Immunogenicity of BNT162b2 SARS-CoV-2 Vaccine in a Multicenter Cohort of Nursing Home Residents Receiving Maintenance Hemodialysis

Abstract

We recently reported that almost all maintenance hemodialysis (MHD) patients mount specific antibodies within a month of COVID-19 onset.1Labriola L. Scohy A. Seghers F. et al.A longitudinal, 3-months serologic assessment of SARS-CoV-2 infections in a Belgian hemodialysis facility.Clin J Am S Nephrol. 2021; 16: 613-614Crossref PubMed Scopus (28) Google Scholar However, evidence concerning the immunogenicity of SARS-CoV-2 vaccines in this immunodeficient population is scarce.2Glenn 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 PubMed Scopus (46) Google Scholar We prospectively assessed the response to BNT162b2, a messenger RNA vaccine encoding the spike protein, in a multicenter cohort of MHD patients living in nursing homes and compared their antibody response with that observed in a group of nondialyzed nursing home residents. Following approval by the European Medicines Agency of mRNA vaccines developed by Pfizer-BioNTech and Moderna, Belgian health authorities prioritized nursing home residents for vaccination. We included all nursing home residents on in-center HD at 5 UCLouvain network hospitals. A cohort of nondialyzed nursing home residents, matched for COVID-19 history, served as controls. All participants received 2 BNT162b2 doses, 21 days apart. Serum samples were taken on day 28 after the first dose (the time of peak neutralizing antibodies in phase 1 trials)3Walsh E.E. Frenck R.W. Falsey A.R. et al.Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates.N Engl J Med. 2020; 383: 2439-2450Crossref PubMed Scopus (1431) Google Scholar and on days 49 and 77, the latter only in MHD patients. Comorbidities listed by the Centers for Disease Control as risk factors for severe COVID-19 were recorded.4Centers for Disease Control and PreventionPeople with certain medical conditions.https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.htmlDate accessed: March 5, 2021Google Scholar Serum samples were tested with 2 electrochemiluminescent assays from Roche Elecsys for SARS-CoV-2 antibodies: a qualitative immunoassay using a recombinant nucleocapsid antigen (anti–SARS-CoV-2 N), and a quantitative immunoassay using the spike receptor-binding domain (anti–SARS-CoV-2 RBD). Both tests have a very high sensitivity and specificity, and the anti-RBD immunoassay correlates well with neutralization tests (Item S1). Groups were compared using Mann-Whitney, Kruskal-Wallis, or χ2 tests, as appropriate. Statistical analyses used Stata (v16) and GraphPad Prism (v8). All tests were 2-tailed and P <0.05 was considered significant. Thirty-four MHD patients and 45 controls were included. SARS-CoV-2 infection was previously diagnosed in 10 MHD patients (by qPCR on a nasopharyngeal swab) and 12 controls (by periodic serologic testing); controls were significantly older and had fewer comorbidities than MHD patients (Table 1). On day 28, anti-N antibodies were detected in all but 3 MHD patients with prior COVID-19, 2 of whom were first qPCR positive the day of the first vaccine dose. All participants without known prior COVID-19 were seronegative for anti-N antibodies.Table 1Baseline CharacteristicsControls (n = 45)MHD (n = 34)PAge, years88 [85-90]81 [74-87]<0.001Female sex29 (64%)19 (56%)0.4Hypertension23 (51%)25 (74%)0.04Diabetes2 (4%)14 (41%)<0.001Obesity4 (9%)6 (18%)0.3Cardiovascular disease10 (22%)14 (41%)0.07Stroke2 (4%)10 (29%)0.002COPD or asthma4 (9%)5 (15%)0.4Liver disease0 (0%)3 (9%)0.04Dementia0 (0%)6 (18%)0.003History of cancer7 (16%)4 (12%)0.6Active cancer2 (4%)4 (12%)0.2Immunosuppressive therapy4 (9%)0 (0%)0.07HIV infection2 (4%)0 (0%)0.2History of COVID-1912 (27%)10 (29%)0.8Age given as median [interquartile range]; other values as count (%). Abbreviations: COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019. Open table in a new tab Age given as median [interquartile range]; other values as count (%). Abbreviations: COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019. On day 28, proportions of those without a history of COVID-19 who developed anti-RBD antibodies were similar (P = 0.6) in MHD patients (19/24 [79%]) and controls (28/33 [85%]). All participants with prior COVID-19 mounted an anti-RBD response, except 1 MHD patient who was first qPCR positive on the day of first vaccination. Anti-RBD levels were not statistically different in MHD patients and controls, both in groups with and without prior COVID-19 (Table 2). The humoral response in MHD patients was sustained until day 77. Responders to the vaccine did not differ from nonresponders in demographics and comorbidities (Table 1, Table S1), except for the presence of anti-N antibodies (more prevalent in responders, P = 0.04) and liver disease (more prevalent in nonresponders, P = 0.007). By June 1, 2021, no case of severe COVID-19 was observed in MHD patients or in controls.Table 2Immune Response to SARS-CoV-2 Vaccination Among MHD Patients and ControlsComparison Between Groups on Day 28 After First DoseLongitudinal Follow-up in MHD PatientsControlsMHDPDay 49Day 77No history of COVID-19No. of participants33242422Presence of anti-N antibodies0 (0%)0 (0%)–0 (0%)0 (0%)Presence of anti-RBD antibodies28 (85%)19 (79%)0.621 (88%)20 (91%)Anti-RBD antibodies, U/mL199 [9-250]25 [5-250]0.4190 [33-250]118 [26-250]History of COVID-19No. of participants1210aIncluding the 2 MHD patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by quantitative polymerase chain reaction (qPCR) on a nasopharyngeal swab on the day of the first vaccine dose.1010Presence of anti-N antibodies12 (100%)7 (70%)aIncluding the 2 MHD patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by quantitative polymerase chain reaction (qPCR) on a nasopharyngeal swab on the day of the first vaccine dose.0.049 (90%)9 (90%)Anti-N antibodiesbCut-off index (chemiluminescent signal of sample/cut-off value).94 [34-158]25 [1-56]0.850 [13-64]44 [31-59]Presence of anti-RBD antibodies12 (100%)9 (90%)0.310 (100%)10 (100%)Anti-RBD antibodies, U/mL250 [250-250]250 [250-250]0.6250 [250-250]250 [250-250]Values given as count (%) or median [interquartile range].a Including the 2 MHD patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by quantitative polymerase chain reaction (qPCR) on a nasopharyngeal swab on the day of the first vaccine dose.b Cut-off index (chemiluminescent signal of sample/cut-off value). Open table in a new tab Values given as count (%) or median [interquartile range]. Around 80% of the included nursing home residents on MHD mounted anti-RBD antibodies 1 week after the second BNT162b2 dose, despite advanced age and multiple comorbidities. Moreover, the humoral response was sustained until day 77 after the first dose. Nevertheless, although this did not reach statistical significance (likely owing to the small sample size), anti-RBD level on day 28 was lower in MHD patients than in controls without COVID-19 history (25 and 199, respectively). Yet, no severe COVID-19 was observed among MHD patients by June 1, 2021; however, their lower peak antibody titers may be associated with a shorter duration of clinical efficacy, as observed with other vaccines.5Labriola L. Jadoul M. The decades-long fight against HBV transmission to dialysis patients: slow but definite progress.Nephrol Dial Transplant. 2010; 25: 2047-2049Crossref PubMed Scopus (17) Google Scholar Grupper et al6Grupper A. Sharon N. Finn T. et al.Humoral response to the Pfizer BNT162b2 vaccine in patients undergoing maintenance hemodialysis.Clin J Am Soc Nephrol. 2021; 16: 1037-1042Crossref PubMed Scopus (201) Google Scholar recently documented a humoral response in 54 of 56 (96%) vaccinated MHD patients. However, their patients were younger (mean age 74) and did not have serologic testing for prior COVID-19, and the level of anti-RBD antibodies was measured 1 month after the second vaccine dose, all factors potentially complicating comparison with our results.3Walsh E.E. Frenck R.W. Falsey A.R. et al.Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates.N Engl J Med. 2020; 383: 2439-2450Crossref PubMed Scopus (1431) Google Scholar,7Krammer F. Srivastava K. Alshammary H. et al.Antibody responses in seropositive persons after a single dose of SARS-CoV-2 mRNA vaccine.N Engl J Med. 2021; 384: 1372-1374Crossref PubMed Scopus (444) Google Scholar In a recent nationwide mass-vaccination study, the clinical effectiveness of BNT162b2 was similar across age groups (with >70,000 participants aged >70 years).8Dagan N. Barda N. Kepten E. et al.BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting.N Engl J Med. 2021; 384: 1412-1423Crossref PubMed Scopus (1366) Google Scholar Our results demonstrate the immunogenicity of the vaccine in elderly patients on MHD with extensive comorbidities. Since the immunogenicity of other vaccines and duration of specific immunity is lower in MHD patients than in the general population,5Labriola L. Jadoul M. The decades-long fight against HBV transmission to dialysis patients: slow but definite progress.Nephrol Dial Transplant. 2010; 25: 2047-2049Crossref PubMed Scopus (17) Google Scholar serological follow-up may help determine optimal immunization schedules. As recently documented in the general population,7Krammer F. Srivastava K. Alshammary H. et al.Antibody responses in seropositive persons after a single dose of SARS-CoV-2 mRNA vaccine.N Engl J Med. 2021; 384: 1372-1374Crossref PubMed Scopus (444) Google Scholar anti-RBD levels are 10-fold higher in vaccinated MHD patients with preexisting COVID-19 than in those without. Moreover, 8 out of 10 seropositive MHD patients elicited rapid and maximal immune responses, with anti-RBD levels above the upper level of measurement (>250 U/mL), even 7-13 days after the first dose in 2 of them. A definite strength of this study is its multicentric design. Clear limitations are the small sample size, and the focus on a specific population of frail and very ill patients. In conclusion, around 80% of nursing home residents on MHD develop anti-spike antibodies 1 week after the second dose of the Pfizer-BioNTech mRNA SARS-CoV-2 vaccine, and this response is sustained over 2 months after the second dose. Follow-up studies are needed to assess the durability of the vaccine response in this high-risk population. Research area and study design: LL, AS, BK, MJ; data acquisition: LL, AS, EVR, AR, GC, GG, JMP, PB, MDS; data analysis and interpretation: LL, AS, JM, MJ; statistical analysis: JM; supervision or mentorship: MJ, JCY, BK, HRV. LL, AS, and BK contributed equally to this work. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual’s own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate. None. Dr Labriola reports lecture fees and travel support from Amgen, and travel support from Vifor Med Care Pharma. Dr Pochet reports lecture fees from Amgen, Vifor, and Fresenius Medical Care. Dr Morelle reports lecture fees from Baxter Healthcare and Fresenius Medical Care, travel support from Sanofi-Genzyme, and research grants from Baxter Healthcare and Alexion outside the submitted work. Dr Jadoul reports personal fees, nonfinancial support, and other from Astra-Zeneca, grants from Amgen, personal fees from Astellas, personal fees from Abbvie, personal fees and other from Fresenius, Vifor Med Care Renal Pharma, personal fees from Menarini, grants from Roche, grants from Otsuka, grants from Janssen-Cilag, grants, personal fees, and other from Merck (MSD), nonfinancial support from Sanofi, personal fees and other from Mundipharma, personal fees from Bayer, outside the submitted work; all grants and fees paid to institution. The remaining authors declare that they have no relevant financial interests. Received April 12, 2021. Evaluated by 2 external peer reviewers, with direct editorial input from a Statistics/Methods Editor, an Associate Editor, and the Editor-in-Chief. Accepted in revised form July 16, 2021. Download .pdf (.11 MB) Help with pdf files Supplementary File (PDF)Item S1; Table S1.