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      Humoral response to a third injection of BNT162b2 vaccine in patients on maintenance haemodialysis

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          Abstract

          Background

          Humoral response against sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after two doses of BNT162b2 (Pfizer-BioNTech) has been proven to be less intense in maintenance dialysis patients as compared with healthy subjects, leading the French authorities to recommend a third injection in this population. Here we investigated the response to the third injection in two cohorts of haemodialysis (HD) patients.

          Methods

          Data from two prospective observational cohorts were collected. In the first (‘systematic’) cohort, patients from two HD centres ( n = 66) received a third injection of BNT162b2, regardless of the response after two injections. In the second (‘conditional’) cohort, the injection was only prescribed to patients ( n = 34) with no or low response to the previous two doses. In both cohorts, the third dose was injected 1–2 months after the second dose. Serology was performed after the second and third doses to assess anti-Spike immunoglobulin G (S IgG) antibody titre.

          Results

          In the systematic cohort, anti-S IgG was found in 83.3 and 92.4% of patients after the second and third doses of BNT162b2, respectively. In this cohort, 6/11 (54.5%) and 20/21 (95.2%) patients switched from non-responder to low responder and from low responder to high responder, respectively. In low and high responders to two doses, 50/55 (90.9%) at least doubled their anti-S IgG titre. Similar trends were observed in the conditional cohort.

          Conclusions

          In maintenance HD patients, humoral response against SARS-CoV-2 was boosted after a third dose of BNT162b2, allowing seroconversion in more than half of non-responders. These data may support an intensified vaccination protocol with a third dose of BNT162b2 in dialysis patients.

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          Most cited references26

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          Results from the ERA-EDTA Registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe.

          The aim of this study was to investigate 28-day mortality after COVID-19 diagnosis in the European kidney replacement therapy population. In addition, we determined the role of patient characteristics, treatment factors, and country on mortality risk using ERA-EDTA Registry data on patients receiving kidney replacement therapy in Europe between February 1, 2020 and April 30, 2020. Additional data on all patients with a diagnosis of COVID-19 were collected from seven European countries encompassing 4298 patients. COVID-19 attributable mortality was calculated using propensity-score matched historic controls and after 28 days of follow-up was 20.0% (95% confidence interval 18.7%-21.4%) in 3285 patients receiving dialysis, and 19.9% (17.5%-22.5%) in 1013 recipients of a transplant. We identified differences in COVID-19 mortality across countries, and an increased mortality risk in older patients receiving kidney replacement therapy and male patients receiving dialysis. In recipients of kidney transplants older than 75 years of age 44.3% (35.7%-53.9%) did not survive COVID-19. Mortality risk was 1.28 (1.02-1.60) times higher in transplant recipients compared with matched dialysis patients. Thus, the pandemic has had a substantial effect on mortality in patients receiving kidney replacement therapy; a highly vulnerable population due to underlying chronic kidney disease and high prevalence of multimorbidity.
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            Humoral Response to the Pfizer BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis

            Coronavirus disease 2019 (COVID-19) is associated with higher morbidity and mortality in patients on maintenance hemodialysis. Patients on dialysis tend to have a reduced immune response to infection or vaccination. We aimed to assess, for the first time to the best of our knowledge, the humoral response following vaccination with the BNT162b2 vaccine in patients on maintenance hemodialysis and the factors associated with it. The study included 56 patients on maintenance hemodialysis (dialysis group) and a control group composed of 95 health care workers. All participants had received two doses of the BNT162b2 (Pfizer-BioNTech) vaccine. The serology testing was done using Quant II IgG anti-Spike severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assay by Abbott a median of 30 days after receipt of the second dose of the vaccine. All subjects in the control group developed an antibody response compared with 96% (54 of 56) positive responders in the dialysis group. The IgG levels in the dialysis group (median, 2900; interquartile range, 1128–5651) were significantly lower than in the control group (median, 7401; interquartile range, 3687–15,471). A Mann–Whitney U test indicated that this difference was statistically significant ( U =1238; P <0.001). There was a significant inverse correlation of age and IgG levels in both groups. The odds of being in the lower quartile were significantly higher for older individuals (odds ratio, 1.11 per year of age; 95% confidence interval, 1.08 to 1.20; P =0.004) and for the dialysis group compared with the control group (odds ratio, 2.7; 95% confidence interval, 1.13 to 7.51; P =0.05). Within the dialysis group, older age and lower lymphocyte count were associated with antibody response in the lower quartile (odds ratio, 1.22 per 1-year older; 95% confidence interval, 1.13 to 1.68; P =0.03 and odds ratio, 0.83 per 10-e 3 / µ l-higher lymphocyte count; 95% confidence interval, 0.58 to 0.97; P =0.05). Although most patients on maintenance hemodialysis developed a substantial humoral response following the BNT162b2 vaccine, it was significantly lower than controls. Age was an important factor in the humoral response, regardless of chronic medical conditions.
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              Impaired humoral and cellular immunity after SARS-CoV2 BNT162b2 (Tozinameran) prime-boost vaccination in kidney transplant recipients

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                Author and article information

                Contributors
                Journal
                Clin Kidney J
                Clin Kidney J
                ckj
                Clinical Kidney Journal
                Oxford University Press
                2048-8505
                2048-8513
                November 2021
                13 August 2021
                13 August 2021
                : 14
                : 11
                : 2349-2355
                Affiliations
                Service de Néphrologie-Dialyse-Transplantation, CHU d’Angers , Angers, France
                Service de Néphrologie-Dialyse-Transplantation, CHU d’Angers , Angers, France
                Service de Néphrologie, CH de Laval , Angers, France
                Service de Néphrologie , CH Le Mans, Le Mans, France
                Service de Néphrologie, CH de Laval , Angers, France
                Centre de Dialyse ECHO , Angers, France
                Service de Néphrologie, CH de Laval , Angers, France
                Service de Néphrologie-Dialyse-Transplantation, CHU d’Angers , Angers, France
                Service de Néphrologie, CH de Laval , Angers, France
                Service de Gériatrie, CHU d’Angers , Angers, France
                Virology Laboratory, Angers University Hospital, HIFIH Laboratory EA3859 , Angers, France
                Laboratoire de Virologie, CH de Laval , Laval, France
                Service de Maladies Infectieuses , CH Le Mans, Le Mans, France
                Service de Néphrologie-Dialyse-Transplantation, CHU d’Angers , Angers, France
                Service de Néphrologie , CH Le Mans, Le Mans, France
                Service de Néphrologie-Dialyse-Transplantation, CHU d’Angers , Angers, France
                INSERM CRCINA1232, Université d’Angers , Angers, France
                [1 ] Service de Néphrologie-Dialyse-Transplantation, CHU d’Angers , Angers, France
                [2 ] Service de Néphrologie, CH de Laval , Angers, France
                [3 ] Service de Néphrologie , CH Le Mans, Le Mans, France
                [4 ] Centre de Dialyse ECHO , Angers, France
                [5 ] Service de Gériatrie, CHU d’Angers , Angers, France
                [6 ] Virology Laboratory, Angers University Hospital, HIFIH Laboratory EA3859 , Angers, France
                [7 ] Laboratoire de Virologie, CH de Laval , Laval, France
                [8 ] Service de Maladies Infectieuses , CH Le Mans, Le Mans, France
                [9 ] INSERM CRCINA1232, Université d’Angers , Angers, France
                Author notes
                Correspondence to: Jean-François Augusto; E-mail: jfaugusto@ 123456chu-angers.fr
                Author information
                https://orcid.org/0000-0003-1498-2132
                Article
                sfab152
                10.1093/ckj/sfab152
                8573007
                34754430
                489bff82-5090-4203-a86c-a6a38bec0815
                © The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 24 June 2021
                : 27 July 2021
                : 08 September 2021
                Page count
                Pages: 7
                Categories
                Original Article
                AcademicSubjects/MED00340

                Nephrology
                bnt162b2 vaccine,covid-19,haemodialysis,immunogenicity,sars-cov-2
                Nephrology
                bnt162b2 vaccine, covid-19, haemodialysis, immunogenicity, sars-cov-2

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