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

Chronic Kidney Diseases, Covid19, SARS-CoV Infection

Kidney transplant recipients, Dialysis, Chronic kidney disease stage 4-5, SARS-CoV-2 vaccination, COVID-19 vaccination, Antibody based immune response

Rationale: COVID-19 is associated with severely increased morbidity and mortality in patients with chronic kidney disease stage G4-G5 and patients on dialysis or after kidney transplantation. Therefore, effective SARS-CoV-2 vaccination would be of great clinical importance in these patients. However, SARS-CoV-2 vaccination studies have excluded these patients so-far. Literature data indicate that vaccination may be less effective in these patient groups. Objective: To assess the efficacy and safety of SARS-CoV-2 vaccination in patients with chronic kidney disease stage G4-G5, patients on dialysis or after kidney transplantation during two years follow-up after vaccination. Study design: prospective single center observational cohort study. Study population: * all Dutch patients on dialysis with data registered in the Dutch Dialysis registry (RENINE) * all Dutch patients after kidney transplantation with data registered in the Dutch national kidney transplant registry (NOTR). * All Dutch patients with chronic kidney disease stage G4-G5 registered in the Santeon hospitals. Intervention: After SARS-CoV-2 vaccination according to standard of care, blood will be drawn for antibody response measurements at day 28 and month 6 after 2nd vaccination at by mailer-based finger-prick in 3400 hemodialysis patients, 600 peritoneal dialysis patients, 4000 patients after kidney transplantation and 4000 patients with chronic kidney disease stage G4-G5. Patients who will undergo a 3rd SARS-CoV-2 vaccination via the national vaccination program for immunocompromised patients will be asked to carry out the mailer-based finger-prick 28 days after the 3rd SARS-CoV-2 vaccination, instead of the antibody measurement 6 months after the 2nd SARS-CoV-2 vaccination. Main study parameters/endpoints: The primary endpoint is efficacy of SARS-CoV-2 vaccination determined as: \- the incidence of COVID-19 after vaccination. Secondary endpoints are * mortality * adverse events of specific interest according to (inter)national authorities in collaboration with LAREB * presence of HLA-antibodies in dialysis patients on the waiting list for a first kidney transplantation * acute rejection and graft failure in patients after kidney transplantation In a subset of patients additional secondary endpoints will be assessed * the antibody based immune response at 28 days after completion of SARS-CoV-2 vaccination. * the durability of antibody based immune response at 6 months compared to at 28 days after having received two subsequent SARS-CoV-2 vaccinations, in 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. The incidence of these endpoints will be compared, if applicable, to those: * in the general population who are vaccinated * in patients on dialysis or after kidney transplant who are not vaccinated Within these patient groups endpoints will be compared between recipients of different vaccines.

1. 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 2. 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. 3. 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.

Netherlands