UCSF pediatric cardiologist Kishor Avasarala, MD, discusses how pediatricians can ensure appropriate cardiac care for children infected with COVID-19. He clarifies keys to understanding MIS-C (such as illness phases and age group factors), as well as testing parameters and follow-up essentials. Bonus: how to safeguard a return to sports for kids who’ve had COVID.
the objectives will is this try and and describe things as a case study for primary politicians. So they can actually really relate to clinical situations in this setting. Um Try and define why this is a problem. What can primary pediatricians do to manage this? Hopefully the very mild ones in their office, the sequins presenting more to the hospital and the er setting. Um What does the primary pediatrician need to refer to a specialist or when rather and can any of these be managed in the office while they're waiting for a specialist to see these kids? Uh and uh telehealth availability from UCSF. So we'll we'll talk about those things. So so briefly we all have been inundated with covid information. So I'm not going to spend a lot of time on the the viral etiology or anything else. And focus will be very narrow. Just stick to pediatric age group cardiovascular manifestations. What we know about it, how that is evolving one of the complications, how to manage those. And so just that small focus. So, um we're clearly seeing a larger number of kids who are testing positive for this virus. Thankfully, majority of them are asymptomatic and or minimally symptomatic, which is what we are happy about. But there is a small subset where these kids are significantly ill And the studies are very variable on what that percentage is for the really sick kids anywhere from 4-10% in various different Chinese studies and Italian studies, but quite variable in this number. And this will evolve as we get larger case series. So we'll be able to further define that percentage better. So what we're seeing is essentially two phases of this illness that reference to the cardiovascular component of Covid. So the early phase, this is kind of a coincident with wherever there's regional peaks of the covid infection And we call it acute covid 19. And the late presentation is about 2 to 6 weeks post peak. And that is the so called M. I. S. C. Uh multi system inflammatory syndrome in Children which we have heard about it and we will discuss briefly at this point. All right. So In general Children represent about 9% of the total COVID cases that representing. And as we again now they don't become as sick as often as the adults do. Our hospitalization rates are much lower than adults at any one point in this hospital. Um The Oakland campus especially we're seeing maybe 3 to 4 kids who are in patients with the illness and uh typically maybe one of them or two of them are in the I. C. U. Um The number of kids who have been on the ventilators are also in literally single digits. Um I think we have had only one kid on ECMO to my knowledge base. Um And again these are changing all the time. So I'm just quoting these numbers because I want you to understand that fortunately these numbers are small. They still are important but they are small. We see um definitely a preponderance of infection and hispanic Children and non hispanic african american ethnicity Children. Um And clearly the outcome seem to be worse in that age group. The morbidity and mortality are also worse in in that ethnicity that that I described. Okay For some reason the Children who are younger than two years of age seemed to have the higher risk and the more severe form of illness when compared to the older Children and newborns, roughly about 2 to 5% of newborns if they are born to covid positive, moms may test positive don't necessarily not manifesting any significant illness. So a majority of our Children, usually mild or cold like presentations and most of them are recovering in about 7-10 days as you all know. So if you look at the acute presentation, it is anti johN mediated and again, common knowledge here that it's the binding of spike protein, those red spikes on the coronavirus picture with the two receptors on the cell surface that allows the virus to enter into the end of the little cells and begin the onset of infection with Verena. This is similar to the adults and the one that causes more respiratory symptoms. So the pre existing conditions that we're seeing in Children also seemed to mimic a little bit the adult age group, which is obesity clearly a significant risk factor, hypertension, diabetes and chronic lung disease is an overlap with adults and I didn't add one here and that is congenital heart disease, even post repair. We're seeing a slightly higher chance in kids who have had congestive heart disease repair. Not well documented in percentage, but we see that as a as a as a risk factor. So the cardiac involvement generally manifests due to myocardial injury. And you can see that as the reflection by seeing that the cardiac enzyme definitely increased in many of these sick kids. And I'll go over those details and we see a decreased left ventricular function due to myocardial injury directly by inflammation related uh, injury to the myocardial. And the way they present when they have cardiac involvement is most of the time as an acute viral myocarditis. Picture very similar to the type that is seen with other types of viral myocarditis. Pictures in general management is very similar to the adult management. Um, if we have significant ventilatory issues then in that small setting uh they need a ventilator support. Otherwise it's mostly oxygen support and non invasive ventilatory support. And we have learned from experience to use the ventilatory support only when absolutely needed and that seems to have helped in decreasing mortality issues and mobility issues. Majority of these kids present with significant refractory hypertension so they end up on china tropic support with either nana preference or epinephrine along with fluid challenge support that we provide them and as you will learn and you already know a lot of these manifestations are related to the cytokine surge. Um And so the anti inflammatory medications are definitely helping This includes high those aspirin, intravenous immunoglobulin infusions, one or two doses as needed, intravenous steroids definitely have changed the outcome substantially as we learned over time. Um antiviral medications like remdesivir, which delay or or stop viral replication and lastly mina modulators which are ill six inhibitor infusions and to close a mob and anakin ra are examples of those. So these are all well known to all of us who are learning management of covid infections. Now the cardiac involvement um again I'm emphasizing is primarily myocardial injury. Uh and we we talked about those two which is decreased decreased function um worsening levels of cardiac enzymes primarily troponin and uh um brain natural diuretic peptide levels BNP. And we'll discuss the acute myocarditis pictures. So the late presentations is the essentially the M. I. S. C. So this is typically 2 to 6 weeks post peak it is antibody mediated. So many of these kids may have a prior history of viral like illness or a positive vantage and test, but at this time there were many times negative on the standard auntie jen mediated covid testing. Um And they have less respiratory component or involvement. And it's it's more G. I. Skin manifestations in younger Children neurologic symptoms and all the Children and cardiac involvement in all ages of the pediatric spectrum. So 80% of Children present with some form of cardiac involvement in the setting of M. I. Sc. Um So cardiology is definitely a big part of evaluation of this key. These kids starting from when they show up in the E. R. Sick to till they get into the I. C. U. And subsequent management. They are significantly take a car look at baseline. Typose heart rates of over 1:30 and very hypotensive requiring very aggressive fluid resuscitation and china tropic resuscitation. And so they are typically on one or 2 pressers by the time they get into the um they a significant percentage of them have left ventricular systolic dysfunction and this we measure Two indices, which is ejection fraction and shortening fraction. Both are towards the same measure, just different ways of measurement. And their numbers are usually less than 55%. Um is the abnormality there And it could be severe. Some of the very severe kids can be as low as ejection fractions of 20% or 30%. And then the intermediate ones are in the 30 and 40% range depending upon the severity of myocardial dysfunction. Yeah, Like in the Kawasaki situation we're seeing coronary artery involvement in about 88% of this uh cohort usually involving the left anterior descending or the right coronary, which is primarily dilation of these eventually leading onto aneurysms. And we have the score numbers for these that we look at with echoes to measure what we call as coronary dilation associated with pericarditis or pericardial effusions and clinically you could hear a rub when you see cardiac dysfunction clinically that correlates with tachycardia and a gallop rhythm. So it's useful as you listen if you're hearing a gallup in attack a cardiac patient with this story quite likely we're dealing with associated myocarditis and ventricular dysfunction. Cardiac enzymes are clearly elevated in a big number of these patients and that would be troponin T. Troponin I and BMPs. Um cardiac arrhythmia is a more of an issue in the adult population in the pediatric population going through different case series. It's mostly more super ventricular arrhythmias and atrial arrhythmias. Few reported cases with pvcs. Very very few with um complicated forms of ventricular district means like V. T. And B. F. And of course in the very severe cases we have the requirement for pulmonary or cardiopulmonary resuscitation. Again, just a few numbers. These numbers are changing the case series are small. So this is the current numbers but you know, we'll see where they are down the line. The key is Tachycardia 97%. So pretty much more than what just fever is so inappropriate to Korea at base climb addressed. It's a very sensitive kind of website finding for people to suspect there is something more than just fever causing tech area. So I would keep reemphasizing inappropriate tachycardia as an important clinical finding to suspect myocarditis. Sometimes it's hard to pick up myocarditis and these patients and if you miss it and they go home or obviously into quarantine if they are positive um it can have worse outcomes so we don't want to miss it. So our suspicion. Um index of suspicion should be very high to start to keep to keep looking for my uncle itis. In this setting, 78% or ticket Nick Over 30% are hypertensive And a good percentage of them, roughly. 40 to 50 have either Kawasaki like or atypical kawasaki like features. And I would kind of describe those in my future slides. Um and 40% of these are showing coronary artery involvement primarily in the form of coronary artery dilation. And a certain percentage of them actually having coronary aneurysms. And again, a huge percentage, 90% of them having elevated BNP levels, substantial elevation of these numbers. Not subtle And about 73% of them with proponents. So normally when kids come in, we beg and plead with the er doctors and pediatrics not to send proponents and these kind of enzymes to confuse the issue. But if we are seeing these symptoms, we actually request them to send these enzymes to give us an idea if there is myocardial enzyme leak, which will make us suspicious of possible myocarditis underlying the presentation. So again, these are the common um cardiac involvement in this setting of M. I. S. C. And that's my Akalaitis and Kawasaki. Like Kawasaki like picture. Um to be very honest, we haven't seen too many of em I sc real complete M. I. S. See kids in this institution. We are very, very highly suspicious because of the story and we're waiting to see more changes if they happen. But we have seen a few who have met a few of the criteria and and we've been aggressively monitoring them, but not many so far in our setting. Myocarditis is the hallmark of myocardial inflammation injury. And it's the old criteria that we're still using the Dallas criteria to to to describe the actual inflammatory change in the myocardial which is necrosis and the generation of uh adjacent minor sites. So again they can present with tachycardia, chest pain, lethargy E. K. G. Changes which show essentially tachycardia and diffuse SD segment abnormalities which are pretty dramatic when you see them elevated troponin and BnP levels. And as expected we will get an E. K. G. And an echo on all these when we have a suspicion. And by echo we are looking and seeing left ventricular dysfunction or LV dilation and my Children agitation which is secondary to the left ventricular dysfunction and dilation. Um If we have any questions we get a cardiac MRI but we never do a biopsy bit used to be something that was done in the past because the mris are quite sensitive to show us delayed enhancement. And also give us an idea about myocardial function, the degree of mitral valve insufficiency uh and other questions. Many of the typical myocarditis we see in Children are virally mediated and it's usually with Enterovirus coxsackie, Arnaud parvo and E. B. B. We're looking at M. I. S. C. And it seems like it's a very similar type of presentation because of the covid 19 viral infection and the treatment and it depends on how severe the cardiac disease is. And again we talked about I. V. I. G. High dose aspirin and the troops and I. V. Steroids. And of course immunoglobulins like uh i. l. six innovators and and as a corollary in the general pediatric population, myocarditis is very rare. Um The viral infections are common so it's a very small percentage of kids who actually develop frank myocarditis following viral infections. So my card itis and covid 19 obviously this is more prevalent in than in the normal population. So if you look at the new york data where more of our premises have been reported um they diagnosed myocarditis in 52% of these M. I. S. See patients, The elevated cardiac enzymes were seen in 90% of the kids who were picked up in the New York Court uh in whom either they were confirmed or suspected. M. I. S. C. Situation. One of the larger studies here is 186 patients. This work from 26 states obviously because the incidents is so low. This is all multi center studies to give us a little bigger sample. So the data is more meaningful. And again in this setting roughly about 80% have cardiac involvement. And Again majority of these are having enzyme leaks. BNP 73%, troponin 50% in this study And about roughly about 40% had systolic dysfunction of the left ventricle by Echo criteria. If you look at this table, um, you can see um try and see if I can move that. You'll see that. Um, in these three categories, the skin manifestations are fairly common. Then come the gi manifestations in different age groups seem to be a little bit more almost the same in all three age groups. The interesting thing is the Kawasaki or a typical picture seem to be more common in the younger kids and less common in the older kids and the opposite is with myocarditis. It's a little less common, like about 40% in the younger ones and almost 73% in the 13 to 20 year kids. So this is kind of opposite presentations here and then the neurologic involvement there. So I'm just trying to highlight that the myocarditis seems to be in the teenage population more. All of you has pediatricians know the classic and um a typical features of Kawasaki. I'll just reiterate just a little bit. They were greater than five days and four out of five of these following criteria. Macular, popularly rash typically on the trunk. As you can see here, conjunctivitis, bilateral and limbic sparing. You can see a nice picture here because it changes red, crack lips, strawberry tongue and palm and sole swelling as you can see here and lymphedema apathy. So these are, these are fairly typical that all of us look all the time in february kids. Atypical presentation is fever greater than five days and 2- three or 5 of the classic symptoms. So here is fever more than seven days. Anemia, white count, high platelets hide low albumin, elevated LTs and sterile diarrhea. Now the echo kinda helps in some situations where we have in a typical picture or borderline pictures because you can see from Yellen study that when they looked at all patients who actually had corner aneurysms backwards and look And they actually saw that a third of them did not really meet the classic Kawasaki criteria of 4-5 and had somewhat atypical presentation. So when in doubt, our I. D. colleagues definitely ask us to look at an echocardiogram to help if there is coronary involvement or not. Mm. This is kind of a funny term that we coined ourselves here where if you have a kid who has a college hockey disease or Kawasaki like picture and has a shock, um we call it Kawasaki because it has a very distinctive presentation. We see it in about 5% of Kawasaki kids. So it's definitely, thankfully a small percentage, it mimics the clinical presentation of toxic shock syndrome. They could have gi symptoms. The difference is that they have thrombosis Dapena here rather than Trumbo psychosis. They have liver involvement with LFTs, collagen properties, the dime er elevations, CRP elevations and again over 80% with elevated cardiac enzymes. And we have um we um noticed cardiac dysfunction with decreased the F. And micro records on echo increased risk for coronary aneurysms in this setting. And the other interesting thing is one in this picture there seem to be more ivy idea assistant and end up either requiring extra doses of I. V. I. G. Or get imminent global ins infusions. So same thing to reiterate a cardiac involvement in M. I. S. C. Is either my card itis or Kawasaki like picture and Kawasaki shock as a combination. And this together is what you tend to see in this setting of MSC. Okay. Um, then I'm going to talk about primarily what you pediatricians have to think about when you're clearing these kids to go back to, um, sports activity, which is going to happen in the next few weeks or months as to how comfortable we are in sending these kids back to sports, especially athletic, not recreational, but very athletic sports. Um, at the varsity level for people either who have been sick with covid infection and recovered or who were just covid positive didn't have the clinical illness. What do we take into consideration and how do we feel comfortable clearing that? So returning to sports participation after a covid infection will be this significant question that you guys will be getting from families and school authorities. And the approach is going to differ in pediatrics when compared to adopt. So what I mean by that is majority of our kids, as you know, have a very mild illness and in those situations once they have recovered fully clinically and have completed their quarantine and they have no evidence of myocardial injury. That means no myocarditis like a picture or you know, those, those kind of issues, they can easily clear them for participation without extensive cardiac testing. So thankfully, majority of our kids will belong to this group. Now, this is a very useful table that I like to highlight. So here it's this is pediatric patients with a history of COVID-19 infection and who are asymptomatic for more than 14 days. Those are the ones that were clear if they're asymptomatic or mild symptoms, no fever and less than three days of symptoms, you hear them for participation right away. On the other hand, if they have moderate symptoms meaning prolonged fevers, bed rest, um no hospitalization and no abnormal cardiac testing and there are less than 12 years. We picked this age because this sports participation is less intense in this age group and so we can then clear them for participation. But the same cohort, if they are greater than 12 then they're more likely to have high intensity competitive activities. And so what we request is this particular group should probably think we should think in terms of getting an E. C. G. Prior to participation, they have a normally CG clear for participation. We have an abnormally CT, then go to a pediatric cardiologist for clearance uh in addition to probably get an echo along with the BCG uh because of the consent from myocarditis, because it can be a subclinical myocardial itis sometimes that you don't want to miss. Obviously this is the more severe symptoms here. So here very likely they have myocarditis. So we're going to treat them like any other viral myocarditis, which is complete rest and exercise restriction for 3 to 6 months after being after they have recovered from the illness, they get testing with the CGs, they get an echo, they get a holter to look for arrhythmias. Um, you would even think in terms of a cardiac MRI and a stress test as part of the work up in this small subgroup of patients. So this is a very useful table on deciding how we can clear them to go back. Okay, Should we test all these Children before they go uh and attend sports? And and the recommendation is that we don't need to test them unless the athlete is symptomatic or the athlete has been exposed to someone who is known to be recently infected with the covid virus. Clearly, there is no recommendation to do antibody testing at this time in this population of kids who want to go back for athletic sports. And we always are asking parents to report if the athletes or any household contacts exhibit any signs or symptoms of the infection or the test positive for the, uh, virus, even if they're asymptomatic. Um, and the individual should be held out of all practicing games until they finish up the CDC recommended isolation or quarantine periods are expired because we don't want other kids to get sick or the coaches to be exposed to them. Now, those with severe presentations, if they're hypertensive, they have atrial arrhythmias less likely ventricular arrhythmias, ventilatory support. Eckman, obviously they're going to get very slow recovery and In those cases will restrict them from exercise for 3-6 months, as I already discussed. Okay. Um, we're clearly seeing a much higher Kawasaki like illness um, in this setting, experience that more in italy uh, and to some degree in the East coast, the possible mechanisms for the cardiac dysfunction are primarily myocardial, stunning or oedema related to the severe inflammatory state and direct myocardial injury by the virus and very mia and to some degree hypoxia secondary to the viral pneumonia. And that's there. So it's probably all of them together. So the issue is primarily the severe systemic immune response with this massive cytokine release, causing direct tissue damage or both. And the the damage to the cardiac tissue is the main contributor to the myocarditis and the resulting heart failure. Okay, so there are a couple of things here again that I was able to summarize from my literature search kids with the past history of heart disease. BpD respiratory respiratory tract abnormalities. Human plumping up to these like sickle cell disease, severe malnutrition and underlying immune deficiency disorders. These are the groups where it seems to be a more severe clinical manifestation of the disease, including cardiovascular this is from the chinese experience that we're seeing. And it's interesting. We don't understand this very well, but pulmonary hypertension seems to be much, much lower in our Children with cardiac um, involvement with covid uh and so also right heart failure. We are mostly seeing left ventricular dysfunction, systolic and to some degree diastolic dysfunction. Um, The mechanism for COVID-19-related injury and shock is still not clear and uh, sorry about this thing. So it's primarily cytokine mediated uh, myocardial inflammation as we already talked about. And I did mention that it's more a trailer with me is that we're seeing them ventricular arrhythmias. All right, couple of things about how to follow these kids long term and and and uh the reasoning behind long term follow up is because we don't know the what type of injury is happening to the cardiac meyer sites once the myocarditis covid related is happening. Are there any long term issues with diastolic dysfunction? Systolic dysfunction? So not having answers to that, the only way to get those answers is to once they have the illness to follow them carefully long term, even if their systolic function improves, we're not sure about their diastolic dysfunction and we need to we need to follow that. So we like to have longitudinal registries um, for that. Um the other concern is we're using many drugs to treat these stations. Um, one of them obviously is hydrochloric in which thankfully we're not using antiviral drugs which can also be cardio toxic in some cases. And this is an inflamed myocardial with ventricular dysfunction. So what are the effects of these drugs on on the inflamed myocardial? And will they increase the cardio toxicity because of that? It's also a good question. We don't have the answers for that. And we have to keep getting those. So this little thing that I wrote there is if you don't look for it you may not find it. And I'm alluding to my card itis especially the subclinical version. So we should have a high suspicion for it. We should watch for inappropriate tacky cardia in these Children and when we have suspicion we have to get the cardiac enzymes and look at E. K. G. Changes in addition to other clinical findings. Okay and lastly what are we doing to learn more about this disease processes? We have to agree on all the definitions, collect the data um And obviously research research, research the fund and get more registries, um better child screening, larger population studies with multi center studies and the inequity is primarily what I mentioned about why the Hispanic and african american kids are getting affected and how we can decrease that inequity with policy changes. And I think that was important. And obviously this slide is our slide for. I'm telling you how to be able to get a hold of us for any questions you have will be glad to um get back to you for those questions.
