Covid-19 vaccination Q&A
- 11 May 2021
Please note: the following information is not personalised medical advice and does not replace a conversation with your own renal team or GP who know you and your other medical problems.
For more information about covid-19 for kidney patients see our coronavirus guidance page
What do the studies tell us so far about how kidney patients respond to the vaccine and are there differences between dialysis patients and transplant patients?
So far the studies have focused on haemodialysis patients – who come to the unit, rather than dialyse at home – and transplant patients. The published studies are mainly from countries other than the UK and almost all use mRNA vaccines (Pfizer or Moderna) with 3-4 weeks between the doses. In the UK much more Oxford/Astra-Zeneca has been used and the interval is often 10-12 weeks - so we should look at the international studies with caution. Data from UK studies will become available over the coming months.
The studies so far measure antibodies that target the viral protein ‘spike’. Spike is on the surface of the Covid-19 virus and works like a key to open the door into human cells to start an infection. Antibodies that bind to spike can get in the way and prevent the virus from infecting cells, and therefore stop it causing disease. The immune system is smart and doesn’t just make antibodies, it has other defences too (like T cells). Antibodies are pretty easy to measure and most people who make antibodies after vaccination also train the other immune defences.
For haemodialysis patients, most international studies show around 4 of every 5 dialysis patients make antibody against the SARS-CoV-2 virus at around 4 weeks after the second dose. The amount of antibody is less than for healthy individuals of a similar age. Whether these numbers hold true in the UK we don’t know yet but we have a multi-centre UK study looking at this, supported by Kidney Research UK, the National Kidney Federation and Kidney Wales.
For transplant patients, the studies are much more difficult to piece together. There are a few reasons for this. The trickiest is that immunosuppression medications vary between centres: does a centre report low numbers of antibodies because they use stronger immunosuppression? Or because something else is different about their patients – for example their group of patients being younger than the others? In the biggest single study, just over half the transplant patients developed antibodies after the second dose.
We don’t have very much data about T cells yet. It’s likely the first few studies will be from other countries, with a 3-4 week dosing interval. Caution again required for UK readers. The OCTAVE study in the UK is likely to report on T cells, and antibodies, later in 2021.
There are some studies looking at antibodies in kidney patients who are pre-dialysis / pre-transplantation, and their responses look pretty similar to dialysis patients. There are only a handful of peritoneal dialysis patients that are reported (usually tacked-on with haemodialysis studies), and again they seem to respond similarly to haemodialysis patients. There are no home haemodialysis studies, but home haemo patients should respond comparably to in-centre patients.
In kidney patients, how long after vaccination are antibodies are produced? Is this different to the general population?
Dialysis patients seem to take about 1-2 weeks longer than individuals of the same age to start making antibodies. After the antibodies are detectable, dialysis patients do not make as quite much as the general population. Transplant patients take longer again to make antibodies, and we don’t really know yet when their peak response is.
Apart from kidney disease, what else affects how a person responds to a vaccination?
Age has an effect, with slightly less antibody being made as you get older. Immunosuppression probably matters – for example a transplant study using belatacept (stronger immunosuppression than tacrolimus, sparingly used in the UK) showed quite low levels of antibody after mRNA vaccination. Sex probably makes a small difference but the studies of kidney patients are not large enough to tell for sure. So far there doesn’t seem to be anything that affects vaccination that could be easily adjusted (you can’t change your age and changing immunosuppression risks episodes of rejection). Skipping or changing your immunosuppression is definitely not recommended.
What about if I’ve already had Covid-19? Does that affect my response?
I’m sorry you’ve have COVID-19. I hope you’re recovered now. Having had the virus means you’re very likely to make even more antibodies to the vaccination. You should still have both doses.
Is there a difference in response between first and second dose?
Yes there is a difference. The amount of antibody that targets the virus’ spike protein goes up a lot after the second dose. Also, some individuals who felt unwell after their first vaccine (sore arm, tired, mild headache, “man-flu” like illness for a day or two) can get similar symptoms after the second dose. If they occur, second dose symptoms tend to be milder with Oxford/AstraZeneca.
Do the studies tell us anything about the best timing between first and second dose?
Most of the published studies are from Israel, USA, France and Germany. Almost all use the mRNA vaccines (Moderna or Pfizer) with a 3-4 week interval between the doses. We are waiting for the UK results, which will be based on our vaccine programme - 10-12 week interval and many more patients given Oxford/Astra-Zeneca. These results will give us an idea of the sort of intervals that would give the largest number of individuals high levels of antibody.
Deciding on the ‘best’ timing in the real world is complex. You have to weigh the above interval against the numbers of virus cases in the community, how vulnerable your population is (are there lots of people aged over 80 years?), the number of doses available in the fridge or freezer, and your capacity to actually administer them … Different countries have decided that ‘best’ for them is a different interval.
I know antibodies are only one part of the immune system, what do we know about the response of other aspects of the immune system to the Covid-19 vaccine?
That’s right – we know the most about antibodies after COVID-19 vaccination as they are the easiest bit of the immune system to measure (same blood bottle and laboratory processing as for measuring creatinine for example). But antibodies are only one facet of the immune system. The antibodies are the first line of defence the vaccine provides if you encounter the virus. The vaccines also stimulate T cells. We know lots about T cells in general (they’re the cells that HIV infects) but we don’t yet know much about T cells after the COVID-19 vaccines, as T cells are more fiddly to study (special blood bottles and a fresh sample required for analysis in a specialised laboratory). There are studies going on to look at T cells and B cells (the cells that make antibody) after the COVID-19 vaccinations which will tell us more.
What do the studies tell us how about much protection the vaccinations can offer kidney patients?
The answer really depends on how you judge ‘protection’ in renal patients. You could look at the number of COVID cases among vaccinated people. The evidence for protection from COVID-19 disease itself in the general population is already convincing: the phase 3 trials reported in December 2020 and there’s now lots of observational data from the UK, Israel and USA showing case numbers plummeting since widespread vaccination. This type of ‘real world’ data about the number of COVID cases among vaccinated UK kidney patients could take several months to collect as most renal patients are just finished / nearly finished with two doses of vaccination and new cases in the UK are already at a pretty low level (May 2021). This means it will take longer to evaluate whether vaccination has led to fewer Covid-19 cases among kidney patients.If you want to judge ‘protection’ as making antibody after vaccination or a T cell response after vaccination, we should get those sorts of answers sooner. It’s likely that antibodies or T cell responses mean the vaccine will protect you from catching the virus, but we don’t know yet exactly what level of antibody or T cell immunity is required.
These two kinds of ‘protection’ are related, but not quite the same. They can be out-of-step with each other. Protection against disease itself is the crucial one, but studies often use antibodies (or T cells) as a short-hand.
Is it even worth me having a vaccine/going for my second dose?
Absolutely: have the vaccine. The second dose is worth having. Arguably the second dose makes even more antibody than the first, so second dose has greater benefits. The only reason not to have the second dose would be if you were advised not to have the second dose, for example because you had a serious side effect from the first.
What’s all this about a third dose – will that be applicable to me and when will it be? Will it be a different make of vaccine e.g. if I had Pfizer last time, might I get AZ or Moderna next time around?
The third dose is a fast-moving target. At time of writing (7 May 2021), UK government are mooting a third dose for all over 50 year olds later in 2021. There are ongoing trials (not in kidney patients) looking at switching between the vaccines – this is called ‘heterologous prime boost’ and has lots of prior examples of working well in the scientific literature – so it is sensible to check it out for COVID-19 vaccines.
For renal transplant patients, some countries have already decided to give a third dose (of an mRNA vaccine). The UK is a bit different – we used much more AstraZeneca doses than the countries doing 3 doses and our 10-12 week gap may mean that the first two doses work a bit better. We need the UK data to come in to pass onto the JCVI to get to a consensus view. It may turn out that a third dose is recommended for transplant patients, and it may be that a particular vaccine is recommended.
If the vaccine doesn’t work for me, is there anything else that reduces my risk of Covid? How will I know if the vaccine is working for me?
There is no simple way to know the vaccine has ‘worked’ for you but the studies that are going on at the moment will give us lots of information about how kidney patients are responding. Social distancing, hygiene measures and face masks remain important, particularly if cases start to creep up as the UK steadily rolls back lockdown restrictions. In addition, from 31 March 2021, JCVI recommended that adult household contacts of severely immunosuppressed patients are offered COVID-19 vaccination as this may reduce the risk of infection in immunosuppressed groups.
Other treatments which may prevent Covid-19 infection or speed up recovery are also being developed. For example, the PROTECT-V is a trial of an inhaled medicine to try to prevent COVID-19 infection. If proven to be effective, the inhaler could ‘buy time’ whilst we wait for the protection from vaccinations to kick-in for patient groups we think could have a delayed response, like transplant recipients. This is a trial that started in Cambridge, but is recruiting across the whole of the UK (as fast as new sites can be added.
Should I get an antibody test?
Wanting to do an antibody test for peace of mind, after all of the fretting and stressing of the last year completely understandable. However, antibody testing after vaccination is not yet routine (7th May 2021). There are two reasons:
We do not know when we should check antibodies in renal patients
An early antibody test, before the antibodies have finished building up is almost certainly unhelpful as some ‘negative’ results could become ‘positive’ a few days or weeks later. From the studies so far, the following time points are probably too early: after only one dose, or less than three weeks after the second dose in dialysis and even longer in transplant. There’s a danger that patients end up with multiple blood tests once every week or so to check antibody levels and a lot more worry all-round, when either not checking or waiting would have been the wiser choice.
What level of antibody is needed to protect renal patients?
We don’t yet have an exact number for what’s too low an antibody level for protection from infection. You could imagine getting a ‘positive’ antibody test result, relaxing, thinking you’re protected and then catching COVID. There are several studies running trying to put a precise number on the amount of antibody you need for protection.
For some patients, your doctor may suggest an antibody test to help guide a decision about an aspect of your care. For example, running an antibody test as a double-check before starting a new course of immunosuppression. At the moment antibody testing is only suggested in these sorts of special situations.
Please see our online Covid-19 guidance for patients with kidney disease for the latest updates on vaccination.
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