This positive news comes from a study by NHS Blood and Transplant (NHSBT) using data on outcomes of Covid-19 vaccination in over 48,000 solid-organ transplant recipients, who had received up to four doses of vaccine. The study found that protection increases with each successive vaccine dose.
For transplant recipients who received four vaccine doses and developed Covid-19, the risk of dying within 28 days of diagnosis was less than one in 100 (1%); this compares with a risk of about 10 in 100 (10%) for unvaccinated recipients who had developed Covid-19.
Did the first two vaccine doses reduce risk?
Dr Rommel Ravanan, Associate Medical Director & Chair, Kidney Advisory Group, NHSBT, and Consultant Nephrologist at North Bristol NHS Trust, says: “We are in a very different place to spring 2020. I’m sure kidney patients felt the same fear then as their clinicians. The first indication of hope came from the RECOVERY trial, which showed the steroid dexamethasone greatly improved outcomes for patients in intensive care. With experience, we also learned how best to deliver non-medical care to Covid-19 patients. So by autumn 2020, the fear had blunted a little, and from January 2021, the roll-out of vaccines began to benefit patients.”
Most kidney transplant patients received their first dose of either Comirnaty (Pfizer) or Vaxzevria (AstraZeneca) Covid-19 vaccine in January-February 2021, followed by a second dose about 10 weeks later. In July 2021, NHSBT reported that after these doses, the risk of dying after developing Covid-19 was nearly 8 in 100 (7.7%) in transplant recipients receiving two doses, compared with a risk of 12 in 100 (12%) in recipients who had only one dose, or who were unvaccinated. Choice of vaccine had no effect on these outcomes.
Rommel adds: “This two-dose study was a good start and some positive news. It was also one of the reasons why transplant patients began to get priority for a third Covid-19 vaccine dose in autumn 2021, with a fourth dose three months later. The benefit from vaccination is not prevention of infection. Currently available Covid-19 vaccines do not produce sterilising immunity – an immune response that stops the virus infecting your body. The benefit of vaccination lies in reducing the risk of severe outcomes such as hospitalisation and death if you do get the infection. This absence of sterilising immunity is the same in both the general population and transplant patients.
“Protection increases with each successive vaccine dose"
“For the average healthy person, good protection lasts about six months after the dose, then starts to wane. In contrast, our work has shown that, for most transplant patients, good protection lasts for about three months, then starts to wane. This was one of the reasons why advice changed about the intervals between Covid-19 vaccination doses, and why a booster dose to top up immunity through the winter began to be rolled out in autumn 2022 – the sixth dose for kidney transplant recipients,” he adds.
Which Covid-19 vaccines are recommended?
The currently recommended adult vaccines are Spikevax (Moderna) and Comirnaty (Pfizer), both mRNA vaccines. These novel vaccines use a manufactured copy of a molecule called messenger RNA (mRNA). The mRNA has instructions to make the Covid-19 spike protein on the surface on the virus, which it needs to enter the body’s cells. In response to these instructions, some of the body’s cells temporarily produce spike protein. The immune system recognises the spike protein as foreign, and produces antibodies and T-cells (white blood cells) to fight the virus.
Nuvaxovid (Novavax) is now available for people who cannot tolerate mRNA vaccines. This vaccine is different from the mRNA vaccines. It contains a version of the Covid-19 spike protein that has been produced in the laboratory (so it is called a recombinant vaccine). The vaccine also contains an adjuvant, a substance to help strengthen the immune response. When Nuvaxovid is given, the immune system identifies the spike protein in the vaccine as foreign and responds by producing antibodies and T-cells.
More than 40,000 kidney transplant recipients in the UK have now received at least four doses of a Covid-19 vaccine. We know some people with kidney disease worry about the safety of these vaccines but please be assured they have been used safely in millions of people. We address some specific concerns here:
Could mRNA vaccines interfere with my DNA?
mRNA cannot enter the nucleus inside the cell that encloses our DNA. Even if it could, mRNA from the vaccines cannot fuse with DNA and, like our own mRNA, has no way of turning into DNA. This means that our DNA cannot be altered by an mRNA vaccine. The mRNA from the vaccines lasts only a few days before the cell removes it, but during that time the cell has produced spike protein to stimulate the immune response.
“In short, it is not possible to change the set of rules in your genetic code. After you have received an mRNA vaccine you have the same genetic code and you are the same person,” explains Rommel.
Can I trust vaccines that were developed so quickly?
One reason vaccines used to take some time to come to market was that their underlying technology made them difficult to manufacture to the standards required by healthcare regulators. mRNA technology – which had already been developed when the Covid-19 pandemic began – means it is much easier and quicker to produce vaccines which meet regulators’ high standards for safety and consistent quality.
“Covid-19 vaccines took less time to develop, not because good pharmaceutical practice was side stepped, but because of intense global effort. In my 30 years as a doctor, I have never seen that kind of concerted and co-ordinated effort between industry, policy makers, regulators and medical researchers. Governments were also willing to spend a great deal of money to support pharmaceutical companies to manufacture vaccines,” says Rommel.
Why were Covid-19 vaccines not tested in kidney transplant patients?
Immune suppressants are the only medicines routinely tested in randomised controlled trials (RCTs) that recruit transplant patients. Otherwise, it is standard practice to exclude high-risk people – such as those with severe kidney disease, kidney failure or a kidney transplant – from RCTs designed to demonstrate the safety and efficacy of a new medicine. So avoiding medicines not tested in clinical trials involving kidney transplant patients would severely limit your choice of treatments.
“Even though Covid-19 vaccines have not been tested in transplant patients in RCTs, they have been tested in the real world. More than 40,000 kidney transplant patients have now had more than four doses in the UK. NHSBT data is exceptionally accurate and neither we, nor clinical teams, are seeing any signals that Covid-19 vaccines affect your kidney function or interact with your medications. All we are seeing is the positive effect that most kidney patients are surviving Covid-19. And published studies from the rest of the world show similar outcomes,” says Rommel.
Should I test my antibodies?
According to Rommel, in 2021 antibody testing seemed the easiest, quickest and cheapest way to measure the effectiveness of Covid-19 vaccines in the absence of other evidence of their effectiveness in transplant recipients. His view has now changed and he regards Covid-19 vaccines like any other vaccine recommended for kidney patients.
Rommel explains: “We do not routinely test antibodies after giving other vaccines in kidney transplant patients or patients with kidney trouble, except for hepatitis B vaccination in haemodialysis patients, in case they are exposed to an infected patient’s blood. We also know now that Covid-19 vaccination is definitely effective in lowering your risk of being admitted to hospital, or dying due to Covid-19.
“Research is under way to study the potential value of antibody testing. For the time being, we do not know whether the presence, or absence, of antibodies reliably predicts protection against Covid-19. So, if I were a kidney transplant patient, until research tells us otherwise, I would not want to test my antibodies as I do not know how to interpret the results,” he adds.
Is the pandemic over?
It is currently unclear when the pandemic will end. Omicron – currently the dominant virus variant – is easily transmitted, but less likely to produce severe disease. This is how viruses generally evolve and eventually Covid-19 is likely to become endemic; that is, the virus will continue to circulate and infections will surge at times, but these infections will have less severe consequences compared to those caused by the original variant.
Rommel says: “My view is that we should not be complacent. Ideally, continuing free access to testing would have been the right thing to do until most of the world has been vaccinated. The UK has good levels of Covid-19 vaccination, but this is not the case globally. We should continue to watch out for new variants which may cause more severe disease than Omicron.”
Conclusion: what would you advise kidney transplant patients in 2023?
Kidney transplant patients remain at higher risk than healthy people if they develop Covid-19 – just as they are if they have other serious infections. Rommel advises that the best chance of protecting yourself is to receive vaccination whenever it is offered.
“You may well be offered a spring booster in 2023. In the meantime, if you have not had six doses of Covid-19 vaccine, and your last dose was more than three months ago, please get in touch with your GP or local vaccine provider to update your protection. It is the best thing you can do to protect yourself.
“The end of universal free Covid-19 testing means that we will not be able to accurately assess the effects of the fifth and sixth doses of Covid-19 vaccine. However, my view is that, as long as you have had four or more doses of the vaccine, you probably do not need to shield in the same way as in spring-summer 2020.
“Each kidney transplant recipient should consider their individual risk in partnership with their clinical teams. However I think that, for most people, the emotional benefits of socialising and continued employment outweigh the risks of strictly shielding despite being fully vaccinated. This applies especially if you are meeting people who have your interests at heart and would avoid meeting you if they felt ill. If I were a kidney transplant patient, I would go to the supermarket or use the bus, but I would not go to crowded, enclosed spaces like a large music venue. In short, I would not shield like I did in 2020, but I would be more careful than I was in 2019,” he concludes.
This article by medical writer Sue Lyon appears in the spring 2023 issue of Kidney Matters magazine.