals without diabetes.

Materials and methods

This prospective, multicentre cohort study analysed people with type 1 and type 2 diabetes and a glycated haemoglobin level ≤58 mmol/mol (7.5%) or >58 mmol/mol (7.5%), respectively, and healthy controls. Roche's Elecsys anti‐SARS‐CoV‐2 S immunoassay targeting the receptor‐binding domain was used to quantify anti‐spike protein antibodies 7 to 14 days after the first and 14 to 21 days after the second vaccination.

Results

A total of 86 healthy controls were enrolled in the study, as well as 161 participants with diabetes, of whom 150 (75 with type 1 diabetes and 75 with type 2 diabetes) were eligible for the analysis. After the first vaccination, only 52.7% of participants in the type 1 diabetes group and 48.0% of those in the type 2 diabetes group showed antibody levels above the cut‐off for positivity. Antibody levels after the second vaccination were similar in participants with type 1 diabetes, participants with type 2 diabetes and healthy controls after adjusting for age, sex and multiple testing ( P  > 0.05). Age ( r  = −0.45, P  < 0.001) and glomerular filtration rate ( r  = 0.28, P  = 0.001) were significantly associated with antibody response.

Conclusions

Anti‐SARS‐CoV‐2 S receptor‐binding domain antibody levels after the second vaccination were comparable in healthy controls and in participants with type 1 and type 2 diabetes, irrespective of glycaemic control. Age and renal function correlated significantly with the extent of antibody levels.

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  1. Version published to 10.1111/dom.14643
  2. ScreenIT

    SciScore for 10.1101/2021.11.05.21265849: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: We included adults with type 1 or type 2 diabetes, aged 18-80 years, who were diagnosed with diabetes prior to receiving a COVID-19 vaccine and willing to give written informed consent.
    IRB: The study protocol was approved by the ethics committees of the Medical University of Graz (33-366 ex 20/21) and the Bayerische Landesaerztekammer (Nr. 21031) as well as registered at the European Union Drug Regulation Authorities Clinical Trials registry (EudraCT-Number 2021-001459-15).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    A CE-marked serological test was used according to the manufacturers’ protocols to determine and quantify specific antibodies against SARS-CoV-2.
    SARS-CoV-2
    suggested: None
    According to Roche’s protocol 19 no converting factor is needed to calculate binding antibody units (BAU) per milliliter, which were retrospectively established for harmonization of different assays’ results and are traceable to the WHO international standard for anti-SARS-CoV-2 Ig 20.
    anti-SARS-CoV-2 Ig 20
    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:
    Our study results are in contrast to a recent observational study from Italy (CAVEAT study) that demonstrated a lower antibody response to COVID-19 vaccination in people with type 2 diabetes having an HbA1c above 7.0% (53 mmol/mol). This was accompanied by a reduced CD4pos T cell response measured by tumor necrosis factor-α, interleukin-2 or interferon-γ response 21. In contrast to our study the Italian study did not prospectively prespecify their diabetes cohort and HbA1c cut-off for the analyses according to the given registration record (NCT04746521). Although we predefined a cut-off of 7.5% (58 mmol/mol) to separate well from insufficiently controlled people with diabetes, the mean HbA1c levels observed in our cohort in the two groups (well and insufficiently controlled) are comparable to those in the Italian study. Another difference between the studies is the antibody assays used; while the CAVEAT study used the GenScript SARS-CoV-2 surrogate virus neutralization test we used the Roche Elecsys anti-SARS-CoV-2 S, that was also shown to correlate with neutralizing antibodies 22. Hence, in direct comparison studies, both assays have demonstrated good correlation with each other with an agreement rate of approximately 90% 23. In contrast to our study, Marfella et al. did not include people with type 1 diabetes 21, which is however of clinical relevance as it was unclear if the immune response to COVID-19 vaccination is determined by the underlying pathophysiology of diabete...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04746521CompletedCellular-Mediated Immunity in COVID-19

    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.

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  3. Version published to 10.1101/2021.11.05.21265849v1 on medRxiv