Improved SARS-CoV-2 neutralization of Delta and Omicron variants of concern after fourth vaccination in hemodialysis patients

Abstract

Background Hemodialysis patients are exposed to a markedly increased risk when infected with SARS-CoV-2. To date it is unclear if hemodialysis patients benefit from a fourth vaccination. Methods A total of 142 hemodialysis patients (median age 72.6 years, 33.8% female) received four COVID-19 vaccinations between December 2020 and March 2022. RDB binding antibody titers were determined in a competitive surrogate neutralization assay. Vero-E6 cells were infected with SARS-CoV-2 variants of concern (VoC) Delta (B.1.617.2) or Omicron (B.1.1.529, sub lineage BA.1) in a biosafety level 3 laboratory to determine serum infection neutralization capacity before and after vaccination. Results After the fourth vaccination serum infection neutralization capacity significantly increased from a 50% inhibitory concentration (IC50, serum dilution factor 1:x) of 247.0 (46.3-1560.8) to 2560.0 (1174.0-2560.0) for the Delta VoC, and from 37.5 (20.0-198.8) to 668.5 (182.2-2560.0) for the Omicron VoC (each p<0.001). A significant increase of the neutralization capacity was even observed for patients who had high antibody titers after three vaccinations (p<0.001). Univariate regression analysis indicated immunosuppressive medication (p=0.001) and hepatitis B vaccination non-response (p=0.046), and multivariate analysis immunosuppressive medication as the only factor associated with a reduced effect against Delta (p<0.001). Ten patients with SARS-CoV-2 breakthrough infection before the fourth vaccination had by trend lower prior neutralization capacity for Omicron (p=0.051). Conclusions Our findings suggest that hemodialysis patients benefit from a fourth vaccination in particular in the light of the highly infectious SARS-CoV-2 Omicron variant. A routinely applied four-time vaccination seems to broaden immunity against variants and would be recommended in hemodialysis patients.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study did not receive any funding

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study, conforming to the ethical guidelines of the Helsinki Declaration, was approved by the Medical Ethics Committee of the Klinikum rechts der Isar of the Technical University of Munich (approval number 163/21 S-SR, March 19th, 2021) and registered at the Paul Ehrlich Institute (NIS592).

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Data Availability

The datasets for this manuscript are not publicly available because written informed consent did not include wording on data sharing (German data protection laws). Reasonable requests to access the datasets should be directed to the corresponding author.

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