COVID-19 Vaccines for Children with Sallie Permar and Jay Varma

DR. JAY VARMA: Thank you very much for taking the time tonight to learn about a really important topic, which is COVID-19 vaccines in children, how they were tested, and why they were needed.

We’re going to do this as a bit of a tag-team. My area of expertise is public health, epidemiology, and public policy. Dr. Permar is an expert in infectious diseases and vaccine development, evaluation, and management. So, I’m going to handle the first part of the talk and give you a little bit of background about where we’re at with COVID-19 and why this topic is important for children, and then Sallie is going to take over for me and go deep into the science and data on vaccines.

So, really, I think the most important messages are what we see on this slide right here, which is that vaccines have done what we expect them to do. They’ve dramatically reduced the number of people who become severely ill or die from COVID-19, and I’ll show you the numbers in just a moment. Vaccines also reduce the risk of becoming infected, and, if you are infected, the risk of transmitting infection to others. Now, of course, there may be questions we discuss later on. That benefit obviously changes a little bit over time, but it remains one of the strongest benefits of all vaccines.

And we all know that the virus will always be concentrated most heavily in the unvaccinated. That’s just the way disease dynamics work in a large population. And extending that benefit, the benefit of vaccination to all children, can protect children and protect the adults that they live with and interact with. So, let’s review what we know and why Dr. Permar and I feel so strongly about the importance of COVID-19 vaccines in children.

So, what I’m going to show you in the next slide is, this is all going to be data from New York City. I know there are some of you in the audience who may be from other parts of the United States or other parts of the world, but since many of us are from the New York City area, I think this data is important. And it really aligns very much with what we see pretty much everywhere around the United States and the rest of the world.

So, this slide really is the message that cases are highest among the unvaccinated. So, what you see here on this slide is on the Y, or the vertical axis, you see the number of cases per 100,000. That’s a standard way in which we present data in public health, the number of people out of 100,000 people that get an infection. And on the bottom you see time, and we’re just showing you the data from the past couple of months. And what you see consistently is that the rate of new infections among people who are unvaccinated is markedly higher than among those who are vaccinated.

Now, what’s the next big thing we worry about? Well, obviously we worry about people getting sick, but we also worry about them getting severely ill. And one of the reasons we had to do such dramatic measures at the beginning of the epidemic in terms of telling everybody to stay at home for several months at a time, is because we needed to prevent our healthcare system from collapsing. So, hospitalizations are a very important metric—severe illness. And we see here an even more pronounced effect, that hospitalizations are much, much greater among the unvaccinated than they are among the vaccinated. And that is an impact that you see consistently over time, where the rate of hospitalizations for those who are vaccinated continues to be very low.

Now, of course, the most extreme outcome, the one we want to prevent, is death. In the original studies vaccines were found to be close to 100% effective. Of course, any time you introduce something into the real world that’s not always the case, so we do still occasionally see deaths in people who have been vaccinated, but as you can see, they are far, far lower than they are among the unvaccinated population.

So, kind of in summary, we see that, at least if you look at the New York City data, since vaccinations became much more widely available in New York, we see that your risk of getting a case of COVID-19 is over 500% greater if you’re unvaccinated, of getting hospitalized, it’s over 900% greater, and of dying is over 800% greater. So, regardless of what endpoint you need—getting sick, getting severely sick, or dying—vaccines are the single best way you can give to prevent yourself from having one of those outcomes.

Now, what do we know about kids? And this slide is a lot busier, so I’m just going to talk you through kind of the highlights. And the highlight, really, here is what’s in the headline. It’s that the infections started to rise in those under the age of 18 after vaccinations became widely available and used by adults in the spring of 2021. So, what you see is the line of 13- to 17-year-olds, and you can see starting in the period in January and then moving forward, even more importantly, into March and April. So, March 14, April 14, if you look at those numbers, you start to see that the case numbers in 13- to 17-year-olds were very high. And that is what we expect in any population. I think it’s really important for people to understand it doesn’t mean the 13- to 17-year-olds were always at very high risk; it just means that when the virus has nowhere to infect in adults because so many are infected, it’s going to naturally end up being transmitted in the populations that are uninfected. And, so, that’s why started in the spring, in April, you started to see more and more infections in teenagers, because a lot of adults, a lot more adults by that time had been vaccinated.

And now we see the same dynamic playing out in children under the age of 13. So, after vaccinations became widely available and used in teens over the past few months, you now see, starting in September, which is also coincidence, of course, when kids are obviously going back to schools, and other places, too. But really, the most important reason you see cases rise at this point is because larger percentages of teens have been vaccinated, which is why you see the rate of infections among 13- to 17-year-olds dropping over time, because now we have a much higher rate of vaccination among them. So, again, the important message is that in population where you have pockets of people that are unvaccinated, the virus will inevitably end up in that population, and the reason children have been unvaccinated is because they just haven’t been eligible because the data wasn’t there yet for their benefit.

So, now I’m going to hand it over to Sallie to talk about the COVID-19 vaccines in children.

DR. SALLIE PERMAR:  Great. Thank you, Jay. So, I’m a pediatric infectious disease physician and also the chair of pediatrics here at Weill Cornell and the pediatrician-in-chief. And, so, I learn about all the diseases that our physicians are seeing in children that are hospitalized and children that are in the outpatient world. And there are three new diseases in children that we didn’t even know about two years ago that we have now seen frequently that are all due to COVID infection in children.

So, the three diseases are now vaccine-preventable, which is the best news, is the acute infection that comes along with the COVID virus itself, which is typically a respiratory infection and can spread to other parts of the body. That’s called acute COVID-19. But there are two other syndromes that follow a COVID infection that also occur in children, and those two are the long COVID, or long-haulers, which is after an infection, that for months later individuals can continue to have symptoms that make it so they can’t participate in their typical activities, including things like feeling very fatigued or tired, brain fog, feeling short of breath for many months.

And then there’s a specific type of post-infectious syndrome called the multi-system inflammatory disease, or MIS-C, the C being for children. This is a disease that occurs somewhere between a month and six weeks after an infection and is a severe inflammatory reaction of your body to the virus having been in the body. This, in particular, occurs in children, and it most often occurs in the age group that just became eligible for vaccination, in that 5 to 11 age group. It occurs 1 out of every 3,000 or so cases and can be very severe, needs often life-saving interventions and therapeutics that land a child in the hospital, and even has resulted in death and long-term disease. So, what is the best news about this vaccine becoming available to 5- to 11-year-olds is these three new diseases that we didn’t even know about two years ago are now vaccine-preventable.

And the final piece of why it’s so important to vaccinate children is that we know that they can spread the infection to other members of their family, other children that they may interact with. And not everybody is able to make a good response to the COVID vaccines. There are immune-compromised people; there are other reasons why people may still remain at risk of the infection, even though they’ve been vaccinated. And, so, we need our children to be part of the protective barrier that we have for ourselves and around those that can’t respond well to vaccines. So, next slide.

And then, of course, we all know, as parents, how much of a secondary impact there was from this pandemic on our children—the amount of time they spent out of school. We know, as pediatricians—now more so than ever—how important it is for is for children to be in school and learning in person. Because not only did we see a wave of COVID infections in children, but we saw a mental health crisis in children that’s still ongoing, that because of the social isolation and other disruptions to typical social activities, children were not doing well in the last year in terms of their wellbeing. Obesity also increased in our children, food insecurity and child neglect, and abuse. These things are all reasons why if we can give children the vaccine immunity that allows them to back in to all the activities they typically were doing before the pandemic, that will help their overall health, as well. Next slide.

So, one question and one area that I work on is developing new vaccines. This, of course, was a brand new vaccine, the COVID-19 vaccine, and it used a technology, the mRNA technology, that researchers had been studying for decades, even, before this became a new vaccine. And I was one of those researchers. I was studying mRNA vaccines for a virus that I studied that also needs a vaccine: cytomegalovirus, which is a key cause of birth defects and brain damage. We were studying mRNA as a vaccine platform long before we knew about the COVID-19 virus.

We were studying mRNA vaccines, and at that top of the tree of arrows there, in animal models—studying them in mice and even non-human primates. After you maybe have a response that looks good in animals, you would go on to try to create the vaccine in a way that can be given to humans. And that was the next step that went forward very rapidly after some very quick evaluations of the first mRNA vaccine for COVID went on in animal models.

After it was ready for human use, then the clinical trials came together. The clinical trials start small, in a small number of healthy adults, and then go into a larger group of healthy adults, hundreds of adults, looking at safety in particular and the immune responses that are elicited. And then in the largest phase of the trials, called the phase 3 trials, is when the vaccines are tested to whether they actually prevent infection and the disease associated with the infection.

It was around that time, after the phase 3 studies in adults were completed, that the pediatric studies began. So, once it was known that this was a very safe vaccine and very effective in preventing disease, we knew that children needed to be part of the vaccine process, as well, and to be able to have the vaccine tested in their populations for use in those populations. And, so, that’s where pediatric trials initiated soon after the adult trials showing how good this vaccine was at preventing the infection were finished.

After those trials yield good results, then what we’ve just seen happen is the vaccines go through review at the FDA and the CDC and they’re recommended by panels of experts. Luckily, for our children the large production and distribution was mostly old hat by this time, with the mRNA being, actually, a very rapid platform that can be produced quickly. Many, many doses can be produced quickly.

And then the next phase that the museum is helping us do now is administering the vaccine. And the final phase is developing that immunity that’s going to prevent the infection and prevent severe disease. One interesting thing that we’ll talk about is the dosing of the vaccine that was determined specifically for pediatrics. Next slide.

So, just to review where we are with all of the different COVID vaccines in terms of their approvals for children, we know that the Pfizer vaccine actually included down to age 16 in their original trials, and it was approved down to that age group. Then, both Pfizer and Moderna started their 12- to 15-year vaccine studies in May and June of 2021, and the approval came in a few months later after that. More recently, our 5- to 11-year-olds, whose trials started in March of 2021, that data was submitted last month to the FDA and then approved by the FDA and recommended by the CDC for use.

Questions have come up, though, about Moderna. The Moderna vaccine is going to be recommended for this group. And while the data has been submitted for the Moderna vaccine for both the 12- to 15-year group and is about to be submitted for the 5- to 11-year group, the FDA has not yet given an emergency use approval for those vaccines because they may continue to be reviewing the data. But also, what’s interesting that now that there’s wide availability of the vaccine, there may not be a reason to give another emergency use approval for another vaccine for COVID-19, since the Pfizer vaccine is already available. So, those of you who may think of waiting for the Moderna vaccine to be approved in the pediatric age groups, we don’t have a timeline on when that might happen.

And then, ongoing are COVID-19 mRNA vaccine trials in the six-month to five-year group. I did actually hear that maybe in January that two- to five-year group may be available for submission to the data to FDA from Pfizer recently. And Johnson & Johnson has planned trials in pediatrics, but may not be initiated yet below age 12. Next slide.

So, just to review again what all these trials in the pediatric age groups have demonstrated so far from the mRNA vaccines. First, that the vaccines and the Pfizer vaccine was highly effective, 95%, against COVID-19 in ages 16 and above. Then when the trials came to include the 12- to 15-year-olds, the vaccine was 100% effective against preventing infection in adolescents, over 2,000 adolescents that were in that trial. And then even more so after following those same vaccinated children that were included in the trials to see if they became infected later and if they ever had severe disease, what has been found is that there has been no COVID-19-associated hospitalizations in children that were included in the trials that are continuing to be followed, down to age 12. Next slide.

Then, of course, because so many 12- to 15-year-olds and older were vaccinated—over 15 million adolescents have been vaccinated at this point—the adverse event reporting system, or the VAERS system from the CDC, gathered a lot of data on what were the potential adverse events that were being recognized after children get the vaccine. And the good news from the almost 10,000 reports that the CDC received is that over 90% of them were non-serious events—things like dizziness, syncope or fainting or headache. But of all the serious events that were recorded from that system, they were all consistent with a single potential side effect, and that was myocarditis.

Myocarditis, as many of you all have heard about associated with these vaccines, does seem to be a very rare side effect of the vaccine that can occur in adolescents and young adults, and particularly in males more frequently than females. This potential complication of the vaccine occurred in somewhere between maybe 10 to 20 cases per 1 million of the second doses that are administered, so it’s still a very rare side effect.

And one thing that is important to know, as someone who has seen a lot of viral-associated myocarditis, the typical type of myocarditis that pediatric infectious disease doctors would see in patients would be from the virus itself. That type of myocarditis is a very severe myocarditis, where often life-saving interventions have to be given—medicines to make the heart work better, even the heart-lung bypass, to oxygenate the blood outside the body.

The myocarditis that occurred with the vaccine was extremely mild compared to what we know of viral-associated myocarditis. The types of myocarditis that children presented with after the COVID-19 vaccine is a self-limited effect, where a child felt not well for a day after the second dose, complained of chest pain, came to the hospital, got a blood test that showed they had some inflammation of the heart, and a check of the heart by sonography and showed that maybe the heart did have some inflammation. Those children often got monitored overnight, maybe some ibuprofen, and walked out of the hospital the next day. And that’s very much in contrast to what we’re used to seeing with the virus-associated myocarditis, where a child can be in the hospital for many, many days and can have permanent damage to the heart, and even die of that infection.

So, an important fact for our parents to know is that myocarditis associated with the COVID-19 virus is six times, or more, higher risk than getting it from the vaccine itself in our adolescent population. So, it is much more beneficial to prevent the virus-associated myocarditis than it is a risk to get the vaccine-associated myocarditis. So, next slide.

So, then comes to the data that came out from ages 5 to 11 group, both the safety and efficacy. The first phase, which is the earliest phase where the dosing of the vaccine was tried across the population. Interestingly—and this is one of the first times that we’ve had such precise dosing that has been done in this age group for a vaccine—a dose of 10μg was able to be selected, which is one-third of the adult dose of Pfizer. And it was selected because it elicited the same level of immunity as the higher dose did in adolescents and young adults, yet it was associated with fewer side effects. And, so, it’s a huge win for children that we’re able to use a lower dose of the vaccine to get the same level of immunity and many fewer side effects.

So, that lower dose of 10μg went in to phase 2 and 3 in the 5 to 11 age group, so over 1,500 5- to 11-year-olds were included as vaccinees, and half that many, 750, were included as placebo recipients. Importantly, there was a similar report of side effects from both the placebo recipients and the vaccinees, and that’s important because some people can have a sore arm just from the needle, and also there’s, of course, the placebo effect, when people may feel that there arm is sore after a day just because they know they got a vaccine.

But it showed us that there were no serious events and no increased side effects that occurred with the vaccine itself and, importantly, there were no severe reactions, such as anaphylaxis or a severe allergic reaction, and there were no cases of myocarditis, either. So, there’s a good chance that with this lower dose and in this age group that already has a lower chance of myocarditis from the many viruses that circulate and cause myocarditis, that we may not see any myocarditis, or we may see a more rare myocarditis effect from this vaccine as we watch the potential side effects as this vaccine gets rolled out.

Then, in the final excellent number that came out of the trials in the 5- to 11-year-olds is the efficacy. So, the efficacy, again, has been consistent across every population that these mRNA vaccines have been tested in was very high. Over 90% effective in preventing the infection in the vaccinated group. There were 17 cases in the placebo group and only 3 in the vaccinated group. And importantly, in those three that occurred, some before there was full immunity, there was much milder disease as compared to those that received the placebo. And again, no severe cases of COVID-19, either. Next slide.

So, finally, the message here that Jay and I want to give is that kids, while they don’t have the same high risk of being very sick or dying as adults do from COVID-19, that they should still get vaccinated. And the reasons are that you will protect children from the acute COVID illness, from long COVID syndrome, and from the multi-inflammatory syndrome in children. You will protect other kids, because a vaccinated child is much less likely to spread the infection, and you’ll protect other adults, including in particular those that do have high risks of becoming very sick from the infection. And so, we, again, are promoting that the best choice for a child is to get your child vaccinated. Next slide.

MODERATOR: Thank you, Dr. Permar and Dr. Varma. We’re going to start taking some questions from the audience, if that’s all right.

>>AUDIENCE QUESTION: My question was that my five-year-old has a lot of food, environmental, pet allergies. This poor little girl has a lot of allergies, so naturally—and asthma. So, naturally I’m a little bit concerned about giving her literally anything new—not necessarily the vaccine itself—but have there been any studies in the 5 to 11 group of children with asthma or any environment, food, or pet allergies? And, if so, what is your recommendation for a child like mine?

PERMAR: That’s a great question. Maybe I can start and Jay can add in.

Yeah, so I hear you, and we see a lot of children that have to be aware of anything new, like you say, because of a history of allergies. And, so, that is something that is very common that we see in children. So, luckily, this vaccine has not been associated with a high chance of allergic reaction. The only type of allergic reaction, that was extremely rare and noted when the vaccine first rolled out, is an allergic reaction to one of the components of the vaccine called polyethylene glycol. Polyethylene glycol is actually something that we very commonly use in pediatrics. It is the main ingredient of a constipation medicine. And, so, if your child has taken that type of medication before, then that would not be a problem for your child.

However, what is noted from the vaccine, because there were some severe anaphylactic reactions to people that specifically have that type of allergy against polyethylene glycol—or MiraLAX is the name of the constipation medicine that it is the component of—is to not get a second dose of the vaccine if you do have a severe reaction to the first dose. And, so, that’s actually the only reason why it is recommended that someone not get a vaccine, would be not get this mRNA vaccine, is if you’ve had a reaction to the first that was a severe allergic reaction.

So, it actually has been in many children that have food allergies without issues. It’s been in many children that have asthma without any issues. And it’s actually been much more safe and less common to have allergies to vaccines, such as the flu vaccine, where we often have to ask people their potential allergy risk to things like eggs, because eggs are used in the production of a flu vaccine. So, this vaccine is actually very safe for children with allergies, and only if you have this known risk of a polyethylene glycol, or allergy to MiraLAX, would that be a reason to not get the vaccine for an allergy reason.

VARMA: Nothing more for me to add. I mean, let me just, I guess, make one general point which may come up over time, which is one of the ways that we think about this and we try to advise people, is to try to compare kind of what is your risk of getting the virus itself. And one of the difficult facts that we have to let people understand and absorb is the virus isn’t going away. It has an animal reservoir that a large percentage of the population will continue to be unvaccinated around the world—for decades to come, in fact. And, so, really what you’re doing is thinking about what is the risk of me getting infected, which is pretty much close to 100% over the next few years versus getting the vaccine. And, so, we know how challenging it is. I have three children myself.

But at the same time, it’s trying to think through what those probabilities are. And everything we know about this virus, it is far worse, especially for kids who might have respiratory issues or other types of diseases that might make a severe respiratory illness worse.

AUDIENCE MEMBER: Can you hear me?

VARMA: We can hear you. Go ahead.

AUDIENCE MEMBER: So, my—I mean, I have many questions, but I’ll try to just start with one. My biggest one is my whole family has already had COVID, including our children. And, so, with no complications—thank God, really, it was nothing for them. What role does natural immunity play, especially for children? I’m just tracking with some of the things that have come out, but that the risks for COVID are so low versus the risks for any adverse effects being higher percentage-wise from—it was 0.4 for adverse effects percent and then 0.002 for severe COVID in children, so—especially for children who have already had it. Why—what would be the advantage of vaccinating?

VARMA: Do you want to answer it first, Sallie, and I’ll follow up?

PERMAR: No, I think that was a numbers question, so you should start. I’ll follow up.

VARMA: Yeah. So, yeah, I didn’t catch the exact numbers that you gave, but let me go through the big-picture points, because we’ve talked about this issue quite a lot—I’m sorry, reviewed this issue quite a lot when I was advising the city—and continue to look at the data on this.

So, there are basically two major ways that your body develops an immune response to a virus. One is by exposure to the virus itself; the other is by exposure to something like a vaccine, which can basically stimulate the body and mimics the impact of the virus without any of the side effects that the virus has. So, oftentimes what we’re talking about is what happens in the situation you’re describing, where you’ve already been infected by the virus. Is there a benefit to also getting vaccinated, as well? Straight out, we know, we’re continuing to learn all the time. We’re always, as scientists, willing to change our mind when new evidence emerges.

What we have seen so far from the data—and this is actually very consistent across many different studies, whether you’re looking at laboratory studies, or you measure different parts of the immune system, or you look at large populations and you follow them out over time, is that getting vaccinated provides two benefits in people who have already been infected before. Number one, it strengthens your immune response, so that’s the total number of antibodies and other immune virus-fighting cells that you have is far greater than you would have just by being infected with the virus itself.

And the second thing it does, it also increases the breadth or quality of your immune response—that is your ability to fight different variants of the virus appears to be much stronger. And we see that consistent across populations, where if you look at a group of people that was previously infected and some are vaccinated and others are unvaccinated, there’s almost a twofold level of protection in the people who are vaccinated. We view vaccination as a very important strategy to strengthen your immune system. Just like you need two or more doses of the vaccine, you often need two or more times for your body to expose, and it’s better that the second time around be the vaccine and not the virus. Sallie?

PERMAR: Yeah, just to add that we do hear that most children do well with this virus, and it is true. However, the risks of them having some kind of severe effect because of the virus are measurable. They’re in the 1% range or so, whereas with the vaccine, especially for the 5- to 11-year-olds right now, we have no indication that there’s any ill effects that come to children from the vaccine at all. And we will have more data, but it’s certainly less, very much less than that 1%. Again, if you’re running the numbers and looking at the risks, the risk is your child getting COVID, even your child getting COVID again, so worth getting the vaccine.

MODERATOR: Thank you. Our next question is “What actually happens to children when the vaccine is being injected into their bodies? Is it giving us more antibodies, or what is it that happens?”

VARMA: Sallie, do you want to go ahead? You’re the infectious disease immunologist.

PERMAR: This is what I love to talk about, actually. So, what’s really cool about this vaccine is that it is the body sort of doing all the work for us, and that was the best part about this mRNA vaccine being so effective and safe. So, the mRNA is the genetic code for a protein that’s on the surface of the virus, the spike protein, which gives it that corona crown-like look to the virus. When the mRNA is injected into our muscle, then it is picked up by some cells that will then use that genetic code of the mRNA to express the spike protein.

That spike protein that’s now on the surface of some of our cells, the immune system immediately recognizes that is a foreign protein, something they’re supposed to respond to. And, so, the immune cells will come in. Some of the spike protein may be taken to a lymph node, where it will be available to more cells to respond to. And then specialized cells called B-cells are the ones that proliferate to that new foreign antigen and then start producing antibodies.

But the other thing that’s great about the mRNA vaccine is that original mRNA, the genetic code that is taken up by our cells, it doesn’t last very long. So, the expression is short-lived. It lasts in the body maybe a day, maybe less, but our innate immune system, which is the arm of the immune system that’s always sensing for things that are foreign, recognizes that mRNA and gets rid of it after a short while.

It’s kind of cool. It’s like a secret code that’s given to your cells and it disappears soon after. And meanwhile, your immune cells have learned everything they need to know about fighting off the virus. So, that’s what happens.

VARMA: Yeah. I mean, I think one thing I would just add, just in general, for people is that we recognize this can be very confusing, immunology is. Even somebody like me that works in infectious diseases but is not an immunologist, this is incredibly complex science. But what’s amazing about it is the decades and decades of work that have gone in to develop this.

Now, the actual vaccines themselves are, again, relatively new, the ones for COVID, but the science behind it, all of the things Dr. Permar just went through, has been stuff that thousands and tens of thousands of scientists spending billions and billions of dollars of research have been doing over years. So, when people talk about these being experimental, I mean, they are experimental in the sense that we’re doing a vaccine against COVID for the first time in children, but it’s built upon a tremendous foundation of knowledge and research. And, so, we know that’s a lot of trust you’re placing in people, but it’s important to understand there are many, many checks and balances along the way. And the reason we report these numbers so rigorously, and even about 1 in 100,000 or 1 in a 1,000,000 chances, we want people to be reassured that we’re doing everything we can to make these as safe as possible.

>>AUDIENCE MEMBER Good evening. I have many questions, but one question is: How will the vaccination of children impact the mask mandates? What levels would you like to see? Because obviously masks are not ideal for children’s learning in school.

VARMA: No, it’s an excellent question, and I’m not going to give you an answer that’s ideal, but I want to talk about this for a moment because it’s a complicated subject that we don’t actually have the right answer to right now. And several things are true at the same time. The first is that we all want masks off of us. And not only do we want them off our children, I want them off of my face, and I’m a doctor and my wife wears this every day. We talk all the time about we don’t like doing it. We still do it because we have to, it’s the right thing to do, but it’s not something we want to do. So, we are absolutely committed to trying to get to a world where we can back to the way we want to be.

At the same time, we’re also still in a difficult situation, where only just recently is a large segment of our population eligible to be vaccinated. And it takes time for us to have the level of immunity in a population and the level of disease to come down, where we as a society—and this is a decision for democracy; it’s not a decision for science—feel comfortable saying, “Okay, we have enough levels of protection from vaccines that we can take away another level of protection, which comes from masks.” And the reality is, this coming winter is going to be another challenging winter. It’s not going to be nearly as difficult in New York City as it was last year. I anticipate it will be much, much better. But still, many people will continue to get sick.

So, what I have said, and my advice, because I continue to give part-time advice to the mayor and other things, is that we’re not in a position yet to remove masks on children in our public schools yet. We may be there by the springtime, and it’s going to depend both on the level of vaccination in schools—we need to get very high levels to make sure there’s that immunity wall—and the level of disease in our population. And I know people would very much like hard numbers for this triggers, but one of the painful lessons that epidemiologists like myself have learned through this time is that every time we put a numeric threshold we learn something different and we have to change it. So, that’s one of the reasons I’m giving you a lot of words but not a firm answer that when we get to this level, all will be revealed. Sallie, do you have any more to add?

PERMAR: Yeah, I just want to add that, also, last year was probably one of the—a very unusual winter, in which children were really well across the whole country, meaning we didn’t have a lot of children filling our hospitals and our ICUs with respiratory infections that we would typically see in the winter. There was no flu epidemic last year, which is the first time in 100 years of recording flu epidemics. There was very little circulation of other respiratory disease. And it’s because of the masks and also that our children often were not in school and being exposed to each other.

So, I think we have to take a lesson from that, to learn that children were very well. We prevented a lot of asthma attacks last year, just by kids not congregating and wearing masks. So, there may be something to—there are certain situations where certain levels of any kind of virus circulating, that we may need to go back to masks. And it’s because it’s going to keep our children healthier in the end. So, I agree that we all have to get to a certain level of vaccination before we talk about getting masks back to putting in our pockets, but we also may want to think about them as a tool going forward.

AUDIENCE MEMBER: Thank you for this informative session. Anyway, my question is, have any other countries started vaccinating that age group? And if so, are there any results that are the same as our lab tests, I guess?

PERMAR: I just heard today that Israel just approved the vaccine for 5- to 11-year-olds. So, that’s at least one other country. And Jay, you may know of some others.

VARMA: I don’t, actually. I haven’t looked into that as well yet, so, no, I don’t. I mean, I can probably google quickly but, yeah, I haven’t heard about the experience in other countries yet.

PERMAR: And I think the U.K., if they’re not approved yet, it nearly is for this age group, as well.

AUDIENCE MEMBER: Hi, yeah, I have a couple of questions, if I may. And by the way, thank you all for doing this this evening. It’s been very helpful.

Studies in Israel suggest that after the first shot it takes about 14 days to get a reasonable level of immunity. The duration of that, of course, is why people go on to get a second. But I was curious if you’d heard of those studies, if you generally believe they’re true, and if for kids there was reason to believe the results are similar.

And a related question. There’s been some discussion that if we weren’t in the middle of a pandemic, the ideal space to give mRNA vaccines may be even further apart in terms of distance between or time between the first and second. Is that true? And for kids, might that be a reason to wait for the second dose?

VARMA: Sallie, do you want to take this one?

PERMAR: Yes. I think you’re thinking like an immunologist. I like that. But one thing that’s important to understand is the only way that the vaccine has been studied so far is with the two doses, and, for Pfizer, the three weeks apart. So, anything else is pretty much a guess at this point, how well it’s going to work.

Now, there are immunologists like me, and we may be doing animal studies and other trials in humans that may space out different vaccines, or even combine different vaccines, and those results will continue to come out over time. I agree that probably the interval between dose was short because we’re in a pandemic, and it was seen that one dose was typically not enough to protect against infection. And even now, we’re learning more and more that adults, at least, need three doses to have long-term immunity that will really protect them against severe disease.

So, I think the thinking that you have is the way experiments are going to roll out in the future, but at this point the only way we know how the vaccine works is the two doses with the recommended number of weeks apart, three weeks for Pfizer.

VARMA: Yeah, I’ll just add a little bit so people understand some of the perspective on this, which is that as much we talked before, or I marveled before, at Dr. Permar’s discussion about the complexities of immunology and how much we know, there’s a lot that we don’t know and that we have to learn, unfortunately, over time. And without a time machine, we can’t actually know these things. And the reason I say that is because the polio vaccine was developed in the 1950s. We are still working out globally—I returned here to New York a few years from Ethiopia, where I had to get another dose of polio vaccine. We’re still working out, actually, the best way to vaccinate in every situation for a vaccine that’s been around for now over 70 years. Measles, it took 30 or 40 years to understand that you needed a second dose of vaccination.

So, even though we’re learning and we’re trying to do this at the speed of the pandemic, the reality is, what we say a few years from now as far the right and perfect dosing interval, and also the—and to get the question about people with prior infection, this may change in the future when we learn more. So, really, what we’re doing right now is really trying to balance safety and effectiveness with everything that we know, and the safety we feel really comfortable about, what we’re going to be learning over time is how we fine-tune effectiveness so that we determine how many doses, at what intervals, and in which populations.

AUDIENCE MEMBER: We have a five-year-old who, we had COVID in January and we tested him for antibodies instead of just going straight to get the vaccine, and he has no antibodies. And, so, now we’re thinking that the vaccine is a good option, but he’s very small. On the growth scale, he’s on the lowest rainbow rung of the little chart that the pediatrician uses. And, so, I was just wondering if it’s smarter for us to wait until it’s approved for children under five. Thank you.

PERMAR: Great. Well, you brought up a number of questions that I think other parents will have. So, one is weight-based versus age-based dosing. Which should we be thinking about in terms of vaccines? So, certainly, we’re all aware that when we give our child any kind of medicine you have to change the dose by the weight, most often. Your pediatrician may ask you how much does your child weigh before deciding what dose of Tylenol. That’s not the same for vaccines. For a medicine, you think about it, it needs to go into your bloodstream after ingesting it and get all around your body, and our bodies take up the drug and metabolize the drug at different rates. But for a vaccine, it’s really just getting the vaccine into the muscle cells, right at the site where the vaccine was given, and then your immune system can really do the work. So, it’s not the same as a medicine that really does need to be dosed by weight.

However, we now are going to learn more about how different weight children are going to respond to this vaccine. So, I think, over time, we may learn things. Like Jay said, when we have our time machine and can go forward. We might be able to better answer this question. But I think you’re asking a question a lot of parents do ask if their child is not the typical weight for age: should they get the dose that is recommended for that age group. And at this point we’re saying yes, that it was tested in an age group, it was tested by age, not by weight, and the dose was specifically selected for that age group. And, so, going ahead with the recommended dose for the age is what I would recommend.

VARMA: Just to maybe touch on the question, what you did with your child, which was to get an antibody test done, this is another topic I think that’s often confusing for people. The challenge is that there are many different types of antibodies that your body generates, and there are very different ways of actually testing those antibodies. And what we really want, as physicians, epidemiologists, scientists, is we want a type of antibody test that we call a correlate of protection, which basically means that when I measure this thing in your blood and it is above a certain level, I have a very high confidence of saying you are protected against being infected.

It turns out that developing that test, what you test, how you test it, what the cut-off is, is a very complicated process, and it can take many years to develop the right answer to that. We have it for certain infectious diseases, like for measles, for example. We don’t quite have it yet for COVID. There are tests that are done in research laboratories that are very predictive. They measure something called, certain neutralizing antibodies, but there isn’t a test like that that’s widely available commercially and can be used and validated. So, it’s going to be some time until we have that.

And that also gets to the question that I think was raised in one of the previous ones about prior infection, that once we have that type of test we may be able to change we have mandates. It may very well be that people who have had more than one COVID infection in the past and have a positive immune response in a very well-validated laboratory test may not need to get vaccinated. That’s the case for some other diseases, for example. So, we will get there at some point in the future. We just don’t know exactly when that is.

MODERATOR: There’s one question that came in directly, they’re asking, and I quote, “So, are schools going to be mandating vaccines? And if so, is that something we should be worried or happy about?”

VARMA: So, it depends on your school and it depends on what you’re doing. So, I’ll give a little bit of insight, because I do a lot of work at the policy level and in governments, and I think Sallie can give the perspective of a chief pediatrician for a very large health system and seeing lots of patients all the time and running that.

So, from my perspective, the challenge is that if I had a school and I was in charge of that school, one individual school, I would absolutely want all of my kids vaccinated. It’s the simplest way to make sure that you have an environment that’s heavily protected. And getting to this issue of mask questions before, honestly, if I had 100% of my staff, 100% of my students vaccinated, I would feel very comfortable not having anybody wear masks on a regular basis, as long as we’re making sure kids don’t come in sick.

The reality is, let’s talk about the New York City Public School System, which is the largest public school system in the country. It has over 1 million kids and 1,600 different schools across 1,000-plus buildings. The reality is, one of the challenges of mandating vaccines is that there are going to be, as we’ve seen with employees and other things like that, a certain percentage that are just going to refuse to do it because we’re at this early stage, because we’re in a situation where there’s an emergency use authorization, not full FDA approval, and it takes time for people to adjust and adapt.

So, at a policy level, what the mayor and other people are balancing is what is the risk of COVID that we can protect without a vaccine mandate versus the risk of if we have a mandate, how many kids are going to drop out of school, and what are the long-term consequences of that happening? So, I can tell you that is the policy challenge that every large public school system is going through. The issues are very, very different for small, private schools or other places where people may have an active choice and an opportunity to decide what they do. So, that’s kind of what the challenge is.

My best guess—and this is not reality; this is just a guess—is that once the vaccines for children, both teenagers and younger children, all school-aged children achieve full FDA approval, that is not just authorization, but approval, I think you’re going to start seeing more large school districts around the country make it a mandate. But I don’t think that time is now, and it’s probably going to be six-plus months until something like that happens. But Sallie, let me turn it to you.

PERMAR: Just to say that I would be grateful when we do get to a place where vaccines mandates for the COVID vaccine, much like we mandate a lot of vaccines for our children before you enter school. That helps me as a pediatrician running a hospital see less children sick in here. And, so, that’s—I definitely am supportive of those vaccine mandates, when the timing is right and the acceptance is going to be high enough that you’re not interrupting school attendance for children.

AUDIENCE MEMBER: I’ve heard a lot of concern about just the long-term effects of such a new vaccine. I, myself, am not too worried about that, given all of what you said tonight about how much research has gone into this type of technology, but what would I say to a parent who says to me, “I’m not going to vaccinate my child because it’s just too new, and we just don’t have enough data on what this could potentially do to my child in the long term”?

VARMA: Sallie, you go ahead first and then I can answer.

PERMAR: I’ll start. Yeah. So, it’s true. We haven’t had this vaccine in children for very long and, so, we can’t say that we know everything that’s going to happen in the long term with this vaccine. However, I think we have a pretty good indication that this is an extremely, extremely safe vaccine, and that’s because, A, it’s been in so many millions of adults, adolescents, and now children, and most or all of the vaccine effects throughout history, for any vaccine, always occur within the first two months after a vaccine. There have never been vaccines that cause long-term effects months later, years later. Really, it’s those first few months—and really, even the first weeks after a vaccine that you have to be concerned about that might be a vaccine-associated reaction.

There’s been a lot of questions about a potential impact of this vaccine on fertility for children, and I think this is a question that parents are asking because we want the best for our children. We want our children to live a long life and be able to have a family of their own. But there is no scientific reason that makes us nervous—those that develop vaccines and doctors and scientists—that makes us concerned that there would be any chance of an effect on fertility for the long term. This is a vaccine that does not travel to other organs. It stays in the muscle, maybe the lymph node nearby. It exits the body after a day or so. And there’s never been any effect of a vaccine on fertility in the past, so there’s no historic reason, no biologic reason, no scientific reason why we would even suspect that would happen. And now, there have been lots of studies that have shown that women can have babies just as easily after getting a vaccine. And, so, pregnancy is one of the times when your hormones are changing the most and, so, that’s a really sensitive readout for if there’s any impact of this vaccine on hormones or fertility.

And then, I did see a question about the myocarditis, as to whether there’s any long-term effects of a potential vaccine-associated myocarditis, and that answer is also no. There have not been severe damage to the heart that makes it so someone would have lasting effects from a vaccine-associated myocarditis. And that’s what makes it very different from a viral-associated myocarditis, where children can have long-term deficits in their heart function because of the viral infection, and can even die from that infection, including the COVID-19 virus causing cardiac complications that have led to death in children.

So, again, running all of the numbers, the benefits all go with the vaccine for your child, as opposed to getting the virus without any vaccine immunity.

VARMA: Great. Nothing more for me to add.

MODERATOR: Well, that’s all the time we have for today, so thank you everyone for joining us tonight, and especially thank you to Dr. Sallie Permar and Dr. Jay Varma for being with us tonight. And now, please join me in thanking all of our panelists tonight. And thank you so much. Have a great night, and we’ll see you next time.