The REnal Patients COVID-19 VACcination Immune Response (RECOVAC IR) Study

OBJECTIVES

Primary objective:

To assess the antibody response after SARS-CoV-2 vaccination in patients with CKD stages 4/5, on dialysis or alive with a kidney transplant as compared to controls.

Secondary Objectives:

To assess in these groups of subjects after SARS-CoV 2 vaccination:

• durability of the antibody response
• the SARS-CoV-2-specific T and B cell response
• adverse events
• antibody response after third vaccination in patients on dialysis and kidney transplant recipients

Exploratory Objectives:

To assess in these groups of subjects after SARS-CoV 2 vaccination:

• the association between baseline (immune) parameters and the immune response to SARS-CoV-2 vaccination
• the neutralizing capacity of anti-COVID-19 antibodies
• the incidence of SARS-CoV-2 infection and outcome of COVID-19 disease during 6 months after SARS-CoV-2 vaccination and in a subset 28 days after third vaccination

STUDY DESIGN

This is a prospective, controlled multicenter cohort study to evaluate the efficacy and safety after SARS-CoV-2 vaccination in patients with CKD4/5, dialysis patients and kidney transplant recipients as compared to controls. Therefore, 4 cohorts will be included in this study.

• Cohort A: Patients with CKD stages 4 and 5 (eGFR <30 ml/min*1.73m2) (n = 175)
• Cohort B: Patients on hemodialysis and peritoneal dialysis (n = 175)
• Cohort C: Kidney Transplant Recipients (n= 300)
• Cohort D: Controls (n = 200)

Assessment of immune response:

Blood samples will be collected at baseline (i.e. prior to first vaccination) and 28 days, and 6 months after the second vaccination and in a subset 28 days after the third vaccination.

Evaluation other parameters:

To evaluate hematology parameters, liver and kidney function, additional blood samples will be collected at baseline, and 28 days and 6 months after the second vaccination.

Information on clinical course, incidence of SARS-CoV-2 infection, outcome of COVID-19 will be collected up to 6 months after second and in a subset 28 days after third vaccination for descriptive purposes.

METHODS

Main study parameter/endpoint:

The primary endpoint is the antibody based immune response to vaccination against COVID-19 on day 28 after the second vaccination as compared to controls.

Secondary study parameters/endpoints:

• Duration and in-depth assessment of immune response through:

• Measurement of SARS-CoV2 specific antibodies at 6 months after vaccination to test the durability of response
• Assessment of SARS-CoV2 specific T and B cell response, 28 days, and 6 months after the second vaccination using a high throughput Interferon ɣ, IL-21 SARSCoV-2 specific T cell ELISPOT and SARS-CoV2 specific B cell memory ELISPOT.
• Safety assessment through:

• Incidence and severity of solicited AEs during 7 days after each vaccination
• Antibody based immune response after third vaccination:

• Measurement of SARS-CoV-2 specific antibodies at 28 days after third vaccination in patients on dialysis and kidney transplantation recipients.

Exploratory study parameters:

• Baseline (immune) parameters associated with vaccination response
• Neutralizing capacity of antibodies to test functionality
• In-depth flow-cytometric analyses for functional and phenotypical characterization of SARS-CoV-2 specific T cell responses will be performed followed by assessment of proliferative capacity, cytokine production and phenotypical markers in a subset of patients.
• Information on incidence of SARS-CoV-2 infection and outcome of COVID-19 disease during 6 months after second vaccination and in a subset 28 days after third vaccination will be collected.
• In a substudy in Radboudumc nasal strips will be collected and mucosal antibody response to COVID-19 analysed

Inclusion criteria

• All patients should be eligible for COVID-19 vaccination as described by the instructions of the manufacturer.
• Age of 18 years or older
• Capable of understanding the purpose and risks of the study, fully informed and given written informed consent
• Either

• CKD4/5, with an eGFR <30 ml/min*1.73m2 by CKD-EPI
• Hemodialysis, or peritoneal dialysis
• KT recipient at least 6 weeks after transplantation
• Partner, sibling or family member of participating patient

Exclusion criteria

• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g. anaphylaxis) to any component of the study intervention(s)
• Multi-organ transplant recipients
• Previous or active COVID-19 disease
• Pregnancy or breastfeeding
• Active (haematological) malignancy
• Inherited immune deficiency
• Infection with Human Immunodeficiency Virus (HIV)
• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.

Additional exclusion criterion for patients with CKD stages 4/5, on dialysis and controls:

• Individuals who receive maintenance treatment with immunosuppressive therapy in the 6 months before inclusion, including cytotoxic agents or systemic corticosteroids.

Additional exclusion criterion for controls:

• severely impaired kidney function, with an eGFR < 45 ml/min*1.73m2 by CKD-EPI