Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar;175(3):371-378.
doi: 10.7326/M21-4176. Epub 2021 Dec 14.

SARS-CoV-2 Vaccine Antibody Response and Breakthrough Infection in Patients Receiving Dialysis

Shuchi Anand  1 , Maria E Montez-Rath  1 , Jialin Han  1 , Pablo Garcia  1 , LinaCel Cadden  2 , Patti Hunsader  2 , Curt Morgan  2 , Russell Kerschmann  2 , Paul Beyer  2 , Mary Dittrich  3 , Geoffrey A Block  4 , Glenn M Chertow  5 , Julie Parsonnet  6
Affiliations

SARS-CoV-2 Vaccine Antibody Response and Breakthrough Infection in Patients Receiving Dialysis

Shuchi Anand et al. Ann Intern Med. 2022 Mar.

Abstract

Background: Whether breakthrough SARS-CoV-2 infections after vaccination are related to the level of postvaccine circulating antibody is unclear.

Objective: To determine longitudinal antibody-based response and risk for breakthrough infection after SARS-CoV-2 vaccination.

Design: Prospective study.

Setting: Nationwide sample from dialysis facilities.

Patients: 4791 patients receiving dialysis.

Measurements: Remainder plasma from a laboratory processing routine monthly tests was used to measure qualitative and semiquantitative antibodies to the receptor-binding domain (RBD) of SARS-CoV-2. To evaluate whether peak or prebreakthrough RBD values were associated with breakthrough infection, a nested case-control analysis matched each breakthrough case patient to 5 control patients by age, sex, and vaccination month and adjusted for diabetes status and region of residence.

Results: Of the 4791 patients followed with monthly RBD assays, 2563 were vaccinated as of 14 September 2021. Among the vaccinated patients, the estimated proportion with an undetectable RBD response increased from 6.6% (95% CI, 5.5% to 7.8%) 14 to 30 days after vaccination to 20.2% (CI, 17.0% to 23.3%) 5 to 6 months after vaccination. Estimated median index values decreased from 91.9 (CI, 78.6 to 105.2) 14 to 30 days after vaccination to 8.4 (CI, 7.6 to 9.3) 5 to 6 months after vaccination. Breakthrough infections occurred in 56 patients, with samples collected a median of 21 days before breakthrough infection. Compared with prebreakthrough index RBD values of 23 or higher (equivalent to ≥506 binding antibody units per milliliter), prebreakthrough RBD values less than 10 and values from 10 to less than 23 were associated with higher odds for breakthrough infection (rate ratios, 11.6 [CI, 3.4 to 39.5] and 6.0 [CI, 1.5 to 23.6], respectively).

Limitations: Single measure of vaccine response; ascertainment of COVID-19 diagnosis from electronic health records.

Conclusion: The antibody response to SARS-CoV-2 vaccination wanes rapidly in persons receiving dialysis. In this population, the circulating antibody response is associated with risk for breakthrough infection.

Primary funding source: Ascend Clinical Laboratory.

PubMed Disclaimer

Conflict of interest statement

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M21-4176.

Figures

Visual Abstract.
Visual Abstract.. SARS-CoV-2 Vaccine Response and Breakthrough Infection in Patients Receiving Dialysis.
This study examines COVID-19 infections among 4791 vaccinated and unvaccinated patients receiving dialysis and describes the longitudinal antibody-based response up to 5 to 6 months after full vaccination and its relationship with breakthrough infections in 2563 patients.
Appendix Figure 1.
Appendix Figure 1.. Flowchart of study participants.
Figure 1.
Figure 1.. RBD IgG index values over time among patients receiving dialysis, in the overall cohort and by prior SARS-CoV-2 infection (A), by vaccine type (B), by age group (C), and by diabetes status (D).
Median RBD IgG index values among patients who had seroconversion on the total RBD Ig assay are graphed by time since vaccination, with error bars representing 95% CIs for the median values. Index values account for age, sex, diabetes status, SARS-CoV-2 RBD serostatus before vaccination, and vaccine type, as applicable. A missing time point indicates insufficient data for the subgroup at that time point. An index value of 1 corresponds to 21.8 BAU/mL according to the World Health Organization standard. Index values <1 indicate a “negative” result on the assay. P values tested for interaction by subgroup, and a significant P value indicates that the trajectory of the response differed by the subgroup depicted. BAU = binding antibody units; RBD = receptor-binding domain.
Figure 2.
Figure 2.. RBD IgG index values among case patients versus control patients.
Overlapping histograms of peak RBD IgG values obtained within 60 days after vaccination (top) and IgG values obtained in the period immediately preceding infection (bottom) are graphed by case patient versus control patient status. The median time between prebreakthrough IgG values and COVID-19 diagnosis was 21 days (interquartile range, 14 to 28 days); the corresponding time for control patients was 21 days (interquartile range, 12 to 27 days). Median peak RBD IgG values were 98.0 (95% CI, 22.3 to 150) versus 15.1 (CI, 6.3 to 71.5) and prebreakthrough values were 11.0 (CI, 2.3 to 47.8) versus 2.8 (CI, 1.2 to 8.6) for control patients versus case patients, respectively. RBD = receptor-binding domain.
Appendix Figure 2.
Appendix Figure 2.. Serial IgG index values among patients with breakthrough infection.
Some panels are missing the gold lines indicating the start of COVID-19 because this date overlapped with the start of hospitalization.
See this image and copyright information in PMC

Update of

References

    1. Centers for Disease Control and Prevention. Table 1. Recommended Adult Immunization Schedule for ages 19 years or older, United States, 2020. Accessed at http://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html on 14 September 2021.
    1. Kroger A, Bahta L, Hunter P. General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP). Accessed at www.cdc.gov/vaccines/hcp/acip-recs/general-recs/intro.html on 4 October 2021.
    1. Plotkin SA . Vaccines: correlates of vaccine-induced immunity. Clin Infect Dis. 2008;47:401-9. [PMID: ] doi: 10.1086/589862 - DOI - PubMed
    1. Marin M , Marlow M , Moore KL , et al. Recommendation of the Advisory Committee on Immunization Practices for use of a third dose of mumps virus-containing vaccine in persons at increased risk for mumps during an outbreak. MMWR Morb Mortal Wkly Rep. 2018;67:33-8. [PMID: ] doi: 10.15585/mmwr.mm6701a7 - DOI - PMC - PubMed
    1. Mast EE , Weinbaum CM , Fiore AE , et al; Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep. 2006;55:1-33. [PMID: ] - PubMed