For our eighteenth podcast, the Voice of the Child speaks with Dr Thomas Waterfield about a new nationwide study he is leading with Public Health England, looking at how children’s immune systems respond to COVID-19.

Dr Waterfield is a paediatric emergency medicine physician and clinical lecturer at the School of Medicine, Dentistry and Biomedical Sciences at Queen’s University in Belfast, Northern Ireland.

The project, which has recruited over 1,000 children, or Covid Warriors, from around the UK to take part in the study, aims to unlock clues about how children’s bodies process the virus and crucially, how long any detected immunity from the disease in children lasts.

Dr Waterfield explains how children were selected for the study, and offers some surprising new findings about how children are managing infection, his concerns around domestic abuse and neglect during lockdown and what he would like his next study to focus on in the quest to understand how COVID-19 affects kids.

You can listen to the podcast here. 

Many thanks to Dr Waterfield for taking part in the series.

Transcript

1 (12s):
Hi and welcome to the Voice of the Child. More than a quadrillion quadrillion viruses exist on earth today. And while they can be rather picky about who and what they infect, the novel coronavirus has caught the world’s attention for being highly infectious and deadly. As the race to find out more about the virus and how it has affected adults around the world begins, children have been largely ignored in the research despite alarming findings, which confirm they’re are also susceptible to infection, and in some cases, at risk of developing life-threatening symptoms.

1 (42s):
Dr. Thomas Waterfield, a paediatric emergency medicine, physician and clinical lecturer at the school of medicine, dentistry and biomedical sciences at Queens university in Belfast is leading a team which together with Public Health England has just begun new and pioneering research to try to find out how COVID-19 is affecting children across the UK. The study aims to measure antibodies in children, to see if the researchers can find any clues about ways in which the virus affects young people and how their bodies are responding to the infection. Dr.

1 (1m 12s):
Waterfield, this is really exciting new research, which will hopefully help us understand COVID-19 and children much better. How did you get involved in this project? And what’s the research going to explore?

2 (1m 24s):
So we spent our time between research, teaching and clinical practice and moved from research to full time clinical practice, which was fine. And then essentially within a week we got phone calls from some colleagues across the country saying, you know, there was interest in looking at COVID and looking at transmission and I said I would be willing to help with the study so this happened very quickly, within a week.

2 (1m 55s):
So I went back to half clinical. So I work in and A&E at a children’s hospital in Belfast and went back to half research as well, and it was strange in terms of research, as we normally spend ages planning. It, it can feel really frustrating going through all the different iterations of the plan and then getting everyone together and building a team. Whereas this, it was, it was just crazy in terms of, from kind of concept to ethical approval was a, was 10 days, which is just unbelievable.

2 (2m 26s):
So the ethics committees, which were set up for COVID studies only, so people were, we had an ethics review at, I think it was eight o’clock at night and it was, it was just sorted and then reached out to contacts from other projects in different parts of the country. And again, the response was incredible. Just, yes, we’ll do it. We can do it, let’s get it done. And then even in terms of funding, you know, what would take months, took a few weeks. So it’s been, it’s been interesting in terms of what you can do when everyone’s, you know, behind one goal to get to get these projects done.

2 (3m 5s):
And the other side of it is it’s, it’s very tiring because you have to be reactive to things in real time and changing and, and amending and improving rather than getting a little piece ready, but it’s been good fun and it’s been hard work. I don’t think I’ll ever get to experience this kind of research again, ever

1 (3m 28s):
In that very short period of time. You’ve also managed to gather over 1,000 children to take part in this study, which I read on your press release on the university website. How did you choose those children?

2 (3m 40s):
So that’s, this was tough. So we wanted to, like part of it was looking at transmission, so we would need to have a reasonable number of people that were exposed to the, to the the virus and although it feels like we’ve had an awful lot of it, it’s still not wide spread within the population. The prevalence is still quite low. So we have the healthcare workers that we thought, they’d be more exposed. We would be able to collect data more quickly. And then the other side of that was to be quite, quite pragmatic.

2 (4m 12s):
So again, we’re asking these children to have a blood test, it’s quite unpleasant. It’s not something they would choose to do normally. And we would usually spend time with them with things like play specialists. You know, we would get them ready for the clinic. And we would also spend time with the parents going through the consent, but with social distance we couldn’t bring them up repeatedly to have face to face chats about the study. We couldn’t use the play specialists.

2 (4m 41s):
So by using healthcare workers, they understood what was involved in the blood tests, the procedures, they could communicate that with the children, which just made some of the day to day less boring and made the design of the study easier. So we went, we went with healthcare workers and even with that, we were concerned that people wouldn’t sign up, that they wouldn’t want to take part. And actually we were overwhelmed with interest. So even in Belfast, we had to run an additional day cause we had people that were disappointed that they couldn’t take spots.

2 (5m 16s):
The same thing happened in Glasgow. The same thing happened in London, the same thing’s currently happening in, you know, Manchester, where there were more willing volunteers. And there are actually spaces in the trial.

1 (5m 27s):
You’re calling the children who are taking part in the trial COVID warriors. Have you had any feedback from the kids that you’ve been interacting with for the study?

2 (5m 35s):
So we’ve got a colleague of mine who is writing up a participant study in kind of public involvement and overwhelmingly they, they were getting messages that they wanted to contribute. That was a big part of that. So it was that they wanted to contribute, wanted to do something. They wanted to do something to help. So that, was quite nice, especially the older children. You see, you know, the young people, if you want to call them that, it’s kind of quite an altruistic thing, they want to come and do something positive.

2 (6m 4s):
I think the other thing here is that also, you know, their parents are working in health care and things are settling a bit now, but there was a lot of anxiety early on, you know, even my, you know, children, you know, asked me, well, you’re going to the hospital now, you know, are you going to be okay and then you come back and you know, say to the kids you can’t touch me, I’m going to, I’m going to change all my clothes and wash everything, and then I’ll come and see you. And so I think them being children of health care workers as well, they probably feel a little bit more the risks and maybe a little bit more aware of what was going on and wanted to do that better in terms of the actual blood tests.

2 (6m 42s):
We’ve only used very experienced paediatric staff. So we’re very clear that early on, they have to be able to have experience in phlebotomy and children. And what we found is actually outside the hospital setting, when they’re sick as well healthy children coming in, we’ve made channels. It’s gone really well and we’ve, but we’ve only had in Belfast kind of one or two children where we couldn’t, you know, for whatever reason get a blood sample. And most of them went very well, and I wouldn’t say they enjoyed it, enjoyment’s not the right word, but I think they were pleased that they took part and we’ve got good numbers coming back this weekend for the second clinic.

1 (7m 23s):
You’re also working within A&E in paediatric units. And I’m assuming from what you’ve just told me that you are coming into contact with children who have been infected with the virus. What’s that been like for you and for the children in the wards?

2 (7m 35s):
It’s been very strange. There was a lot of theory on a lot of uncertainty a week with the hospital being completely redesigned. So with outpatients and routine operations canceled, our department took a much bigger footprint. So we spread ourselves across patients, and we split them into areas where you have the children that are thought to be at higher risk of infection, and then the children who are thought to be at a lower risk and try and manage that.

2 (8m 7s):
And we split our staff across the two sites and as time has gone on, and we’re seeing kind of the children on children and how they have been affected certainly compared to adults. And I think people will start to relax. And actually then what started to happen is the other side of it is that our anxiety was growing in terms of wanting outpatient unites to re-open. We want schools to reopen. We’re getting worried about our children that are not getting to get outpatient clinics or coming in late with, with health problems because they’ve been too scared to attend.

2 (8m 39s):
So it’s been a strange journey, from, the redesigning of the service, starting to accept the children. And then moving on to actually the biggest worry for children as we can’t go back to school, we can’t get that routine going on. Meaning there’s lots of safeguarding worries. We’re not seeing children who may be suffering abuse. There’s less opportunities to catch that and intervene. We’re also seeing lots of problems with anxiety, mental health, you know,.

2 (9m 12s):
So actually the biggest risk for the children is that we’re not able to provide their normal services.

1 (9m 20s):
The current data that we have, as you said, suggests that children are at less risk of being infected with the virus. Do you think that is a result of their physiology or is that perhaps something to do with the context in which they’ve been provided perhaps with an additional layer of shielding within the context of their community and their way of life and their routine?

2 (9m 40s):
In terms of COVID-19 and children there are underlying reasons which relate to the illness itself. They definitely have a milder illness. There’s no, there’s no doubt about that. Young children essentially have almost no illness. And the reason for that I really still don’t know but people have ideas, but we don’t really know why. So even if they get the infection, they’re not seeing the symptoms. And certainly even the early data from us, is that about a third of children have no symptoms despite having developed antibodies, which means they must have been exposed at some point in terms of being exposed to the virus.

2 (10m 19s):
I think children overall have been shielded. I think that’s the right way to describe them. Not maybe intentionally. So some of it’s intentional, but the children, you know, how shops are saying, please don’t bring your children to the shop. And you know, so we’re not taking children to shops. We’re not, they’re not going inside anyone else’s houses and only just recently starting to be able to go outside a little bit more and enjoy some fresh air, but most children have been at home, essentially not interacting. So then the only people that are going out and mixing are parents, so parents are bringing it home and passing infection on, but children have had almost no kind of role in the spread of the infection so far.

1 (10m 58s):
Your study is going to be looking at children within the ages of two to 16. Is there a reason why a very small children and babies and teenagers between the ages of 17 to 18 have been excluded from the study.

3 (11m 11s):
It’s more to do with an, the amount of blood that you need to take. Once you’re over two, the phlebotomy becomes easier as a procedure, it’s less traumatic. So it’s a bit of a trade off for saying that we can’t use, or it’s very difficult for us to use play specialists, limited opportunities to conduct with face to face, you know, discussions everything’s over the telephone. We just come in and have a blood test and leave. So from a pragmatic point of view, we’d be taking a significant amount of you know, blood from very, very young children and then also without having some of those other measures in place.

3 (11m 44s):
So it was kind of a pragmatic thing to set it up to 16, it’s just a debate about where paediatrics stops and starts and finishes. And then some of the things around consent. So most of that kind of falls on the governance, legal side of things, rather than from a medical point of view. That makes sense. A lot of trials that look at prevalence will often include some children, but they rarely can include the younger age group. So yeah, two to 16,

2 (12m 15s):
It’s kind of pragmatic. I mean, in an ideal world, you’d just have every single, you’d just include everyone, children, adults, and you know, the entire family unit.

1 (12m 24s):
Your study is going to look at antibodies within children and whether or not those give you any indication as to how the virus has impacted children. And this is probably a very silly question, but can children actually fight off a virus with preexisting antibodies from a previous unrelated infection to COVID-19 or do you have to have had exposure to a very specific infection to then develop antibodies for that infection?

2 (12m 51s):
So there are other Coronaviruses. We have our own kind of Northern Irish Coronavirus, that is unique to us here. So we wouldn’t expect that to be the best way. It doesn’t generate much immediate data. If you, if you have one of the other clone of viruses, you make up antibodies for a few months and there is almost very little immune response. So I don’t think they would offer you any kind of protection against the current virus. And what we don’t know is actually, if, if you’re exposed to the virus, which I think is kind of your question, and if you’re asymptomatic, do you develop antibodies or do you need to be sick to show an amount of antibodies?

2 (13m 30s):
Well, certainly from the early data we’re getting, it looks like you can be completely asymptomatic and have antibodies. So we know about a third of the children have had antibody response with no history of any illness. So you don’t necessarily need to be sick to develop antibodies.

3 (13m 45s):
The kind of million pound question is, you know, do those antibodies confirm immunity, and we don’t know. So, the antibody tests at the minute are directed mostly at the nuclear

2 (13m 56s):
Capsid, which is useful in telling if you’ve been exposed, but not necessarily indicative of immunity. There are some tests being developed and finalized looking at the spike proteins, which certainly kind of previous SARS viruses, the spike protein antibodies were the ones that were associated with immunity. So it would be reasonable. It would be a reasonable assumption, guess, that if you have antibodies that you would expect some form of immunity, but we don’t know how long it lasts and how good it is, you know, and how that would affect you of your disease progression.

2 (14m 33s):
So again, if you’re an animal, you know, you’ve been that you’ve got some antibodies, does that mean that you won’t get it in future? And when if got it would it be milder and also how long does those antibodies last three, four months, like other coronaviruses or do they last a bit longer?

1 (14m 49s):
I was just wondering whether you could fight off a new virus with existing antibodies or preexisting antibodies inside your system, which you develop from a completely unrelated. Yeah,

2 (15m 2s):
Yeah, no, I don’t think, I don’t think there’s any evidence that that’s, that’s possible with the, with this, sort of virus. I know things like BCG vaccination and certain things that might modulate your immune response to make you able to maybe have a less severe illness are being looked into, but I’m not aware of anything that would suggest if you had a previous form of coronavirus or other viral illness, that you have antibodies that are protective in some way,

1 (15m 28s):
With all of the children taking part in the study have they all been asymptomatic, if they have been exposed to the virus and potentially infected with it?

2 (15m 35s):
So two thirds of the children so far have had symptoms. So will we ask about illness, episodes and history, and then kind of marry that up with some of the results and children’s symptoms and none, none of them were admitted to hospital. None of them required, you know, anything beyond kind of self care at home. And the main symptoms were temperature, lethargy, some mild, gastrointestinal upset. So not seeing people coming in with children rarely come in with a cough, even if they’re symptomatic, but from what we’ve seen from early data that was coming through not in this study, which is interesting.

1 (16m 13s):
So going to the science for a moment, how are you going to be using the scientific tools available to you, to isolate the antibodies and extract the information that you need from them?

2 (16m 23s):
So the antibody tests that we are using are actually commercially available so we’re working in partnership with Public Health England, and also Public Health in Northern Ireland, but a public health thing that you go on that is actually publishing all of the data in terms of the test accuracy. So we’re using at the moment, the Rush and Abbott tests which we see in the media have both been confirmed they’re both immunoglobulin G so that’s an antibody response that presents kind of more of a longterm memory.

2 (16m 57s):
So your body usually makes a temporary response, which involves M immunoglobulins initially, and then the G ones are associated with longer term immediate memory, the downside for those that it takes about two weeks to develop them. So if you’re infected within two weeks of being tested, you may actually go on and have antibodies, but they’re not detectable yet. So if you have either the Abbott or the Rush and test positive for the immunoglobulin G they’re very specific, which means you, you will have had that of infection and was certainly announced as a genuine, the downside of these tests is a small number.

2 (17m 38s):
So kind of one or two in 10, potentially test negative. And, and actually are just in the process of developing antibodies that aren’t detectable yet. And we do see that with some of the results coming through that are borderline and you suspect how that has to look for it and properly, because it’s just coming through in real time, but those children may have had symptoms for the last two weeks, which is why their response hasn’t, maybe isn’t meeting the special for detection, but, but there’s evidence that there’s probably would be another week or two, which is why we’re following them up a repeated.

2 (18m 10s):
We’re seeing them more than once. So a lot of other studies only bring the children in for one point prevalence. Whereas by doing this, we can see as antibodies develop, and also how do we assist for.

1 (18m 23s):
And you’ve chosen two points to, to revisit the, well one point revisitation and one initial consultation with kids, why not three or four?

2 (18m 33s):
So we’ve moved on at the baseline to do a first appointment, two months and six months we may do more, so it’s partly about funding. So at the moment, as I kind of alluded to with the restructuring of services and goodwill, there’s a lot of interesting activity around this, but as normal research resumes, as services resume, we would have to look for significant ongoing funding. So I, there may well be follow-up studies from this. So I would like to, for example, all the children that test positive and then follow them up for another two years would be what would be my ideal with repeated appointments to see how long the antibody response persists for, and also do they develop any COVID-19 during the interval period.

2 (19m 19s):
So all of these things, unfortunately it sometimes come down to governance, you know, ethics and, and money

1 (19m 29s):
Beyond detection of antibodies within children what else are you hoping to discover from the research?

2 (19m 37s):
So certainly some more information around transmission it’s, if you can understand the transmission and how likely someone is to spread it within the close contacts, it can help and predict things at schools. So for example, if the data that we’ve collected and you’ve already alluded to the kind of a lockdown that the children have been in, we can be pretty sure that if a parent’s symptoms was first, they have a swab test positive, which we’re recording all of this data. And then their children develop antibodies that, that infection has passed from the parent t the child, not the other way, which is an opportunity just because we conducted this during the kind of lockdowns.

2 (20m 14s):
And then we can start to record things like the attack rate. So we could, and we’ve got a paper that we’re just preparing, which is, which is going to report that we’ve submitted that for publication to The Lancet infectious diseases, which is reporting that attack rate. So by knowing that data and that attack rate data, we can, we can help with planning, measures things like opening to schools.

1 (20m 37s):
Are you also going to be looking at things like immunity?

2 (20m 40s):
In terms of whether they develop immunity and whether that persists more? Yeah, so that’s, so us, what we’re doing is we’re obviously doing the,

3 (20m 49s):
The immunoglobulin to the nuclear capsid for when we start doing the spike protein antibodies. And those are the positive, which we think will be system with immunity. You can then monitor those children, which we’re doing to see if they develop COVID-19 despite having these antibodies, which if it had a spike protein antibody and they don’t develop COVID-19, you know, during a prolonged period. So within six months, you can be fairly confident that that antibodies offered them some sort of immunity, but that’s why you need to follow them up. And it may be that we need to, we’ll continue to follow them up beyond the six months, depending on what the landscape is with the research funding and things going forward.

1 (21m 26s):
There’s been a new study, that’s come out and it’s suggesting that the virus could be a blood vessel virus, that it inflames blood vessels, and that children have been able to stave off the virus largely because they tend to have healthier blood vessels than we do as adults. Do you have any thoughts on that new study?

2 (21m 43s):
In terms of the paper in particular, so certainly there’s something to do with the ACE2 receptors in terms of how the virus affects individuals. And what’s interesting in children is that younger children probably don’t or do not express ACE2 receptors in the same way in the, within the respiratory epithelium. So one of the theories, which I, I think has got something in is that the younger children don’t express ACE2 to as much, which means they’re less likely to have, suddenly have serious disease.

2 (22m 16s):
And also do you remember how we talked about, how very few children are having a cough, and coming in with respiratory symptoms. It’s quite rare even amongst the symptomatic children. Yes. That’s probably to do with ACE2 to expression within the respiratory tract. So I think we’re not seeing the respiratory symptoms because they don’t express ACE2 to the same extent within the respiratory tract. A similar argument may exist for not expressing the receptors for the virus to actually infect the cells that are not going to get some severe disease.

2 (22m 47s):
So it’s probably multifactorial in terms of young children, who are like the Olympic athletes, incredibly fit, and the blood vessels are healthy and they can tolerate far more stress than physically than adults can. We see that when we’re training our doctors about, you have to be very careful, the child may look relatively well, but be sick. I also think there’s something around those ACE@ receptors, which keep coming up in different studies in terms of being a mechanism by which the virus is infecting and affecting cells.

2 (23m 18s):
So in that paper, it was looking at ACE2 and vascular and endothelial cells, and its affects. But I think it’s also probably has an impact in terms of the respiratory side, as well.

1 (23m 29s):
As you’ve been taking care of children within COVID wards, has anything jumped out at you?

2 (23m 34s):
Yes. That we don’t have any, so that the children just aren’t coming in, they’re not sick. And we are seeing some of the children with this post post COVID inflammatory Kawasaki’s type illness,

3 (23m 47s):
But we’re just not seeing severe acute illness and, and children, it’s just not, it’s, it’s remarkable how little effect the illness has on children. And that’s, again, the kind of bit from before, we were very worried, very fearful about what was coming and now actually the biggest harm to children is that they’re being kept at home. And, and, and the harm is coming through the greatest harm to children is the education they’re missing, the interaction with their health visitors, the interaction with the social services, and their ability to attend kind of routine paediatric hospital appointments.

3 (24m 28s):
That’s by far the biggest harm to children, the most.

1 (24m 31s):
We’re definitely seeing some concerning reports about children suffering mental health problems and distress from being locked away as they are. And as you say, there are concerning reports about rises and domestic violence, but going back for a moment to, to the virus itself, you mentioned that you had seen children who had developed Kawasaki disease, like symptoms, what’s that been like on the ward and how have children coped with that kind of disease?

3 (25m 2s):
Children are very resilient. They, I don’t

2 (25m 5s):
I think for them, in a strange way, they don’t, it’s no different to them than if they have Kawasaki. Kawasaki’s as a horrible illness to have, you know, in terms of it’s usually a miserable, prolonged admission, and then uncertainty about complications afterwards. So I think whether that Kawasaki’s illness was related to a post was triggered from COVID or triggered from something else that outcome for the children they face is very similar, I don’t think their actual patient journey changes all that much from that.

2 (25m 37s):
So it’s a horrible illness either away, whether it’s COVID related or, or they just have it through some other route.

1 (25m 50s):
Once this project is finished, what would you like to study next in relation to children and COVID-19?

2 (25m 56s):
Schools. So the schools. So I, I think this is a good template and a good model for how you conduct this study on a larger scale within schools. I think we need to be doing that, I think that we need to be going into schools and we need to quickly work out what the role of children is in the transmission of COVID-19 within schools. Because if we can show that perhaps it’s the ACE2 receptors, perhaps it’s some other factor, but if children are not sick, that’s useful because we can reassure parents to say, you know, you can send your children to school and they are going to be okay.

2 (26m 30s):
And then also we need to look to say what their role is. So what’s the attack rate from children to adults. And we don’t know that that’s unknown, so, you know, how safe are the teachers teaching in that class? Can they go and teach without, without fear there’s there’s, we’ve got to be careful as well, in terms of there is a lack of evidence that the children have much of a role in the transmission of the virus, for the lack of evidence isn’t evidence of a lack of effect. And what I mean by that is you kind of hit the nail on the head for me early on, where children have been shielded, essentially, they are not going to the shops and not going to go to schools and not mobilizing.

2 (27m 7s):
It can almost be seen as their own population, which is where this data is useful in terms of, I don’t think children have seen as much coronavirus as adults. I think early infections were probably centered around major transport centers and where adults traveling between areas. And so until we actually see them, the infection spreading between children we won’t really know what their role is. We all say the children don’t have a role. Actually, we just don’t have any evidence that they have a role, but we haven’t really, they haven’t returned to normal activities yet.

2 (27m 39s):
So until they’re back at school, we won’t really know for certain what’s happened.