MODERATORS: Luuk Hilbrands, NL – Ron Gansevoort, NL

PANELLISTS:
Fiona Loud, UK Patient representative (Policy Director at Kidney Care UK)
Piergorgio Messa, IT Expert on vaccination in CKD
Marta Crespo, ES Expert on vaccination in transplant patients
Marjolein van Egmond, NL Expert on immunology and vaccination
Coretta van Leer-Buter, NL Virologist

e-seminar Summary

Written by Jasna Trbojevic-Stankovic
Reviewed by Ronald Gansevoort

Since medications to treat COVID-19 are unlikely to be developed soon, effective and safe vaccines and continuous infection mitigation strategies are currently the only realistic options to curb the ongoing pandemic. While vaccination is a powerful and cost-effective method to reduce infection-related morbidity and mortality, vaccine efficacy has historically not been rigorously studied in chronic kidney disease (CKD) patients, and COVID-19 vaccines immunogenicity is largely unknown in this high-risk population.

As we move into 2021, several vaccines have either received or are about to receive emergency use authorization, with many more in development. Do COVID-19 vaccines offer the same high level of protection in CKD patients as has been reported for generally healthy participants in recent trials? What are the differences in efficacy and safety between them? Should the standard vaccination regimens be changed in CKD patients? These were the most important questions among many that were sent to the ERA-EDTA by the concerned public. In an attempt to elucidate this issue, ERA-EDTA organized a round table webinar with a selected group of experts who tried to provide the best answers based on the currently available scientific information.

Prof. Piergiorgio Messa, an expert on vaccination in CKD and dialysis, agrees that the vaccination is the only possible way to drive down COVID-19 and that kidney disease patients need to be promptly prioritized for COVID-19 vaccination. Nevertheless, the historical data for established vaccines, such as those for influenza or hepatitis B, suggest that vaccine efficacy and response in CKD patients can substantially vary. “To get the best results in CKD and dialysis patients, we will probably need to increase the vaccine doses and/or the number of vaccinations. Although it is currently hard to make any predictions based on the data we have, I hope that the efficacy of 60-70% of vaccines in dialysis patients could be a good starting point,” suggested Prof. Messa.

The COVID-19 pandemic also significantly affects kidney transplant patients. This population is at increased risk of serious adverse outcomes if they develop COVID-19 because of the high-dose immunosuppressive therapies they are receiving. “Nothing is known about the possible efficacy of the currently available vaccines in this group of patients because they haven’t been included in any trial yet,” said Prof. Marta Crespo, an expert on vaccination in patients with a kidney transplant. “Some immunosuppressants, specifically anti-CD20 therapies (e.g. rituximab), are known to abrogate immune responses to vaccinations, so these drugs will certainly reduce the efficacy of COVID-19 vaccines,” explained Prof. Marjolein van Egmond, an expert on immunology and vaccination. Decisions on whether to delay or interrupt immunosuppressant treatment to find an appropriate vaccination window, use alternative immunosuppressive therapies or increase the dose or number of vaccinations need to be considered in addition to weighing the potential risk of autoimmune disease relapse versus the risk of infection if vaccination is delayed. “It’s still early days to give any definitive advice in this regard. We are expecting new data from the follow-up studies, but for now, it is not known how immunosuppressive patients will respond to vaccines,” Prof. van Egmond added.

Without a doubt, the most frequently asked question was for how long does the immunity from COVID-19 vaccines last? Dr. Coretta van Leer, a virologist and vaccination expert, explained that the first results from those who received mRNA vaccines are encouraging as these individuals have both measurable immune responses and are protected from infection. “But we still don’t know for how long this is going to last” disclosed doctor van Leer. She also suspects that in CKD and kidney transplant patients the immunity against the infection is going to wear off sooner than in healthy individuals.
Prof. Messa and Prof. Crespo share the opinion that COVID-19 vaccines can be considered safe in both dialysis and kidney transplant patients and that there should be no substantial differences in side effects compared to a healthy population. There were no reported cases of graft loss in kidney transplant recipients infected with COVID-19 even after withdrawal of immunosuppressive agents during infection. However, caution and further research are needed in this area because of the controversial findings that mRNA influenza vaccine may induce the development of anti-human leukocyte antigen (HLA) and anti-major histocompatibility complex class I – chain A (MICA) antibodies which may negatively affect graft survival and that the same scenario might happen to COVID-19 mRNA vaccines too.
The greatest concern of patients with autoimmune diseases is whether the risk of flare or exacerbation of the disease is higher after vaccination. “Current reviews and guidelines state that autoimmune disease patients are not endangered by exacerbation or worsening of their primary disease,” confirmed Prof. Crespo.

There is also no evidence that spike proteins encoded by mRNA vaccine can spread all over the body, attach to the angiotensin-converting enzyme-2 (ACE-2) receptors in the kidneys and provoke any negative effects. “After vaccine injection, the spike proteins will be produced by myocytes of the arm, they stay locally and can’t travel beyond the regional lymph nodes,” explained Dr. Van Leer. Besides, there should be no worries about the rumors that vector vaccines (e.g. Oxford vaccine) are contaminated with remnants of the cells that could express HLA antigens, as no study confirmed such speculations.
Fiona Loud, a patient representative and a policy director of Kidney Care UK, believes that the best way forward for kidney disease patients is to get the vaccine. “Kidney disease patients have had a horrible time during the last year and the impact of COVID-19 can’t be overestimated. They see vaccines as a way out or a path back to some kind of normality so they want to collect all the necessary information about the right balance between the safety and efficacy of COVID-19 vaccines,” said she and emphasized how important is to be aware that the benefits of vaccines outweigh their theoretical risks. Mrs. Loud works with kidney patients and has herself received a kidney transplant 14 years ago.

All experts argued with suggestions that the vaccination should be delayed in patients with renal diseases because long-term data are lacking. The exceptions should only be patients who recently received a kidney transplant and those with a history of kidney transplant rejection. “At the moment, the danger is very high for kidney disease patients and I think this is the biggest argument to get the vaccines,” said Dr. Van Leer. On the other hand, “kidney transplantations should be delayed in high-risk groups including patients older than 70 years who are at high-risk of COVID-19 infections, or in those who are highly sensitized if they are not vaccinated,” clarified Prof. Crespo. “Living kidney donors and their recipients should also be vaccinated as soon as possible,” agreed Prof. Crespo, Prof. Messa, and Mrs. Loud.

Prof. Ron Gansevoort and Prof. van Egmond stressed out that based on the available data on efficacy and safety, mRNA vaccines should be considered as the best candidates for renal patients. “In Britain, however, nephrologists are advising that both vector and mRNA vaccines are appropriate,” added Mrs. Loud. Experts also agree that the sample type approach is the most practical for the follow-up of immunological responses and possible side effects after vaccination.

Prof. Van Egmond recommends vaccinations even in kidney disease patients who recovered from COVID-19 as it can greatly amplify their antibody levels. Measuring IgG titers after re-vaccination could be of value to identify patients with eventually inadequate response to vaccines. “If their IgG antibodies vanish or get low too fast, third vaccine shot should be considered,” advises Prof. Gansevoort. “Still, it is not all about antibodies, memory B and T cells may also aid protection against reinfection severity,” reminded Prof. Messa.

Getting the flu and other vaccines is also important for high-risk groups such as kidney patients. Still, manufacturers of COVID-19 vaccines are against their co-administration with other vaccines, since there is no data about their compatibility. “It would be impossible to distinguish the side effects that people may experience from any one of them. From the immunological standpoint, there should be no worries, the immune system is simply more powerful than one pathogen you get through vaccination”, explained Prof. Van Leer.

Post-vaccination symptoms such as fever, fatigue, headache, chills, myalgia, or arthralgia indicate the immune system is responding to the vaccine, but they could also cause confusion as they overlap with symptoms of COVID-19. These symptoms typically occur within the first three days of vaccination and resolve in a day or two. “On the other hand, cough, shortness of breath, sore throat, and loss of taste or smell are not typical following vaccination. If someone develops these symptoms or if fever persists for more than 3 days, the person needs to be PCR tested,” explained Prof. Messa.

In the closing remarks, Prof. Gansevoort emphasized the importance of joining forces all over Europe and conduct new studies about the efficacy and safety of COVID-19 vaccines in kidney disease patients. Dutch researchers are already investigating four cohorts of patients including 175 participants with CKD stages 4 and 5, 175 participants on hemodialysis and peritoneal dialysis, and 300 kidney transplant recipients stratified for different immunosuppressive regimens and a matched healthy control cohort of 200 participants. All participants in this study will be vaccinated with only one vaccine, then at certain time points, their blood samples will be collected and finally, their immune responses will be measured as the serologic response (antibodies), neutralizing antibodies, and T and B cell-mediated responses. Another type of study will be needed to examine the efficacy and safety of vaccines in preventing COVID-19 in a real-life setting. The study could collect the data from national registries of kidney transplant recipients and dialysis patients, which already routinely collect the data about patients’ characteristics. The efficacy of vaccines could be compared with a healthy control group, which could be partners of KD patients or matched samples of the national vaccination registry. COVID-19 infections and adverse events reports after vaccination will be registered in ERACODA for detailed disease and treatment characteristics and the data from ERACODA will be linked with the data from national registries of kidney transplant recipients and dialysis patients. Final endpoints could be vaccination coverage rate, the incidence of COVID-19 in vaccinated vs. non-vaccinated patients, the incidence of COVID-19 comparing various vaccines, and the incidence of special adverse events (e.g. transplant rejection rates). Such studies should be harmonized and performed all over Europe or even globally, designed with similar protocols, and should include all of the currently available COVID-19 vaccines.

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