Long‐term humoral immunity decline in hemodialysis patients following severe acute respiratory syndrome coronavirus 2 vaccination: A cohort study

  1. Eibhlin Goggins
  2. Binu Sharma
  3. Jennie Z. Ma
  4. Jitendra Gautam
  5. Brendan Bowman

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Abstract

Background and Aims

Dialysis patients are extremely vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection with high rates of hospitalization and mortality rates. In January 2021, the University of Virginia Dialysis Program initiated a program‐wide vaccination campaign to administer the Pfizer BioNTech messenger RNA SARS‐CoV‐2 (BNT162b2) vaccine. The aim of this study was to characterize the long‐term time‐dependent decline in humoral immunity in hemodialysis patients.

Methods

A prospective cohort study measuring serial monthly semiquantitative IgG antibody levels to the SARS‐CoV‐2 spike protein receptor binding domain in fully vaccinated in‐center hemodialysis patients. Samples were collected monthly and tested for anti‐SARS‐CoV‐2 antibodies against the anti‐spike S1 domain for 2–6 months post full vaccination. Results were presented as internationally harmonized binding antibody units (BAU/ml). To analyze the change in antibody levels over time, a linear mixed model with random intercept and random slope was used for longitudinal antibody levels. A multivariable model was used to estimate the slope of antibody levels by adjusting for selected patient characteristics. Based on the estimated intercepts and slopes for each subject from the unadjusted model, 10‐month antibody levels were projected.

Results

The mean baseline antibody level was 647.59 BAU/ml and 87.88% (29/33) of patients were considered qualitatively positive. Two patients were negative at baseline and an additional two had borderline results. Patient antibody levels declined at an adjusted average rate of 31% per month. At 6 months postvaccination, 40% of patients remaining in the cohort possessed either negative or borderline IgG antibody levels. Projecting future antibody levels suggests that 65% of the cohort will progress to borderline or negative antibody levels at 10 months post full vaccination.

Conclusion

The long‐term vaccine response following vaccination with the BNT162b2 in hemodialysis patients was characterized. Our data add to the limited pool of data in this patient population and emphasize the critical need for vaccine boosters.

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  1. Version published to 10.1002/hsr2.854
  2. Version published to 10.1101/2021.12.01.21265957v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.12.01.21265957: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    RandomizationTo analyze the change in antibody levels over time, a linear mixed model with random slope and random intercept was used for longitudinal antibody levels to account for patient-specific changes and variation over the entire follow-up period.
    Blindingnot detected.
    Power AnalysisSample size was based on pragmatic considerations of sample volume processing capability.

    Table 2: Resources

    Antibodies
    SentencesResources
    All monthly EDTA plasma samples were tested for anti SARS-CoV-2 antibodies against anti-spike S1 domain using the commercially available Anti-SARS-CoV-2 QuantiVac ELISA (IgG) from Euroimmun (EUROIMMUN US, Inc., 1 Bloomfield Ave, Mountain Lakes, NJ, USA).
    anti SARS-CoV-2 antibodies against anti-spike S1
    suggested: None
    Anti-SARS-CoV-2 QuantiVac ELISA ( IgG
    suggested: None
    2 Total Ab assay (Bio-Rad Laboratories, Inc., Hercules, CA, USA) was used for qualitative detection of total antibodies (IgM/IgG/IgA) to SARS-CoV-2 nucleocapsid protein.
    SARS-CoV-2 nucleocapsid protein.
    suggested: None
    Univariate models were used to test the association of the trajectories of antibody levels with patient characteristics including prior COVID-19 infection, immune suppression, gender, age, race, Charlson Comorbidity Index (CCI), and access type.
    CCI
    suggested: None
    Software and Algorithms
    SentencesResources
    2 Total Ab assay (Bio-Rad Laboratories, Inc., Hercules, CA, USA) was used for qualitative detection of total antibodies (IgM/IgG/IgA) to SARS-CoV-2 nucleocapsid protein.
    Bio-Rad Laboratories
    suggested: (Bio-Rad Laboratories, RRID:SCR_008426)

    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 has limitations which may limit generalizability. Notably, we had a small sample size and a non-representative sample. Our population was majority African American and had a large proportion of patients considered immune suppressed. Because we obtained early access to vaccine relative to the U.S. dialysis population, we were not able to obtain pre-vaccination or peak antibody levels at the typical 14 days after second immunization. We also reported solely on antibody response to BNT162b2 and not other COVID-19 vaccines. Lastly, although data has described a correlation between spike protein IgG levels and infection vulnerability, protective antibody levels have not been clearly determined. Thus, results should be cautiously interpreted. Strengths of our study include the long term nature, diverse clinical background of our cohort, and the relatively complete data set allowing the development of antibody level trajectory curves. In conclusion, we present long term IgG spike protein antibody decline rates in response to vaccination with BNT162b2. These results suggest that dialysis patients vaccinated with BNT162b2 and without prior infection may benefit from receipt of a booster dose.

    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.
    • Thank you for including a protocol registration statement.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  4. Version published to 10.1101/2021.12.01.21265957v1 on medRxiv