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 Jun 2;11(11):3187.
doi: 10.3390/jcm11113187.

Effect of Third and Fourth mRNA-Based Booster Vaccinations on SARS-CoV-2 Neutralizing Antibody Titer Formation, Risk Factors for Non-Response, and Outcome after SARS-CoV-2 Omicron Breakthrough Infections in Patients on Chronic Hemodialysis: A Prospective Multicenter Cohort Study

Frank-Peter Tillmann  1   2 , Lars Figiel  3 , Johannes Ricken  4 , Hermann Still  2 , Christoph Korte  3 , Grete Plaßmann  4 , Ana Harth  1 , Achim Jörres  1 , Philipp von Landenberg  5
Affiliations

Effect of Third and Fourth mRNA-Based Booster Vaccinations on SARS-CoV-2 Neutralizing Antibody Titer Formation, Risk Factors for Non-Response, and Outcome after SARS-CoV-2 Omicron Breakthrough Infections in Patients on Chronic Hemodialysis: A Prospective Multicenter Cohort Study

Frank-Peter Tillmann et al. J Clin Med. .

Abstract

The aim of this study is to determine the effect of repeated vaccinations on neutralizing SARS-CoV-2 IgG antibody titers, evaluate risk factors for immunological non-response, and to report breakthrough infections in chronic hemodialysis patients.

Methods: A prospective, multi-center cohort study in 163 chronic hemodialysis patients was conducted. Antibody titers were measured three months after second, third, and fourth (10 pts) booster vaccinations. SARS-CoV-2 neutralizing antibody titers in BAU/mL and % inhibition were divided into three categories (<216, 216-433, >433 and <33, 33-66, and >66%). Somers's test, paired t-test, and univariable and multivariable logistic regression analysis were applied to evaluate differences in antibody levels and search for risk factors for vaccination failure defined as neutralizing titers <50% and/or need for repeated booster vaccinations. Furthermore, we report on a case series to describe characteristics of patients after four vaccinations (n = 10) and breakthrough infections (n = 20).

Results: Third dose boosters resulted in higher proportions of patients with neutralizing antibody levels >66% as compared to after the second dose (64.7% after second dose vs. 88.9% after third dose, p = 0.003), as well as in a respective increase in neutralizing titer levels in % from 68 ± 33% to 89 ± 24 (p <0.001). The proportion of patients with IgG-titers below 216 BAU/mL decreased from 38.6 to 10.5% (p ≤ 0.001). Age (p = 0.004, OR 1.066, 95% CI 1.020-1.114) and presence of immunosuppressive medications (p = 0.002, OR 8.267, 95% CI 2.206-30.975) were identified as major risk factors for vaccination failure. Repeated booster vaccinations ≥4 times were effective in 8 out of 10 former low-responders (80%) without any side effects or safety concerns. Breakthrough infections showed a clinically mild course but were associated with prolonged viral shedding on PCR-testing ranging 7-29 (mean 13) days.

Conclusions: Third and fourth mRNA-based booster vaccinations resulted in higher and longer lasting SARS-CoV-2 antibody levels as compared to after two dosages. The presence of immunosuppressive medication and repeat vaccinations are major potentially modifiable measures to increase antibody levels in non-or low-responders. Breakthrough infections with SARS-CoV-2 Omicron were associated with prolonged viral shedding but clinically mild disease courses.

Keywords: COVID-19; SARS-CoV-2; booster vaccination; breakthrough infection; hemodialysis; neutralizing antibodies; omicron; vaccination failure.

PubMed Disclaimer

Conflict of interest statement

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. The authors declare that they have no relevant financial interests.

Figures

Figure 1
Figure 1
% of participants with SARS-CoV-2 antibodies in categories (BAU/mL) after a third (booster) vaccination in 153 chronic hemodialysis patients.
See this image and copyright information in PMC

References

    1. Yang Z.H., Pan X.T., Chen Y., Wang L., Chen Q.X., Zhu Y., Zhu Y.-J., Chen Y.-X., Chen Y.-N. Psychological profiles of Chinese patients with hemodialysis during the pandemic of coronavirus disease 2019. Front. Psychiatry. 2021;12:616016. doi: 10.3389/fpsyt.2021.616016. - DOI - PMC - PubMed
    1. Couchoud C., Bayer F., Ayav C., Béchade C., Brunet P., Chantrel F., Frimat L., Galland R., Laurain E., Lobbedez T., et al. Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients. Kidney Int. 2020;98:1519–1529. doi: 10.1016/j.kint.2020.07.042. - DOI - PMC - PubMed
    1. Alberici F., Delbarba E., Manenti C., Manenti C., Econimo L., Valerio F., Pola A., Maffei C., Possenti S., Lucca B., et al. A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection. Kidney Int. 2020;98:20–26. doi: 10.1016/j.kint.2020.04.030. - DOI - PMC - PubMed
    1. Hoxha E., Suling A., Turner J.J.E., Haubitz M., Floege J., Huber T.B., Galle J.C. COVID-19 prevalence, and mortality in chronic dialysis patients. Dtsch. Arztebl. Int. 2021;118:195–196. doi: 10.3238/arztebl.m2021.0160. - DOI - PMC - PubMed
    1. Williamson E.J., Walker A.J., Bhaskaran K., Bacon S., Bates C., Morton C.E., Curtis H.J., Mehrkar A., Evans D., Inglesby P., et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020;584:430–436. doi: 10.1038/s41586-020-2521-4. - DOI - PMC - PubMed

LinkOut - more resources