February 18, 2022
As the wave of COVID-19 continues across the country, cases of multi-system inflammatory syndrome in children (MIS-C) are increasing as well. Two years into the pandemic, what have we learned about this disease? On this episode of Talking Pediatrics, Dr. Gabi Hester will dig into the MIS-C guidelines and some frequently asked questions with two of the Kid Experts at Children’s Minnesota: Dr. Tamara Pozos, medical director of pediatric immunology, and Dr. Brad Chu, pediatric cardiologist at Children’s Heart Clinic.
Transcript
Dr. Angela Kade Goepferd: This is Talking Pediatrics, a clinical podcast by Children’s Minnesota, where the complex is our every day. Each week we bring you intriguing stories and relevant pediatric health care information, as we partner with you in the care of your patients. Our guests, data, ideas, and practical tips will surprise, challenge, and perhaps change how you care for the most amazing people on Earth, kids.
Welcome to Talking Pediatrics. I’m your host, Dr. Angela Kade Goepford. We are coming up on two years of the COVID-19 pandemic. And while we certainly can’t argue that children haven’t been affected by COVID-19, one of the most profound ways they’ve been affected is through the severe illness of MIS-C or multisystem inflammatory syndrome in children. On today’s virtual conversation of Guidelines with Gabi, Dr. Gabi Hester talks with two of our kid experts at Children’s Minnesota, about what we’ve learned about this disease and how it’s evolved in kids over the last two years.
Welcome to Guidelines with Gabi.
Dr. Gabi Hester: We’re over two years into the COVID-19 pandemic and the impact on children, both direct and indirect, continues to build. One of the direct impacts to kids has been through the disease called multisystem inflammatory syndrome in children, or MIS-C. As of early January, 2022. The centers for disease control and prevention has documented over 6,400 cases of MIS-C. Many of these children required intensive care, including ECMO, which is similar to a heart and lung bypass machine. Furthermore, there have been at least 55 children in the United States alone who have died from this disease. We’ve had previous podcast episodes on Talking Pediatrics where we’ve covered MIS-C basics, how kids present with their labs and imaging show and the key management strategies. Today, we’re going to dive deeper into some of the frequently asked questions and things that we’ve learned or updated in our management over the last year.
I’ll be joined today by two of the kid experts at Children’s Minnesota, Dr. Tamara Pozos, medical director of pediatric immunology and Dr. Brad Chu, pediatric cardiologist at the Children’s Heart Clinic. So first up is Tam. We’re going to talk today a little bit about the evolution of MIS-C and how we’ve really come to know a lot more about this disease. So, Tam, we’ve talked with you on Talking Pediatrics before about MIS-C and covered some of the key symptoms and lab findings we might expect. In two years now, almost, of dealing with this relatively new disease. What have we learned? What has changed? Were our initial disease definitions holding up to what we’re seeing today?
Dr. Tamara Pozos: The things that have stayed the same over the approximately two years are that it’s typically going to be a school age kid. So in that median age, about nine years of age, the clinical symptoms that they have are always going to be fever. They’re going to sometimes have red eyes and rash and very often they’re going to have significant GI symptoms, so bad stomach pain, vomiting, diarrhea, almost to the point of looking like appendicitis. So those things have stayed the same. What is different is we understand better what is happening with their labs and why it’s happening.
There are certain things like different immune markers that have become clear to be patterns that help us make the diagnosis. Another thing that’s changed in terms of the lab evaluation is in the beginning, we could look for memory to COVID. So what we call an IgG antibody that shows that somebody had COVID before, but that doesn’t help us as much anymore because so many people have had COVID. So that is something that’s become less helpful over time. The other thing that’s changed and updated is we know how to treat these kids better. So if it can be recognized early and we can start basically two different types of medications early to calm their immune system freak out down, they can start to get better, faster. So I feel like we recognize it quicker, we understand it better, and we know how to treat it better.
Dr. Gabi Hester: So you mentioned two different types of treatments for kids who are diagnosed with MIS-C, I think previously described to me, IVIG being used as a cytokine sponge. And for some reason that terminology just has really stuck with me. Can you review briefly what we know about the treatments for MIS-C and what really has evolved to become a gold standard?
Dr. Tamara Pozos: IVIG, I love that analogy stuck with you. There’s so many different things to calm your immune system down, including sopping up the alarm signal cytokines. It may even be able to sop up little bits of virus, if there’s still some circulating around and can make some immune cells settle down. The other group of medications that we use are steroids. And the way I usually explain those to families is if you think about your immune system as a group, a family, and everybody’s got different skills, and some people are watching the front of the house, and some people are inside running the show and everybody’s got different skills and different abilities. If you just gave everybody a chill pill in the water, that would be like steroids, it affects every part of your immune system and calms it down, so it’s a very powerful type of medication.
And we know that many parts of your immune system are freaked out with MIS-C. So initially we were giving the antibody, the IVIG infusions first and then waiting. But a number of groups have studied this since, and they’ve compared kids who got only IVIG to the kids who get IVIG in steroids, and the ones who both medications early in the process do better in many ways. Their heart disease is less, they’re in the hospital shorter amounts of time. They just get better, faster. So that’s something that’s definitely evolved in our understanding since 2020.
Dr. Gabi Hester: And with all great treatments, there’s usually some side effect profile that we expect to encounter. And I think one of the things that’s been surprising to me in taking care of kids with MIS-C is the impact it can have on the adrenal system, and really needing to watch out for these kids who are on prolonged tapers of steroids for risk of developing adrenal insufficiency. What other side effects do you tend to counsel families might happen later? Not necessarily as a result of MIS-C the disease itself, but of some of the things that we’re doing to help treat that disease?
Dr. Tamara Pozos: So the first thing I’ll say is something positive that happens from the treatment, which is IVIG being passive protective antibodies from hundreds of people. I tell people that sometimes there’s reactions in the first day or so after getting that infusion. But after that, the IVIG is going to protect the child for months with higher levels of protective antibodies for all sorts of different things. I often start with that as a positive, because one of the longer term from side effects of steroids, as you might predict for being like a chill pill for all parts of your immune system, is that your protective immune responses also can be somewhat dampened for a number of weeks while you’re on the steroids and the steroids are slowly weaning off.
So being a little bit more careful about exposures, which you would want to do with a kid who was sick enough to be in the hospital anyway, is one of the side effects, just additional immune suppression for some period of time, less so when you get to the lower doses, but there are some kids who do get a little bit more aggravated when they’re on the higher dose of steroids. So there can be a behavioral impact but that often gets better by the time they’re going home. Puffiness and fluid shifts are part of MIS-C and the big inflammation, but steroids can also make you retain more water and get more puffy. But again, as the steroid doses go down, all of those symptoms tend to get better. So those are the typical things I would tell the families about.
Dr. Gabi Hester: Let’s shift a little bit to thinking about vaccines. And in particular, I’m wondering what we’ve been learning over the last few months about as kids are becoming vaccine eligible for COVID-19 vaccination. What is the impact of vaccine status on the likelihood of a child developing MIS-C? Are kids who get vaccinated at higher risk for developing MIS-C, or is it protective?
Dr. Tamara Pozos: It’s protective. And there’s two studies that I would refer people to. There’s a smaller one from France that was in JAMA in December of 2021. And this was only a small number of teenagers who had been eligible to be vaccinated. And of those kids, it was only the unvaccinated kids who got MIS-C. None of the kids who were fully vaccinated had MIS-C at all. So that was the first sign of something that was encouraging.
The other is a study that was in MMWR. And it was just posted on January 7th, 2022. And they, again, looked at the effect of vaccines using a vaccine efficacy design, a test negative case control design. And they looked at 102 kids with MIS-C and 97 out of 102 were the unvaccinated kids and 5 out of 102 were fully vaccinated. So they used that to calculate that the effectiveness of two doses, they used the Pfizer mRNA vaccine in this study, against MIS-C was 91% efficacious in preventing it. So this I think is really powerful evidence that another reason that kids should get vaccinated is not just to prevent disease, but to prevent MIS-C.
Dr. Gabi Hester: One question that I’ve been hearing a bit is can kids get the COVID vaccine after they’ve had MIS-C? So after they’re done with their hospital stay, assuming they were unvaccinated previously and are age eligible.
Dr. Tamara Pozos: Yes, absolutely. We support vaccination. There is a standard recommendation to do it 90 days after MIS-C, but I would take that with a little bit of a grain of salt. I would wait until somebody was completely off of their steroid treatment that calmed down the immune system freak out from their MIS-C. And I understand why people would hesitate, because they’re like, her immune system just freaked out, won’t the vaccine make her immune system freak out again? But what we understand now is that the way your body responds to the vaccine helps you clear COVID more effectively. And we believe that not clearing the initial infection completely a hundred percent is part of the reason why some kids get MIS-C. So not only is it safe and recommended, but potentially could help them not get it again.
Dr. Gabi Hester: Is MIS-C known to be more common with any of the particular variant strains? What sorts of patterns are we seeing with prevalence with the different waves?
Dr. Tamara Pozos: I think that’s kind of a TBD question. People have just started looking at the difference between MIS-C at the very beginning at the pandemic versus the peak with the alpha variant, which was in the winter of 2020. And there’s some subtle differences between those time periods. Although, I wonder if some of it is because of better recognition of the condition than in the beginning of the pandemic. There were not significant differences in how the kids presented. I think what is going to be very interesting is to look at the MIS-C that happened after the Delta wave and the MIS-C that’s happening now after the Omicron wave, because the clinical presentations of Delta versus Omicron acute COVID are so different. And the spike protein is so different between those two strains that I think we might see something in these most recent waves, but it’s not clearly known yet.
Dr. Gabi Hester: What do we know so far about the demographics of kids who are impacted by MIS-C? And are there any systemic factors that might be at play?
Dr. Tamara Pozos: I would say another thing that we have observed that is important to pay attention to is that many more kids who are children of color are affected by MIS-C. So about a third of the cases in the entire US have been kids who are Black and about another third are Latino. And this is likely in part due to some genetic differences, because this is seen worldwide. And for example, a related condition called Kawasaki’s disease, mostly affects kids who are of Asian descent, not Black or Latino kids. So there’s some genetics, but I think it’s also important for all of us to continue doing everything we can to address the socioeconomic differences that lead kids of color to be exposed to COVID more in the first place, to try to fight misinformation and make vaccines available and appealing to families of color, so that we can prevent this really serious complication in all kids, from all different backgrounds and ethnicities.
Dr. Gabi Hester: What else would you tell families? If you could say one thing to families right now, what would it be about MIS-C?
Dr. Tamara Pozos: Be determined and stubborn if your child has fever and rash and GI symptoms and you bring them to an urgent care and they say, oh, they don’t have COVID right now, it’s just a viral illness. Say, I’ve been reading about this condition called MIS-C. My child had COVID four to six weeks ago and has these symptoms, could you please consider this diagnosis and do those labs? Because I really want to empower families as well as colleagues to recognize this condition, because it’s so treatable. And we have met just so many families who are like, but our team didn’t know about MIS-C and some of them even brought it up. So just wanted to encourage families to be persistent, to link to the resources, to encourage the labs that really could help make the diagnosis. And then again, we talked about this before, but please vaccinate your children as soon as they’re eligible, because that will prevent you having to advocate for them in the scenario of MIS-C in the first place.
Dr. Gabi Hester: And as Tam and I discussed, one of the systems most impacted in MIS-C is the heart. So let’s talk now with Brad about some of the specific findings we might see in children who have MIS-C. So Brad, thanks so much for joining today. How has our knowledge of some of the key findings related to the heart evolved over the last couple of years related to MIS-C?
Dr. Brad Chu: We’ve definitely learned a lot more about MIS-C. It seems to have come in waves with different variants and recently we’ve seen a lot more. But definitely over the last two years, we’ve learned that there are defined entities of patients that have MIS-C in the middle, and then some patients that we’ve actually reclassified as just having COVID myocarditis and COVID related Kawasaki disease, or just Kawasaki disease like we see in general. So I think we’ve kind of narrowed down a little bit in terms of the presentation of MIS-C and learning more about it.
Dr. Gabi Hester: For the heart, what are the key symptoms with that middle bucket of kids with more pure classic MIS-C, how does it impact the heart?
Dr. Brad Chu: Yeah, what we’re seeing is as this overwhelming inflammatory response is presenting in these patients, the heart presentation is fast on and fast off. So if we do see heart dysfunction or ventricular dysfunction in these patients with MIS-C, it seems to be very transient. So going from normal heart function to abnormal function within the matter of hours, or just a day, and with prompts treatment, we’re seeing that the dysfunction can go away fairly quickly as well within a day or two.
Dr. Gabi Hester: As far as formal studies looking at cardiac outcomes in kids after MIS-C, what is the literature showing us as far as how quickly do kids return to normal function?
Dr. Brad Chu: Yeah, the published data in the past year has been encouraging. Midterm studies are looking at series of patients from single institutions, looked at six to 12 month follow up. One of those studies out of New York looked at about 40 to 50 patients with MIS-C and looking at their midterm outcomes is very positive. So even though the initial presentations in 2020 seemed quite scary with more severe presentations, but we’ve seen is these patients really don’t look like they have persistent heart disease. So if there’s coronary artery dilation, it’s never large aneurysms or persistent aneurysms like you might see in bad forms of Kawasaki disease.
And like I said, many patients have been actually reclassified as having just Kawasaki disease and not actual MIS-C, and so those patients got pulled out of the cohort of patients with MIS-C. And then patients who had heart dysfunction, it was very transient. So almost all patients left the hospital with normal heart function and looking at other imaging studies other than echo cardiography, there is myocardial edema that’s present on heart MRIs, but really not the true marker of myocarditis, which is fibrosis or [inaudible] enhancement in really any of the patients. So only a couple of patients really had findings that looked like classic myocarditis on those MRIs.
Dr. Gabi Hester: As a hospitalist, my colleagues and I are on often getting to prepare families for discharge and looking at what the next few weeks and months will be like. And one of the challenging things that families hear from us is about activity limitations that we’re recommending for their child. And I had one patient when I said, oh, unfortunately you can’t take up jogging all of a sudden. And he said that won’t be a problem, he was more of a video games guy. But we get a lot of questions from families about specific activities. And can you tell me a little bit about starting off maybe the why behind activity limitations and patients after MIS-C and then we can talk about a few specific activities.
Dr. Brad Chu: Yeah. So we talk about activity limitations after patients have had heart inflammation. If you have significant heart inflammation in swelling, some of those areas of edema and injury can turn into scar. And when you have fibrotic changes in the myocardium, it can be an area that can present with ventricular arrhythmias. As I said before, we’re turning out to be lucky and it’s always better to be lucky than good, that these patients on heart MRIs don’t have a lot of scarring. But it’s hard to really say with any certainty that patients that had real myocardial inflammation won’t end up with scarring. So we’re trying to prevent inducible ventricular arrhythmias. And then the other is to really optimize the ability for the heart to remodel. So areas of the myocardium that are injured, we don’t want to stress or strain it with either high after load or with high heart rates.
So the real guidelines that we’re looking at mimic post myocarditis activity restrictions, which is no heavy weight lifting, or really no lifting of items greater than 10 pounds, and then no sustained elevations in your heart rate. So that really takes you out of any organized or intentional activity or exercise and we usually institute this for about three to six months. Most patients with true myocarditis and not MIS-C, we say at least six months. And we’re being a little bit more liberal on MIS-C patients and we’re saying about three months of those types of restrictions. It kind of stinks. Most of our patients are not just video gamers and they want to get out there and do things like normal, even if they’re feeling back to normal, but things that are organized, we really don’t want them doing for a few months.
MIS-C patients are a little bit of an older cohort, so younger kiddos, it’s hard to keep them down, right? Toddlers and preschool age kids. It’s hard to keep them from being a little crazy and wild. Luckily, MIS-C patients are a little bit older, you can kind of tell them to stay away from some things, but walking and enjoying the outdoors and things like that are certainly fine. Bike riding and really trying to be active, we’re trying to keep patients really keeping their heart rates low. Some patients that leave the hospital with persistent heart dysfunction, and we might actually get them on blood pressure medications or other medications like beta blockers to keep their blood pressure and their heart rate a little lower.
Dr. Gabi Hester: Are there any things you would encourage children to do with their families?
Dr. Brad Chu: There are some pretty good guidelines for activity limitations for different types of heart disease that are put out every maybe decade basis by Bethesda group, looking at this in pediatrics and really for a post MIS-C patient, we recommend low static activity and low dynamic components. So that really puts us into things like golf, things like yoga, things like bowling. Obviously you don’t want to bowl with a very heavy ball. So things that are maybe a little bit of movement, but really not a lot of exertion.
Dr. Gabi Hester: How long are most children kept on aspirin after they leave the hospital?
Dr. Brad Chu: Aspirin prophylaxis is also born out of Kawasaki disease guidelines, but most institutions say to use it for about six weeks, just like Kawasaki disease, as long as the coronary arteries are normal. It’s probably also a little more conservative, but it is within the recommended guidelines and timetables for the follow up for MIS-C patients. So we’re seeing patients at two weeks post-hospitalization and six weeks post-hospitalization. And so after that sixth week, visit an echo if things are looking good, then it seems to be low risk to keep them on aspirin until then, and then we’ll just stop it.
Dr. Gabi Hester: When you think about COVID and the impact in the heart, one of the categories you’ve mentioned previously was COVID-19 related myocarditis. Can you briefly speak to COVID-19 from the impact of the disease related myocarditis versus the vaccine and how you approach vaccination recommendation through the lens of myocarditis risk?
Dr. Brad Chu: I think we were seeing more COVID-19 myocarditis with the other variants with Delta and Omicron, we just haven’t seen much at all. And then for some reason, we also saw more vaccine related myocarditis initially. Maybe those are patients that had the original illness and then were re immunized with the vaccine. And so you just saw a little bit of a spike in vaccine related myocarditis, but we’re seeing a lot less now. I’ve been interviewed by the CDC vaccine adverse events task force a couple of times regarding a couple of our patients that had diagnosed vaccine related myocarditis. And we just haven’t had many cases of that in the past six months or so, myocarditis is bad. It’s worse than what we’re seeing in MIS-C. And usually that illness really is not as transient. If you’re going to have heart dysfunction and troponin elevation from myocarditis, it’s usually a lot more severe from the acute illness. That is definitely what people are worried about with adults having cardiac complications from COVID-19.
Dr. Gabi Hester: If a parent or caregiver approached you and said, Dr. Chu, I really want to avoid my child getting myocarditis. Should I get the vaccine, or should I wait and see if natural illness overtakes them? What would you counsel a family to do in that circumstance?
Dr. Brad Chu: The vaccine has been proven to be safe and effective. And like I said before, vaccine related myocarditis is so rare that really we’re trying to avoid all types of other illnesses related to COVID 19, not just myocarditis from the vaccine. So vaccination has been proven to be effective in reducing things like MIS-C, the lower rates of COVID-19 myocarditis that we’re seeing now I’m sure is at least in part due to vaccination in the general population.
Dr. Gabi Hester: So Tam, Brad, how do you respond when you hear people say, or news articles describing that COVID is mild in kids?
Dr. Brad Chu: Like I said, I think we’ve been really lucky that most patients that have MIS-C and other illnesses related to COVID-19 have been more mild in general than we initially thought and the outcomes are generally very good if it’s recognized in the proper timeframe and treated appropriately, but we still have multiple patients in the ICU at any given moment with illness related to COVID-19, even previously healthy kids. So if you consider being on a ventilator and sedated in the ICU and having central lines and tons of lab draws as a mild illness, then so be it. But I think most families would really like to avoid such a thing for their kid. And so obviously vaccination is best way to prevent that. I think the majority of patients that have MIS-C after a COVID-19 illness have been unvaccinated.
Dr. Tamara Pozos: I heard something recently that has really struck me in terms of how I see my patients even before the pandemic, but certainly with MIS-C. There’s people who think about the top part of a fraction, the numerator, the individual patients, and immunology patients are all rare and different. And when you’re taking care of a patient in the hospital, you’re taking care of just that kid. And then there’s people who think about the bottom part of the fraction and the whole population as a whole, right? And policy makers need to do that. And vaccine policy or COVID policy, school policies, those kind of things, you need to think about all kids. But what I would say to those people is, yes, most kids will have mild COVID, but this complication of COVID is so serious, you can go straight to the ICU.
We’ve had kids completely on the highest level of bypass with MIS-C. So if you could prevent that, if it was your kid, even if it was rare, why would you not want to give them a very, very safe, preventative treatment that will not only avoid their acute illness, very likely prevent their chance of getting long term COVID, brain fog, fatigue, all of those things, that might have something to do with a freaked out immune system also, but also to prevent MIS-C, which 55 kids have died in the United States. And that may not even capture all of them if the disease wasn’t recognized. So I think it’s thinking about the individual kid, if it’s one in 3,500 and it’s your kid, it doesn’t matter what the odds are. It’s very serious and we now understand better that it’s preventable.
Dr. Gabi Hester: And just to be really specific that preventative measure that you’re referring to is…
Dr. Tamara Pozos: Is the vaccine. Yes.
Speaker: Take home points.
Dr. Gabi Hester: Number one, COVID 19 vaccines are protective against the development of MIS-C. Number two, after having MIS-C, children should consider having a COVID-19 vaccine if they’re age eligible approximately 90 days after diagnosis. Number three, thankfully for most children with MIS-C, the impact on the heart is transient and they will regain normal function. Number four, children with MIS-C should be counseled to limit activity for at least three months after a hospital discharge. This includes not lifting weights above 10 pounds and not achieving a sustained heart rate elevation. Number five, clinical guidelines for MIS-C are available at www.childrensmn.org on the health professionals page, as well as on Star Net and the AvoMD guideline app for Children’s providers.
Dr. Angela Kade Goepferd: Thank you for joining us for Talking Pediatrics. Come back each week for a new episode with our caregivers and experts in pediatric health. Our executive producer and showrunner is Ilze Vogel. Episodes are engineered, produced, and edited by Jake Beaver. Lexi Dingman is our marketing representative. For more information and additional episodes, visit us at childrensmn.org/talkingpediatrics, and to rate and review our show, please go to childrensmn.org/survey.