Voiceover: This podcast is for informational and educational purposes only. It is not medical care or advice. Clinicians should rely on their own medical judgements when advising their patients. Patients in need of medical care should consult their personal care provider. Welcome to "That's Pediatrics", where we sit down with physicians, scientists, and experts to discuss the latest discoveries and innovations in pediatric healthcare.
Dr. Amanda Poholek: From UPMC Children's Hospital of Pittsburgh, welcome to "That's Pediatrics." I'm your co-host, Amanda Poholek, Assistant Professor in the Department of Pediatrics and Immunology.
Dr. Arvind Srinath: And I'm your other co-host, Arvind Srinath, Associate Professor of Pediatrics in the Division of Gastroenterology.
Dr. Poholek: Our guest today is Dr. Tyler Harris. Dr. Harris is an Assistant Professor in the Department of Pediatrics and the Associate Program Director for Cardiology. He joined the UPMC Heart and Vascular Institute in 2016, and his clinical interests include inpatient cardiology, Kawasaki disease, and complex pediatrics, patients with congenital heart disease. Welcome, Dr. Harris.
Dr. Tyler Harris: Thanks for having me. Really appreciate you guys having me here.
Dr. Poholek: So it would be great if you could just give us a little bit about your background and what's brought you to Pittsburgh and a little bit more about your research and clinical interest.
Dr. Harris: Absolutely. I grew up in Southeastern Ohio and not too far west of here and traveled all over during my training and was recruited to come here out of cardiology fellowship in Chicago. My wife actually spent time here at Carnegie Mellon and did her PhD here. So we were happy to return to Pittsburgh and join one of the best cardiology programs in the country, in a place that really valued what I did and provided great care to our patients. And so brought us back to Pittsburgh in 2016. So I've been here about five and a half years.
I primarily focus on inpatient cardiology and congenital heart patients and acquired heart disease patients who need to be hospitalized and spend a lot of my time there. And when I'm not on the inpatient ward, I spend a lot of my time in cardiology clinics, both in Pittsburgh and in the surrounding areas. And I have a particular interest in complex congenital heart disease and kids who have higher healthcare needs as well as in Kawasaki's disease.
And now, this new entity, MIS-C, and I see a lot of those patients, both on the inpatient side of the world. And then once they leave the hospital on the outpatient side of the world. And then my other kind of academic and research interests or in medical education, I have roles both with the pediatric cardiology fellowship, and I help out with some of the pediatric residency and our advanced practice provider fellowships. I do a lot of work with medical education here.
Dr. Srinath: And Dr. Harris, before we get into our content, just for the readers, can you give like a fun fact about yourself or something interesting about yourself to break the ice?
Dr. Harris: Sure. Fun fact about me, maybe that I'm not all that fun. No, I was a swimmer growing up and spent a lot of my time staring at the bottom of a pool in a straight line and swam throughout college. And still, I'm a very active supporter of swim teams and now have become a swim parent, which has been an interesting change to life and now starting to feel for my parents.
Dr. Srinath: That's fantastic. I'll let you take the first question.
Dr. Poholek: Yeah, so obviously, the last couple years have probably been a very different clinical experience than you initially imagined it would be when you came in 2016.
Dr. Harris: Absolutely.
Dr. Poholek: With SARS-CoV-2 and COVID, and in particular, the myocarditis that is often associated with MIS-C. I'd really love to start just by getting sort of your overall impression of that experience the last couple years. Some things that have really stood out to you clinically and kind of where you think we are now, 'cause from my perspective, it's been one of those things where the last couple years, we've learned a lot in a very short period of time and sort of thinking about MIS-C from the beginning to where we are now, what's changed in the last two years?
Dr. Harris: Everything. It didn't exist. I think that's been the most interesting part of this is really learning a new diagnosis and how to manage it and counsel families in real time, which is different, especially in pediatric cardiology where we've had the same group of diagnoses for a long time, 'cause most of them are congenital and few acquired congenital heart diseases.
But this has been a completely new entity that we've had to figure out what it is, how to treat it, how to counsel families and how to manage it. And I think over the course of the last two years, we've gone from not knowing what it is or what to do to really at this point having fairly robust treatment protocols and guidelines so that when kids come in fairly sick, between the many different groups in this hospital who take care of patients with MIS-C from our intensive care unit to our pediatric hospital service to all the subspecialist that get involved, including the rheumatology, infectious disease, cardiology, endocardiology, gastroenterology, lots of people get involved and we now kind of do it fairly routinely, it feels like, which I prefer not to be routine, but we've started to develop protocols and practices so that it feels like we actually know what we're doing from two years ago where we didn't know what this was, and that's been a fun change.
It's been challenging. At times, a little bit scary to not know something and not being able to go find a textbook to answer that question, 'cause there's no spot in the textbook that has this in it. But we've applied knowledge of previous illnesses and other illnesses that are similar and been able to collaborate together both as an institution and as a international medical community to find answers. And I think we're starting to get good answers for patients and families. There's still a long way to go and there's still a lot we don't understand. But I think being part of this big group here in nationally that have kind of gone from two years ago to now has been pretty impressive. And as I think about it now, we just recently revised our inpatient MIS-C guidelines for patients and how far that is from where we started.
Dr. Poholek: Yeah.
Dr. Harris: - Is really cool.
Dr. Poholek: It's incredible, really, when you think about it. How do you feel like your prior experience with Kawasaki informed the process of learning about MIS-C? And I guess the second question I also have is how do you think things will change or will they change as vaccination of children continues to increase?
Dr. Harris: Great question. So first, I trained at an institution that historically took care of a lot of patients with Kawasaki's. And I felt like I got really great robust training in Kawasaki's as a pediatric resident, a pediatric fellow and pediatric cardiology fellow. And so when I came here, partially because I spent so much time in the inpatient ward and partially because I had some experience, I started to manage more of the Kawasaki's disease patients. Although many of my other partners also manage patients with Kawasaki's disease. But I had some baseline knowledge and some great contacts and great friends and people to help me out.
And so I was already starting to do a lot more of that management, and then when MIS-C came along, it looks similar to Kawasaki in lots of ways. In other ways, it looks very different. I've described it to families as the evil cousin from the other side of the country who came to visit, where there are very many similar features of a post-infectious inflammatory disorder that affects the heart and the rest of the body. Prolonged fevers, many of these kids have some of the findings that are classic to the diagnosis of Kawasaki disease. And even some of our patients who now get diagnosed with MIS-C probably meet criteria for Kawasaki disease. And in 2015, would've had that diagnosis. But now, it's hard to separate the two.
So they're related, but they're not the same. And the therapy and the outcomes are a little bit different, but we've figured that over time. But two years ago, when we did know what this was, and we knew it looked a little bit like Kawasaki, it gave us a framework to build upon. And so my initial cardiac management for these patients involved, all the things that I did for patients with Kawasaki disease, 'cause I know they had data and I knew they had particular outcomes associated with those therapies. So I knew I could start there.
We've modified that over time as we've learned that they are slightly different. The coronary findings in MIS-C are less than in Kawasaki's. The dysfunction is a little bit more. The abdominal pain and the vomiting and the diarrhea and the GI symptoms are way different than Kawasaki and much more prevalent in MIS-C. And the shock is much more prevalent in MIS-C. So they're similar. It was a framework and a lot of the existing national research groups that look into Kawasaki's disease have now pivoted to starting to study and use existing framework, and we are able to get up and running with research and collaboration much faster 'cause we use an existing framework.
Dr. Poholek: Yeah.
Dr. Harris: As far as your question about vaccination, we are still learning this, but we do have some data recently. So if you look at the CDC tracking data of MIS-C, their last winter, this time last year kind of peak of alpha strain. There were about 35 to 40 cases of MIS-C reported nationally each day to the CDC through Departments of Health. The Delta wave this most recent Fall, we saw about 15 cases a day. And then we do not have data yet on Omicron because it kind of hit us in end of November, December into January. And there's a four-to-six-week lag. So we're gonna probably start seeing it now, if it were going to happen. We don't have that data yet.
So we don't know about Omicron yet, but there definitely was less cases with Delta than Alpha despite more kids being exposed. So why is that? Is that because Delta causes less MIS-C or is it because some of those kids were vaccinated? Now, that data looks at a period where 12 and above was vaccinated, but only the 5-12 age group was not yet vaccinated towards the end of that. So what we see now that five and above is more vaccinated and hopefully soon, less than five is vaccinated. We do have some data, both from the CDC. It was published last month in January, as well as I've seen some data out of France that have shown that vaccination reduces MIS-C significantly.
So the CDC data looked at July to December of 2021 and saw that 91% of kids with MIS-C were unvaccinated. And every kid who went to an intensive care unit was unvaccinated. And so most of the people who were getting MIS-C were unvaccinated and people who got very, very sick with MIS-C were unvaccinated. So it appears vaccine is very protective for MIS-C, both local data and the, like I said, there's some studies out of France that have suggested the same thing. So I told families that I thought it would help. And I really did. Now, I'm very thankful over the last couple weeks. I can say it with a little bit more authority that we have some data that shows it's been effective.
Dr. Srinath: And Dr. Harris, just for our patients and families listening, can we just go over some definitions just to help illuminate and differentiate? So can you overview what myocarditis is? Is it life threatening? Do COVID vaccines cause myocarditis? And what's the relationship between myocarditis and COVID itself?
Dr. Harris: Yeah, that's a lovely question, and one I've spent a lot of time talking with, and one I would love to continue talking about with friends and family members and patients. So myocarditis is a very nonspecific term that refers to inflammation of the heart muscle. Just like any other organ, it can get inflamed and you can have hepatitis or encephalitis or myocarditis. And in fact, there's three layers of the heart. There's the endocardium, which you can get endocarditis, the myocardium with myocarditis and the pericardium, which is the outside layer which can get pericarditis. And those are all just nonspecific inflammations of those tissues.
Historically, most inflammation of tissue is caused by viral illnesses in the same things that cause the common cold. One of the most common causes being influenza or common enteroviruses that cause GI distress and then can cause inflammation of the heart. And so it's a rather nonspecific term that means heart is inflamed.
The reason myocarditis is such a concern and why we get concerned about life threatening illnesses with myocarditis is when the heart muscle gets inflamed and you stress that heart muscle, it can become angry, and typically can cause abnormal heart rhythms that then lead to death. And so if you look at national historical data series on kids and young adults who die suddenly during activity, who die during sports activities, there are many, many causes, but the third most common cause is myocarditis, after hypertrophic cardiomyopathy and coronary anomalies and before other genetic abnormalities of the electrical system.
People who get inflammation of their heart and then go rigorously exercise can get a ventricular arrhythmia and die. And so when we get kids with myocarditis, we try to prevent that. So the way we prevent that is by restricting activity. So if you sprained your ankle playing basketball, you'd have an itus of your ankle. You'd have inflammation of your ankle. I'd put a brace on it and tell you to watch some Netflix and relax for a little while and not go back to basketball too quickly. And if you did, you'd hurt your ankle again, and then you'd be back in my office and I'd tell you the same thing.
I try to explain to families that exercise restriction after myocarditis is the same thing. It's a brace and some ice for your heart, which is basically, relax your heart for a little bit, let it recover, let the inflammation go away and so that you're not straining it to then reinjure it. And so we typically recommend for kids who have myocarditis from all causes to rest for a period of time until we know that the inflammation is recovered.
So that's myocarditis.
Myocarditis becomes relevant in COVID for three different reasons.
So for first of all, what we found out very early on in the pandemic is that if you have very bad primary COVID infection, it affects the heart more than other respiratory illnesses, more than influenza or parainfluenza or rhinovirus or other respiratory illnesses that cause people to have breathing problems. It tends to affect the heart more. We saw this initially in hospitalized adults who were on ventilators had more heart damage than would be expected typically.
And so there was a big concern early on that people who got primary COVID infections would have inflammation in the heart muscle. And this is where a lot of the restrictions from activities, there were delays in a lot of college sports early on until we found some data. And what we've found over the last two years of COVID is that is true. If you're very sick in a hospital, on a ventilator, and have very severe COVID, you're very likely to have inflammation of your heart muscle. But what we found is if you're younger, if you're not as severely infected, if you just had a random positive COVID test or you had a stuffy nose for a couple days or even a fever for a day or two, you're much less likely to have inflammation of the heart muscle. But that's myocarditis due to primary COVID.
The second way you can get myocarditis related to COVID is with MIS-C, which is a post-infectious inflammatory disorder where typically, four to six weeks after a COVID infection, your heart muscle gets inflamed due to a reaction of the immune system that occurs. That can cause inflammation of the heart and cause myocarditis. One in about 3,000 to 7,000 kids who gets COVID we think can get MIS-C based on data we're looking at. And that can cause inflammation of the myocardium. We have not seen large numbers of sudden cardiac death with exercise afterwards, but these kids with MIS-C do get very sick in the hospital and need lots of medications to reverse that inflammatory process. We typically restrict kids for a short period after this illness to let their heart muscle recover.
And then there's a third way you can get myocarditis related to COVID and that's the vaccine itself. And so when the vaccine was coming out, there were reported cases of inflammation, primarily of the pericardium, but also the myocardium itself, primarily in males between the ages of about 14 and 30. It tends to be old teenagers, young adult males after the second dose. It turns out myocarditis has been reported after vaccines, going back all the way to the smallpox vaccine in the '40s and '50s. And it's been reported with most every vaccine. It's been reported with all three available vaccines, the Pfizer, the Moderna, and the J&J vaccine. It's just we're giving more Pfizer to younger kids 'cause that's what's approved.
So it's been more commonly associated with that, but other places where other things have been approved, we've seen it with all doses. And what we've seen is kids after their second dose of the vaccine, three to four days later, have chest pain and fevers and trouble breathing. And we see inflammation of their heart muscle. The good news is it's been very mild. Most kids come to the hospital and we observe them briefly, but are not here very long, and typically responds to Ibuprofen and recovers very quickly with minimal long term side effects. And it's also much, much less common than either of the other two ways that COVID can affect the heart.
We think it's based on the most recent data. It's one in a hundred thousand, one in 50 to a hundred thousand kids, especially once we've seen younger age groups vaccinated where it's much less common. The 5-12 age group, it's way less common than the 12 to 18 age group or the 18 to 29 age group. And so it's be much less common to get myocarditis related to the vaccine than it is to get MIS-C or to have inflammation related to COVID itself.
So what I've discussed with families is the answer that are concerned about the vaccine causing myocarditis is this is not a zero sum game. The reality is you have a chance of getting myocarditis any of the ways you wanna approach this. So which is the least likely way to get myocarditis? And actually, the least likely way to get myocarditis is to get the vaccine versus getting it from primary COVID infection itself or getting from the MIS-C complication after that. So that's a very long answer to a very short question.
Dr. Poholek: No, that's a great, it's a great and comprehensive answer. And actually, I guess I have a follow up, if I may. So broadly, it sounds like your likelihood of getting myocarditis from the vaccine is the lowest. And then there's a likelihood of getting myocarditis through MIS-C, and then there's also acute infection. Is it the case that all of these are sort of driven by inflammatory processes? And I guess what I really wanna know is, is myocarditis from acute infection really the highest likelihood? And does getting myocarditis from each of those potential options other than sort of the severity and the percentage, is the long term outcomes different and is the treatment protocol different? For example, myocarditis from acute infection, is that really the most severe, the hardest to treat, and therefore, potentially the longest lasting for long-term effects?
Dr. Harris: That's a lovely question. I would love to know the answer to a lot of those things. And I think we're still figuring that out. Certainly in children, myocarditis related to acute COVID appears to be very low likelihood and/or very mild, unless you're very sick with COVID and most kids do not get very sick with COVID. Some do, and we have had some kids in the hospital who have gotten very sick with COVID. They seem to be much less common than people my age who get sick with COVID and need to be hospitalized. And it seems to be very directly correlated with how bad was your COVID and how much did you need a ventilator. Were you in the hospital for two to four weeks or more?
Dr. Poholek: Or how much inflammation did you have?
Dr. Harris: Based on how much inflammation you have. And we think the mechanism is slightly different in each of these situations. There at least three different mechanisms proposed for initial myocardial damage related to COVID. Some of which is related to inflammation, but some can be direct toxicity of the virus itself to the muscle. We don't understand that as well yet. There's a lot of data in the adult world. There's a lot of increased propensity for clotting and microvascular injury. And recent data just came out looking at coronary events and cardiac events in adults a year after COVID and showed that if you were unvaccinated and hospitalized with COVID, you had much higher incidence.
So basically, all cardiovascular comorbidities in adults. We've not seen that in kids. And so I think the likelihood of significant cardiovascular involvement with primary COVID is low, but the likelihood of catching COVID is fairly high. So that the number of people who have had COVID is fairly high. MIS-C is definitely a post-infectious inflammatory disorder and has its own cascade and requires a very specific treatment, primarily steroids and IVIG and sometimes additional anti-inflammatory medications. And then myocarditis related to the vaccine appears to respond very well to things like Ibuprofen. And so it's probably slightly different, but we don't understand the molecular mechanisms perfectly yet, although there's lots of interesting data out there looking at that.
Dr. Srinath: So for patients who have COVID, what symptoms would prompt them to seek attention for raising concerns for myocarditis? If they have myocarditis from COVID itself or from the vaccine, can they get the vaccine later on or a booster?
Dr. Harris: So as far as symptoms related to acute COVID, as they return to activity, I've seen lots of kids who got COVID, sat in their house for their 10-day quarantine and went back to their sports who are more tired than usual, who are a little bit more short of breath than usual, not quite back to their normal athletic selves. I don't think that's indicative of myocarditis. I think that's indicative to sitting on the couch for two weeks.
And so what the AEP has recommended is a gradual return to play. And in looking at it, the symptoms that I would most worry about kind of in return to play for myocarditis is passing out with exercise, significant chest pain during exercise, and what we call palpitations or irregular heartbeats during exercise. Those would be the three big things I'd wanna know about. Progressive fatigue that just doesn't get better after a slow progressive return to play, I would think about, but I would say a number of kids that I've seen with that that have had completely structurally normal hearts and normal heart testing is fairly high. And most of the time, it's just what we call deconditioning or just getting outta shape, which is what I deal with on a daily personal basis.
Dr. Srinath: And if I had COVID from, I'm sorry, if I've had myocarditis from COVID or myocarditis in vaccine, can I get the vaccine later on?
Dr. Harris: So currently, if you previously had myocarditis or pericarditis for any reason previously, you can get the vaccine except for the patients who had it from the vaccine itself. The current CDC recommendations is to hold off on further vaccination doses, unless there's a high risk of getting severe COVID and then it's risk-benefit analysis you discuss with your pediatrician and your cardiologist. But I would say that most patients should still be able to get the COVID vaccine. And in fact, we're recommending the COVID vaccine for our MIS-C patients after a period of time that they've recovered from MIS-C. The current recommendation is to wait about 90 days and then allow to vaccinate at that point.
Dr. Srinath: And my last question, just for patients or families who maybe listening or maybe wondering if they're at higher risk than other families, are there any risk factors that predispose people to get myocarditis from COVID or the vaccine itself?
Dr. Harris: We've not seen any risk factors so far that are predictive for myocarditis, either from COVID itself. There's been some signal that kids that are significantly overweight and could be at higher risk, but other than that, with primary COVID, no. With MIS-C, there's no known associations just yet. And the vaccine has been no associations that we've seen yet. They've almost exclusively been healthy normal kids who just had a reaction. We've given the vaccine to lots of kids with underlying congenital heart disease, including significant structural congenital heart disease, heart transplants, and things like that. And all those kids have done well. And we've continued to recommend the vaccine for our patients with mild, moderate, and severe congenital heart disease. There's almost none of our congenital heart patients or acquired heart patients that we haven't recommended the vaccine for.
Dr. Srinath: That's fantastic.
Dr. Poholek: So I guess my last thought or question is as we, maybe it's a moment too soon to say this with certainty, but as we hopefully move into a phase where this becomes more of an endemic virus and not a pandemic, what kind of predictions do you see going forward over the next few years? Do you feel that you'll always have consistent MIS-C coming through the door, hopefully at a low level, or will it become more and more rare as we're able to increase vaccination rates among children?
Dr. Harris: I'm certainly hopeful that increasing the vaccination rate will cut down on our MIS-C significantly, 'cause the amount we are seeing is much more than with something like Kawasaki disease. I would anticipate this would slowly move towards something like we see with Kawasaki disease, where we see some cases per year. I think we average here, ballpark 30, 40 cases per year of Kawasaki disease in an given year. And they tend to come in waves that are related to either environmental triggers or infectious triggers.
That is a whole field of Kawasaki study. And I would anticipate we see a low level of MIS-C moving forward, that diagnosis crosses over with Kawasaki's, and I expect it to continue to cross over. But I'm hopeful that with vaccination and with lower community rates, our rates of MIS-C do drop because we've, in and around, surgeons had a lot of kids in the hospital with MIS-C. We've seen, I think, close to a hundred if not more kids here in Western Pennsylvania with MIS-C at this point over the last couple years. Luckily, most of the kids are doing really well. And thanks in part to the care they get in our intensive care units, in our pediatric floors, and the therapies that they get. And I've seen a lot of those kids in follow up and most of them are doing really, really well.
But I'm hopeful that our rates will start to drop and we've started to see a drop nationally as vaccination has come through and things have changed, but I don't think it's gonna completely go away. And we also need to follow these kids long term to make sure they don't have any long term risk factors, which I have two years of data at this point, but I don't have the 30 to 40 years of data like we have with Kawasaki's disease to be able to give them long term prognosis, which is what I'm looking for as we move forward.
Dr. Srinath: So along Amanda's lines about moving forward, what is the likelihood of folks recovering from myocarditis either from COVID itself or the vaccine?
Dr. Harris: Highly likely. Most kids recover very, very well. So historical data has looked at fulminant myocarditis, which is myocarditis so bad that your heart doesn't squeeze very well, is that some of those patients don't recover. Some of those patients recover and then relapse. And then some of those patients completely recover. Most of the patients that we've seen related to COVID or MIS-C and certainly with the vaccine is their myocarditis has been much more mild in that they didn't have significant changes in their heart function. And those have almost exclusively recovered back to normal.
And what I would assume and what I think based on our previous data is that their heart function will remain normal for a long time. What I don't know is that if it puts you at more risk when you're 30, 40, and 50 years old. That, we need to follow, because we do know that for example, women who had myocarditis as younger kids and then have a very big strain on their body called pregnancy, are more likely to then have dysfunction of the heart muscle and it can come out, whether that comes out with these causes, I don't know yet. I don't think so, based on what we've seen and that mainly since, because the amount of myocardial inflammation is much more minimal.
Some of the studies that have looked at MRIs have not seen profound scarring in the heart on cardiac MRI. And most of these patients' heart function recovers very quickly, especially the patients with MIS-C who can come in with abnormal heart function early on. And as soon as they get steroids and IVIG and therapy, recovers very quickly, typically before they leave the hospital, which is not the case with other causes of viral myocarditis that we're used to seeing where doesn't recover anywhere near that quickly and need to follow with cardiologists and cardiomyopathy doctors for a long time.
Dr. Poholek: Great. Well, Dr. Harris, thank you so much for joining us today. This has been an incredibly informative and wonderful conversation. And I just wanna thank you for the hard work that you do, treating these patients and continuing to research this disease. And hopefully, we'll have you back in the future to learn more about these long-term prognosis.
Dr. Harris: I appreciate you guys having me. It's a huge team that takes care of these patients here, both within the cardiology division itself, and then across the hospital. I could not even begin to do it without the work that takes place in our ICUs and our pediatric hospitals floors. And the help of our rheumatology team have been at the forefront of doing this. It's a multi-system illness. It's in the definition of MIS-C itself and really requires the whole hospital to band together. And it's been, that's probably been the most rewarding part of this is getting to work with so many people across the hospital that allow us to take care of these kids. And hopefully, we'll see less of this as we can increase our vaccination rates, 'cause I really do think that's the way we move forward with this and the way we have much less, less kids in the hospital and less kids who have to see me, which is always a good thing.
Dr. Poholek: Great, but we look forward to having you back.
Dr. Srinath: Dr. Harris, I echo Amanda's gratitude in our team. Can I just end with one just little something, motivating perhaps for patients and families listening? So for kids out there who are thinking about going into medicine, so can you give them one reason why they should be doing what you're doing?
Dr. Harris: Why they should be doing what I'm doing. If they like math and science, but they also like getting to play with kids at work, pediatrics is a great job for you. I was a math and science nerd and a biology nerd as a kid, but I didn't wanna spend all of my time in a lab. And I wanted an excuse to play with kids for a living. And that's kind of what I get to do. Is at my job, I get to wear my Ninja Turtles T-shirt that I'm currently wearing for Superhero Day on our floor. And there's very few jobs where you get to be that involved in the cutting edge of science, but also be that involved in your patient's lives.
Dr. Srinath: Thank you.
Dr. Poholek: Great, thanks so much.
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