 This is Donna Prosser, Chief Clinical Officer with the Patient Safety Movement Foundation. I'm so excited to be joined today by Dr. Tom Murray, who's a pediatric infectious disease specialist and an assistant professor at Yale School of Medicine, as well as Dr. Sarah Candle, also an assistant professor at Yale School of Medicine and a pediatric intensivist. They're here today to come and speak with us about multi-system inflammatory syndrome in children. This is a new phenomenon that we've seen over the last couple of months related to COVID-19. Welcome, Tom and Sarah. Thanks so much for joining us today. Good to speak with you. Thank you, Donna, for the invitation. Happy to talk today. I'd love for you to give us a little bit about your background. Sarah, can you start and tell us a little bit about your background? Sure. Again, thank you for the invitation. As you mentioned, I'm an assistant professor at the Yale School of Medicine. My training is in critical care medicine, so I'm a pediatric intensivist. I work in the PICU, and I was on the front lines during the COVID pandemic. I am also a deputy quality and safety officer for the Yale New Haven Children's Hospital. So also worked with our team on implementing guidelines and some recommendations during the pandemic. Excellent. Thank you so much for joining us. And Tom, tell us a little bit about yourself. Hi, so I'm an associate professor in infectious disease and global health and pediatrics for the Yale School of Medicine. I'm also the associate medical director for infection prevention for Yale New Haven Children's Hospital. So during the pandemic, I had two different roles. One role was involved in direct care and planning of treatments for children who came to the hospital with COVID. And then another role in developing infection prevention guidelines and working to ensure that our families and staff did not get COVID when they came to the hospital. Great. So Sarah, let me ask you the first question. As a pediatric intensivist, I imagine you began seeing this syndrome in your hospital early on. Tell us a little bit about your experiences with that and how you identified this as a COVID related illness. Sure, so really when all of this started with the pandemic, there was, I think so much uncertainty going on. There wasn't a lot known. In the PICU, we actually were taking care of patients with COVID-19, the illness, the acute illness, both adolescents and young adults. And we ended up seeing a handful of those patients over 13 patients, I believe. And that was sort of April into May. And then starting mid-May, we started seeing patients presenting with shock-like pictures and Kawasaki-like illness. And these patients had had recent infections with COVID-19 as well. And so that sort of started the association. And this was similar to what was being seen globally. I believe it was the end of April that the UK put out some case reports about this post-infectious phenomenon that they were seeing. And then starting in May, this was being seen in the US. And it had this temporal relationship where it was several weeks after the actual active infection. And it was May then, mid-May, that the CDC actually put forth criteria to diagnose this clinically. So this is a clinically diagnosed syndrome. It's made up of six criteria, you have to fill these six criteria, with the first one being it causes serious illness. So these were patients presenting who required hospitalization, either general hospital care or ICU level care. It was described primarily in pediatric patients. So they were patients less than 21. They presented with fever and they had evidence of laboratory evidence of general inflammation. So we saw sky-high inflammatory markers in these patients. And a lot of them were just general inflammatory markers, things like CRP and ferritin. And then the last two criteria was that it had to involve more than two systems. So it's described as a multi-systemic inflammatory process. And then the last criteria was that had to have an association with the SARS coronavirus in virus. And so this could be done either by PCR testing, antibody testing, as I mentioned, this happened often somewhere two to three weeks after the acute infection or a patient may have been asymptomatic and not known they had the virus. And if they did not have antibody testing or PCR testing, if there was sort of validated very close contact with someone with the known virus, that could count as well. Great, great. And so from a parent's standpoint, what were the signs and symptoms that parents were seeing prior to bringing in their children for this illness? So a lot of what parents were seeing were fever. Patients often presented with high fevers and for many days it was the fever that didn't really go away. Many patients as well had gastrointestinal symptoms, so vomiting, diarrhea. And prior to this pandemic, these would have been symptoms that we said it's just a virus and it'll run its course. But it seemed to not, it seemed to go on for days and days. And then patients also had things like unusual rashes that may wax and wane. And then when we saw them in the hospital, often these patients, as I mentioned, had very elevated inflammatory markers and evidence of organ dysfunction. So we could see depressed cardiac function. These patients might come in and have shock. They would be in a shock-like state. They would need aggressive fluid resuscitation. They may need basal active medications to support their blood pressure. A few of them would have respiratory complications. So we saw probably about a fifth of the patients needed some kind of respiratory support. And that could be just oxygen support or more invasive measures of respiratory support. Tom, I'm curious as to your experiences as an infectious disease physician, when did your specialty become involved with this and start to realize that this was an infectious illness? Yeah, as Sarah mentioned, there were reports coming out of Europe and then later from the New York area that there was this inflammatory illness kind of post-acute COVID. So we were on the alert very early that this could be coming to Connecticut. And so what we did in our hospital to prepare is we assembled the multidisciplinary team to think about how to recognize and treat the syndrome should we see kids with it. So that team consisted of infectious disease doctors, pharmacists, intensivists like Sarah, cardiologists and rheumatologists who also treat inflammation, as well as hospitalists who take care of the patients when they don't quite require ICU level care. So that group got together and really looked at the available literature on how the disease presented, tried to come up with criteria on how you would assess that in the emergency room, what kind of tests you would order and then looking at what treatments had been tried. A lot of it originally coming from the Kawasaki disease literature and that treatment approach with intravenous immunoglobulin as an anti-inflammatory. We tried to design the best therapy with what knowledge was available to us. I think one of the challenges with everything COVID that's gotten better but still remains a problem is it's still a very new disease. And the way I equate that is influenza has been around for 100 years and we still don't know a ton about influenza in terms of prevention and treatment. We don't have a magic pill for it. COVID's been around less than a year. And so on the one hand we've learned so much but there still continues to be a lot to know. So we took that knowledge and we put together a treatment algorithm to really help us manage patients and then we get together every month or so and we look at what's new in the literature as new information becomes available and we update our treatment guidelines. I'll also mention the other thing that we did on this from an infection prevention and a community pediatrician side of things is we got a group of community pediatricians and we put together an algorithm that they could use in trying to evaluate when a family calls with a child who has fever and abdominal pain or fever and rash. These are very common problems in pediatrics and we didn't want every child who had fever to go to the emergency room. On the other hand, you don't wanna miss cases of MIS-C because of the potential complications that Sarah described. So we worked with our community pediatricians and provided them kind of a way to think about these patients and which to try to understand which kid needed to go to the emergency room right away, which child might benefit from getting an initial laboratory evaluation and which kid could be watched closely. And how is MIS-C effectively treated? So there's a number of different ways it's treated depending on the severity of the presentation. In general, the idea is to control the hyper-inflammatory response that has occurred. So the first line of therapy are steroids and some sort of steroid therapy. If the disease is presenting very much like a Kawasaki disease-like picture and it fits those criteria because there's a lot of overlap. When you have syndromes with many different signs and symptoms to make the diagnosis, there's gonna be some overlap and then we'll use intravenous immunoglobulin like we described before. And those really are the two first line therapies at the moment, and then there are additional immunomodulators that can be used to target the inflammation. However, I'll defer to Sarah to talk about the children who come in very sick in shock require care in the intensive care unit and that will involve supporting blood pressure and other intense interventions while we're getting these other drugs to take effect. The final thing I'll note is that it's pretty consistent now that any of the treatments for the virus itself, like you may have heard about remdesivir or other anti-advocations, are not indicated in MISC because there's an emerging literature that there's not active virus replication happening during this disease. It's really a post-infectious inflammatory response. And I'll just add, as Tom mentioned, that the treatments are really aimed at trying to reduce the inflammation that's going on, but in the meantime, there's a lot of therapies geared towards supportive care. So we see organ dysfunction and by what I mean by that really is, for example, the heart may have dysfunction. So you may have to press cardiac output. You may not have effective blood pressure. Your liver may be elevated, enzymes may be elevated in sort of a shock-like state. So a lot of the therapies that we do in the intensive care unit are to try and support that organ system until the inflammation can go down. So often there are medications for cardiovascular dysfunction, blood pressure medicines, but there's even the extreme that someone might need complete support. And there have been reports of patients going on to need something called ECMO or extra corporeal membrane oxygenation, where it's a complete support of the cardiovascular system. So there's really a spectrum of what type of support patients may need. Some need respiratory support. And really all of this is to support the body through this inflammatory process until this inflammation can hopefully start to go down. Yeah, I just wanted to add one other organ system that therapy is directed against, and that's hematological in the clotting system. So most of the kids who are hospitalized receive some kind of anti-clotting medication like aspirin, and some of them can be on it for quite some time because there is concern about blood clots forming and an increased coagulability state that these kids can have. What have your outcomes been with these treatments that you have been doing? So we've had 13 patients that required admission to the hospital for MIS-C, five of those required intensive care. They are all in the hospital for quite some time. This is not a diagnosis where you come in Monday and leave on Tuesday. Most of the kids are there for at least four or five days and some of the sicker kids are there longer. However, we're very fortunate in that with our aggressive interventions, we've had no mortality in any of these children. So we're fortunate in that regard. In terms of long-term outcomes, that's something that we're gonna continue to monitor. Oftentimes when you end up in the intensive care unit, as Sarah mentioned, it's because of problems with heart function. And so that's something that people are monitoring very closely to make sure that heart function does return to normal. And with all things COVID, long-term effects, we just don't have the experience yet, but it's gonna be something we're gonna need to keep a close eye on. Just to add, so a lot of people when this syndrome first started being described as Kawasaki-like syndrome. And in children, one of the classic things for Kawasaki disease that people may or may not know about is coronary artery aneurysms. And so this was sort of one of the first things we really started looking for in patients, especially when they're in the ICU setting. And one thing they have described in the literature is that it does seem like there are higher rates of coronary anomalies in patients with MISC than the typically described Kawasaki disease. But I would say anecdotally, when I've talked to our cardiology colleagues, they said in follow-up, all of those seem to be resolving with these patients. So I think the hope is that we're able to get a handle on the inflammatory process much sooner and hopefully alleviate some of those long-term effects. But I think as Tom said, there's still so much to be learned and sort of what this may mean for the future is still unknown. Wow. And so for parents, is there anything that any prevention measures that parents can take to prevent this from happening to their children? So the good news is that this is a relatively rare event in children. So despite there being lots of COVID around, especially more recently in some parts of the country, it's not a common complication. So that's one reassuring thing. In terms of prevention, we don't have a great handle on which child who has COVID will go on to develop MISC or not. So therefore prevention really centers around preventing your child from contracting the SARS-CoV-2 virus and getting COVID infection. So that's not gonna surprise you what the recommendations are. It's masking, it's social distancing, it's outside is better than inside for just about every activity. It's staying away from people when they're sick and washing your hands and those kinds of risk mitigation strategies. Sarah, any additional thoughts about this topic that you'd like to share? Well, I think it's such a new thing as we've been saying and I wouldn't be surprised if in a year we have sort of different recommendations. But I do think, as Tom mentioned, talking with your pediatrician and not rushing to the emergency room with any fever, I think we really need to be thoughtful in evaluating for this. And a lot of places similar to what we're doing are putting out recommendations about when patients should be tested. And I think this is, as we continue as a public health a movement really just to ensure that people are using masks and washing their hands because that really is right now the best strategy that we have. Yeah, I think if I could add one additional thing to what Sarah said, even in the last month these patients are undergoing intense study and there's been several publications where researchers are getting a better understanding of how the immune system is affected and where that becomes important is in terms of the available treatments. So there are lots of new immunomodulatory drugs that target different aspects of the immune system. So I'm hopeful, there's no guarantee that in the next six months to a year we may have very directed therapy against specific aspects of the immune system that that may help because that information is emerging and other researchers, including some people at Yale are looking at predisposition from a genetic perspective trying to understand if they can identify children who have something different about their immune system that makes them at increased risk. And that would be another, if they find something that would be another potential way to identify who might be at risk to really watch those children more carefully. Wow, well thank you so much for joining us today. I hope that we can have you back in a year to tell us all of the great things that have changed. Thank you. And a pleasure, thank you. Excellent, all right, well both of you have a wonderful day and thank you so much for what you're doing to save the children in Connecticut.