COVID‐19 vaccine failure in chronic lymphocytic leukaemia and monoclonal B‐lymphocytosis; humoural and cellular immunity

  1. Yandong Shen
  2. Jane A. Freeman
  3. Juliette Holland
  4. Ann Solterbeck
  5. Kartik Naidu
  6. Asha Soosapilla
  7. Paul Downe
  8. Catherine Tang
  9. Ian Kerridge
  10. Lucinda Wallman
  11. Nenna Van Bilsen
  12. Vanessa Milogiannakis
  13. Anouschka Akerman
  14. Gabriela Martins Costa Gomes
  15. Kerrie Sandgren
  16. Anthony L. Cunningham
  17. Stuart Turville
  18. Stephen P. Mulligan

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

Chronic lymphocytic leukaemia (CLL) is associated with immunocompromise and high risk of severe COVID‐19 disease and mortality. Monoclonal B‐cell lymphocytosis (MBL) patients also have immune impairment. We evaluated humoural and cellular immune responses in 181 patients with CLL (160) and MBL (21) to correlate failed seroconversion [<50 AU/ml SARS‐CoV‐2 II IgG assay, antibody to spike protein; Abbott Diagnostics)] following each of two vaccine doses with clinical and laboratory parameters. Following first and second doses, 79.2% then 45% of CLL, and 50% then 9.5% of MBL patients respectively remained seronegative. There was significant association between post dose two antibody level with pre‐vaccination reduced IgM ( p  < 0.0001), IgG2 ( p  < 0.035), and IgG3 ( p  < 0.046), and CLL therapy within 12 months ( p  < 0.001) in univariate analysis. By multivariate analysis, reduced IgM ( p  < 0.0002) and active therapy ( p  < 0.0002) retained significance. Anti‐spike protein levels varied widely and were lower in CLL than MBL patients, and both lower than in normal donors. Neutralisation activity showed anti‐spike levels <1000 AU/ml were usually negative for both an early viral clade and the contemporary Delta variant and 72.9% of CLL and 53.3% of MBL failed to reach levels ≥1000 AU/ml. In a representative sample, ~80% had normal T‐cell responses. Failed seroconversion occurred in 36.6% of treatment‐naïve patients, in 78.1% on therapy, and in 85.7% on ibrutinib.

Article activity feed

  1. Version published to 10.1111/bjh.18014
  2. ScreenIT

    SciScore for 10.1101/2021.10.28.21265549: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study was approved by the Northern Sydney Local Health District Human Research Ethics Committee (approval number: LNR/14/HAWKE/181) and all patients provided an informed consent.
    Consent: The study was approved by the Northern Sydney Local Health District Human Research Ethics Committee (approval number: LNR/14/HAWKE/181) and all patients provided an informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    24 Blood samples (FBC, biochemistry, immunoglobulins G, A, M, IgG subclasses, phenotyping and COVID-19 antibody levels) were taken pre-vaccination, then following vaccination doses 1 (D1) and 2 (D2) approximately 2 to 4 weeks following each dose.
    COVID-19
    suggested: None
    D1
    suggested: None
    Software and Algorithms
    SentencesResources
    SARS-CoV-2 IgG II Quant assay® (Abbott Diagnostics) was performed in accordance with the manufacturer’s instructions.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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 10.1101/2021.10.28.21265549v1 on medRxiv