Pros and Cons of COVID-19 Vaccination in Children: Weighing the Evidence

Activity Transcript

George Kassianos, CBE, MD(Hons), FRCGP: Hello, a very warm welcome to all of you to this Medscape Educational Global program on Pros and Cons of COVID-19 Vaccination in Children: Weighing the Evidence. I'm George Kassianos. I'm a family physician and the national immunization lead for the Royal College of General Practitioners in London and also president of the British Global and Travel Health Association. With me, I have a Professor Federico Martinon-Torres who is head of pediatrics and research at the Hospital and Institute of Santiago de Compostela in Spain.

In this program, we will discuss the burden of COVID-19 in children and adolescents. Then we'll look at COVID-19 vaccines and scientific evidence in pediatric populations and we'll try and answer the question, what we need to know, vaccine recommendations and of course expert opinion.

We need to look first at COVID-19 in children and adolescents. We all agree, I think that children and adolescents generally have fewer and milder symptoms than adults. On the other hand, 21%, that's one in 5 cases of COVID-19 infection care in people who are under the age of 20 years. And in the United States the incidence rate of Omicron variant is worse, about 6 to 8 times higher than what it was during the Delta period in children younger than 5 years. As regards to deaths, 0.4% of deaths actually occur in persons under the age of 20 years.

In the UK over 99.9% of infected children do survive. Looking now at severe COVID-19 cases that is not just coming into hospital but needing to go into intensive care, needing mechanical ventilation or dying, an incidence of up to 30% of severe COVID-19 has actually been reported in children who have been admitted to hospital.

Severe clinical outcomes generally were less frequent with Omicron infection compared with the Delta variant. Now, here we see the COVID-19 associated hospitalization rates among children and adolescents by age group and on the left you see the Delta predominant period in white and on the right you see the Omicron predominant period in gray. And what is evident there is that during the Omicron predominance, you see the largest increase in hospitalizations is among the children age zero to 4 years represented here with the continuous blue line.

What's more, hospital admission rates due to COVID-19 were higher in unvaccinated children. That's about 70.3% versus the fully vaccinated children, that's 40.8%. And similarly, in the ICU admission rates were high in unvaccinated children, 30.3% while they were actually half of that, that's 15.5% in the vaccinated.

Here we see children age zero to 4 years who at the time who are not yet eligible for vaccination. And what you see here, COVID-19 hospitalization rates were 5 times higher during the peak of Omicron compare with the Delta period on the left, the white area. And during the Omicron predominance, what was actually noticed was this, that 63% of hospitalized infants and children had no underlying medical conditions, 63%. And again, admissions to the intensive care unit, they were lower during the Omicron 21% versus the Delta period which was 27%.

Federico Martinón-Torres, MD, PhD: Thank you, George. I think that the burden of the disease of COVID-19 in children is important, but we also have to be careful in trying not to over-interpret the data. And I think that this example may help us because there are maybe other confounding factors when trying to measure the true burden of COVID-19 in children. This is a paper that one of the many papers on the burden of disease and CDC when recommending vaccination for children was one of the evidence they used to support it.

In the hospitalizations rates for children with flu who are similar to that of Omicron, here we can see blue bars and gray bars although with a different age distribution. But we have to be careful in this interpretation because it's at the beginning of the pandemic and at the beginning of the pandemic, any child with COVID-19 that be admitted will be relatively more proactive to just in case or scared about what to do or what we could expect.

Many of these children probably were admitted because of having COVID, but not because necessarily of the severity of COVID. And I like very much this other paper coming from the UK where they specifically look at these cases in more detail trying to address if the true reason for the admission was the COVID or if it was just a contributory cause or if it was just an incidental finding in that child that was admitted. And we can see here that when you do the breakdown of the pediatric cases, severe COVID was the reason for admission only in 10% of the cases, mainly older children. Those above 16 years of age.

It was an incidental cause in almost 60% of the cases and a contributory cause in 33% of the cases. So, what I'm saying is not that the burden is not important or negligible, but we have to carefully interpret the true burden of COVID-19 in the pediatric age group.

Dr Kassianos: Indeed. And really we need to look at other risks of COVID-19 infection in children. Here we see long COVID which can occur in about one in 4 children, 25% in adolescents. In the UK 7.4% of the 2- to 11-year-olds and 8.2% of the 12- to 16-year-olds actually reported continued symptoms, long COVID.

The multi-system inflammatory syndrome in children can occur after COVID-19 infection, but it's rare and is very, very serious. Now, if you compare the incidents with white children, the incidence is much higher among those that are black or Hispanic or Asian ethnicities. Now, what about myocarditis? The risk of myocarditis is over 30 times higher in the under 16-year-olds after COVID infection. And something which is very important for primary care is actually diabetes risk.

Here we see that the risk of newly diagnosed diabetes over 30 days after infection with SARS-CoV-2 is up to 2.5 times more likely in the under 18-year-olds.

Martinón-Torres: Well, I think that you have already mentioned very important, other dimensions of the burden of COVID in children. One of this is the long COVID. I think we could cover the rest of our discussion talking about long COVID. But I think this is a complex [topic]. This is the elephant in the room. Long COVID does exist. Long COVID is difficult to measure. It became some sort of ragbag of several entities in general, not only in the pediatric population.

We need to be very careful when interpreting the data on long COVID in children. There are several studies but those that are better powered with longitudinal cohorts, et cetera, indeed show that long [COVID-19] exists also in adolescence. But the dimension and the importance and the duration of this long COVID may be not so important as at least if we compare that with the burden of long COVID in the older population.

This is an example know where they specifically look at children from 6 to 17 years. We can discuss about the definition of long COVID if we agree or not, which is another of the things we always discuss. But specifically, they found a difference between those suffering COVID or not COVID about experiencing later long COVID. The difference is significant but it's 0.8% and in most of the cases these symptoms will result one to 5 months later.

I'm not saying it's not important, but the dimension may be much less important than in the older population. Another story is the PMC or the multi-inflammatory syndrome or PIMS. Different acronyms are used. I think all the pediatricians were really scared when this showed up and this is an entity we were not prepared [for]. The answer is not prepared but was new and confounded the clinicians and we were really scared for the first time with COVID in children because it was a severe entity that could lead to cardiovascular failure and the development of arrhythmias and other cardiac complications and with a mortality that could reach as high as 4%.

I won't go into details on the different peculiarities of the syndrome, but this was probably one of the more scary news we have with COVID in children by the time COVID arrived, the MIS-C syndrome. The good news is that the incidence was already rare but now it has almost disappeared. It can be related to the fact of the use of the vaccines also, but it also can be related to the evolution of the virus.

Maybe the epitopes involved in eliciting this response in susceptible children, whatever. We don't know for sure. But the good news is that MIS-C has almost disappeared. So this was a very important burden but now it seems relatively under control. And you mentioned another very important dimension of COVID, which is the myocarditis risk. And I think it's important from 2 sides. First, from the disease side. Clearly myocarditis is one of the most frequent presentation or one of the most frequent complications of COVID-19.

But then when the vaccines arrive, in certain age groups, and we will be discussing this later, myocarditis was a safety sign linked to some of the vaccines in some specific groups, particularly in males, in young adolescents and young adults after particularly the second dose. But I think it's important, and this is summarized in this slide that indeed it clearly looks like that myocarditis risk was increased after natural infection.

The risk used to be higher in males as compared with females and particularly adolescents and young adults. It's important and we can anticipate that this risk is much higher than after vaccination. So a safety sign was found. For the mRNA vaccines, it looks like that for specific conditions there may be an increased risk of myocarditis but that risk is much lower than actually suffering the natural disease.

Dr Kassianos: Now, here we have got really to discuss the physical and mental health after COVID-19 in adolescents. We have got the CLoCK study in England which run between January and March 2021. This was really in adolescents aged 11 to 17 years that were not hospitalized. And there were 23,000 of them who tested by PCR positive for COVID-19. And there was another group of just under 28,000 adolescents who actually test tested by PCR negative. And they look 3 months later what symptoms they had. What they found is that just under one in 3, 30.3% of those who tested positive and about one in 6, that 16.2% of those who tested negative, actually had 3 or more symptoms.

One of the points that really connected the 2 groups was that 4 out of 10 among them actually reported feeling worried, reported feeling sad reported feeling unhappy. Now, looking now at the symptoms at 3 months, those who tested positive, 39% that's 4 out of 10 actually complain of tiredness. Headaches and shortness of breath was in about 23% of them. Those who tested negative also complain of tiredness but much less 24.4%. Headaches, 14%. Other unspecified symptoms, 15.8%.

So what do we learn from this? We actually see that adolescents that tested positive had generally a higher prevalence of symptoms 3 months later. Now, in the United States, there are vaccines available authorized from 6 months and to 4 years and so on. But the uptick is actually very, very low.

What can we do about children under 6 months of age? Now cocooning, yes, is something that we can do whereby we vaccinate people around the baby. But very, very important is to offer the COVID-19 vaccine to the pregnant mother because if we vaccinate the pregnant mother, she will pass the antibodies to the neonate and give it really immunity in the very first few months of life.

What about the role children and adolescents play in generally viral transmission? We all accept I think that children of all ages can become infected. Not only that, but they can also spread the virus to others. But the SARS-CoV-2 viral RNA shedding in the respiratory tract is actually similar in children, in adolescents, and in adults. Now, we all agree that vaccination cannot completely prevent SARS-CoV-2 infection in children.

What it does do is to reduce really the spread of the virus. And also the spread of the virus is very important. And what we see here is child to child spread is much higher in the primary school compared with children in the secondary school. We see something very, very similar in influenza. Now, looking now at the European Union and the European Economic Area, the recommendations for COVID-19 vaccination in children adolescents which are approved by the European Medicines Agency, what we see is these 3 vaccines here.

The first vaccine is Comirnaty which is the Pfizer-BioNTech product, and we have the original strain which can be used as a primer vaccination from 6 months onwards and as a booster from 5 years onwards. Then we have got the 2 bivalent vaccines. And the first bivalent vaccine is the one that use as the original strain, the Wuhan strain plus the Omicron BA.1 and is license to be used as a booster from the age of 12 years.

And then we have got the second bivalent which is the original strain plus Omicron 4-5 and this is also licensed to be used as a booster 5 to 11 years. And there is a recommendation by the emergency task force to be used also as a primary series and we're waiting for the final decision by the EMA. Then we have got the Spikevax, which is the Moderna product. The original strain can be used as a primary vaccination from 6 months onwards and as a booster from 6 years.

And then we have again 2 bivalent vaccines. One with the original strain and BA.1 used as a booster from 6 years onwards. And the other is the bivalent with the original strain and Omicron BA.4-5, you can be used as a booster from 6 years onwards. But again, there is a recommendation by the emergency task force to be used as a primary series and we're waiting really the final decision of the EMA. And of course Novavax vaccine, Nuvaxovid is also available for primary vaccination in children age 12 years and above.

Looking now at the latest bivalent vaccines we have in Europe. We have 2, the Pfizer-BioNTech vaccine which is 30 micrograms. 15 is the Wuhan ancestral virus strain and 15 micrograms, the Omicron BA.4-5 and is licensed from 5 years upwards. And the Moderna which is 50, not 100, 50 micrograms of which 25 micrograms is the ancestral and 25 micrograms is the BA.4-5. And again is licensed from the age of 6 years and above. As regards to adverse effects of these new bivalent vaccines in the 12-year and over are really very, very similar to the monovalent vaccines.

Dr Martinón-Torres: Well, I think that all the indications or the labels of these vaccines we can say that are based on robust data and based on the one hand on the clinical development program and we will be seeing now the main studies, but also in real life effectiveness data. For example, this is the pivotal trial to justify the indication in 12 to 15 years from the Pfizer vaccine.

It was a randomized controlled trial comparing the non-inferiority of the immune response to young adults and they have been able to show no problems in safety and the non-inferiority of the immune response. In addition, they estimated the vaccine efficacy by then. This was pre-Omicron era and the vaccine effectiveness, the vaccine efficacy estimated at that point was 100%.

Similarly, for the vaccine from Moderna, pretty similar design comparation of the immune response non-inferiority to those age 18 to 25 years, non-inferiority, good safety profile, no safety alarms and a vaccine efficacy estimation again of 100%. We are still talking on the 12 to 17 years age group.

And also you mentioned this one also approved here in Europe is the Novavax vaccine that has been also tried in adolescence from 12 to 17 years. Similar approach. In this case the non-inferiority was proof, no signs with regards to safety and the efficacy estimation was 79.5%. But we have to take into account that the studies are not comparable and this particular study was performed during Delta variant predominance And we know with the different variants when you include all symptomatic disease, the capacity of the vaccines is different.

Now, we know that the vaccines work very well against severe disease but against symptomatic disease, the original strains lose some degree of protection when we include all the mild and let's say less severe cases. If we move now to the 5 to 11 years group, similar approach in this case for the Pfizer vaccine. No problems with safety. Non-inferiority as compared with young adults and the efficacy estimated was around 90%.

If we look at the KidCOVE trial which is for the same age group or the pretty much the same age group 6 to 11 from the Moderna vaccine, again non-inferiority achieved, no problems with safety and it was an estimation of 88% in terms of efficacy for this particular age group. Also, although no license yet or not approved this indication, the Novavax vaccine has been also trialed in children below 5 years from 2 to 17 years of age. And again the data is very robust and so in no problems with safety and fulfilling non-inferiority as compared with adults.

In the range from 12 years we have 3 vaccines with robust data and in the range from 5 to 12 years or 6 to 11 years, we'll have already 2 vaccines approved based on this data. Also, there has been trials performed in lower age groups. In this case we are seeing the results of the Pfizer trial for children 2 to 4 years. Again, similar results in terms of non-inferiority as compared with young adults. No safety signals in this trial and an early estimate of efficacy of 82.4%. And in this case Omicron was already the circulating strain, the predominant circulating strain.

Also, Pfizer went down to 6 months. We see the actual approval you have shared with us and in the age group from 6 to 23 months of age, again non-inferiority was fulfilled. No safety signals arose during the trials. And the estimation of the efficacy at that moment was 75.6% against Omicron, that was the predominant strain. Similarly, for the Moderna vaccine, it was studied in infants and children from 6 months to 5 years.

Again, non-inferiority fulfilled, no problems with safety in this clinical trial. And the vaccine efficacy estimated here, different endpoints, different definitions was around 36.8% in 2 to 5 years and it was 50.6% in those 6 months to 23 months off. But again it was Omicron and it was Omicron B.1.1. So it was in a different phase, different variant. So you cannot directly compare these data.

But as I mentioned there are a lot already of real-life data. In this example we are sharing in the screen, this is a recent systematic review and meta-analysis. It's mainly focused on mRNA vaccines and specifically in the Pfizer vaccine data. But it gave us an idea that the data that we were seeing in the clinical trials were reproduced in real life, which is the real good news, that is when they were used at greater scale and in natural conditions.

Here we can see the summary of the main results showing that actually was able to decrease infection, to decrease symptomatic infections by half, but more importantly to decrease the risk of hospitalization with an effectiveness of above 70%, to decrease the risk of MIS-C which was important at that moment. We know that now the incidence naturally decreased but we know that the vaccines protect and more important, or as important as this, the accumulated safety profile of these vaccines is good and it seems that there are no problems.

This is another example in this case on the efficacy in real life in the Omicron area for the Pfizer vaccine. And again very high effectiveness in the 5 to 11 and in the 12 to 17 years age group. And also I think it's important to align, we mentioned that in the early part of our discussion today, the risk of myocarditis. It was acknowledged not during the clinical trials where the cases were very low, there was no any safety signal. But in the post marketing, let's say or the post introduction surveillance, more cases arise of myocarditis related to the use of the mRNA vaccines.

 Particularly this safety sign was focused on the second dose, particularly in males and particularly adolescents and young adults. So clearly this was a safety sign that was acknowledged by the regulatory agencies including in the label of the vaccines. But it's important to outline like we are showing in this slide that this risk is much lower than that of suffering the natural infection.

Dr Kassianos: Yes, that's very important.

Dr Martinón-Torres: And I think there's another important thing, this was noted with in the particular case of the vaccines, after the first and the second dose of the primary series. But now with the booster doses for example, this is not happening anymore. As a matter of fact, a few days ago CDC released the data for the second booster dose in more than 29 million doses above 18 years of age and only 3 cases of myocarditis were reported.

We don't know exactly what could that mean, but we know in most of the cases this is very rare, certainly limited and tends to self-resolve, which I think is good news. If we go down in the age and we look to the 5 to 11 years for the primary series, there was no ever any sign in terms of myocarditis. And again a few days ago CDC released that for this age group with a bivalent booster, no cases of myocarditis were reported.

It looks like that the safety profile of these vaccines, it's very good. It's in accordance to the clinical trials and when use widespread in different cities in different countries, this safety looks or remains very, very, very good and very affordable.

Dr Kassianos: Yeah. Very important data. I would like to take our viewers back now to August 2022 when the World Health Organization gave us an interim recommendation as regards to COVID-19 vaccination in children. And what we point out is that children and adolescent do remain susceptible to SARS-CoV-2 infection and what more they can also transmit the infection to others. Also, children and adolescents are generally tested less often than others and that may actually lead to under-reporting.

Again, children under the age of 5 years have a high risk of other diseases which have symptoms that may just overlap with COVID-19. Examples are given here, pneumonia or other viral upper respiratory tract infections and that may just lead to miscalculation, misclassifications sorry. Now, the benefits of vaccinating all age groups and that includes also children, adolescents is really to reduce the number of infections, reduce the number of hospitalizations, the number of deaths and also long COVID.

The direct health benefit of vaccinating healthy children and adolescents is lower if we compare it with older adults who are really at greater risk. And the reason for this is the fact that they show lower incidence of severe COVID-19 and deaths. Now, there are some important benefits to be had if we vaccinate children, adolescents. We can minimize disruption of their education. We may even help to reduce the medication measures they take in schools, for example, wearing masks, distancing from each other and so on.

We can help them maintain their overall wellbeing, health and safety. And we may also reduce transmission from children, adolescents to older adults that are at greater risk. But the important message that the WHO is giving us is the fact that we must continue offering the routine vaccinations to children for the other infectious diseases.

Back last summer, the ECDC gave out these 2 important points. The first one is that with the circulation of variants such as the Omicron and also the lower risk of severe outcomes of COVID-19 in children without comorbidities, the direct benefits of vaccination for children are therefore likely to be lower than others. But very important is to actually take a look at the consideration the vaccination remains beneficial for children at higher risk of severe disease.

Dr Martinón-Torres: Well, if try now to, let's say, compile what we have said, every country has made their own decisions. I share here the example of Spain, what the authorities have decided in terms of official recommendations with regards to children vaccination. And the summary is that any child with risk group pertaining to any risk group, the vaccine is recommended. And then for those above 5 years of age irrespective of being on a risk group or not. This would be the summary of what is actually being recommended in my country in Spain.

Dr Kassianos: Well, in the UK from last September to the 12th of February, we are actually doing what we call the Autumn COVID booster. We are given the fourth dose, if you like to call it fourth dose to anybody aged 5 years and above who is in one of the clinical risk groups. Also, if they have learning disability. Also from 5 years upwards if they are household contacts of an immunosuppressed person. And also some of the adolescents can be carers and from the age of 16 in onwards, we also give them that fourth dose.

We're using the Comirnaty bivalent vaccine which is the original wild type with Omicron BA.1 and also the standard Comirnaty vaccine for the children age 12 to 17 years. For the younger children, 5 to 11 as a booster off label, we're using the pediatric dose of Comirnaty which is just 10 micrograms.

In the UK, we have bivalent vaccines now licensed and we have got the Moderna Spikevax 25 micrograms of the original strain and 25 micrograms of the BA.1 for children aged 12 years and above as a booster. We have got the 3 vaccines from Pfizer, Comirnaty. We have got the one with BA.1. Then we have got 2, the one with BA.4-5. Both those are licensed from 12 years onwards. And we have just licensed another bivalent 5 micrograms of the Wuhan original strain and 5 micrograms of the BA.4-5 Omicron for children 5 to 11 years as a booster.

The important point here is actually who is at risk? And of course there are some factors that are associated with very severe COVID-19 infection. And by that, I mean children who have been not only just admitted to hospital, but they go on to be admitted to the ICU or they have mechanical ventilation or they may actually die.

What we see here in this study is that just under one in 3 28.7% of children with severe COVID-19 infection actually have an underlying condition. The most common conditions are asthma, neurodevelopment and disorders, anxiety, depression, obesity. But the strongest risk factors for severe COVID-19 are in children, are really type one diabetes, obesity, cardiac or circulatory congenital abnormalities. And for children under the age of 2 years, pre-term birth.

Also here, the ECDC has just given us really the rate of vaccination in children and adolescents age 18 years and below. And you can see that at the very bottom you see there that primary course has been given to about one in 4 children, 24.2%. The first booster has been given to 1.8%. No children have received the second booster, but 73.3% are unvaccinated.

Dr Martinón-Torres: Well, I think that your previous slide summarized the reality. One thing is the licensure of the vaccines and the data to support their indications. Another thing is what the authorities recommend in each country, depending on the epidemiology, on the available products. And another thing is what the health practitioner does. So there are 3 levels of decision.

In this slide, I think we have tried to summarized which are the pros and cons of vaccinating children, healthy children against COVID or in other words universal vaccination against COVID. So, I think it's out of discussion that irrespective of age, any child with a high risk condition should be vaccinated with the available products in that particular country for that age group.

But clearly, and even in the case of doubt, because sometimes the high-risk groups for pediatric age are not as clear as [for the] adult population or you align the main ones or the ones that most of the experts agree. So probably when there is a high-risk condition or you have a doubt about an additional risk for that patient, there is no problem to vaccinate and to give priority. And most of the countries will agree on that. But when we talk about healthy children, then there may be differences depending on the countries.

There are reasons to vaccinate and there are reasons that may, let's say, not negating the vaccination but less beneficial or that the net benefit is lower. So clearly we know the vaccine are efficacious. We know that they are safe, but we also know that in general the burden is lower, that healthy children tend to defend themselves better against the disease. We don't know which is the exact role of the vaccines with regards to long COVID or other complications of COVID-19.

But we also know that these problems exist and may be higher after natural infection. So, there are reasons to really vaccinate and other reasons to be less proactive, let's say with regards to vaccination. But I think that the main take home message we can say in this regard is that first we should follow the official recommendations in our particular countries depending on which products are available and which vaccines are indicated in which groups or in which age groups.

Second is that according to the evidence give an honest recommendation to our families or anyone that interrogate us or ask advice about vaccination of healthy children considering that vaccines are safe not only after the trials but after long experience in the real life and that the benefits do exist. Although, they may be more limited depending on the age or depending on the specific conditions, but the benefit will be positive for the one that receives the vaccine.

Dr Kassianos: So what remains is for me really to thank Federico very, very much for joining me today for this discussion we have just had. And I would like to thank you for participating in this activity. Goodbye.

This transcript has not been copyedited.