SARS-CoV-2 vaccine antibody response and breakthrough infection in dialysis

Abstract

Background: Patients receiving dialysis are a sentinel population for groups at high risk for death and disability from COVID-19. Understanding correlates of protection post-vaccination can inform immunization and mitigation strategies.

Methods: Monthly since January 2021, we tested plasma from 4791 patients receiving dialysis for antibodies to the receptor-binding domain (RBD) of SARS-CoV-2 using a high-throughput assay. We qualitatively assessed the proportion without a detectable RBD response and among those with a response, semiquantitative median IgG index values. Using a nested case-control design, we matched each breakthrough case to five controls by age, sex, and vaccination-month to determine whether peak and pre-breakthrough RBD IgG index values were associated with risk for infection post-vaccination.

Results: Among 2563 vaccinated patients, the proportion without a detectable RBD response increased from 6.6% [95% CI 5.5-8.1] in 14-30 days post-vaccination to 20.2% [95% CI 17.1-23.8], and median index values declined from 92.7 (95% CI 77.8-107.5) to 3.7 (95% CI 3.1-4.3) after 5 months. Persons with SARS-CoV-2 infection prior-to-vaccination had higher peak index values than persons without prior infection, but values equalized by 5 months (p=0.230). Breakthrough infections occurred in 56 patients, with samples collected a median of 21 days pre-breakthrough. Peak and pre-breakthrough RBD values <23 (equivalent to <506 WHO BAU/mL) were associated with higher odds for breakthrough infection (OR: 3.7 [95% CI 2.0-6.8] and 9.8 [95% CI 2.9-32.8], respectively).

Conclusions: The antibody response to SARS-CoV-2 vaccination wanes rapidly, and in persons receiving dialysis, the persisting antibody response is associated with risk for breakthrough infection.

Figure 1:. RBD IgG index values over time among patients on dialysis in the overall cohort and by prior SARS-CoV-2 infection (A), by vaccine type (B), by age group (C), and diabetes status (D).

Among patients who seroconverted on the total RBD Ig assay, median RBD IgG index values are graphed by time since vaccination, with error bars representing 95% CI for the median value. 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 on the WHO Standard. Index values < 1 indicate a ‘negative’ result on the assay. P values test for interaction by subgroup and significant p values indicate that the trajectory of the response differed by the subgroup depicted.

Figure 1:. RBD IgG index values over time among patients on dialysis in the overall cohort and by prior SARS-CoV-2 infection (A), by vaccine type (B), by age group (C), and diabetes status (D).

Among patients who seroconverted on the total RBD Ig assay, median RBD IgG index values are graphed by time since vaccination, with error bars representing 95% CI for the median value. 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 on the WHO Standard. Index values < 1 indicate a ‘negative’ result on the assay. P values test for interaction by subgroup and significant p values indicate that the trajectory of the response differed by the subgroup depicted.

Figure 2:. RBD IgG index values among cases versus controls

Violin plots represent peak RBD IgG values obtained within 60 days prior to vaccination (A) and the IgG values obtained in immediate period preceding infection are graphed (B) by case versus control status. Median time between pre-breakthrough IgG values and COVID-19 diagnosis was 21 days (25^th, 75^th percentile: 14-28 days); the corresponding time for controls was 21 days (25^th, 75^th percentile 12, 27 days). Median peak RBD IgG values were 98.0 (22.3, 150) versus 15.1 (6.3, 71.5), and pre-breakthrough values were 11.0 (2.3, 47.8) versus 2.8 (1.2, 8.6) for controls versus cases respectively. All cases had index values < 36.