Saul Faust (00:00:08): Welcome everybody to the final session of ESPID 2023. This is a Medscape sponsored session on the updates and advances in COVID-19 trends and prevention in pediatric patients. We have a joint faculty between the panel here who I'll introduce in a minute and the United States. So I'm Saul Faust. I'm a clinical academic from Southampton, the United Kingdom. On my left I've got George Kassianos, who is a general practitioner and national immunization lead for the Royal College of GPs in the United Kingdom. And on my right, your left Barbara Rath who is co-founder and chair of the Vaccine Safety Initiative in Berlin, Germany and has roles in France and elsewhere in the world as well. So we also, in the United States have a virtual chair, Dr. Tan, who is going to chair a discussion of our US attendees who wish to, as a virtual panel meeting after at the end of the event. (00:01:17): So we're going to run this session as a conversation between the three of us. Barbara and I probably will stay here. George has got a bit of a longer session halfway through where he runs through some slides. So you might see George wander over there and come back. But we're going to have a conversation between the three of us on the burden and trends relating to COVID-19 and COVID-19 vaccination in children and on new and emerging data on vaccines and boosters for COVID-19 in pediatric patients. So we're going to start off with a question. How knowledgeable are you on the burden of COVID-19 amongst pediatric patients? And you're not going to see the answers until the end when we ask you the question again. (00:02:01): So if you could answer on your buttons from one, not knowledgeable through to five, very knowledgeable assuming that most of you are here because you want to know more. And we will just run that for a minute and then the poll and then we will do the second question. Sometimes there's music when they do the polls, isn't it? Not today. Okay. And I should have said at the beginning too, you can ask questions on the MedscapeLIVE! on your apps as well. They'll come up and be moderated and we'll come to those towards the end. But please put your questions in when you think of them. So we'll go to question two, which is how confident are you right now before the session in recommending COVID-19 vaccines to your patients or the caregivers of your patients? Again, from not confident, number one through to very confident number five. (00:03:10): Oh see music this time. (00:03:11): Okay, thank you very much. We will go on. So by way of introduction, COVID-19 in children and adolescents is generally much less severe than for adult disease. Globally among 4.4 million people who've died of COVID nor 0.4% occurred in children or adolescents less than 20 years. And in the UK the data shows that 99.9% of infected children survived during the first pandemic year. But of course inflammatory syndrome, Mis-C or PIMS-Ts is a rare but serious adverse event and although it's much less frequent, long COVID can occur in children and adolescents, although it happens more in adults. Barbara. Barbara Rath (00:04:09): Yeah. So a question that we sometimes need to ask ourselves as pediatrician is, so we look at a patient who shows up with potential COVID or flu-like illness and we have in our head, what do I need to do next? Admit to the hospital, admit to the ICU, make some phone calls to transfer the patient, can they go home? What are the parents saying, what we've realized with the vaccine safety initiative is that what we're not so fully aware of is how the patient themselves feels, functions and survives, which happens to be the language of the FDA for example, on clinical endpoints. And that's been the trigger of some research we've done on understanding the subjective impact of COVID or flu-like symptoms on the individual which can be either the child itself or the parent and caregiver or somebody who's taking care of that elderly relative also. (00:05:05): So we've been working with the symptom survey on something very unique. I don't think it's any similar to the ZOE COVID by the way. And it is a chatbot that allows people to provide us information on how they subjectively experience the different symptoms and signs of COVID and how they want those to be understood by us as physicians. So if you want to ever change your perspective, take a look at symptomsurvey.org to understand that you can participate as an individual as well. It's a collaboration with the European Academy of Pediatrics and several patient organizations. So the question here is which symptoms are important? (00:05:48): What does improvement look like? What do I want to see prevented through a vaccine? What do I want to see treated by an antiviral and what does recovery mean to you? So what's really important is what role do children and adolescents play in the transmission of viruses if we now shift back to our viewpoint as healthcare providers or healthcare professionals, the question is basically children of all ages can be infected and spread the virus any time in the traditional world of virology we've been looking at viral load as a key outcome measure on the laboratory side, but that is rather similar in children, adolescents and adults with COVID, which is very different from flu where children start with a very high virus load and take longer to recover. (00:06:43): For the current variants, the vaccines have been able to hamper transmission to some degree people aren't sterile when they've been vaccinated they can still have detectable positive PCR. But as you all know, PCR doesn't really tell you about infectivity of a person. And we can see in the public health statistics and the studies that have been done so far that vaccination has a huge impact on transmission, especially at events like this one, you would hope that most people here are vaccinated. Saul Faust (00:07:14): So we're going to think about long COVID and then Barbara will think about inflammatory syndrome. For long COVID. Some of you might have gone to Terrence Stevenson's session this meeting where he described the clock study in the United Kingdom where he compared and his team compared, prospectively, national sample of children and young people aged 11 to 17 years with PCR confirmed SARS-CoV-2 infection against test negative controls in the wintertime 2021. And the study showed no significant differences in mobility, self-care, doing usual activities or pain and discomfort at three months. Most worryingly, one third of all children in both groups reported feeling, worried, sad or unhappy irrespective of their test result. And a Norwegian study showed similar results. There was no association of biomarkers linked to viral infection, but there was with COVID infection with symptom severity and psychosocial factors such as low physical activity and loneliness. So mental health's a really huge impact of the pandemic on children and young people whether we're going to be able to immunize against mental health. That's another question against COVID and that would help for children. I'm not so sure, Barbara. Barbara Rath (00:08:36): Well, so we have a number of these questions around children. So there was of course, as you all know, the very prominently discussed Multi Inflammatory Syndrome in children. It seems to be rare we don't quite yet understand which children are prone to developing these kinds of complex symptoms. It's on our side as physicians to understand, to detect it, to understand the features of it and to be prepared. But what we can say about many of the respiratory viruses is that they are multisystem diseases which we see especially in flu and COVID when the cases have gone bad, meaning you know, you have a patient with rhabdomyolysis with flu or a patient with COVID who develops foggy brain fog or long insomnia problems much later down the road. It's not entirely clear how this plays out immunologically and how we could predict who would be at risk. (00:09:34): So I'm always kind of on the side of caution if we look at the next slide that what is happening in children. I think we're still at the very beginning they were sidetracked in the research and I think we should all advocate for more research in children on COVID and other respiratory infections to understand without bias what's actually going on. So there of course we all know there have been massive disruptions in school and social and physical activities. We're not even at the beginning of measuring what that means and we need to collaborate with social scientists and anthropologists and educators to understand what that means. There has been limited access to support services, there have been elective surgeries, delayed routine visits delayed while child visits disrupted. I was in the US for some part of the pandemic and there were entire children's hospitals shut down for months on end and the staff was sent to adult ICUs. (00:10:30): For example. Routine vaccination services have been disrupted. I'm part of a special edition that's going to post in a journal of vaccines very soon on how do we get people back on track after this disruption. Pandemic related measures have had increased emotional, of course this has increased emotional distress as we all agree. The levels of symptoms were fairly similar in the beginning of the pandemic between non-infected and infected children/adolescents. But in my personal opinion, that had a lot to do with the infection control measures that we had. So if kids don't go to school and don't get infected themselves as much, that may have contributed to the epidemiological picture, there's no way to measure this because you don't have a control group where there was no pandemic to actually measure what a baseline situation would've looked like. And then of course these symptoms, many of them are vague and difficult to metrically measure such as concentration and memory loss, listlessness headache, abdominal pain, all of this gets lumped up somewhere with a GP or pediatrician and hardly ever gets recorded systematically. (00:11:41): So the question is really who's at risk? I think that was you. Saul Faust (00:11:45): Still you. Barbara Rath (00:11:47): Okay, so basically there was a study done in the US that showed that 28.7% of the children with severe COVID had underlying conditions. What is really important to me to convey to you, if you remember one thing of this slide is that this means reversely, that more than two thirds of the children didn't have anything that would point in the direction of them having a bad case. And that's very similar to flu, right? So if 66% or more don't have anything that will tip you off, you have to be very humble as a provider to be clear of your level of uncertainty here, the percentage of children with underlying conditions is higher in many European countries, that's quite possible. There's also a lot of things that are dependent on how people experience the disease from anxiety, depression, obesity and comorbid conditions like that, but also pulmonary issues and developmental disorders. The strongest risk factors is very interesting and I don't think all pediatricians are aware is type one diabetes, cardiac issues and preterm birth. (00:13:01): And so the risk factors for severe COVID in children, if you look at these data in the US, which is not the first time that we see this with COVID, it's also true in adults and in other diseases in the US there's a big disparity in socioeconomic background and it reflects itself in the ethnicity and racial background of people, but we don't know how much that is confounded by actually difficulty accessing care in time. So if there's a higher risk for Hispanic and not Hispanic Black children in the US, what exactly does that mean? Do they have a genetic predisposition or do they just have difficulty seeing a provider in time? It is something that in the US is captured routinely also in routine care, not just in studies and in Europe we're lagging behind a little bit. I think on social determinants of health, we should be doing a better job. (00:14:01): I was involved in the Swiss National Science Foundation program on COVID and they have learned that lesson that even in the hardcore clinical studies we need to do a lot better on understanding the social determinants of health to get these outcomes figured out. There are arguments for and against vaccinating children for COVID, this is a controversial topic also Saul and I agree to disagree on sort of how we see it. He's a optimist. I see the glass half empty, he sees it half full I would say. Both are correct, right? Unless we have studies that show us a clear direction, which we don't have quite yet. The disease burden in children overall has been low. That is confounded to some degree with school closures and all these other things that we did that slowed children down in their overall development. I think that's something you definitely agree on. (00:14:53): Severe COVID has been rare, but it's also not really been measured. So we're not quite sure if severe COVID in children looks like severe COVID in adults. The multi-organ disease is very rare, but when it happens, it's serious and there have been long-term outcomes that we still haven't studied as I mentioned earlier. Against the vaccine, you can say, well it may be a lot more feasible to just focus on these at-risk children. We need to be realistic and see how many people can be vaccinated and how will people understand our programs. But it's unclear, number one, whether it prevents the severe outcomes, especially the multisystem organ disease. And what's humbling is that we don't know upfront who the at-risk children are. And my half empty view is also that at-risk vaccination programs like we had for flu in Germany have failed. We've done studies to show that the majority of the at-risk children were not vaccinated and even less likely to be vaccinated than those who are not at risk, which means poor communicators of vaccine recommendations on top of everything else. (00:16:02): The transmission, yes, you may be able to reduce overall transmission, which has impact on the grandparents and other people. If you think about cocooning, which I know was discussed in the last session, but they're limited data on transmission and we're currently discussing some of that in future conferences. We've just submitted a proposal on that because transmission studies are notoriously hard to do and we need to do them, all of us. Post-COVID sequela are hard to understand as well. So do we prevent long COVID through vaccination? There are studies that say that we do. In children, they haven't been done in big enough numbers. It's more for the teenagers I think that we need to think about long COVID because when they have difficulty in school year, it's easier to diagnose that. Do we prevent other long-term outcomes? We don't quite know. And we both agree that there are limited data and prevalence and severity of long COVID in children and on the impact that vaccination may have on children. (00:17:01): So these things are difficult to settle at this point. There is a lot more homework for us to be done, not to rest on our laurels and say a pandemic's over, next topic but to think about the things we haven't understood yet. COVID vaccines are definitely generally safe and well tolerated in children. So we have a very low risk of vaccination. That's a very rare self-limited AFI of myocarditis that's been seen in pediatric patients. We need to know about that and we need to know how to consult patients and how to find them when this should happen. This may reduce confidence in the safety of vaccines and we need to be handling these AFI with great care in our communication. Then economically, yes, vaccination in children has a huge impact on being able to go back to normal life and activities for the rest of the population. (00:17:56): Can parents go back to work? Those kind of things. But vaccine resources from an ethical viewpoint, if you have a limited number of vaccines, you give it to those who are most at risk and you don't want to delay other vaccines because you've focused just on COVID and then you forget about all the rest. New variants may provide some, vaccines may provide some protection against those, we don't know. Many believe that COVID becomes a seasonal disease. Also for pediatric respiratory viruses, which it has been coronaviruses studied them for years in children with just different variants and regular coronaviruses are not studied right now actually where they have gone since the pandemic, they're difficult to study. The PCR aren't as easy as for other viruses. So that is something we need to look at and understand where we are in comparison to pre-pandemic COVID. (00:18:52): So WHO, EMA and others have taken a stance on pediatric vaccinations. In the US it's very clearly they propagate vaccination with children against COVID and flu with a very simple public health message. In Europe it's a bit more complex. So on one hand there's the recommendation to use the vaccine in children greater than six months and that would be sort of the US idea and the W H O supports that and to say, okay, six months and up flu vaccine COVID vaccine. The advantage is it's easy to communicate and everybody knows what to do. The disadvantage is you may have a lot of people don't comply with this recommendation and then you have it scattered all over the place. Other recommendations could be children greater than 12 years and to give them the Novavax COVID vaccine. (00:19:45): I think to me this is a moving target and it indicates that the recommending bodies aren't sure yet. The [inaudible 00:19:52] aren't sure the WHO, EMA. EMA and FDA have been responsible for the licensing, but they don't issue recommendations normally. So you have to read between the lines and understand that this may change and keep posted on the recommendations that are relevant to your clinical practice. So yeah, so you see this is a nice comparison. The C D C makes it very easy to remember for us clinicians there are criticisms of that especially since at the same time the diagnostics for COVID are no longer free of charge. So how do you measure vaccine effectiveness in the setting when you just vaccinate without testing? When people get sick afterwards, the [inaudible 00:20:36] has a very long recommendation. Reading through that takes a day which many clinicians don't have an understanding exactly what's meant need. (00:20:46): You need to write that down as a practitioner. But long story short, they talk about at-risk children, six months older get a full immunization, but then it gets complicated with healthy children. Those five to 11 get a single dose only, which hasn't really been studied to be honest, unless there's a cocooning request by the parents or a cocooning need that the doctor has identified that. And indeed I find interesting and I think cocooning should show up in vaccine recommendations more often. That's actually a very good idea. In the NHS in the United Kingdom it's much more uniform and children five years and older can be vaccinated if they're at risk due to a health condition or living with somebody that needs cocooning again. And then in Netherlands, children age five to 11 are eligible if they have an elevated risk again. So that there is sort of a trend towards a risk gratification. I'm a bit unsatisfied because I don't think we know upfront who's at risk and who isn't or to say we know some people who are at risk but not all of them. Saul Faust (00:21:49): So I mean I think our message overall and George is going to come back to hesitancy later is use the recommendation for your country because otherwise we risk both diluting the public health message and perhaps creating hesitancy by causing confusion. But COVID-19 RNA vaccines are quite new and we thought we'd show you a little video of the technology and then during the video, George will have made his way across and he'll tell us a little bit more in detail about the mRNA vaccine technology. So I guess you guys are going to play the video, IT people. Speaker 3 (00:22:33): The mRNA COVID-19 vaccine contains mRNA encapsulated by a lipid nanoparticle encoding the SARS-CoV-2 spike protein that is responsible for inducing host immune responses. Once the vaccine is administered by intramuscular injection in the upper arm of the patient, the vaccine particles bump into antigen presenting cells like dendritic cells and infiltrate them upon release. So the mRNA inside the cytoplasm of the dendritic cell, ribosomes translate it into the viral spike protein. The mRNA from the vaccine is eventually destroyed so no traces are left in the vaccinated cells. The newly synthesized spike proteins are transported through the gold G apparatus where they are assembled into tremors. These tremors are exposed on the cell membrane at the same time spike proteins are degraded inside the cells into peptide fragments that bind to MHC 1 and MHC 2 molecules. The spike peptides loaded in MHC molecules migrate to the surface of the vaccinated cell leading to the activation of T-cells. (00:23:49): B-cells bind to the tremors on the antigen presenting cells activating B-cell responses with the production of neutralizing antibodies against the spike protein CD4+ helper T-cells bind to the MHC 2 complex and interact with the B-cells to promote antibody production. Viral infected cells also present spike peptides in the MHC one complex, giving them the mark to be killed by CD8+ cytotoxic T-cells. As such two adaptive immune responses can prevent viral spread and protect against severe disease. One, neutralizing antibodies binding the spike proteins and blocks viral entry while two, host cells that become infected can be eliminated by cytotoxic T-cells sells. The mRNA COVID-19 vaccine contains... George Kassianos (00:24:51): Right. Thank you. So let's look now at the phase trials of the Pfizer BioNTech study. You can see here that 1,517 children were vaccinated with and in the placebo group there was 751 children age five to 11 years. The efficacy of the vaccine for against confirmed COVID-19 and with onset seven days after the second dose was 90.7% in the placebo control observer behind the trial of the same vaccine, 1151 children, similar number in the placebo group aged now 12 to 15 years. The efficacy against seven days after the second dose was 100%. The safety profile was favorable generally and there were the adverse effects were mild to moderate and in the form generally of injection site pain, headaches, fatigue, but no vaccine related serious adverse effects. (00:26:05): Looking now at the Moderna vaccine age six months to five years, first 6 to 23 months, you see there that the efficacy was 50.6% two weeks after the second dose. And at that time the Omicron was dominating. In the age of two to five years, the efficacy was calculated at 36.8%. Again two weeks after the second dose. Children age six to 11 years, the efficacy two weeks after the first dose when the Delta was dominating was 88%. And in children 12 to 17 years of age, two weeks after the second dose, the efficacy was a hundred percent. Again, a good generally favorable safety profile with [inaudible 00:27:02] mild to moderate adverse effects mainly in the form of fatigue, irritability, headaches, injection site, but again, no vaccine related serious adverse effects. In the Novavax study, which was an extension to the prevent study age 12 to 17 years, the efficacy of the vaccine seven days after the second dose when the Delta was dominating was 79.5%. (00:27:35): Generally the adverse effects were mild to moderate and there were more in the vaccine group than the placebo group. But serious adverse effects were really balanced in the two groups. Now we're looking here at the Pfizer biotic study in 12 to 18 years and first 94,354 children, adolescents actually received the vaccine and the same number actually were unvaccinated. In the randomized trial with 1983 12 to 15 year olds, the vaccine effectiveness was 100% against symptomatic infection with non-Delta variants and that's important. (00:28:25): But when the Delta was dominant, the real world evidence data showed the vaccine effectiveness slightly lower at 88 to 97%. Looking now at the effectiveness of the vaccine among the adolescents 12 to 18 years of age, two to three weeks after the first dose, the effectiveness against document the SARS-CoV-2 infection was 59% and against symptomatic infection was 57%. Again, after the first dose, three to four weeks, the efficacy, the effectiveness was 66% for document the SARS-CoV-2 infection and 82% for symptomatic COVID-19. While one to three weeks, now after the second dose, the effectiveness of the vaccine was 90% for document the SARS-CoV-2 infection and 93% against symptomatic COVID-19. (00:29:34): So looking now at the data from the United States, we have a study where they looked at children age five to 11 years between November the third and December 19th in the year 2021. And as you can see there, 8.7 million doses of the Pfizer BioNTech vaccine was given. 42,504 children were enrolled in the [inaudible 00:30:01] study after the second dose. What they found there was that local side effects occur in 57.5% of vaccines and 40.9% had actually systemic reactions and mainly in the form of headaches, fatigue, injection, side pain. So the CDC actually points out that parents or guardians of children age five to 11 years should be warned that local and systemic reactions are expected after vaccination. Looking at the vaccine adverse events reporting system device, there were 4,249 reports of adverse effects. The vast majority, 97.6% were actually not serious. On the other hand, as you can see there were a hundred reports of that's 2.4%, which were serious and they were in the form of fever, 29%, vomiting, 21%, increased troponin and that was in 15%. (00:31:10): But there were also 12 reports of seizures and two deaths in children. But these children were in fragile health with multiple chronic conditions and none of the data they looked at actually suggested a causal association between death and vaccination. Now on the 18th of April this year, the FDA took some very drastic decisions in my view. What they did, they amended the emergency use authorization for their Bivalent vaccines of Moderna and Pfizer BioNTech. Their aim was generally to simplify the vaccination level for most individuals. And what they did, they authorized the current Bivalent vaccines which contained the Wuhan plus BA.4 and BA.5 strains to be administered. And this is the important thing for all doses to administer to individuals age six months or older. Of course some individuals like the immunosuppressed may need more than one dose of the vaccine and the monovalent Moderna and Pfizer BioNTech vaccines are no longer authorized in the United States. (00:32:28): And the FDA said that they will come back in June with the composition, suggested composition of the COVID-19 vaccine for the autumn 2019 [inaudible 00:32:39]. And then you can see the manufacturers must be able to produce the vaccines quickly so that we can actually have them for auto vaccination. So the Omicron variant is really quite a different variant. There are 54 mutations if you compared with the ancestral sequence and more than half of them are in the spike protein. Omicron displays pathological, genetic and antigenic features that clearly distinguish it from prior SARS-CoV-2 variants and therefore vaccines now really ideal should contain the most recent circulating strains of variants. (00:33:25): The maternal immunization really interests me a lot because I'm a family physician and looking at the various studies, I couldn't find always that the COVID-19 infection actually may result in stillbirth. So I had to dig further. And this study actually involves 1,249,634 deliveries in 736 centers in the United States between March, 2020 and September, 2021. And what you see there, they had 8,154 stillbirths. So we need to now look at these cases and see whether the mother developed COVID-19 infection during pregnancy or not. And what they found was among the COVID-19 uninfected pregnant women, the rate of stillbirth was one in 156 deliveries while among the COVID-19 infected women, pregnant women, the rate was one in 80 deliveries, which is nearly double. And this magnitude was really much higher during the Delta period rather than the pre-Delta period. So in primary care where I work, we want combination vaccines because that's convenient for the children, for patients generally, but it is more convenient for parents as well when they see only one injection instead of two. (00:35:02): But also for vaccinators and the messenger and the technology, but also the protein subunit technology, they're potentially able to combine really these diseases, influenza, RSV, human metapneumovirus and others if for the convenience of primarily of our patients. In fact, we have used extensively the messenger RNA technology during the pandemic and we have learned a lot of lessons from using it and we are hoping that they will be able to actually give us vaccines for all these infectious diseases as we see there, but also personalized immunotherapy for cancer. We are really looking forward to that kind of technology coming to us. Thank you. Saul Faust (00:35:59): Thanks very much George. And you're going to walk over here and we're now going to have a small discussion about some of the controversies, conversations and controversies around COVID vaccines. And I would say again, please do post your questions either live or in the app because we're going to have time for them come the end. So George, tell us a little bit more about the pros and cons of combination vaccines. George Kassianos (00:36:28): Well combination vaccines are really convenient for the parents, they're convenient for the children, they're convenient for the vaccinators. But I wonder whether the reactogenicity will be similar to the single vaccine. What will be the effectiveness of the vaccine, will be less effective, more effective, perhaps the adverse effects, but also will the antibodies for COVID-19 actually proceed for a whole year. So we only need one reinforcing dose every year. And what about influenza antibodies? Will they last throughout the season? If we have the new technologies they need time to do that, that's fine. Also, some countries like the UK, the vaccinators family doctors for example, and receive a fee for each injection they give in. If you have two injections, there are two fees. If you have one combined injection, it's one fee. So there are all these things to take into consideration, but I will very much welcome combined vaccines. Saul Faust (00:37:39): So Barbara, you are not so sure that we know all the answers yet about respiratory syndromes, right? Right. Barbara Rath (00:37:46): So if we wanted a combined vaccine, one thing that we learned with the Vaccine Safety Initiative is that people would like to remember the name of a vaccine by the disease they're meant to prevent, such as tetanus vaccines pretty easy or rubella vaccine. With respiratory viral infections this is a lot more complex. So here we presenting a study we did on this eight most common respiratory viruses in children and our illusion that we can distinguish based on symptom, which one we have in front of us has been busted by this publication of ours where we looked at the literature on the top with the very wide confidence intervals and a 6,000 children pediatric cohort with very intense monitoring. (00:38:32): Long story short, you cannot tell based on the symptoms which disease somebody had specifically. So when you now vaccinate against some of them such as RSV, flu and COVID, we still run into the risk of people saying, well I got the vaccine for the fall, but maybe the pneumonia vaccine, whatever, I'm going to call it the flu-like illness vaccine. But soon after I had the flu-like illness of my lifetime, we know this from flu and it's very difficult without much diagnostics to deal with this conversation and to explain to people upfront, okay, we are preventing some causes but not all of them. So my opinion is optimistic in that case I would say would like to have a vaccine to protects at least against those eight viruses and not just two or three of them. Saul Faust (00:39:19): Yeah. So we've heard a lot in this meeting about co-infections. Barbara Rath (00:39:22): Yes. And so we did some work on that as well, especially bacterial viral. And if you look at this slide, this was a study one of my doctoral students did. We worked on monitoring every patient who came through our hospital with a case definition for flu-like illness ally. And we did both viral diagnostics at the Robert Koch Institute and bacterial diagnostics using [inaudible 00:39:47] and cultures. And if you line this up and you measure disease severity in these patients consistently, you see that the things that people are most worried about traditionally, which is the combination of flu and pneumococcals, that's the big black dot here in the lower half, that's actually not the one we should worry about most in unvaccinated children, but it is really complex combinations of metapneumovirus and RSV with some other bacteria that has been creating the highest level of disease severity. So we need to study that and understand how much of an impact can we have on bacterial causes of pneumonia or low respiratory tract disease by vaccinating against the viral causes of it. Saul Faust (00:40:30): Okay. And George, we can't possibly do the whole of vaccine hesitancy in five minutes, but can you just give us some insights Okay. Into what your perspective is. George Kassianos (00:40:39): Well, when we talk about vaccine hesitancy, our glasses have empty. When we talk about vaccine acceptance, our glasses half full, I prefer to talk about vaccine acceptance, but generally it's vaccine hesitancy we are talking about. And really vaccine hesitancy is not just a refusal of vaccination, it's actually also a delay in acceptance of vaccination when the vaccination services are available. And that delay can be because I haven't got round to it or I didn't have transport or the time of vaccination you gave me and the date was not convenient for me. So it comes under vaccine hesitancy. So a lot of confidence in the vaccine. The COVID-19 vaccine really poses a direct and indirect threat to our health to the point that the WHO in 2019 actually declare vaccine hesitancy as a major global health problem. Barbara Rath (00:41:41): And this is not a new problem, as we all know actually in my first research interest, history of medicine, if you go back, this has been as around as long as inoculations have been around. And this is a complex thing about something artificial, you to somebody that may have a problem afterwards leads people to be hesitant. Historically, there've also been some very dark periods in the German history of a vaccine hesitancy was rampant for political reasons. So this is a complex topic, it's amplified in modern days by social media and there have been very interesting studies on how actually much revenue is generated by people who get scared about a very controversial topic online when it comes to the advertising revenue for big social media companies. (00:42:30): And they have not shown much accountability during the pandemic on this aspect. Attitudes towards vaccines have always been volatile and it's inherent to the topic with the Vaccine Safety Initiative. We're trying to build tools and ways to bridge that gap, to terminate fear and to create an open conversation knowing that the quality of the relationship between you and your healthcare professional is what determines your level of trust. So today, acceptance of vaccines is more dynamic and rapidly changing than it has ever been. Also because we have more vaccines that we have ever had. Saul Faust (00:43:08): So George, you've stuck a lot of needles into children in your time as a family doctor, give us some top tips. George Kassianos (00:43:14): Well it's important, that interview with the parents, the guardian and the child is really crucial, absolutely crucial. The one thing not to do is to dismiss your patient, the parents and so on, really acknowledge their concerns and their mistrust in the vaccine that you're discussing. And listen, really listen and listen again and try and elicit what their concerns are. You need to personally engage with your patient and give them really accurate information that is based on evidence and expand it in a way that that individual will actually understand it and make it simple to understand. (00:44:00): And at the same time know that if they go on the web and they put vaccination, the first thing that is going to come up and plenty of that will be anti-vaccination websites. So really give them perhaps printed and that's what I do. The websites that they can get on and get really good information in the UK will be the NHS, will be the vaccine, the oxo vaccine group and so on. In no way and at no time criticize really their stand, their position. And also whatever you do, do not use any stigmatized language during that interview. (00:44:40): Don't press for them to give you a decision there and then allow them time. They may want to go home, they may want to discuss it with other members of the family, but offer them for you to be available again for them. And above all, make sure that you make available the vaccine at a convenient time for them. That's what I would do. Saul Faust (00:45:01): Yeah. And you alluded to, I think just to let the audience know, the reference online you referred to as the Vaccine Knowledge Project from the University of Oxford, Oxford Vaccine Group, which is an excellent resource to help to point patients to. What about during the pandemic and the routine immunizations click? George Kassianos (00:45:19): So this has been a huge problem all over the world because children's vaccinations have dropped really more or less everywhere. There are only three countries, more or less that didn't. But everywhere else they have dropped. And we know that in the year 2020, 23 million children actually missed their basic routine vaccinations, which are detrimental if you look at what may happen to measles, to polio, meningitis and cholera. Now routine vaccinations have been disrupted, sometimes have been suspended in some countries, especially the middle income countries. So what we need to do is to work together a very proactive way to do it. So family physicians, pharmacists, pediatricians, midwives, everybody needs to work together to advise mothers and parents about really the need to vaccinate their children. And also we really need to take action as quickly as we can as regards to measles because in 2021, a record of 40 million children actually miss their measles vaccine in the UK from January to April. We have 54 cases of measles now the whole last year and we only have 49. So that is a big problem. Saul Faust (00:46:45): Thanks Barbara. You've got a UNICEF European Academy perspective. Barbara Rath (00:46:49): Yeah, so as the Vaccine Safety Initiative, we've been working with the European Academy of Pediatrics very closely. Namely, if you're looking for educational resources on vaccination such as this seminar, you can find this on SEKI, which is the Strengthening Education and Knowledge on Immunization, S-E-K-I dot EU. And this is a collaboration between us and the European Academy Pediatrics who has really become very active in the field of vaccination. They have been starting to run big campaigns together with UNICEF. (00:47:24): And what I like about this campaign is that we have come to the conclusion that it is better to discuss vaccination in the context of keeping children safe. And that starts with protecting electric outlets in the house when a baby is going to come into the family, safety helmets, seat belts, all these things that we normally consider keeping children safe from the threats of modern life screen protectors on digital devices, whatever many of you are parents, you know what I'm talking about. So the idea here is to campaign and to communicate the concept of vaccine protection through keeping children safe in general and not as some extraterrestrial little outlier in life that is debatable. Saul Faust (00:48:10): Thank you very much. Right. Well that's the end of our main sort of conversation. So we'd like to go back and find out whether we've increased your knowledge on COVID immunization in children, so we've posed the question again, the musical, come on. Please do answer the question how knowledgeable you are on the burden of COVID-19 among pediatric patients from one, not knowledgeable to five, very knowledgeable. It's a bit of a lucky [inaudible 00:48:40] in the room because I don't know whether the answers are coming up one by one or whether we're going to do both questions and then both of them. (00:49:00): Okay so, oh, we've only had, have I gone? Won't go back. Okay. So beforehand you mostly actually thought you were quite know knowledgeable and were glad to see that three, four and five have increased somewhat during the session. So thank you for that. And then we will go to the next question if the clicker works, which is the second question about how confident you are in your region about recommending COVID 19 vaccines to your patients, the children or their caregivers. From one, knowledgeable to five, very knowledgeable. (00:50:08): Thank you. And here are the answers. So many of you were quite moderately to very confident at the beginning and that's increased a little bit while you've been here. So thank you for that one. Okay, so now we move to Q&A, the last Q&A of the last session of ESPID 23 in the room. We haven't got any questions yet live, so before don't think so. Would anybody like to ask a question live if you're not writing it in, but you can scan in, you can go to the symposium link. We've got some questions that were submitted beforehand. So Barbara, after seeing the odds and as low as they are, as low as the odds are of the prevent preventing the virus, and we are still worried about the adverse side effects, why do you still advocate COVID-19 vaccine for all children? Barbara Rath (00:51:27): Well, in an ideal world, I think we would, since the safety margin is very wide and in most cases it's relatively safely tolerated in children. And children, in general, tolerate vaccines better than adults. We have seen every year with other respiratory viruses as well, particularly flu and RSV, which been surveilled more thoroughly before the pandemic that you see much less transmission when children have been staying away from school, let's say for the Christmas time for example. And you'd see it's starting to ramp up than schools are closed, then the families are spending time together and by the end of year holidays it's the grandparents who end up in hospital sometimes. So I think if we look at it from a family approach, the protection of other people in the context, even if you think that the children themselves don't benefit as much as the adults do, the adults will greatly benefit from pediatric vaccination as do neonates coming into a family or others. Saul Faust (00:52:26): I'm going to push you there because we know that the transmission does, protection from COVID vaccines doesn't last very long. And we know now, especially in Europe, the very high sterile prevalence of COVID vaccines is this really a good use of our time to immunize children in the autumn when that transmission prevention's not really going to be there. Barbara Rath (00:52:46): So there's work to be done to improve the vaccines. And I'm not denying that. I think the efficacy duration of the efficacy is something that needs improving and that's something we need to push industry to keep working on. I think I'm much more disappointed about the duration of efficacy of flu vaccine in fact than I am about COVID. Okay. If it's done regularly, if it's done reasonably and widely, we can prevent a lot of things that are transmitted in school, keeping parents out of work, keeping the whole tale of affected family members secondarily protected. So I would personally recommend it for that reason even now. But I'm not denying that there's a lot of room for improvements. Saul Faust (00:53:29): Okay. And George, you were talking about the bivalent vaccines, if they're the same as the flu vaccines, are people going to be able to choose, will it just be a bivalent virus, a RSV and flu? I don't mean bivalent, I mean will it be an RSV and flu recommendation or will people be able to choose to have the single disease vaccines if they don't want me? George Kassianos (00:53:49): Yeah, the problem with the combined vaccines, introducing them straight away. If you have, for example, COVID, RSV and influenza, we need to get the parents to know why we are giving the RSV vaccine. Because at the moment, because we haven't got RSV vaccine, we don't really talk about that. So the patient education is actually very, very important. But generally once we have established the vaccination program, then we, it's much easier for us to use the combined vaccines. Saul Faust (00:54:20): And Barbara, somebody's picked up on your syndromic question and they've said, is there anything that can distinguish COVID and RSV infections? Barbara Rath (00:54:29): No. What we're working on right now is actually we are working on an app that helps measure disease severity where you really capture the key elements that we've been researching to identify over the last 10 years quickly as a healthcare professional. So you look at whether things are present and absent. Something that we as clinicians don't think is the things that are absent sometimes are a bigger tip off than the things that are present. That's how a computer thinks, but humans usually don't. So we need to have a more holistic view of the patient to capture all the elements that are relevant. And we're currently working on developing machine learning algorithms with a colleague at Free University of Berlin to see whether we can train algorithms to help us to understand which diagnostic test might show the highest yield. But you'll never be a hundred percent and you'll never be much better than a good modern day diagnostic test including point of care diagnostics. Saul Faust (00:55:22): Okay, thank you. And now George, really important question because we've talked pretty much in all regions of the world, in all countries about a universal recommendation for vaccines in the vulnerable children. And there's a really important question here, particularly with regard to people's anxiety about the side effects. Is it safe to administer mRNA vaccines to children with severe congenital heart disease? George Kassianos (00:55:49): If I had a case, I would really speak to the pediatrician that is looking after the child. It will be a joint decision before we go to parents to give them our joint decision. Saul Faust (00:56:02): So I think as a specialist in PID I think I would say absolutely the myocarditis that we see very rarely for children with congenital cardiac disease is extremely rare and doesn't bear any relation to the congenital syndrome, which will make children much more vulnerable from respiratory infections of all types. So I think I can see Barbara nodding. I think my recommendation would be just go ahead. Yes, we can be totally reassuring of all the COVID vaccines currently in children with all severe vulnerabilities, that was on one of the slides. George Kassianos (00:56:42): A situation where you have got a child with severe problem, there has to be really a joint decision between the specialist and the family doctor. That's how I do it. Although I know what to do and I would vaccinate that child, but it's best to actually also inform and discuss with the treating pediatrician. Saul Faust (00:57:02): So that's a really important point is communication between health professionals so that you don't get this strange situation during the pandemic of different people saying different things. Midwives, advising moms, one thing, family doctors advising another, specialists in hospitals taking a different view. So I think that's a really, really important, and in fact, George Kassianos (00:57:21): There's one initiative Barbara Rath (00:57:21): That's maybe of interest to the audience here. It's called the EU Coalition for Vaccination, which is an effort by the European Union to create a more shared voice on vaccines in my healthcare professionals of all strives, including pharmacists, midwives, nurses, all these professional associations are combined in this forum, the European Federation of Nurses and Pharmacist Associations. This is the first step in the direction of creating more of a shared statement on vaccines so that the recipient doesn't feel like, oh dear, even the experts don't agree so why should I follow through with this? That's an important, I think, step in the right direction. George Kassianos (00:58:00): Yes, it is so important to really cover with COVID vaccination children that in the clinic groups at risk, to the point that you saw there that in the UK we are vaccinating five and above five years and above who are in the groups at risk. But in fact, mid-June we are starting to vaccinate children age six months to four years as well that then in the clinical groups at risk, not the healthy children, only those in the clinical groups at risk is very, very important to cover them. Saul Faust (00:58:29): Yes. So really important last message, George, but also brings us very nicely to our key messages. So in terms of what you recommend, I think the most important thing is that you stick to your national guidelines, don't go off peace within your country or you we will cause tremendous trouble. We hope we've shown you that COVID-19 vaccine trials and deployment in children have shown mRNA and protein vaccines to be safe and immunogenic in the age groups for which they've received their approvals from the regulatory agencies around the world. COVID-19 vaccines should be given to high-risk children according to national schedules. And these do vary by age, depending on region and country, which is why we've not gone into the detail so much today. (00:59:19): We've just given you a flavor of some of the differences and COVID-19 vaccines for healthy children are safe and immunogenic, but again varies very much depending on the country as to whether they're currently used or whether they might be held in reserve to be redeployed if the pandemic were to change again. Regardless of anything we do, it's our role as healthcare professionals in any specialty or domain to support parents to make that informed decision and young people themselves for teenagers and emphasizing the direct and indirect benefits of immunization and take the opportunities to talk about the whole immunization program, not just individual vaccines where we have the chance. And I'm going to leave Barbara with the last word. Barbara Rath (01:00:04): Don't wait to vaccinate. Saul Faust (01:00:07): Okay. Thank you very much indeed. I thought there was another slide, but we are out of time. Thank you very much indeed for your participation. Thank you for your questions, which did come through eventually. We hope you have safe travels and that you've enjoyed both this session and the hold of ESPID 2023. Thank you very much and goodbye for now. And the American audience will have a moderated session now online with their chairman.