ABSTRACT
Rationale & Objective: SARS-CoV-2 infections are likely underdiagnosed, but the degree of underdiagnosis among maintenance dialysis patients is unknown. Durability of the immune response after third vaccine doses in this population also remains uncertain. This study tracked antibody levels to 1) assess the rate of undiagnosed infections and 2) characterize seroresponse durability after third doses. Study Design: Retrospective observational study Setting & Participants: SARS-CoV-2 vaccinated patients receiving maintenance dialysis through a national dialysis provider. Immunoglobulin G spike antibodies (anti-spike IgG) titers were assessed monthly following vaccination. Exposure(s): Two and three doses of SARS-CoV-2 vaccine Outcome(s): Undiagnosed and diagnosed SARS-CoV-2 infections; anti-spike IgG titers over time Analytical Approach: "Undiagnosed" SARS-CoV-2 infections were identified as an increase in anti-spike IgG titer of [≥]100 BAU/mL, not associated with receipt of vaccine or "diagnosed" SARS-CoV-2 infection (by PCR or antigen test). In descriptive analyses, anti-spike IgG titers were followed over time. Results: Among 2660 patients without prior COVID-19 who received an initial two-dose vaccine series, 371 (76%) SARS-CoV-2 infections were diagnosed and 115 (24%) were undiagnosed. Among 1717 patients without prior COVID-19 who received a third vaccine dose, 155 (80%) SARS-CoV-2 infections were diagnosed and 39 (20%) were undiagnosed. In both cohorts, anti-spike IgG levels declined over time. Of the initial two-dose cohort, 66% had a titer [≥]500 BAU/mL in the first month, with 23% maintaining a titer [≥]500 BAU/mL at six months. Of the third dose cohort, 95% had a titer [≥]500 BAU/mL in the first month after the third dose, with 76% maintaining a titer [≥]500 BAU/mL at six months. Limitations: Assays used had upper limits. Conclusions: Among maintenance dialysis patients, 20-24% of SARS-CoV-2 infections were undiagnosed. Given this population's vulnerability to COVID-19, ongoing infection control measures are needed. A three-dose primary mRNA vaccine series optimizes seroresponse rate and durability.
Subject(s)
COVID-19 , Severe Acute Respiratory Syndrome , InfectionsABSTRACT
Given the increased morbidity and mortality from COVID-19 among patients undergoing maintenance dialysis, we examined the seroresponse to an additional dose of SARS-CoV-2 mRNA vaccine, using a hypothesized protective anti-spike protein IgG antibody threshold of 7 based on prior work. Among 395 patients, 384 (97%) had seroresponse [≥]7 following administration of the third dose. Among those with suboptimal (peak <7) and minimal (peak <1) seroresponse to an initial mRNA vaccine regimen, the rate of seroresponse [≥]7 following a third dose was 97% (36 of 37) and 64% (14 of 22), respectively. Given ongoing high rates of COVID-19 and rapidly waning immunity after an initial vaccine series, we recommend a third mRNA vaccine dose be standard for all patients receiving maintenance dialysis.
Subject(s)
COVID-19ABSTRACT
Among patients receiving maintenance dialysis with a national US dialysis provider, fully vaccinated dialysis patients were significantly less likely to be diagnosed with COVID-19 or be hospitalized than unvaccinated patients. Ad26.COV2.S/Janssen vaccine had significantly worse outcomes, and mRNA-1273/Moderna the best. Among the 27 patients with breakthrough COVID-19 and anti-spike IgG antibodies measured, 23/27 (85%) breakthrough COVID-19 cases occurred at titers <2 U/L (lower limit of a positive response); 14 of these patients never developing Ab titers above 2 U/L. Only 3/27 were receiving immunosuppression. The potential use of antibody titers to guide vaccinations should be explored.
Subject(s)
COVID-19 , Breakthrough PainABSTRACT
Background and ObjectivesWhile most maintenance dialysis patients exhibit initial seroresponse to vaccination, concerns remain regarding the durability of this antibody response. This study evaluated immunity over time. Design, setting, participants, and measurementsThis retrospective cohort study included maintenance dialysis patients from a midsize national dialysis provider who received a complete SARS-CoV-2 vaccine series and had at least one antibody titer checked after full vaccination. Immunoglobulin G spike antibodies (SAb-IgG) titers were assessed monthly with routine labs beginning after full vaccination and followed over time; the semiquantitative SAb-IgG titer reported a range between 0 and [≥] 20 U/L. Descriptive analyses compared trends over time by prior history of COVID-19 and type of vaccine received. Time-to-event analyses were conducted for the outcome of loss of seroresponse (SAb-IgG < 1 U/L or development of COVID-19). Cox proportional hazards regression was used to adjust for additional clinical characteristics of interest. ResultsAmong 1898 maintenance dialysis patients, 1567 (84%) had no prior history of COVID-19. Patients without a history of COVID-19 had declining titers over time. Among 441 BNT162b2/Pfizer recipients, median [IQR] SAb-IgG titer declined from 20 [5.99-20] U/L in month 1 to 1.30 [0.15-3.59] U/L by month 6. Among 779 mRNA-1273/Moderna recipients, median [IQR] SAb-IgG titer declined from 20 [20-20] in month 1 to 6.20 [1.74-20] by month 6. The 347 Ad26.COV2.S/Janssen recipients had a lower titer response than mRNA vaccine recipients over all time periods. In time-to-event analyses, Ad26.COV2.S/Janssen and mRNA-1273/Moderna recipients had the shortest and longest time to loss of seroresponse, respectively. The maximum titer reached in the first two months after full vaccination was predictive of the durability of the SAb-IgG seroresponse; patients with SAb-IgG titer 1-19.99 U/L were more likely to have loss of seroresponse compared to patients with SAb-IgG titer [≥] 20 U/L (HR 23.9 [95% CI: 16.1-35.5]). ConclusionsVaccine-induced seroresponse wanes over time among maintenance dialysis patients across vaccine types. Early titers after full vaccination predict the durability of seroresponse.
Subject(s)
IgG Deficiency , COVID-19ABSTRACT
Abstract Importance: Patients receiving maintenance dialysis patients are at high risk for morbidity and mortality from COVID-19. The immunogenicity of SARS-CoV-2 mRNA vaccines is unknown in this vulnerable population where immune compromise is common. Objective: To determine seroresponse to vaccination against SARS-CoV-2 utilizing mRNA vaccines among patients receiving maintenance dialysis. Design: Retrospective observational study. Setting: Dialysis Clinic, Inc. (DCI) outpatient dialysis clinics in the United States. Participants: All patients receiving maintenance dialysis that received two doses of SARS-CoV-2 mRNA vaccines with SARS-CoV-2 spike-antibody test results drawn at least 14 days after the second dose, as documented in the electronic health record through March 18, 2021. Exposure: Two doses of BNT162b2/Pfizer or of mRNA-1273/Moderna vaccines administered per manufacturer recommendations. Main Outcomes and Measures: Levels of immunoglobulin-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike antigen (seropositive: 2 or greater) using FDA-approved semi-quantitative chemiluminescent assay (ADVIA Centaur XP/XPT COV2G). The DCI clinical protocol for in-clinic administration included baseline and follow-up levels although initial administration of the vaccine occurred primarily elsewhere (e.g. long-term care facilities, hospitals, etc.) during the evaluation period. Hence, only post-vaccination antibody levels were reported. Results: Among 186 patients receiving maintenance dialysis from 32 clinics in 8 states tested an average of 23 days after receiving 2 vaccine doses, mean age was 68 years, with 47% women, 21% Black, 26% residents in long-term care facilities and 97% undergoing in-center hemodialysis. Overall seropositive rate was 165/186 (88.7%) with 70% at maximum titer and with no significant difference in seropositivity between BNT162b2/Pfizer (N=148) and mRNA-1273/Moderna (N=18) vaccines (88.1% vs. 94.4%, p=0.42). Among patients with COVID-19 history, seropositive rate was 38/38 (100%) with 97% at maximum titer. Conclusions and Relevance: Most patients receiving maintenance dialysis were seropositive after two doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine. Early evidence suggests that vaccinated dialysis patients with prior COVID-19 develop robust antibody response. These results support an equitable and aggressive vaccination strategy for all eligible patients receiving maintenance dialysis, regardless of age, sex, race, ethnicity, or disability, to prevent the extremely high morbidity and mortality associated with COVID-19 in this high risk population.