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Evaluation of the SARS-CoV-2 Antibody Response to the BNT162b2 Vaccine in Patients Undergoing Hemodialysis

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  What is the serologic response to the BNT162b2 COVID-19 vaccine in patients undergoing hemodialysis?

Findings  In this cohort study of 142 patients receiving hemodialysis, humoral response was compared in 66 patients sampled 28 days after receipt of 1 dose of vaccine with 76 patients who received 2 doses of vaccine sampled 14 days after the second dose. Among those receiving 1 dose, 6% had antireceptor binding domain response above the median level of convalescent serum vs 41% of those who received 2 doses at 1 week, increasing to 60% by 2 weeks.

Meaning  The findings of this study suggest that, given that patients receiving hemodialysis appeared to exhibit a poor humoral response to a single dose of BNT162b2 vaccine, the second dose should not be delayed.

Abstract

Importance  Patients undergoing hemodialysis have a high mortality rate associated with COVID-19, and this patient population often has a poor response to vaccinations. Randomized clinical trials for COVID-19 vaccines included few patients with kidney disease; therefore, vaccine immunogenicity is uncertain in this population.

Objective  To evaluate the SARS-CoV-2 antibody response in patients undergoing chronic hemodialysis following 1 vs 2 doses of BNT162b2 COVID-19 vaccination compared with health care workers serving as controls and convalescent serum.

Design, Setting, and Participants  A prospective, single-center cohort study was conducted between February 2 and April 17, 2021, in Toronto, Ontario, Canada. Participants included 142 patients receiving in-center hemodialysis and 35 health care worker controls.

Exposures  BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine.

Main Outcomes and Measures  SARS-CoV-2 IgG antibodies to the spike protein (anti-spike), receptor binding domain (anti-RBD), and nucleocapsid protein (anti-NP).

Results  Among the 142 participants undergoing maintenance hemodialysis, 94 (66%) were men; median age was 72 (interquartile range, 62-79) years. SARS-CoV-2 IgG antibodies were measured in 66 patients receiving 1 vaccine dose following a public health policy change, 76 patients receiving 2 vaccine doses, and 35 health care workers receiving 2 vaccine doses. Detectable anti-NP suggestive of natural SARS-CoV-2 infection was detected in 15 of 142 (11%) patients at baseline, and only 3 patients had prior COVID-19 confirmed by reverse transcriptase polymerase chain reaction testing. Two additional patients contracted COVID-19 after receiving 2 doses of vaccine. In 66 patients receiving a single BNT162b2 dose, seroconversion occurred in 53 (80%) for anti-spike and 36 (55%) for anti-RBD by 28 days postdose, but a robust response, defined by reaching the median levels of antibodies in convalescent serum from COVID-19 survivors, was noted in only 15 patients (23%) for anti-spike and 4 (6%) for anti-RBD. In patients receiving 2 doses of BNT162b2 vaccine, seroconversion occurred in 69 of 72 (96%) for anti-spike and 63 of 72 (88%) for anti-RBD by 2 weeks following the second dose and median convalescent serum levels were reached in 52 of 72 patients (72%) for anti-spike and 43 of 72 (60%) for anti-RBD. In contrast, all 35 health care workers exceeded the median level of anti-spike and anti-RBD found in convalescent serum 2 to 4 weeks after the second dose.

Conclusions and Relevance  This study suggests poor immunogenicity 28 days following a single dose of BNT162b2 vaccine in the hemodialysis population, supporting adherence to recommended vaccination schedules and avoiding delay of the second dose in these at-risk individuals.

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Article Information

Accepted for Publication: June 27, 2021.

Published: September 2, 2021. doi:10.1001/jamanetworkopen.2021.23622

Correction: This article was corrected on February 14, 2022, to fix errors in the Abstract Results and the key in Figure 1.

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Yau K et al. JAMA Network Open.

Corresponding Author: Michelle A. Hladunewich, MD, MSc, Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, D4 Room 474, Toronto, ON M4N 3M5, Canada (michelle.hladunewich@sunnybrook.ca).

Author Contributions: Dr Hladunewich had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. These authors contributed equally: Dr Yau and Mr Abe. These authors contributed equally: Drs Gingras and Hladunewich.

Concept and design: Yau, Naimark, Oliver, Perl, Leis, Bolotin, Tran, Straus, Gonzalez, McGeer, Chan, Gingras, Hladunewich.

Acquisition, analysis, or interpretation of data: Yau, Abe, Mullin, Shadowitz, Sukovic, Garnham-Takaoka, Quinn de Launay, Takaoka, Chan, Colwill, Gingras, Hladunewich.

Drafting of the manuscript: Yau, Oliver, Gonzalez, Sukovic, Colwill, Gingras, Hladunewich.

Critical revision of the manuscript for important intellectual content: Yau, Abe, Naimark, Perl, Leis, Bolotin, Tran, Mullin, Shadowitz, Garnham-Takaoka, Quinn de Launay, Takaoka, Straus, McGeer, Chan, Hladunewich.

Statistical analysis: Yau, Abe, Oliver, Hladunewich.

Obtained funding: Chan, Hladunewich.

Administrative, technical, or material support: Yau, Leis, Bolotin, Mullin, Shadowitz, Gonzalez, Sukovic, Garnham-Takaoka, Quinn de Launay, Takaoka, McGeer, Chan, Colwill, Gingras.

Supervision: Perl, Gonzalez, Straus, Gingras, Hladunewich.

Conflict of Interest Disclosures: Dr Oliver reported receiving fees from the Ontario Renal Network as a contracted regional medical lead outside the submitted work. Dr Perl reported receiving speaking honoraria and consultancy fees from Baxter Healthcare; grants from Agency for Healthcare Research and Quality grant support; speaking honoraria from Fresenius Medical Care, AstraZeneca, Davita Healthcare, and US Renal Care; and consultancy fees from LiberDi Dialysis outside the submitted work. Dr Tran reported that Public Health Ontario received funding from the Public Health Agency of Canada and test kits from the Canadian Immunity Task Force for COVID-19 serosurveillance studies. Public Health Ontario is also involved in a COVID-19 mix-and-match vaccine clinical trial examining safety and immunogenicity. Dr McGeer reported receiving an investigator-initiated grant from Pfizer; collaborative grant to the institution from Pfizer; investigator-initiated grant to the institution from Merck; and advisory board fees from Pfizer, Merck, Medicago Moderna, Janssen, GSK, and AstraZeneca outside the submitted work. Dr Colwill reported receiving funding from Medivolve Inc for initial development of an enzyme-linked immunosorbent assay at Sinai Health System outside the submitted work. Dr Gingras participates in the working party (testing) and working party (immunology) of the CITF, chairs the CIHR Institute of Genetics Advisory Board, and is a member of the SAB of the National Research Council of Canada Human Health Therapeutics Board. Dr Hladunewich reported receiving grants from Pfizer for a focal segmental glomerulosclerosis study, Ionis for a immunoglobulin A study, Chemocentryx for a focal segmental glomerulosclerosis study, Calliditas for an immunoglobulin A study, Roche for a preeclampsia study, and consultant fees from an Alynylam pregnancy study outside the submitted work. No other disclosures were reported.

Funding/Support: This project was funded by the COVID-19 Immunity Task Force (grant 2122-HQ-000071). The equipment used is housed in the Network Biology Collaborative Centre at the Lunenfeld-Tanenbaum Research Institute, a facility supported by Canada Foundation for Innovation funding (grant CFI 33474), the Ontarian Government, and Genome Canada and Ontario Genomics (grant OGI-139). Dr Gingras is supported by the Canadian Institutes of Health Research (FDN 143301) and a Canada Research Chair, Tier 1, in Functional Proteomics. Mr Abe is a recipient of an Ontario Graduate Scholarship from the Ministry of Training, Colleges and Universities Ontario.

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank lead study coordinators Anny Gonzalez, BSc, and Tatjana Sukovic, BSc (Sunnybrook Health Sciences Centre), for coordinating this study and the Sunnybrook Health Sciences Centre hemodialysis staff for assisting with sample collection. We also thank Shiva Barati, MD, Darlene Cann, BSc, Gary Chao, PhD, Karen Green, RN, MSc, Lois Gilbert, BSc, Nazrana Haq, MD, MSc, Angel Xin Liu, MSc, Mohammad Mozafarihashjin, MSc, Aimee Paterson, BSc (Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital), Nimitha Paul, MPH (Li Ka Shing Knowledge Institute, St Michael’s Hospital, Unity Health Toronto), and Philip Samaan, BSc, and Salma Sheikh Mohamed, MSc (Department of Laboratory Medicine and Pathobiology, University of Toronto), who assisted in data collection and management of samples from health care worker controls. We thank Sharmistha Mishra, MD, PhD, Stefan Baral, MD, Christine Fahim, PhD, Mario Ostrowski, MD (Li Ka Shing Knowledge Institute, St Michael’s Hospital, Unity Health Toronto), Adrienne Chan, MD, MPH (Sunnybrook Health Sciences Centre), and Jennifer Gommerman, PhD (Department of Laboratory Medicine and Pathobiology, University of Toronto), for sharing health worker data from the Wellness Hub initiative (#20-0339-E, Mount Sinai Hospital). The antibody measurements and initial data analysis were performed by Bhavisha Rathod, BSc, Mahya Fazel-Zarandi, Jenny Wang, BSc, and Adrian Pasculescu, PhD (Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital). The individuals acknowledged did not receive compensation specifically for their assistance with the study.

Additional Information: Convalescent serum data were obtained from the Toronto Invasive Bacterial Diseases Network (REB studies #20-044 Unity Health, #02-0118-U/05-0016-C, Mount Sinai Hospital).

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