Rationale: COVID-19 is associated with severely increased morbidity and mortality in patients with severely impaired kidney function, on dialysis or alive with a kidney transplant. Therefore, effective SARS-CoV-2 vaccination would be of great clinical importance in these patients. However, SARS-CoV-2 vaccination studies have excluded patients with chronic kidney disease (CKD) so-far. Objective: To assess the efficacy and safety of SARS-CoV-2 vaccination in patients with CKD stages 4/5, on dialysis or alive with a kidney transplant as compared to controls. Study design: prospective, controlled multicenter study Study population: 175 patients with CKD stages 4/5 (eGFR < 30 ml/min/1.73m2), 175 on dialysis , 300 alive with a kidney transplant and 200 controls (partners or sibblings of patients) Intervention: SARS-CoV-2 vaccination according to standard of care. Blood will be drawn at 4 different time points (baseline and at day 28, month 6 and in a subset 28 days after a third vaccination). Main study parameters/endpoints: The primary endpoint is the antibody based immune response on day 28 after the second vaccination. Participants will be classified as responders or non-responders based on a spike (S)1 specific antibody levels of >=10 or
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:
1. 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.
2. Safety assessment through:
- Incidence and severity of solicited AEs during 7 days after each vaccination
3. 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
Biological: SARS-CoV-2 vaccination
All participants will receive two vaccinations against COVID-19 according to the manufacturer's instructions.
Inclusion Criteria:
1. All patients should be eligible for COVID-19 vaccination as described by the
instructions of the manufacturer.
2. Age of 18 years or older
3. Capable of understanding the purpose and risks of the study, fully informed and given
written informed consent
4. 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
Radboud university medical center
Nijmegen, Gelderland, Netherlands
Amsterdam University Medical Center
Amsterdam, Noord-Holland, Netherlands
Erasmus Medical Center
Rotterdam, Zuid-Holland, Netherlands
University Medical Center Groningen
Groningen, Netherlands