Determining the Longitudinal Serologic Response to COVID-19 Vaccination in the Chronic Kidney Disease Population: A Clinical Research Protocol.

Background

People living with chronic kidney disease (CKD) have been disproportionately affected by the coronavirus disease 2019 (COVID-19) pandemic, including higher rates of infection, hospitalization, and death. Data on responsiveness to COVID-19 vaccination strategies and immunogenicity are limited, yet required to inform vaccination strategies in this at-risk population.

Objective

The objective of this study is to characterize the longitudinal serologic response to COVID-19 vaccination.

Design

This is a prospective observational cohort study.

Setting

Participating outpatient kidney programs within Ontario and British Columbia.

Patients

Up to 2500 participants with CKD G3b-5D receiving COVID-19 vaccination, including participants receiving dialysis and kidney transplant recipients (CKD G1T-5T).

Measurements

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies (anti-spike, anti-receptor binding domain, anti-nucleocapsid) will be detected by ELISA (enzyme-linked immunosorbent assay) from serum or dried blood spot testing. In a subset of participants, neutralizing antibodies against novel variants of concern will be evaluated. Peripheral blood mononuclear cells will be collected for exploratory immune profiling of SARS-CoV-2 specific cellular immunity.

Methods

Participants will be recruited prior to or following any COVID-19 vaccine dose and have blood sampled for serological testing at multiple timepoints: 1, 3, 6, 9, and 12 months post vaccination. When possible, samples will be collected prior to a dose or booster. Participants will remain in the study for at least 1 year following their last COVID-19 vaccine dose.

Strengths and limitations

The adaptive design of this study allows for planned modification based on emerging evidence or rapid changes in public health policy surrounding vaccination. Limitations include incomplete earlier timepoints for blood collection due to rapid vaccination of the population.

Conclusions

This large multicenter serologic study of participants living with kidney disease will generate data on the kinetics of SARS-CoV-2 immune response to vaccination across the spectrum of CKD, providing insights into the amplitude and duration of immunity conferred by COVID-19 vaccination and allowing for characterization of factors associated with immune response. The results of this study may be used to inform immunization guidelines and public health recommendations for the 4 million Canadians living with CKD.

Contexte

Les personnes atteintes d’insuffisance rénale chronique (IRC) ont été touchées de façon disproportionnée par la pandémie de COVID-19 ayant notamment présenté des taux plus élevés d’infection, d’hospitalisation et de décès. Les données sur la réactivité aux stratégies de vaccination de la COVID-19 et à l’immunogénicité sont limitées, mais elles sont nécessaires pour développer des stratégies de vaccination dans cette population à risque.

Objectif

Caractériser la réponse sérologique longitudinale à la vaccination contre la COVID-19.

Conception

Étude de cohorte observationnelle prospective.

Cadre

Les programmes ambulatoires de santé rénale participants en Ontario et en Colombie-Britannique.

Sujets

Jusqu’à 2 500 personnes atteintes d’IRC G3B-5D recevant un vaccin contre la COVID-19, y compris des patients suivant des traitements de dialyse et des receveurs d’une greffe rénale (IRC G1T-5T).

Mesures

Les anticorps IgG anti-SARS-CoV-2 (anti-spike, anti-domaine de liaison au récepteur, anti-nucléocapside) seront détectés par ELISA à partir du sérum ou de taches de sang séché. Un sous-groupe de sujets participera également à l’évaluation d’anticorps neutralisants dirigés contre les nouveaux variants préoccupants. Des cellules mononuclées de sang périphérique seront prélevées pour établir un profil immunitaire exploratoire de l’immunité cellulaire spécifique au SARS-CoV-2.

Méthodologie

Les sujets seront recrutés avant ou après toute dose du vaccin contre la COVID-19 et se soumettront à des prélèvements sanguins pour les tests sérologiques à 1, 3, 6, 9 et 12 mois post-vaccination. Lorsque possible, des échantillons seront prélevés avant l’administration d’une dose ou d’un rappel. Les sujets demeureront dans l’étude pendant au moins un an après leur dernière dose de vaccin contre la COVID-19.

Points forts et limites

La conception adaptative de l’étude permet d’apporter des modifications planifiées fondées sur de nouvelles données ou des changements rapides dans les politiques de santé publique entourant la vaccination. Les résultats sont limités par l’absence de certains prélèvements sanguins antérieurs (point temporels) en raison de la vaccination rapide de la population.

Conclusion

Cette vaste étude sérologique multicentrique menée auprès de personnes atteintes de néphropathie fournira des données sur la cinétique de la réponse immunitaire à la vaccination contre le SARS-CoV-2 dans l’ensemble du spectre de l’IRC. Elle fournira des informations sur l’amplitude et la durée de l’immunité conférée par la vaccination contre la COVID-19 et permettra de caractériser les facteurs associés à la réponse immunitaire. Ces résultats serviront à orienter les recommandations de santé publique et les lignes directrices en matière d’immunisation pour les quatre millions de Canadiens et Canadiennes qui vivent avec l’IRC.

Informations de copyright

© The Author(s) 2023.

Déclaration de conflit d'intérêts

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Kevin Yau has received speaker fees from AstraZeneca. Adeera Levin reports being a scientific advisor to, or member of, AstraZeneca, Bayer, Boehringer-Ingelheim, Canadian Journal of Kidney Health and Disease, Canadian Institutes of Health Research, Certa, Chinook Therapeutics, Johnson and Johnson, Kidney Foundation of Canada, National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Otsuka, Reata, Retrophin, and The George Institute; receiving research funding from AstraZeneca, Boehringer-Ingelheim, Canadian Institute of Health Research, Janssen, Johnson and Johnson, Kidney Foundation of Canada, Merck, NIDDK, NIH, Ortho Biotech, Otsuka, and Oxford Clinical Trials; and having consultancy agreements with Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Johnson and Johnson/Jansen, Reata, and Retrophin. Marc Romney has received research support from Public Health Agency of Canada and the COVID-19 Immunity Task Force. Jeffrey Perl reports 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. Shelly Bolotin reports funding from the Canadian Institutes of Health Research, the Canadian Immunization Research Network, the COVID-19 Immunity Task Force, and the Public Health Agency of Canada, outside the submitted work. She is a member of the Canadian Immunization Research Network Management Committee, COVID-19 Immunity Task Force Leadership Group. Vanessa Tran reports 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. Shelly Bolotin and Vanessa Tran are employees of Public Health Ontario. Anne-Claude Gingras has received research funds from a research contract with Providence Therapeutics Holdings, Inc, for other projects, participates in the COVID-19 Immunity Task Force (CITF) Immune Science and Testing working party, 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. Matthew Oliver and Michelle Hladunewich are contracted Medical Leads at Ontario Renal Network, Ontario Health. Matthew Oliver is owner of Oliver Medical Management Inc., which licenses Dialysis Management Analysis and Reporting System software. He has received honoraria for speaking from Baxter Healthcare. Michelle Hladunewich reports receiving grants from Pfizer for a study in focal segmental glomerulosclerosis; Ionis, Calliditas, and Chinook for studies in Immunoglobulin A nephropathy; and Roche for a preeclampsia study. No other competing interests were declared.