Neutralizing SARS-CoV-2 antibody response in dialysis patients after the first dose of the BNT162b2 mRNA COVID-19 vaccine: the war is far from being won

Abstract

On December 21, 2020, the European Commission granted conditional marketing approval to the BNT162b2 coronavirus disease 2019 (COVID-19) mRNA vaccine developed by BioNTech.1Cavaleri M. Enzmann H. Straus S. et al.The European Medicines Agency's EU conditional marketing authorisations for COVID-19 vaccines.Lancet. 2021; 397: 355-357Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar,2Polack F.P. Thomas S.J. Kitchin N. et al.Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.N Engl J Med. 2020; 383: 2603-2615Crossref PubMed Scopus (6854) Google Scholar In the general population, the first dose of BNT162b2 was reported to produce a rapid antibody response with 52% efficacy in preventing severe infection, similar to the protection induced by the natural disease.2Polack F.P. Thomas S.J. Kitchin N. et al.Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.N Engl J Med. 2020; 383: 2603-2615Crossref PubMed Scopus (6854) Google Scholar,3Manisty C. Otter A.D. Treibel T.A. et al.Antibody response to first BNT162b2 dose in previously SARS-CoV-2-infected individuals.Lancet. 2021; 397: 1057-1058Abstract Full Text Full Text PDF PubMed Scopus (245) Google Scholar There was great hope that vaccination would protect fragile individuals, and societies of nephrology asked that patients with end-stage kidney disease should be given priority in being vaccinated.4Francis A. Baigent C. Ikizler T.A. et al.The urgent need to vaccinate dialysis patients against severe acute respiratory syndrome coronavirus 2: a call to action.Kidney Int. 2021; 99: 791-793Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar The situation of in-center hemodialysis patients is a double challenge: their fragility and their proximity to others have made this population particularly vulnerable. In France, for instance, the cumulative incidence of COVID-19 is now >10% in dialysis patients, with a mortality rate of about 15% in those who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the response to SARS-CoV-2 vaccine in dialysis patients is still unknown, as is the need for a second dose and what its timing should be.5Glenn D.A. Hegde A. Kotzen E. et al.Systematic review of safety and efficacy of COVID-19 vaccines in patients with kidney disease..Kidney Int Rep. 2021; 6: 1407-1410Abstract Full Text Full Text PDF Scopus (39) Google Scholar,6Windpessl M. Bruchfeld A. Anders H.J. et al.COVID-19 vaccines and kidney disease..Nat Rev Nephrol. 2021; 17: 291-293Crossref PubMed Scopus (62) Google Scholar We therefore wish to report on the antibody response to the first dose of BNT162b2 vaccination in a cohort of high-comorbidity patients on in-center hemodialysis. All the chronic hemodialysis patients treated in our center between January 1 and February 28, 2021, were enrolled in this observational analysis. We dosed specific IgG anti-spike protein (anti-S IgG) (Elecsys Anti-SARS-CoV-2 S; Roche Diagnostics) at the time of the first vaccine injection (T0) and at the time of the second one (T1) 3 weeks later (Figure 1). Of the 132 eligible patients (mean age, 67.54 ± 15.71 years; 57% males; average dialysis vintage, 2.21 years), 101 (77%) gave their consent to be vaccinated (Table 1). At baseline, only 2 patients tested positive (anti-S IgGs, 1200 and 22 U/ml, respectively). Both had previously had symptomatic COVID-19. At T1, only 35 (35%) of the patients had developed neutralizing antibodies, with a median titer of 8.22 U/ml [interquartile range, 1.73–28.70] (Figure 1). The patients who developed neutralizing antibodies were younger and had a lower comorbidity burden (Table 1). However, in this subset of cases, no correlation was found between antibody titer and age, comorbidity, or dialysis vintage.Table 1Characteristics of our cohortBaselineAllVaccinatedNot vaccinatedPn (%)132 (100)101 (77)31 (23)—Age, yr67.54 ± 15.7168.89 ± 14.8663.13 ± 17.740.0739Male, n (%)75 (57)60 (59)15 (48)0.3054Dialysis vintage, yr2.21 [0.80–4.68]2.28 [0.81–4.58]2.21 [0.41–5.97]0.5637Charlson Comorbidity Index8 [5–10]8 [5–10]8 [6–9]0.3649T1RespondersNonrespondersPNo.3560—Age, yr62.31 ± 16.2073.72 ± 11.180.0001Male, n (%)20 (57)35 (58)0.9999Dialysis vintage, yr1.44 [0.67–3.97]2.99 [0.96–5.99]0.3149Charlson Comorbidity Index6 [4–8]9 [7–10]0.0006Anti–SARS-CoV-2 S IgG titer, U/ml8.22 [1.73–28.70]——S, spike; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; T1, time of the second vaccine injection.Age is expressed as mean ± SD; dialysis vintage and Charlson Comorbidity Index are expressed as median [interquartile range].Bold P values indicate statistically significant variables. Open table in a new tab S, spike; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; T1, time of the second vaccine injection. Age is expressed as mean ± SD; dialysis vintage and Charlson Comorbidity Index are expressed as median [interquartile range]. Bold P values indicate statistically significant variables. To our knowledge, this is the first report on the initial response to COVID-19 vaccine in patients on hemodialysis. At difference with other recent reports in health care workers,7Bradley T. Grundberg E. Selvarangan R. et al.Antibody responses after a single dose of SARS-CoV-2 mRNA vaccine [e-pub ahead of print]. N Engl J Med.https://doi.org/10.1056/NEJMc2102051Google Scholar our data suggest that only about one-third of hemodialysis patients develop neutralizing antibodies after the first dose of BNT162b2 COVID-19 mRNA vaccine, and that these are at low titers, as could be expected, in a high-comorbidity cohort (median Charlson Comorbidity Index: 8). Younger patients, with lower comorbidity, are more likely to mount an antibody response. Although, because of a shortage of vaccine, some institutions proposed a policy of delayed second-dose administration in the general population,8Kadire S.R. Wachter R.M. Lurie N. Delayed second dose versus standard regimen for Covid-19 vaccination.N Engl J Med. 2021; 384: e28Crossref PubMed Scopus (44) Google Scholar,9Pimenta D. Yates C. Pagel C. Gurdasani D. Delaying the second dose of covid-19 vaccines.BMJ. 2021; 372: n710Crossref PubMed Scopus (21) Google Scholar a timely second dose of the BNT162b2 COVID-19 mRNA vaccine seems necessary to ensure protection in hemodialysis patients. In the wait for long-term studies on larger groups, needed to enable us to assess the vaccine-induced immune response and kinetic, we considered that this first report could be of help by suggesting that to best protect dialysis patients, for the time being we cannot let our guard down, even after vaccination. The urgent need to vaccinate dialysis patients against severe acute respiratory syndrome coronavirus 2: a call to actionKidney InternationalVol. 99Issue 4PreviewThe coronavirus disease 2019 (COVID-19) pandemic is causing extreme stress to many health systems and an ever-mounting death toll. Out of the darkness of the last 14 months comes a beacon of hope in the form of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. To best utilize this precious resource, we must efficiently deploy vaccination to high-risk groups. Full-Text PDF Immune response to SARS-CoV-2 infection and vaccination in patients receiving kidney replacement therapyKidney InternationalVol. 99Issue 6PreviewIn this issue of Kidney International, the initial experience regarding the immunogenicity of prior coronavirus disease 2019 (COVID-19) infection and the response to the COVID-19 vaccines among patients on maintenance dialysis and kidney transplant recipients is summarized. Preliminary data suggest that there is durability of immune response after COVID-19 infection. Although immune response to the first dose of vaccine is less in infection-naïve patients than healthy individuals in both groups, after the second vaccine dose a significant portion of patients receiving maintenance dialysis develop robust antibody titers, whereas kidney transplant recipients show a less-strong immune response. Full-Text PDF Anti–SARS-CoV-2 spike protein S1 receptor-binding domain antibody after vaccination with inactivated whole-virus SARS-CoV-2 in end-stage kidney disease patients: an initial reportKidney InternationalVol. 100Issue 5PreviewPatients with end-stage kidney disease (ESKD) are at greater risk for morbidity and mortality following coronavirus disease 2019 (COVID-19) than the general population.1 Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for this vulnerable population is the main priority to prevent COVID-19 and mitigate unfavorable or severe complications. However, the immune responses to vaccination in patients with ESKD may be altered by accumulation of uremic toxins and comorbidities. Full-Text PDF