Longitudinal SARS-CoV-2 neutralization of Omicron BA.1, BA.5 and BQ.1.1 after four vaccinations and the impact of breakthrough infections in haemodialysis patients

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. LAY SUMMARY Haemodialysis (HD) patients are a vulnerable patient group when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Immunity after vaccination is less pronounced and diminishes more quickly in these patients when compared with healthy individuals. We matched and compared 26 HD patients experiencing a SARS-CoV-2 breakthrough infection after full vaccination with 26 virus-naïve patients and followed them up for 6 months after the fourth vaccination. We found rapidly decreasing immunity in the form of virus neutralization capacity for the current Omicron variants BA.5 and BQ.1.1 in SARS-CoV-2-naïve patients 6 months after the fourth vaccination, whereas in convalescents from infection, relatively stable titres in real-virus neutralization assays were observed. Overall, the recent Omicron BQ.1.1 sublineage showed the highest immune escape capacity, arguing for a booster vaccination with an adapted vaccine in SARS-CoV-2-naïve HD patients.