RECOVAC - Long Term Efficacy and Safety of COVID-19 (SARS-CoV-2) Vaccination in Kidney Disease Patients

• OBJECTIVES

Primary objective:

To assess the efficacy of SARS-CoV-2 vaccination by the incidence of COVID-19 in patients with chronic kidney disease stage G4-G5, on dialysis and patients after kidney transplantation who received SARS-CoV-2 vaccination

Secondary Objectives:

• To assess the safety of vaccination

In a subgroup of participants:

• To assess the level of antibody response at 28 days and 6 months after SARS-CoV-2 vaccination
• To assess durability of the antibody response at 6 months after having received two subsequent SARS-CoV-2 vaccinations, in a subset of patients that have not received a 3rd SARS-CoV-2 vaccine
• the antibody based immune response at 28 days after having received the 3rd SARS-CoV-2 vaccination.

Exploratory Objectives:

• The vaccination coverage rate
• The severity of COVID-19 in case of infection
• The influence of vaccination on health-related quality of life by patient reported outcome measures (PROMs) in patients on dialysis.
• The SARS-CoV-2 genotype in patients with COVID-19

In a subgroup of participants:

• To assess the level of antibody response after vaccination between patients with COVID-19 and without COVID-19 at:

• 28 days after the 2nd SARS-CoV-2 vaccination
• 28 days after the 3rd SARS-CoV-2 vaccination
• 6 months after the 2nd SARS-CoV-2 vaccination in patients who have not received a 3rd vaccine.
• To assess change in behaviour towards measures against COVID-19 before and after vaccination

If data are available and applicable, outcomes in vaccinated patients on dialysis or after kidney transplantation will be compared:

• with outcomes in the general population
• with outcomes in patients with severely impaired kidney function (CKD stages G4/5), on dialysis or with a kidney transplant who are not vaccinated.
• according to the type of vaccination they received
• STUDY DESIGN

This is a prospective observational registry-based cohort study to evaluate the long-term efficacy and safety after SARS-CoV-2 vaccination on clinically important outcomes in patients with chronic kidney disease stage G4-G5, on dialysis or after kidney transplantation.

All participants will receive vaccination against COVID-19 via the national vaccination program and according to the manufacturer's instructions. To assess the immune response after vaccination, blood samples will be collected at 28 days after the 2nd SARS-CoV-2 vaccination, 28 days after the 3rd SARS-CoV-2 vaccination, and 6 months after the 2nd SARS-CoV-2 vaccination in patients who have not received a 3rd vaccination. In total a maximum of 1 ml blood will be drawn.

Data of the following cohorts will be analyzed in this study.

• Patiens with chronic kidney disease stage G4-G5, data to be derived from the Santeon hospitals.
• Patients on hemodialysis and peritoneal dialysis, data to be derived from the existing national registry RENINE
• Kidney transplant recipients, data to be derived from the existing national registry NOTR
• Patients on dialysis or after kidney transplantation with COVID-19 disease, data to be derived from the ERACODA database.
• METHODS

Main study parameter/endpoint:

The primary endpoints is the incidence of COVID-19 in a two years period after SARS-CoV-2 vaccination in patients with chronic kidney disease stage G4-G5, on dialysis or after kidney transplantation.

Secondary study parameters/endpoints:

Safety in all patients:

• Incidence of mortality
• Incidence of adverse events of specific interest as defined by (inter)national authorities in collaboration with LAREB
• Incidence of a combined endpoint of acute rejection or graft failure in patients after kidney transplantation
• Incidence of HLA antibodies defined as calculated Panel Reactivity Antibodies (cPRA) > 5% in patients on the waiting list for their first kidney transplantation

Efficacy in a subgroup of patients:

• The antibody response against the SARS-CoV-2 Receptor Binding Domain at 28 days after the final SARS-CoV-2 vaccination.
• The antibody response against the SARS-CoV-2 Receptor Binding Domain at 28 days after the 3rd SARS-CoV-2 vaccination.
• The durability of antibody based immune response against SARS-CoV-2 Receptor Binding Domain at 6 months compared to 28 days after completion of SARS-CoV-2 vaccination in patients who did not receive a 3rd SARS-CoV-2 vaccination.

Exploratory study parameters:

• Vaccination coverage rates
• Disease severity in patients who develop COVID-19, assessed as
• Hospitalization
• ICU admission
• Mechanical ventilation
• Mortality
• The influence of vaccination on health-related quality of life by patient reported outcome measures (PROMs) in dialysis patients
• SARS-CoV-2 genotype in patients with COVID-19

In a subgroup of participants:

• To assess the level of SARS-CoV-2 Receptor Binding Domain antibody response after vaccination between patients with COVID-19 and without COVID-19 at:

• 28 days after the 2nd SARS-CoV-2 vaccination
• 28 days after the 3rd SARS-CoV-2 vaccination
• 6 months after the 2nd SARS-CoV-2 vaccination in patients who have not received a 3rd vaccine.
• To assess change in behaviour towards measures against COVID-19 before and after vaccination

These data collected after SARS-CoV-2 vaccination in patients with chronic kidney disease stage G4-G5, on dialysis and after a kidney transplantation will (if applicable data are available) be compared:

• to those obtained in the general population
• to those obtained in patients with chronic kidney disease stage G4-G5, on dialysis or with a kidney transplant who are not vaccinated
• according to the type of vaccination received These comparisons will allow us to analyze whether SARS-CoV-2 vaccination offers efficacy to prevent COVID-19 and sufficient safety in patients with chronic kidney disease stage G4-G5, dialysis and kidney transplant patients when compared to non-vaccinated patients with chronic kidney disease stage G4-G5, dialysis and kidney transplant patients, whether the efficacy is similar as in the general population, and whether there are differences in the risk-benefit ratio between the various vaccines.

Inclusion criteria

• 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 (signed informed consent form has been obtained)
• Either

• eGFR < 30 ml/min/1.73m2 but not on dialysis or with a kidney transplant
• Hemodialysis, or peritoneal dialysis
• Kidney Transplant recipient at least 6 weeks after transplantation

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).
• Patients who opted out for research in the Santeon, RENINE and NOTR registries.
• Patients who participate in the RECOVAC-IR study.
• Of note, patients will be eligible whether or not they have a history of COVID-19. Analyses will be performed in the overall population, but also shown separately for those without and with a history of COVID-19.