Early reports of a multi-system inflammatory disorder in children with COVID-19 began in April 2020 in the United Kingdom. Since then, cases have appeared throughout the United States including our region. Known as “Multisystem Inflammatory Syndrome in Children (MIS-C)”, the illness is characterized by prolonged fever, inflammation in the body and involvement of one or more organ systems.
In this episode, Dr. Alexis Elward, Chief Medical Officer at St. Louis Children’s Hospital and Washington University pediatric infectious diseases specialist, shares more about the frequency of this syndrome, symptoms and treatment options.
Selected Podcast
Multisystem Inflammatory Syndrome in Children (MIS-C)
Featured Speaker:
Alexis Elward, MD
Dr. Elward is Professor of Pediatrics, Infectious Diseases, at Washington University School of Medicine and the Chief Medical Officer for St. Louis Children's Hospital. Transcription:
Introduction: Radio Rounds, the podcast series from St. Louis Children's Hospital. Here's Melanie Cole.
Melanie Cole: Welcome to Radio Rounds with St. Louis Children's Hospital. I'm Melanie Cole, and today we're discussing multisystem inflammatory syndrome in children. Joining me is Dr. Alexis Elward. She's the Chief Medical Officer at St. Louis Children's Hospital and a Washington University Pediatric Infectious Disease Specialist. Dr. Elward, it's a pleasure to have you join us today. First start by telling us what is multi-system inflammatory syndrome in children?
Dr. Elward: Yes. Well this is a recently recognized entity that is a severe illness that can include a prolonged fever, multi-system organ failure in association with COVID-19 and this is in children who are younger than 21 years of age. It is in association with COVID-19. So it's people who are either PCR positive antibody positive or who have had known exposure to somebody with a confirmed case of COVID-19.
Host: When was this illness first recognized Dr. Elward? I mean, you mentioned it's pretty new when?
Dr. Elward: Yes. Well this was first recognized at the end of April. So there were a group of people in Bergamo, Italy who published on this. And the publication actually came out May 6th in the United States. This was really recognized about four weeks after COVID-19 became very, very prevalent in this part of Italy. And there were a group of children who were presenting with Kawasaki like symptoms. Kawasaki's is an entity that we don't know the cause of, but it has a very distinct cluster of findings with prolonged fever, rash, red eyes, red palms and soles, swollen hands and feet, sometimes a swollen lymph node. It's fairly unusual, but this group recognized that all of a sudden they had a cluster of these cases and they associated it with the COVID-19 and then shortly after that, some investigators in the United Kingdom also sent out alerts because they had made the same association. Meanwhile, here in the US where we have had more cases in New York State and New York City those pediatricians had also been seeing clusters of children with this severe inflammatory syndrome. So this was all coming together at about the same time. The very end of April, very beginning of may. And then on May 14th, the CDC and the health department sent out very, very broad communication asking that people to begin to report these cases of this multi-system inflammatory syndrome.
Host: Absolutely fascinating. And as we learn more, how is it presenting Dr. Elward? What are you seeing? Have you seen it?
Dr. Elward: Yes, yes, I have seen it. And so basically this happens in children who are less than age 21 years they have fever. They have some lab findings that indicate inflammation. So that can be elevated lab tests including a C reactive protein, an erythrocyte sedimentation rate, fibrinogen, procalcitonin, D dimer Farrington, lactic acid dehydrogenase, IL six. Things like that. And then they require hospitalization and then they have at least two organs that are involved and they're having organ failure. And that can be the heart, the kidneys, respiratory system, hematologic system, GI, skin findings or neurological symptoms. And then they have no alternative diagnosis that really fits. And then plus all of those things, they are positive for a SARS COV2 infection, which is the virus that causes COVID-19 either by PCR, which means their virus still around or by serology or they've had COVID-19 exposure within the four weeks prior to these symptoms beginning.
Host: Wow. Now is it just presenting in children and not adults? And if so, do we know why?
Dr. Elward: Well, this has really been described in children. We have not seen description of this entity in adults quite yet and we don't know the answer for that. We do know that the entity that this looks a lot like and has a lot of over lap with is Kawasaki syndrome and Kawasaki syndrome is very uncommon in adults. But we don't know why.
Host: So you've mentioned that you have seen it. Where else in the country is it? Is it spreading around? Are we seeing it in our region? Is this something that's becoming more common or is it still relatively rare?
Dr. Elward: This is still relatively rare, so that's important for everyone to recognize. We are seeing cases of this across the country and I think we're going to see more because now the CDC and the local health departments are asking that people report it. So I do expect the numbers of this to increase. The very most of these cases have been seen in New York State and New York City probably because that's where most of the cases in the U S have occurred. So even though it's rare, the absolute numbers are going to be higher there. In general, children account for three to 5% of all of the cases of COVID in the United States, which is a little bit higher than the information that we got initially coming out of China, which suggested that they were between one and 2% of all of the cases. But that said, there have been about 130 cases reported in New York. So that kind of gives you some perspective when you think about the tens of thousands of cases that have been diagnosed in New York. This is a relatively rare syndrome.
Host: And does it also follow that if a child presents with this syndrome that they test positive for COVID-19?
Dr. Elward: Yes. That's part of the case definition. That they either test positive for a currently active infection or they have a serology that's positive that would indicate they've had a recent infection or we know that they've had contact with somebody who had a positive test for COVID-19 within the four weeks before symptom onset.
Host: Are there any predictors, do you have any way to tell or since it's so relatively new, do we have any risk factors we could point to at all?
Dr. Elward: Well, I think we need to be careful about that because this is still a relatively newly described entity and we're still learning about that. But we from what we've seen in the literature so far, the average age of this child is a little bit older than the kids who present with Kawasaki syndrome. So depending on the paper that you read or the series, the average age is somewhere between eight and 10 years. There are some distinguishing features. These are usually kids who are fairly sick and they're, they're coming to medical attention because they're dehydrated or they're having trouble breathing. And so these are kids who have generally been admitted to hospitals. But again, we're learning more about the spectrum of presentation with this and there seems to be a more prominent involvement of the GI tract in terms of GI symptoms. So there's abdominal pain, vomiting, diarrhea, and that's not something that we typically see with Kawasaki very commonly. We can see it with Kawasaki, but it's not one of those hallmarks of Kawasaki disease.
Host: Wow. This is so interesting. So do you have a treatment plan? Is there an algorithm that's been developed? What are you doing? You mentioned organ failure. So is there a way to slow down the progression or stop it altogether? Tell us what you're doing.
Dr. Elward: Well, this is still a topic of conversation and expert circles about the best way to treat this. Many people are approaching this the way that they would approach Kawasaki's disease. And when we diagnose that, we give IV immune globulin. And so that is pooled immune globulin. It's a blood product that decreases inflammation. And then we also treat with aspirin and that helps both with inflammation and to decrease the risk of blood clots, which can be a complication of Kawasaki’s disease and can be a complication of COVID-19. There is some other therapies that people are discussing including steroids and some other medications like Anakinra that modify the immune response. But there's not an agreed upon universal approach right now that is being discussed by some of the national groups.
Host: Is it highly contagious, Dr. Elward in a family? If one child shows these symptoms and they have other children, what should they do and is this really an emergent condition?
Dr. Elward: Well, I think as with any prolonged illness, you want to definitely seek advice from the pediatrician. And, and I think what we are doing right now is if we're hearing about kids who have had these symptoms, if they've recovered, we really encourage people to reach out to an infectious diseases specialist for further consultation. In some cases we might get an echo and some lab findings to try to figure out if there's still ongoing evidence of inflammation. If there still is inflammation, then we might consider treating with IVIG and aspirin. If the inflammation is resolved, kind of depending on the time course. We might decide the person's no longer at risk if they're past six weeks after the acute symptom onset, if they're still within that six week window. We might approach this the way that we do Kawasaki's and treat with low dose aspirin if they're improving in terms of whether it's contagious among families. I think that the jury is out on that. Certainly with Kawasaki's disease that is not commonly seen among more than one person in the household. That seems to be probably an acute insult with an infectious agent and then a hyper immune inflammatory response. But typically you do not see multiple cases in a household with Kawasaki's. I think it's too soon to say about COVID-19. And so I do think that these children do need to be carefully thought through and evaluated on a case by case basis.
Host: Well, thank you so much for that answer. As we wrap up, Dr. Elward, if you suspect, if another provider suspects their patient has multi-system inflammatory syndrome, what should they do and when do you feel it's really important that they refer?
Dr. Elward: So I would recommend that they reach out and seek consultation from an infectious diseases specialist with Kawasaki's disease. There's evidence that if you treat within the first 10 days of onset of fever that that's when you're going to have the most benefit to the immune globulin in terms of protecting against that effect of coronary artery dilatation or coronary artery aneurysm. We don't know if this is exactly the same process or if it follows the same pathophysiology. But I think that's probably the window in which you want to be seeking consultation. We can look for alternative explanations for the child's symptomatology. Try to really establish whether they indeed have SARS COV2 or not. So I would say within the first 10 days of symptom onset, you really want to get infectious diseases consultation. I think probably somewhere between day five and seven, a fever that gives us some time to do some workup, get some other tests back, and then if we decided is this syndrome, to potentially treat it.
Host: Thank you so much, Dr. Elward for coming on today and sharing your expertise. Please join us again and keep us updated as more information comes out. That concludes this episode of Radio Rounds with St. Louis Children's Hospital. To learn more about multi-system inflammatory syndrome or to speak with a pediatric infectious disease specialist at St. Louis Children's Hospital, please call the children's direct physician access line at 1-800-678-HELP. You can also learn more about this and other healthcare topics at StLouischildrens.org. Please remember to subscribe, rate, and review this podcast and all the other St. Louis Children's Hospital podcasts. I'm Melanie Cole.
Introduction: Radio Rounds, the podcast series from St. Louis Children's Hospital. Here's Melanie Cole.
Melanie Cole: Welcome to Radio Rounds with St. Louis Children's Hospital. I'm Melanie Cole, and today we're discussing multisystem inflammatory syndrome in children. Joining me is Dr. Alexis Elward. She's the Chief Medical Officer at St. Louis Children's Hospital and a Washington University Pediatric Infectious Disease Specialist. Dr. Elward, it's a pleasure to have you join us today. First start by telling us what is multi-system inflammatory syndrome in children?
Dr. Elward: Yes. Well this is a recently recognized entity that is a severe illness that can include a prolonged fever, multi-system organ failure in association with COVID-19 and this is in children who are younger than 21 years of age. It is in association with COVID-19. So it's people who are either PCR positive antibody positive or who have had known exposure to somebody with a confirmed case of COVID-19.
Host: When was this illness first recognized Dr. Elward? I mean, you mentioned it's pretty new when?
Dr. Elward: Yes. Well this was first recognized at the end of April. So there were a group of people in Bergamo, Italy who published on this. And the publication actually came out May 6th in the United States. This was really recognized about four weeks after COVID-19 became very, very prevalent in this part of Italy. And there were a group of children who were presenting with Kawasaki like symptoms. Kawasaki's is an entity that we don't know the cause of, but it has a very distinct cluster of findings with prolonged fever, rash, red eyes, red palms and soles, swollen hands and feet, sometimes a swollen lymph node. It's fairly unusual, but this group recognized that all of a sudden they had a cluster of these cases and they associated it with the COVID-19 and then shortly after that, some investigators in the United Kingdom also sent out alerts because they had made the same association. Meanwhile, here in the US where we have had more cases in New York State and New York City those pediatricians had also been seeing clusters of children with this severe inflammatory syndrome. So this was all coming together at about the same time. The very end of April, very beginning of may. And then on May 14th, the CDC and the health department sent out very, very broad communication asking that people to begin to report these cases of this multi-system inflammatory syndrome.
Host: Absolutely fascinating. And as we learn more, how is it presenting Dr. Elward? What are you seeing? Have you seen it?
Dr. Elward: Yes, yes, I have seen it. And so basically this happens in children who are less than age 21 years they have fever. They have some lab findings that indicate inflammation. So that can be elevated lab tests including a C reactive protein, an erythrocyte sedimentation rate, fibrinogen, procalcitonin, D dimer Farrington, lactic acid dehydrogenase, IL six. Things like that. And then they require hospitalization and then they have at least two organs that are involved and they're having organ failure. And that can be the heart, the kidneys, respiratory system, hematologic system, GI, skin findings or neurological symptoms. And then they have no alternative diagnosis that really fits. And then plus all of those things, they are positive for a SARS COV2 infection, which is the virus that causes COVID-19 either by PCR, which means their virus still around or by serology or they've had COVID-19 exposure within the four weeks prior to these symptoms beginning.
Host: Wow. Now is it just presenting in children and not adults? And if so, do we know why?
Dr. Elward: Well, this has really been described in children. We have not seen description of this entity in adults quite yet and we don't know the answer for that. We do know that the entity that this looks a lot like and has a lot of over lap with is Kawasaki syndrome and Kawasaki syndrome is very uncommon in adults. But we don't know why.
Host: So you've mentioned that you have seen it. Where else in the country is it? Is it spreading around? Are we seeing it in our region? Is this something that's becoming more common or is it still relatively rare?
Dr. Elward: This is still relatively rare, so that's important for everyone to recognize. We are seeing cases of this across the country and I think we're going to see more because now the CDC and the local health departments are asking that people report it. So I do expect the numbers of this to increase. The very most of these cases have been seen in New York State and New York City probably because that's where most of the cases in the U S have occurred. So even though it's rare, the absolute numbers are going to be higher there. In general, children account for three to 5% of all of the cases of COVID in the United States, which is a little bit higher than the information that we got initially coming out of China, which suggested that they were between one and 2% of all of the cases. But that said, there have been about 130 cases reported in New York. So that kind of gives you some perspective when you think about the tens of thousands of cases that have been diagnosed in New York. This is a relatively rare syndrome.
Host: And does it also follow that if a child presents with this syndrome that they test positive for COVID-19?
Dr. Elward: Yes. That's part of the case definition. That they either test positive for a currently active infection or they have a serology that's positive that would indicate they've had a recent infection or we know that they've had contact with somebody who had a positive test for COVID-19 within the four weeks before symptom onset.
Host: Are there any predictors, do you have any way to tell or since it's so relatively new, do we have any risk factors we could point to at all?
Dr. Elward: Well, I think we need to be careful about that because this is still a relatively newly described entity and we're still learning about that. But we from what we've seen in the literature so far, the average age of this child is a little bit older than the kids who present with Kawasaki syndrome. So depending on the paper that you read or the series, the average age is somewhere between eight and 10 years. There are some distinguishing features. These are usually kids who are fairly sick and they're, they're coming to medical attention because they're dehydrated or they're having trouble breathing. And so these are kids who have generally been admitted to hospitals. But again, we're learning more about the spectrum of presentation with this and there seems to be a more prominent involvement of the GI tract in terms of GI symptoms. So there's abdominal pain, vomiting, diarrhea, and that's not something that we typically see with Kawasaki very commonly. We can see it with Kawasaki, but it's not one of those hallmarks of Kawasaki disease.
Host: Wow. This is so interesting. So do you have a treatment plan? Is there an algorithm that's been developed? What are you doing? You mentioned organ failure. So is there a way to slow down the progression or stop it altogether? Tell us what you're doing.
Dr. Elward: Well, this is still a topic of conversation and expert circles about the best way to treat this. Many people are approaching this the way that they would approach Kawasaki's disease. And when we diagnose that, we give IV immune globulin. And so that is pooled immune globulin. It's a blood product that decreases inflammation. And then we also treat with aspirin and that helps both with inflammation and to decrease the risk of blood clots, which can be a complication of Kawasaki’s disease and can be a complication of COVID-19. There is some other therapies that people are discussing including steroids and some other medications like Anakinra that modify the immune response. But there's not an agreed upon universal approach right now that is being discussed by some of the national groups.
Host: Is it highly contagious, Dr. Elward in a family? If one child shows these symptoms and they have other children, what should they do and is this really an emergent condition?
Dr. Elward: Well, I think as with any prolonged illness, you want to definitely seek advice from the pediatrician. And, and I think what we are doing right now is if we're hearing about kids who have had these symptoms, if they've recovered, we really encourage people to reach out to an infectious diseases specialist for further consultation. In some cases we might get an echo and some lab findings to try to figure out if there's still ongoing evidence of inflammation. If there still is inflammation, then we might consider treating with IVIG and aspirin. If the inflammation is resolved, kind of depending on the time course. We might decide the person's no longer at risk if they're past six weeks after the acute symptom onset, if they're still within that six week window. We might approach this the way that we do Kawasaki's and treat with low dose aspirin if they're improving in terms of whether it's contagious among families. I think that the jury is out on that. Certainly with Kawasaki's disease that is not commonly seen among more than one person in the household. That seems to be probably an acute insult with an infectious agent and then a hyper immune inflammatory response. But typically you do not see multiple cases in a household with Kawasaki's. I think it's too soon to say about COVID-19. And so I do think that these children do need to be carefully thought through and evaluated on a case by case basis.
Host: Well, thank you so much for that answer. As we wrap up, Dr. Elward, if you suspect, if another provider suspects their patient has multi-system inflammatory syndrome, what should they do and when do you feel it's really important that they refer?
Dr. Elward: So I would recommend that they reach out and seek consultation from an infectious diseases specialist with Kawasaki's disease. There's evidence that if you treat within the first 10 days of onset of fever that that's when you're going to have the most benefit to the immune globulin in terms of protecting against that effect of coronary artery dilatation or coronary artery aneurysm. We don't know if this is exactly the same process or if it follows the same pathophysiology. But I think that's probably the window in which you want to be seeking consultation. We can look for alternative explanations for the child's symptomatology. Try to really establish whether they indeed have SARS COV2 or not. So I would say within the first 10 days of symptom onset, you really want to get infectious diseases consultation. I think probably somewhere between day five and seven, a fever that gives us some time to do some workup, get some other tests back, and then if we decided is this syndrome, to potentially treat it.
Host: Thank you so much, Dr. Elward for coming on today and sharing your expertise. Please join us again and keep us updated as more information comes out. That concludes this episode of Radio Rounds with St. Louis Children's Hospital. To learn more about multi-system inflammatory syndrome or to speak with a pediatric infectious disease specialist at St. Louis Children's Hospital, please call the children's direct physician access line at 1-800-678-HELP. You can also learn more about this and other healthcare topics at StLouischildrens.org. Please remember to subscribe, rate, and review this podcast and all the other St. Louis Children's Hospital podcasts. I'm Melanie Cole.