RESUMEN
Background: Individuals on haemodialysis (HD) are more vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the general population due to end-stage kidney disease-induced immunosuppression. Methods: A total of 26 HD patients experiencing SARS-CoV-2 infection after a third vaccination were matched 1:1 with 26 of 92 SARS-CoV-2-naïve patients by age, sex, dialysis vintage and immunosuppressive drugs receiving a fourth vaccination with a messenger RNA-based vaccine. A competitive surrogate neutralization assay was used to monitor vaccination success. To determine infection neutralization titres, Vero-E6 cells were infected with SARS-CoV-2 variants of concern (VoCs), Omicron sublineage BA.1, BA.5 and BQ.1.1. The 50% inhibitory concentration (IC50, serum dilution factor 1:x) was determined before, 4 weeks after and 6 months after the fourth vaccination. Results: A total of 52 HD patients received four coronavirus disease 2019 (COVID-19) vaccinations and were followed up for a median of 6.3 months. Patient characteristics did not differ between the matched cohorts. Patients without a SARS-CoV-2 infection had a significant reduction of real virus neutralization capacity for all Omicron sublineages after 6 months (P < .001 each). Those patients with a virus infection did not experience a reduction in real virus neutralization capacity after 6 months. Compared with the other Omicron VoC, the BQ.1.1 sublineage had the lowest virus neutralization capacity. Conclusions: SARS-CoV-2-naïve HD patients had significantly decreased virus neutralization capacity 6 months after the fourth vaccination, whereas patients with a SARS-CoV-2 infection had no change in neutralization capacity. This was independent of age, sex, dialysis vintage and immunosuppression. Therefore, in infection-naïve HD patients a fifth COVID-19 vaccination might be reasonable 6 months after the fourth vaccination.
RESUMEN
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 four vaccinations. A total of 142 hemodialysis patients received four COVID-19 vaccinations until 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) to determine serum infection neutralization capacity. Four weeks 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) compared to four months after the third vaccination. A significant increase in the neutralization capacity was even observed for patients with high antibody titers after three vaccinations (p < 0.001). Ten patients with SARS-CoV-2 breakthrough infection after the first blood sampling had by trend lower prior neutralization capacity for Omicron (p = 0.051). Our findings suggest that hemodialysis patients benefit from a fourth vaccination in particular in the light of the highly infectious SARS-CoV-2 Omicron-variants. A routinely applied four-time vaccination seems to broaden immunity against variants and would be recommended in hemodialysis patients.