The RIVASTIM trials aim to identify strategies to improve immunological responses to a 3rd booster dose of the mRNA Pfizer Comirnaty COVID-19 vaccine in a cohort of kidney transplant patients who have failed to achieve an adequate immune response to a standard two-dose COVID-19 vaccine course. Kidney transplant patients are a highly vulnerable group of immunosuppressed patients who suffer from disproportionately high COVID-19-related morbidity and mortality. The transplant medication sirolimus shows promise in enhancing immune responses to COVID-19 vaccination. In this study kidney transplant patients receiving standard of care immunosuppression with tacrolimus, mycophenolate, and steroids will be randomised to either switch from mycophenolate to sirolimus, or remain on standard of care immunosuppression. Four weeks after randomisation, participants will receive a 3rd COVID-19 vaccine dose, and immunological responses will be assessed 4-6 weeks later. https://anzctr.org.au/ACTRN12621001412820.aspx

The goal of this retrospective study is to evaluate the proportion of seroconversion after 2 doses mRNA anti-SARS-CoV2 vaccination in a cohort of high risk liver transplanted patients. Seroprevalence is a secondary objective in order to identify seronegative patients with a history of COVID-19 (ie who lost antibodies) and seropositive patients with no history of COVID-19. The hypothesis is that the degree of immunosuppression is determinant on the seroconversion rate and therefore, although at higher risk of severe forms of COVID-19, liver transplanted patients have a lower chance of being protected after vaccination. Seroconversion rate in previously seronegative and with no history of COVID-19 liver transplanted patients is the main evaluation criteria. The factors associated with the absence of seroconversion will be identified as a potential tool to better adapt the vaccination strategy in this population. The rate of seroconversion after the 1st dose will also be evaluated. Safety of the 1st and 2nd injection will be reported as well as their value to predict seroconversion. A control group of patients listed for transplantation will also be included both in the seroprevalence and the seroconversion analysis. Persistance of the antibodies in long-term after transplantation and after transplantation for the patients who have been vaccinated before transplantation will also be reported. https://clinicaltrials.gov/show/NCT05079165

Immunocompromised individuals, such as solid organ transplant (SOT) recipients are at high risk of COVID-19 associated complications and mortality. Retrospective studies so far have shown that a majority of SOT recipients did not develop appreciable anti-spike antibody response after a first, second, or even third dose of mRNA vaccine. Treatment with antimetabolites was associated with poor vaccine response. The goal of this study is 1) examine whether transient immunosuppression reduction improves the immune response to a third dose of SARS-CoV-2 mRNA vaccine in kidney transplant recipients and 2) to assess the safety of immunosuppression reduction before and after third dose SARS-CoV-2 mRNA vaccination. https://clinicaltrials.gov/show/NCT05060991

Fifty living donor liver transplantation recipients during maintenance immunosuppression phase will be vaccinated against COVID-19 followed by assessment of immune response to the vaccine and further investigation of correlation of immune response to genetic polymorphisms of HLA DRB1(rs2647087) gene and IL-18 (rs187238 and rs917997) gene. https://clinicaltrials.gov/ct2/show/NCT05051605

Introduction: Inadequate antibody response to mRNA SARS-CoV-2 vaccination has been described among kidney transplant recipients. Immunosuppression level and specifically, use of antimetabolite in the maintenance immunosuppressive regimen, are associated with inadequate response. In light of the severe consequences of COVID-19 in solid organ transplant recipients, we believe it is justified to examine new vaccination strategies in these patients. Methods and analysis: BECAME is a single center, open label, investigator-initiated randomised controlled, superiority trial, aiming to compare immunosuppression reduction combined with a third BNT162b2 vaccine dose versus third dose alone. The primary outcome will be seropositivity rate against SARS-CoV-2. A sample size of 154 patients was calculated for the seropositivity endpoint assuming 25% seropositivity in the control group and 50% in the intervention group. A sample of participant per arm will be also teste for T-cell response. We also plan to perform a prospective observational study, evaluating seropositivity among ~500 kidney transplant recipients consenting to receive a third vaccine dose, who are not eligible for the randomised controlled trial. Ethics and dissemination: The trial is approved by local ethics committee of Rabin medical center (RMC-0192- 21). Results of this trial will be published; trial data will be available. Protocol amendments will be submitted to the local ethics committee. https://clinicaltrials.gov/show/NCT04961229

Adaptive immune responses are essential for clearing viral infections and retention of virus specific memory populations is required for long-term immunity. However, there is still uncertainty about whether adaptive immune responses to SARS-CoV-2 are protective. Such knowledge is of immediate relevance, as it will provide insights into immunity of SARS-CoV-2 infection and thus help define future immunization strategies. Because of the importance of asymptomatic cases in children, a specific study is needed in this population in order to determine their individual and collective protective capacity. This is even truer for immune compromised children that likely have severe forms of the disease with active and prolonged viral replication in whom it is therefore essential to determine the extent of sero conversion but also the quality and duration of the memory responses. For this purpose, we plan to analyze the anti-SARS-CoV-2 humoral and memory T cell responses, in different groups of immuno-compromized children (i.e with different levels/type of immunosuppression; HIV, renal or stem cell transplantation, anti-TNF or methotrexate treatment) and healthy controls seen in 3 University Hospitals, in order to determine the proportion of children with SARS-CoV-2 specific humoral responses, their protective capacity, the magnitude and the quality of the SARS-Cov-2 memory T cells but also their long term persistence at 1 year. https://clinicaltrials.gov/show/NCT04916847

This study aims to measure the efficacy of the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and BNT162b2 mRNA (Pfizer-BioNTech) COVID-19 vaccines in transplant recipients and patients on dialysis, and in their close household contacts. Early reports indicate that kidney transplant recipients receiving immunosuppressive medications have a reduced protective immune response to COVID-19 vaccines. This is of concern as these are the individuals most at risk. These patient groups are adept at avoiding exposure to pathogens out in the world, and are therefore most likely to be exposed to the SARS-CoV-2 virus via a close household contact e.g. a spouse. In this study, transplant recipients and dialysis patients will receive their vaccination at the same time as a close household contact. By comparing the immune response of patient and cohabitant, we will develop an understanding of whether priority vaccination of household contacts is a worthwhile strategy for protecting transplant and dialysis patients from COVID-19 in the future. https://anzctr.org.au/ACTRN12621000532808.aspx

The RIVASTIM trials aim to identify strategies to improve immunological responses to a 3rd booster dose of the mRNA Pfizer Comirnaty COVID-19 vaccine in a cohort of kidney transplant patients who have failed to achieve an adequate immune response to a standard two-dose COVID-19 vaccine course. Kidney transplant patients are a highly vulnerable group of immunosuppressed patients who suffer from disproportionately high COVID-19-related morbidity and mortality. The dietary fibre supplement inulin shows promise in enhancing immune responses to vaccination. In this study kidney transplant patients will be randomised to either take inulin supplements or placebo. Four weeks after randomisation, participants will receive a 3rd COVID-19 vaccine dose, and immunological responses will be assessed 4-6 weeks later. https://anzctr.org.au/ACTRN12621001465842.aspx

The RIVASTIM trials aim to identify strategies to improve immunological responses to a 3rd booster dose of the mRNA Pfizer Comirnaty COVID-19 vaccine in a cohort of kidney transplant patients who have failed to achieve an adequate immune response to a standard two-dose COVID-19 vaccine course. Kidney transplant patients are a highly vulnerable group of immunosuppressed patients who suffer from disproportionately high COVID-19-related morbidity and mortality. The transplant medication sirolimus shows promise in enhancing immune responses to COVID-19 vaccination. In this study kidney transplant patients receiving standard of care immunosuppression with tacrolimus, mycophenolate, and steroids will be randomised to either switch from mycophenolate to sirolimus, or remain on standard of care immunosuppression. Four weeks after randomisation, participants will receive a 3rd COVID-19 vaccine dose, and immunological responses will be assessed 4-6 weeks later.