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Tiffany Kaczorowski (Host): Welcome to Inside Pediatrics, a podcast brought to you by Children's Hospital of Alabama in Birmingham. I'm Tiffany Kaczorowski. Today, we're giving a COVID-19 vaccine update with Dr. David Kimberlin. He is a Professor of Pediatrics at UAB, the University of Alabama at Birmingham and is Co-Director of the Division of Infectious Diseases. He is also one of two, AAP, that's the American Academy of Pediatrics liaisons to the CDC Advisory Committee on Immunization Practices. Welcome Dr. Kimberlin.

David Kimberlin, MD (Guest): Thank you for having me.

Host: You're welcome. So, talking about the CDC and you have an advisory role there. Brand new CDC guidelines that came out recently. Can we unpack that first for people and it is a little bit confusing. It's not quite black and white, right?

Dr. Kimberlin: That's correct. The recently released CDC guidance on what people who have been fully vaccinated can do, it's a bit of a complex document. Good news, is we're at a point in this pandemic that we can begin thinking about what people who are fully immunized can do. I mean, that's a real positive, that's a real plus.

Host: That's a win.

Dr. Kimberlin: It is a win. Now that said, it's not a you know, get out of jail free card and likely it won't be at any point, but certainly it is not right now. What we know, and really, I guess I would say the science upon which the CDC recommendations are based are kind of as follows:

Number one, in order to be fully immunized, you need to be two weeks after your final dose of the vaccine. So, with the Moderna and the Pfizer vaccines, those are two dose vaccines, two weeks after the second dose. For the J & J vaccine, it's a single dose vaccine. And so, it's two weeks after that one dose. That's sort of a definition of what is fully vaccinated. And then when you get out beyond two weeks, following your either first or final dose of the vaccine, in that situation, when you get to that point, you are highly protected against getting COVID, certainly getting severe COVID disease and even getting COVID infection, symptomatic or asymptomatic infection. So you, as the person who's been fully vaccinated really are safe. And, you know, I guess nothing in this world is completely a hundred percent, but your risk is very minimal. So, that's point number one. And then you've got to think about, well, if my risk as a fully vaccinated person is minimal, what about the risk of the other person or other people?

And then you start having to think about, well, have they been vaccinated? Yes. No. If yes, then, you know, the recommendations are that you can be with another fully vaccinated person, someone who's two weeks out from their final dose, you can be with that person and you don't have to have a mask on because you both are highly protected.

On the other hand, if the person or people you're getting together with are not fully vaccinated, then you've got to start thinking about what is the chance, what is the risk that they are going to have if you do transmit something to them. It's a whole lot less likely to happen since you're fully vaccinated, but it can, at least to the extent we know right now, it's not impossible.

So, so we've got to think about how do we protect them. And so you start thinking, what are their risk factors? Are they at high risk or do they have risk factors that put them at higher risk? And if the answer is no. Then the recommendations currently, the new recommendations, relatively new recommendations, are that a person who is fully vaccinated can go into even a single household with unvaccinated people, as long as those people are at low risk and be there without masks. So, that's good news. So, that means like a grandparent who is fully immunized could visit their son or daughter and grandchildren, assuming the son and daughter and grandchildren don't have high risks.

On the other hand, if one of the unvaccinated people does have a high risk, then you should continue to do everything we're doing now. You're not indoors, not, you know, unmasked, those types that you want to be wearing a mask. You want to be outdoors. You don't want to be in large groups. And then as well, there's some other nuances about, you know, living in kind of group settings that would be like college dorms or jails or whatever it may be.

And that's the kind of situation where even if you're vaccinated, the same rules from before still apply, you want to be masked. You want to be socially distanced. You want to be separate from other people. So, there is a reason to the madness. You can tell, by the way, I've had to talk through this. It's not a, yes, no answer to a question, but there is scientific basis for thinking about how we can begin, if we're fully vaccinated to take these masks off, it's not all the time, but we can begin thinking about when and where.

Host: So, you're saying that there is a chance I have been fully vaccinated, but there is a chance, that I could carry, still carry the virus and pass it along to someone. And so we always have to be again, thinking about masking, distancing, not for ourselves, but for those other people who may be at high risk.

Dr. Kimberlin: That's correct. And it may be over time, Tiffany, that we, that we learn things different from that, that we learn that the risk of asymptomatic infection in someone who's fully vaccinated is sufficiently low. And that if someone is asymptomatically infected, the risk of them transmitting it, if they've been fully vaccinated is even lower, where we can loosen up some of these recommendations further. But we're not there yet. We can't presume to know something that's not been fully studied yet.

My guess is we might get to that point. But I can't guess on people's lives. So, what we know right now is that from some preliminary data out of Israel and other places, is that people that are fully vaccinated, they of course can still get the infection. A lot less likely than if you're not vaccinated, but it's possible. And we saw that even in the big studies of the vaccines and out of the Israeli data that are not yet peer reviewed, but they're hot off the press so to speak, is that if someone who is fully vaccinated does get the infection, they have a whole lot less virus in their nose and in their respiratory tract.

And the presumption is that if you have a lot less virus there, it's a lot less likely to transmit. So, that's one of the pieces of data that kind of are the foundation for these new recommendations.

Host: So, that answers one question. Now let's get to the J & J vaccine, which has started to roll out in the country. How does that one work compared to the Pfizer and Moderna vaccines, which we have seen previous to that?

Dr. Kimberlin: There's some real key differences. And then there's a couple of things that are quite similar. So, let's start with the ones we are now more familiar with the Pfizer and Moderna mRNA vaccines, messenger RNA vaccines. What messenger RNA is, is a little piece of like computer code that in this case, the mRNA is for the spike protein of the Coronavirus. So, what the mRNA vaccines do is they take this piece of code, this mRNA code that encodes for the spike protein, and they put it in a little bubble of fat and then they inject really small, tiny amounts of that into your arm muscle cell. And what that does then is goes into the cell, and the mRNA that's inside the vaccine, tells the machinery of the cell, the muscle cell to make spike protein. And it does so, and that little spike protein goes to the surface of the muscle cell and your immune system sees that and responds to it and mounts an immune response.

And that's what gives you the protection when you see the real thing, the real virus. So, that's kind of how the mRNA vaccines work. And I'll say as well that the amount of mRNA that's being injected is minuscule compared to the amount of mRNA you're going to see if you get infected. If you're infected with the SARS, COV-2 virus that causes COVID, you are riddled with this mRNA. Whereas if you get a vaccine, you're getting like a hundred micrograms. I mean, there's not even a comparison. So, the concerns that somehow the vaccines are gonna, you know, do something bad, that's not a concern. The concern is the bad stuff that happens if you get the real virus. Cause then you're chock full of it as they would say.

The J & J vaccine, it also uses the mRNA for the spike protein, but it has a different platform or a different sort of foundation that it uses to get that mRNA into the cells. That's called a viral vector vaccine. The virus that's the vector sort of the car that the mRNA is driving in to get inside your cell, that viral vector is called an Adenovirus and Adenoviruses are extremely common. They cause the common cold and what they've done with this particular adenovirus vector, is they have taken out a gene in that viral vector. So, it can't replicate. It can't make more of itself. It's not like a regular adenovirus that can replicate in your body.

And so they've taken out that gene, so it's kind of a one and done, it goes into the muscle cell and then it can't replicate itself. And then they've added the spike protein, the mRNA. So, it becomes this viral vector becomes again, the car, to use a metaphor that kind of is injected into your arm muscle and drives into your cell. And then it releases the mRMA, the spike protein into the cell muscle, you know, makes spike protein. It moves it out to the surface. It, the immune system sees it and it stimulates everything. So, from that point forward, once the mRNA is in your muscle cell, it's pretty much the same process as with the mRNA vaccines. It's just a different way to get it in.

Host: So, that one, the studies show is not quite as effective as the other two, but you're saying, you know, at this point, we need to get vaccines in arms. If that is the vaccine that's available, you should get it.

Dr. Kimberlin: Yeah. I do want to sort of visit something you just said, but let me start by saying that the best vaccine that you can get is the one that can be injected in your arm, period. It doesn't matter what it is. It has to be a COVID vaccine, but you know, mRNA, J & J, it doesn't matter. So, you did mention something that I think is getting some attention. And that is an attempt to look at just the number of the vaccine efficacy and say, well, the J & J vaccine is different than the mRNA vaccines.

And I get that. I understand why we do that, but it's not valid. And the reason is as follows: These vaccine studies, these were huge trial, 30,000 people. And in this study for Moderna 44,000 people, and the study for Pfizer, 44,000 people in this study for J & J. These were done at different times. They were done in different locations and they were done under different circumstances.

So, for instance, the J & J vaccine was studied heavily. I mean, it was in many, many countries, but it was in the United States, Brazil and South Africa and some European countries. And during the time it was in South Africa, during that study, was when that South African variant, the 1351 variant was circulating widely, 95% of infections in South Africa when J & J was doing their study was that variant.

And that variant has been shown to be less impacted by the immune response of the mRNA vaccines, the Pfizer and Moderna vaccine. And yet, the J & J vaccine did really well against it. And I can't say it's a head to head comparison with the other kinds of vaccines, but it still had really good efficacy under a very different circumstance because there was a different variant in South Africa that we know of.

Now, there are other variants around, all through the country here and around the world. And those variants have emerged as the pandemic has continued. So, if Moderna did their study back X number of months ago. And Pfizer was Y number of months ago. And, J & J was Z number of months ago. You Just can't say that X equals Y equals Z.

It's not a, it's not an possible.

Host: It's not that simple.

Dr. Kimberlin: So, these are all excellent vaccines and they all can save our lives and they can all save us from severe disease and Moderna and J & J have shown that they can decrease asymptomatic infection. Likely, Pfizer can too, but they didn't look at it that way when they were doing the studies.

These are our way through this, this very long night that we've been living in for so long. Daylight is ahead.

Host: You mentioned the variants and the South African variant. How concerned should we be about these variants? I mean, I'm assuming this is the virus changing itself, mutating so that it can spread more widely, right?

Dr. Kimberlin: You're exactly right with the way you described it. It's kind of like the flu virus that changes from year to year to year, which is why we have to change the vaccine from year to year to year. It's sort of like that. It's not quite, but it's sort of like that. And as this pandemic has continued, what it does is it allows for the virus to experiment. And the virus kind of says, well, I'm going to kind of tweak this aspect of my ability to latch onto a human cell. And if that doesn't work, then the version of the virus that did that, fades away. But if it works better, if it latches on better than the original version of the virus did, then all of a sudden it gets at what's called a replicative advantage.

And you can imagine if it's better at latching onto the cell and infecting the cell, over time, it's going to become the predominant virus in a community. And so do we need to be concerned about the variance? Of course we don't know for sure. That's the honest answer. My belief is that yes, we do. I hope I'm wrong. But the models that we have suggest that the 117 variant, that's the UK variant will become the predominant virus in the United States for COVID by the end of this month, by the end of March. Now, whether that pans out or not, we'll see, but that's what the models have consistently been showing for some time now.

That's not awful because the UK 117 variant, if someone's been fully immunized, they will still have protection against that 117 variant. But if the same thing happened with the South African variant, that the data that are coming out suggest with the Pfizer and Moderna vaccines, that you have some protection, but not as much. And so I really believe this is going to sound kind of sensationalistic, but we are in a race against time here. We are racing against these variants and the way that we win that race, is we vaccinate so many people that the virus cannot find a new person as easily to replicate in and to do those experiments, to create new variants.

So, we have the tools to win this battle, but we've got to have number one enough of them. We've got to have enough of the vaccine, right. And as we get, and we're getting there, as we get more and more vaccine, we've got to have people saying yes, rolling up their sleeves and doing what's going to protect them and protect all the rest of us.

Host: One of the things I wanted to touch on is MISC which we are seeing in some children who have had the COVID virus and then are later developing another disease basically, right?

Dr. Kimberlin: Yeah. MISC is of course a year ago, no one even knew what it was. As best we know, it follows the COVID virus infection, the SARS COV-2 infection. It was first recognized as something unusual toward the end of it April of 2020 in the UK. And everybody else went, yeah, we're seeing that too. It's very rare. I do want parents to hear that and I'm going to say it over and over again. It's very rare. When it occurs, we see increasing number of cases, usually three or four weeks after we've seen a big surge of the virus in a community.

And by definition, it occurs in children. That's what the C is for MISC. We see it in children who have been previously infected. They may not have realized they were infected previously. They Could have been asymptomatic. And a lot of times it is. But, but in order to define it as MISC, they have to either have the virus detected in their nose or much more likely antibody to the virus from their blood, which shows prior infection. What the disease is, is just kind of this massive hyper inflammation in your body, just a lot of inflammation in your, in your heart, in your lungs, on your skin, you get a rash. Persistent fevers for several days, day after day, GI track is a big, common area where, you know, they come in with pretty severe abdominal pain. A lot of times they can think it's appendicitis even.

And then they'll also, they'll be so inflamed from this, that their blood pressure is low. They're kind of in shock. A lot of times they have to go to the ICU. Sometimes they can be managed on the floor as well in the hospital, but at least as we recognize it, now they all are hospitalized because they're that kind of sick.

Host: So, what should parents be looking for?

Dr. Kimberlin: First parents should keep in mind this is rare. And, and there's a lot of things that can cause the kinds of constellation of symptoms that I'm about to describe. But if you're seeing it, you should go to your pediatrician to see whether or not it's one of those more common things, or whether it's, you know, potentially MISC.

The first thing is fever, prolonged fever. And I'm not talking 99.5. I'm making these numbers up, but 101, 103, 104 kind of temperatures. The kind of things that a parent's always going to be concerned about in a child. And so that would be one thing. Persistence of fever really is hallmark.

Host: Not able to get it down and keep it down.

Dr. Kimberlin: Correct. It might come down with Tylenol or Advil, but it's not going to stay down. That's correct. And then skin rash would be a real common thing. Abdominal pain would be a real common thing. Maybe some difficulties breathing if the inflammation's in the lungs and sometimes, you know, not being able to exercise as much or you see that they're really slowed down and sluggish because of the inflammation in the heart.

Those are the kinds of things, when a parent should say, well, I think we ought to go get this checked out. Now, honestly, most of the time it's going to be something else, because this is a rare condition. But when it occurs, you can get real sick, real fast. And so we want to be to the extent possible ahead of it. We're fortunate that we now know to a much greater extent than we did last summer, what to do for it when it's happening. And when we do what we know to be helpful now, when we do that, a lot of times, most of the time, children bounce back very quickly. Not all, some stay in the hospital for long periods of time.

There have even been deaths, but we're better at knowing how to treat it now than certainly we did when we were just learning about it, to begin with.

Host: Very rare. But just something to keep in the back of your mind.

Dr. Kimberlin: Exactly. And the other thing I'd say is that it can happen at any age. It's more likely to happen in the older child and the adolescent than the younger child, say someone four years of age and younger. It can happen in the younger children too, but it's just less likely. Over time, we're going to understand why this happens and that's going to be fascinating because this virus does some weird stuff and this is one of them. As is you know, the long haul are effects that adults sometimes can experience.

We've got a lot to learn about this virus. We've learned a lot already, but we've got a lot more to learn still.

Host: Okay. So, now onto the next topic. Let's talk about an approximate timeline for vaccines to be available to kids. We know right now the Pfizer vaccine is authorized for 16 and older. When do we think that the studies will be completed and enough data will be out there that we can get shots in arms for younger kids?

Dr. Kimberlin: Each of the companies that either have currently authorized vaccines, that would be Pfizer, Moderna, J & J, or that have programs that are leading to what we hope will be authorization in the future, like Novavax; each of these companies has committed to studying their vaccines in children. And you know, some people might say, well, they should have already done that, but I do understand why they started with adults.

You know, the 70 year olds, the 80 year olds, the nursing home patients, the older people with heart disease or with diabetes, they're the ones who were dying in larger numbers from this. And you got to go where the biggest need was. And they did that and they did it beautifully. But now is a great time to be pivoting and expanding, to include the pediatric and adolescent age ranges. And so that Pfizer, as you mentioned, you know, they actually did enroll 16 and over in their original study, the big 44,000 person study. And so when they got authorization, it's authorized technically in a pediatric age range because it includes 16 and 17 year olds. Moderna, and J & J did 18 and over for their big studies. And so that's what they have authorization for.

Now, as I understand it, for each of these vaccine trials, as they move into adolescents and younger children, they're not going to have to do 44,000 children, because they've already shown the benefit in 44,000 adults. So, I'm making these numbers up, but they're going to be in the low thousands range, couple of thousand, maybe 3000 children.

They vaccinate the children. They look and see what kind of immune response they get. And hopefully that gives enough information that the vaccine that you know, X, that we're talking about gets authorized for an adolescent or a child. My understanding is that Moderna and Pfizer have completed their enrollment on studies of 12 year olds through 17 year olds for Moderna and 12 year olds through 15 year olds for Pfizer, because you know, again, Pfizer already studied in 16 and 17 year olds.

And we may see, no one's committed to this, to my knowledge, but the word on the street is that we may see submissions to the food and drug administration for authorization, emergency use authorization in adolescents, you know, 12 and older, you know, even with that filing being as soon as late April. If that happens, you know, we could be looking at the opportunity to vaccinate more adolescents, not just the 16 and 17 year olds with the Pfizer vaccine as early as May for the adolescent.

And then as they're fully enrolled, those studies, they are actively developing and rolling out the protocol for the under 12 year olds. And generally speaking, they're going to start with an older child, like say a five through 11 year old. And then as they get information about the vaccine in that population, they might go down to the two through four year old and then to the, you know, zero through two year old. They're going to back it down into younger and younger ages, which is a safe way to do it.

Host: Is it the same vaccine, the same dose, or are we looking at something different?

Dr. Kimberlin: It's the same vaccine. So, for Moderna, it's the Moderna mRNA, Pfizer, Pfizer mRNA, and a J & J the Adenovirus vector vaccine. The dose though is part of why they're doing the study. Because they want to see whether the dose that they've used in older people is the correct dose to use in a child. And so that's a big part of why they're doing these studies. And the good news is since we're looking for the immune response to the vaccine, rather than the immune response, plus direct evidence that it prevents the infection, it allows for fewer children to need to be enrolled. They're called bridging studies.

Once you enroll, you know, say a couple of thousand adolescents and you see what their immune response is, you can bridge that to the immune response that the adults had. And then you can bridge that to the benefit that the adults received, the benefit of protection against disease. And so you kind of, learn from the people that came before you, in this case, the adults. That'll mean that we have availability of this vaccine initially for adolescents and then for the younger children as well, more rapidly. And that's a good thing.

Host: Last question. What keeps you up at night?

Dr. Kimberlin: I think what concerns me most right now is that we have the tools to put this in the rear view mirror and that's the vaccines. And yet I'm hearing people say, well, I might not get that vaccine. I might not, you know, I'm drowning right now. And I might not grab the life preserver that's thrown from the boat to me. And that breaks my heart because it's, it's through science and through faith and through perseverance and through sacrifice, we find ourselves at this moment in time, on the cusp of stepping into the daylight and out of the darkness.

And yet some people are scared of moving into the daylight. So, my recommendations, if I could be so bold, is to not listen to your Facebook friends, not listen to the chatter that you hear. Listen to the scientists and listen to your doctors. And what you're going to hear from them is when your group's called, get your vaccine and the amounts of vaccines are increasing really quite exponentially.

We're not quite there yet. But we're moving into a good place from a vaccine supply standpoint. Don't let it sit on the shelf at the CVS, roll up your sleeve and get it in your body. And that way you're protected. And that way the people around you, the people you love and the people you don't even know, but you're passing on the street, they're protected.

Host: Well, thank you so much, Dr. Kimberlin. I appreciate your time today.

Dr. Kimberlin: Thank you for the opportunity to visit with you.

Host: Thanks for listening to Inside Pediatrics. More podcasts like this one can be found at children'saol.org/inside pediatrics.