SARS-CoV-2 vaccine antibody response and breakthrough infections in patients receiving dialysis (preprint)

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.

COVID19 vaccine type and humoral immune response in patients receiving dialysis (preprint)

BackgroundPatients on dialysis vaccinated with the attenuated adenovirus SARS-CoV-2 vaccine might mount an impaired response to vaccination. MethodsWe evaluated the humoral vaccination response among 2,099 fully vaccinated patients receiving dialysis. We used commercially available assays (Siemens) to assess prevalence of no response or diminished response to COVID-19 vaccination by vaccine type. We defined "no seroconversion" as lack of change from negative to positive in total RBD Ig antibody, no detectable response on semiquantitative RBD IgG antibody (index value <1) as "no RBD IgG response", and a semiquantitative RBD IgG index value <10 as "diminished RBD IgG response" ResultsOf the 2,099 fully vaccinated patients on dialysis, the proportion receiving the mRNA1273, BNT162b2, and Ad26.COV2.S were 62% (n=1316), 20% (n=416) and 18% (n=367), respectively. A third (33.3%) of patients receiving the attenuated adenovirus Ad26.COV2.S vaccine failed to seroconvert and an additional 36% had no detectable or diminished IgG response even 28-60 days post vaccination. ConclusionOne in three fully vaccinated patients receiving dialysis had evidence of an impaired immune response to the attenuated adenovirus Ad26.COV2.S vaccine.

SARS-COV-2 antibody prevalence in patients on dialysis in the US in January 2021 (preprint)

Background: To estimate seroprevalence of SARS-CoV-2 antibodies in the US, the country with largest absolute numbers of COVID19 cases and deaths in the world, we conducted a cross-sectional assessment from a sample of patients receiving dialysis in January 2021. Methods: We tested remainder plasma of 21,424 patients receiving dialysis through the third-largest US dialysis organization, with facilities located nationwide. We used the Siemens spike protein receptor binding domain total antibody assay to estimate crude SARS-CoV-2 seroprevalence, and then estimated seroprevalence for the US dialysis and adult population by standardizing by age, sex and region. We also compared January 2021 seroprevalence and case-detection rates to that from a similar subsample of patients receiving dialysis who had been tested in July 2020. Results: Patients in the sample were disproportionately from older age and minority race/ethnic groups. Seroprevalence of SARS-CoV-2 was 18.9% (95% CI: 18.3-19.5%) in the sample, 18.7% (18.1-19.2%) standardized to the US dialysis population, and 21.3% (20.3-22.3%) standardized to the US adult population (range 15.3-20.8% in the Northeast and South respectively). Younger age groups (18-44 years), and persons self-identifying as Hispanic or living in Hispanic neighborhoods, and persons living in the poorest neighborhoods were among the subgroups with the highest seroprevalence (25.9% (24.1-27.8%), 25.1% (23.6-26.4%), 24.8% (23.2-26.5%) respectively). Compared to data from July 2020, we observed diminished variability in seroprevalence by geographic region and urban-rural status. Estimated case detection rate increased from 14% to 23% in July 2020 to January 2021. Conclusions: A year after the first case of SARS-CoV-2 infection was detected in the US, fewer than one in four adults have evidence of SARS-CoV-2 antibodies. Vaccine roll out to majority minority neighborhoods and poorer neighborhoods will be critical to disrupting the spread of infection.