DISCLAIMER: This text is not a verbatim transcript. Communication Access Real Time Translation (CART) is provided in order to facilitate communication credibility and may not be a totally verbatim record of the proceedings.


>> With the emergency risk communication branch up the CDC control of prevention. I would like to welcome you Tuesday's trying to call. Clinical management multisystem inflammatory syndrome in children MIS-C associated with coronavirus 2019 COVID-19. VCC is putting these two platforms to enable close captioning is located either on the top or bottom of your screen. 

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Clinicians should not refer patients to CDC to find out where or how to get tested for COVID-19 or obtain test results. Also, please continue to visit emergency.cdc.gov/coca over the next several days as we intend to host more COCA calls to keep you informed of the latest guidance and updates from COVID-19. For instance, please join again Tuesday, July 28, at 2 PM Eastern time for another COCA call for the topic focuses on the importance of diabetes support during the COVID-19 pandemic. In addition to our webpage, COCA announcements for upcoming COCA calls will be sent via email. Subscribe to receive notifications by going to emergency.cdc.gov/coca. 

That is emergency start CDC.gov .asp. Please share call announcements with your colleagues. I would now like to welcome presenters for today's COCA call. Team lead as part of CDC COVID-19 response, Dr. Eva Cheung, who is from clumsy University Irving Medical Center New York Presbyterian Morgan Stanley Children's Hospital. Matthew Oster serves on the MIS-C team and Associate Professor of Pediatrics at Children's Healthcare of Atlanta Simply Heart Center and Emory University School of Medicine. Adriana Tremoulet, a professor of pediatrics and associate director of the Kawasaki Disease Research Center at the University of San Diego and Rady Children's Hospital of San Diego. I would like to turn it over to Dr. Ermias Belay. Please proceed. 
>> ERMIAS: Thank you and good afternoon, everyone. I would like to thank today's presenters for taking the time to share experiences on the management of patients with MIS-C. I will just provide a little background, and briefly share MIS-C data we received here at CDC. MIS-C as you know was first reported in late April from the United Kingdom in association with the COVID-19 pandemic. Patients present with fever, G.I. symptoms such as abdominal pain and diarrhea, and (Indiscernible) manifestations. 

Although some MIS-C patients have typical manifestations, others appear to have substantial overlap with acute severe COVID-19 infection in other -- and other hyper inflammatory conditions such as Kawasaki disease and toxic shock syndrome. On May 14, here at CDC, we summarize what was known about MIS-C at the time, with published case definition, and requested clinicians to start reporting suspected cases of MIS-C to the local and state departments. Following our request to report cases as of July 15, as of yesterday, total 342 MIS-C patients meet the case definition we reported to CDC. As you can see on the slide, over half of the MIS-C patients reported to us were boys. It is eight years as shown is that right hand corner of the slide. The median age was eight years. As shown in the blue bars, a vast majority of patients are between one and 14-years-old. 

Close to 40% of the MIS-C patients were among Hispanics or Latino. About 35% were among men Hispanic and black slope. These two racial and ethnic groups together, made up about 70% of the MIS-C cases reported to CDC. We have just posted some of this data and it will become live today on the CDC website. I encourage you to visit our MIS-C website if you would like to see some of the data from the surveillance system. 

Getting back to the topic at hand, which is the clinical management of MIS-C patients, this slide which is produced by Dr. Abraham, who is part of our team, summarizes data from eight major studies that were recently published in journals. The slightest -- the slight focuses on the eight studies. Just to give you an idea, two studies are from the United States. Two were from the United Kingdom. Three studies from France. One from Italy. 

The studies used different criteria, which is summarized on the right-hand side of the graph. Inclusion criteria for the patient. If you look on the left side of the graph, on average, about more than 75% of patients were given IVIG. That used Kawasaki disease as are criteria, which is shown in the blue dots and close to 100%. The studies that use criteria had a lot of patients receive IVIG. On average, more than 50% were given cortisone steroids, the second bar and close to 50% received vasopressors. This is just to give you a flavor of what has been published in literature. The speakers who come after me and summarize in great detail the experiences and knowledge about the clinical management of MIS-C patients. 

This is just to acknowledge local and state departments who continue to investigate and report suspected MIS-C cases to CDC. Team here at CDC that is working on the data. Thank you, and at this point, I will turn it over to Dr. Cheung, to give her presentation. Thank you. 
>> EVA: Thank you. I will introduce myself. I am Dr. Eva Cheung, a cardiac intensive at the New York Presbyterian Morgan Stanley Children's Hospital in New York City of Columbia University. I think the organizers of the COCA call today to present our experience in New York City, when it comes to this multisystem inflammatory in children. I will refer to as MIS-C related to COVID-19. As this webinar is concentrated on treatment and approaches to treatment, I would like to present our approaches and how we came about it in the form of two cases and lessons we learned from them with early experience with MIS-C. 

As Dr. Belay mentioned, there is data published out there. The CDC COVID-19 response team as well as the New York State Department of Health in the last two weeks, have released these two great studies reported in the New England Journal of Medicine that are truly one of the largest case series of the MIS-C we have seen so far. They really help to detail in terms of patient presentation, symptoms, epidemiology, so I very much encourage that both studies for anybody interested, be right because they contain valuable information that I won't go through today. 

This is a graph taken from that New England Journal of Medicine article that depicts the presentation of MIS-C at least in New York State. This is the patients that reported to the New York State Department of Health. In the blue bars you see the positive testing over the course of time seeing that the major spikes were seen in the late March to early April times. What you see in the red to orange bars is the admissions of MIS-C cases to New York State's hospitals during the later April into early May time, demonstrating that we were dealing with a very different phenomenon that was not necessarily active COVID-19 infection, either delayed response or immunological response to COVID-19 exposure. 

One major thing to state moving forward as we detail our treatment approach to the patients with MIS-C, real major disclaimer is there is much to learn about the effectiveness of all these treatments. What I'm about to present today is really our institutions approach and experience. It was really formulated out of a multidisciplinary team with expert consensus and available data that we had at the time. Certainly, they are updated as we learn more. Please note because this is a novel syndrome, we really are not basing this on any evidence-based approach because things are so novel. This is our single institution approach. 

To give you an idea in terms of what the experience is in York city, we saw the first case probably in early April 2020, about one month after the height of COVID-19 positive cases in New York City. As of last week, we admitted 60 patients with MIS-C in our institution with approximately 60% of patients requiring intensive care unit care mostly for shock and support. To give you an idea also, before early May, before we could promptly recognize, and really into to an institutional protocol for treatment, 70% of patients needed an ICU care. In the later half, it has come down to about 40%. 

Unlike the cohort of patients that we were hearing who were pediatrics affected by active COVID-19 infection, these patients are the majority really did not have any comorbidities. They were healthy children. As Dr. Belay presented, it affects males and females equally with our experience at a mean age of seven years ranging from too much to 20 years. This makes down and coincides with the New York City area that we serve. In our experience, we did not see an ethnic predilection towards this disease. Dr. Belay showed data otherwise. 

This case is not -- this is probably one of the earliest cases we thought New York City. This four-year-old male who had asthma presented to the emergency room with four days of fever. He had fatigue and lethargy for four days and not taking very well oral intakes. He did have vomiting and diarrhea that was fairly significant, non-bloody, but he really had no respiratory systems, no rash. Unexamined the emergency room, he was tachycardic, hypotensive, demonstrated signs of dehydration with mucous membranes but did not have the other hallmarks we were looking for in terms of Kawasaki symptoms in terms of conjunctivitis, rash. His abdomen was soft and evidence of shock in the sense of delayed refill. 

In emergency room he was given supplements oxygen in the form of (Indiscernible). Because of tachycardia and hypertension, he was given IV fluid resuscitation. On the assumption this might be sepsis, started on antibiotics. He was started on presser support and transfer to our ICU. To highlight here, the admission laboratory data which has been quite characteristic about how these patients look like in terms of lab data from MIS-C, when you can see is there is a predominance of potentially (Indiscernible) and overall laboratory evidence of significant inflammation. 

The protein and I give you the normative value in black, the C protein was (Indiscernible) and others representative of inflammatory process. I point out the absolute the site at around 1000 as it was our expense, we saw low lymphocyte in patients with MIS-C. The biomarkers of the troponin, the values are in black and from our institution. They were quite markedly elevated in this patient. As well as evidence of acute kidney injury with (Indiscernible) and creatinine have frequent sex. This patient was stars PCR make -- SARS negative but we had (Voice Low) fairly early on and he did come back quickly positive for serology's. It's an indiscriminate serology but he was positive for COVID-19 I serology. 

A brief description of the hospital course basically shows that on admission, he had a very prompt echocardiogram which is part of our protocol for MIS-C workup ergo he had normal LV function, trivial (Indiscernible) and at the time, or more coronary arteries. We see the top part of the graph you see the infusions of dopamine, epinephrine and norepinephrine craft out in terms of doses. He ended up requiring (Indiscernible) for six days for shock. His blood culture was negative, but because this was early inexperience, he completed in biotics regardless. 

His acute kidney injury improved with intravenous food resuscitation, and we did place them on a (Indiscernible). He did not require mechanical intubation, but they require respiratory support in (Indiscernible). As the press a requirement improved, during this time, is pretty customary for septic shock in our institution to institute hydrocortisone is a stress was steroid in patients who present with shock. In the early parts of his presentation, we use hydrocortisone first at high doses, and over the course of time where the pressers were weaned, the hydrocortisone was weaned as well. 

Several days after the pressers were weaned off, his inflammatory and biomarkers started to trend up. What was surprising to us in this patient, is his echo at this time purely done on surveillance as well as to work on the up-trending biomarkers, showed new onset of LAD aneurysm and left artery of the artery with a score of five. I present this case mostly because I think this case comes closely, maybe most closely because it was an early presentation, to the hazards of the natural history of this disease. With the presentation of this new LAD aneurysm as well as uptrend inflammatory markers, at that time we did give him IVIG and (Indiscernible). This is a graph of the protein in blue and troponin in pink. 

As you see throughout the course of the hydrocortisone, ECD protein decreases to 300 to the 100 range. And hydrocortisone his inflammatory markers never result. It was not until the institution of a higher dose of multiple (Indiscernible) that the inflammatory markers really decreased down to normal levels. This is a very quick image to show you on the left is an image of his left anterior descending coronary artery. The when I mentioned that we had discovered which is increasing normal had now dilated to a Z score of five. That was on May 12, halfway in his hospital admission. What you see on the right is a follow-up echo which is almost one month later on June 2. See that has essentially been resolved. 

As I mentioned, this was in earlier cases of MIS-C, and we had a lot of lessons learned as an institution and clinicians. From what I mentioned before, the closest to possibly the potential hazards of the natural history of this. One of the major lessons we had learned from this is patients with clinical shock, whether or not they had cardiac dysfunction or not, seemed to improve with early institution of immunomodulators. In our institution, we reach for (Indiscernible) fairly quickly in patients we suspected head MIS-C. Certainly, the one that had symptoms of shock. I will put the caveat that we have to take into context the epi-gemological incidence of COVID-19 in your particular area, just make sure you are not missing something else. 

If you are in Vermont right now in the COVID-19 number of cases is not that high, MIS-C should be suspected but not in the top of your differential. In other parts of the country where the cases are searching, MIS-C should definitely be in the back of your mind. It's important to standardize her echo protocols to make sure we thoroughly evaluated myocardial function and coronary arteries in anyone we suspected MIS-C. Anybody who be admitted with MIS-C got an echo right away. They had an echo on admission and throughout the house position, as well as upon discharge at two and six weeks, six months and on your post discharge. 

Finally, another lesson from the case is inflammatory credit biomarkers really should be trended on as a monitor for the inflammatory status even in recovery phase. What we saw, it can spike in symptoms can return, and we need to trend even after shock is result. 

Very quickly, I present a second case which was after the first case presented. This three-year-old male who had no past medical history presented with fever for four days. He did have a rash, and also known to be PCR positive for SARS-CoV-2. He had strong exposure to COVID-19 and his family, approximately one month ago. He had no respiratory symptoms. Even though he was tachycardic in the emergency room, he was not toxic appearing. He did not have conjunctivitis, but did have cervical (Indiscernible) and a rash on his chest, hands, and feet. This patient was not so much in shock like the first patient was. 

Because we were still suspecting MIS-C, we admitted to the pediatric floor. What I want to point out here in terms of the laboratory data compared to the last patient, is what you see in red is once again, another example of how inflammatory markers can be elevated in these patients. (Indiscernible) Was mildly located. The C reactive was not as dramatically height. If I can also point out that the NT-ProBNP, the troponin was normal and the NT-ProBNP the last patient which was on the tens of thousands, was not as dramatically high in this particular patient. 

We did not detect with our admission but had positive for COVID-19. What I want to say is we opted not to initiate any modular treatment and ended up admitting for clinical trending. However, with clinical observation his fever continued into the following day as well as a rash. As I mentioned, echocardiographic evaluation is standard in all admissions, and his function was normal. He had a trivial pericardial effusion in normal arteries. His workers as well as troponin trended in the upper direction. We decided we would give them a lower dose and not as high as the post dose we saw in the earlier case at 2 mg per kilo per day as well as a dose of IVIG. 

The next day his fever had really improved and he became afebrile. The rash dramatically absolved (Indiscernible), his abdominal pain and he was discharged two days later. As a standard, we discharge everybody home on low-dose aspirin until they can have follow-ups of the coronary arteries as well as a prednisone taper. 

What I hope to illustrate with this case, is with more experience with -- I think there may have been one that was skipped. With more experience with MIS-C, our institutional experience really was to initiate immunomodulators pretty early. Next slide. My mistake. Here is a very small excerpt of our protocol. What you see here is when we suspect MIS-C essentially screening them by the State Department of Health criteria and guidelines, these patients are admitted and put into a category that we designate as mild, moderate or severe. Basically, looking at their clinical needs, evidence of shock, what cardiac function is like, and whether or not they have evidence of organ failure. 

Within those categories, have as a mentioned, adopted a philosophy of instituting mean a modulator therapy fairly early. Doses vary depending on the presentation of mild, moderate or severe. What I would put is a caveat in a mild category which I put in the bottom left, is like the case I just presented, we will hear more about it from her future presenter. It is probably reasonable to defer treatment in milder cases if they are not presenting the shock, as you trend inflammatory markers to their cardiac evaluations and watch clinically. 

Lessons learned later on as we had gained more experience with MIS-C in institution is really the patient who came to the emergency room presenting the shock, it was certainly something we had to recognize quickly. We certainly adopted instituting immunomodulators therapy very early. What we found is a different population in the latter half of our experience was much more mild. It wasn't as striking in terms of the shock symptoms when they presented. These pose their own challenges. General pediatricians in a mean -- in emergency rooms face a challenge about how to evaluate triage patients with mild MIS-C symptoms. 

As I mentioned, those without shock and normal echoes, and what was appropriate in terms of admitting or treating them. I think we will hear more about the American College of (Indiscernible) but we certainly adopt in terms of following in order to decide later on if treatment is warranted for these mild cases. 

Certainly, I know I am a cardiac intensivist but we work closely with pediatricians in the world. There was a lot of worry about whether or not we had missed a case of MIS-C in the community. Children who may have a low-grade fever and subtle symptoms may have since improved, but pediatrician and parents were worried they were missing manifestations if they can get evaluated. Quick advice I would give for those patients, do you have to refer them to the emergency room? Probably not unless they are symptomatic or ill appearing. Do you refer for laboratory valuation? We did find this helpful, but you have to take into account local resources and ability to get labs and trained labs. 

If the patient is currently a symptomatically and results in fever, do you still refer for cardiology evaluation? I will tell you that because we didn't know what MIS-C what outcomes would become there was a number of children that we saw on a cardiology outpatient basis that may have had prior result in symptoms. I'm happy to report that all those types of evaluations did turn out to be normal. Again, it may be reasonable if it's within your resources to seek cardiology evaluation at the symptoms sound like they might fit with MIS-C. 

Finally, to give you a summary about how we treated MIS-C in New York press petition -- New York Presbyterian Morgan Stanley churches hospital, a lot of the difference is because of the evolution of protocol in terms of time. We were earlier institution in the epicenter of the U.S. to see MIS-C. Our treatment protocol really had to evolve with all of that. In our total experience, the patients that received both (Indiscernible) and IVIG from MIS-C was 67%. If you made it to the ICU it was about 81%. Those that received steroids was 9% patients by 30% if you made it to the ICU. 

If you see 94% of patients, if you made it to the ICU, received (Indiscernible). We found a pretty dramatic difference was shock with steroids. There were 17 patients that received IVIG only a minority that had supported treatment only. In our experience for about the 60 patients we treated with MIS-C, we do not have to ventilate anyone, anyone required circulatory support. Everyone was discharged home life. 

I want to point out there are experiences and reports in other pediatric institutions that have had to intubate patients with MIS-C, they have had to put patients with MIS-C on ECMO. There are varying experiences in terms of severity of the disease. I would certainly take that with a grain of salt. Our hospital length of stay was four days, with range of 1 to 19 days. We have had the fortune to see about three quarters of these patients on follow-up so far, as soon as a little over a week to as far as the most two months and some earlier patients. 

I am happy to report the majority of patients are doing quite well. 95% have normal echo with only one that has mild and another that has moderate dysfunction. All have normal coronary arteries. Finally, just to summarize the major lessons learned our experience in New York, again, to really emphasize that this is a single institution of evaluation and treatment protocol. This is our experience in New York. I think the speakers that are to follow, will show you what's being done to really look at, observe and evaluate what's optimal treatment for MIS-C and what outcomes can be. What I can say is that our job, despite how pressing, and quickly we had to both learn, and create our protocols, I cannot strongly emphasize enough that a multidisciplinary team was really imperative in creating our evaluation and treatment protocol. 

Because that was so well organized and well done early upfront, we all had a very uniform approach to screen, admit, diagnose, and treat MIS-C. The more that institutions can really organize this upfront, truly the better. Access to cardiology and intensive care, certainly patients have shock or cardiac dysfunction, it's really an important part of the evaluation and management of MIS-C. If you are not into the institution that cannot provide those things, think about sending those children to an institution that can. 

Ultimately, the multidisciplinary follow-up, our children follow-up at those time intervals that I mentioned. At that visit, they see cardiologist, get an echo, see a rheumatologist, an ID person, and there is a slew of labs and other types of workup that we follow. That also required an organized approach. That's what's needed to both understand and monitor this disease as we go forward, and what the outcomes may be. 

I thank you very much for listening to our institutions experience with MIS-C in treatment. I will pass this on to the next part of the webinar. 
>> MATTHEW: Thank you very much, Dr. Cheung. That was excellent to hear the early experience in New York. Based on that, a lot of hospitals are starting to implement their own protocols for what they will do to treat this. I will be presenting on clinical management MIS-C based on a survey that we did. 

I just wanted to disclose I am (Indiscernible) just in Atlanta. This work I'm presenting as part of that work in that role. While I do work part-time at CDC, and helping with the COVID-19 response, this is not part of that work and it does not represent (Indiscernible). 

To better understand what hospitals have been doing, how have they incorporated a lot of the data you see in the literature of the early experience? We instituted a survey at U.S. institutions from the middle of June, up until last week. We asked about a variety of elements in the assessment and management. I will present some hospital characteristics; what definition institutions are doing. What people are doing for initial evaluation. What are the standardized treatment protocols at their institution? What follow-up is being arranged at discharge? 

We had a very good response to the survey. We had 41 centers across the United States from East Coast to West Coast, a very well represented. 35 of the responding institutions have established protocols. They answered the survey based on what their particles were. Others responded with what their usual standards will be. 

For this study, we had a good representation of different sized hospitals. Most were medium-sized pediatric hospitals with 200 to 350 beds. Many were also small hospitals, less than 200 beds. We had larger hospitals also contribute to the study. The experience with treating MIS-C varied as well. About half of the institutions had only seen just a few patients or none at all. There were about seven institutions that have seen quite a number of patients with greater than 25 so far. 

It will not be shown today but I will let you know we did look at differences in how institutions responded whether they had treated more than 10 patients, 10 patients or fewer, and results are very similar. This is a learning process. Things are changing as we are going. Although institutions that have protocols already in place, more than half responded. The particle has changed and many have commented that it's being updated on a weekly basis or as new information comes along. 

I want to remind people of the CDC definition for multisystem inflammatory syndrome. This was presented in an alert that was sent in mid-May. It was meant to be a very sensitive definition to capture any cases that we thought may have MIS-C. This definition that you can see on the website that I listed here as well, has a few key components. It includes fever for at least 24 hours. Laboratory evidence of inflammation with at least one lab being elevated. At least two organ systems involved. There needed to be some sort of COVID-19 link, whether that be resent SARS infection by PCR or serology, or some known exposure within four weeks prior to onset of symptoms. 

When it comes to fever, most places were following the CDC definition with more than half saying that the only required one day of fever in their definition. A few had other numbers of minimum days of fever with many at least three days before they entertain the diagnosis. 

For labs, almost all required labs as part of their definition but if you did not, and were making this assessment without any necessarily requirement for what lab criteria had to be. Of those abnormal labs, most followed the CDC definition with at least one lab needing to be abnormal. A few required more. 

In terms of organ systems involved mostly all CDC definitions with the most all requiring at least two. One did require at least three to be involved. If you said as long as one system was involved, that would meet criteria for MIS-C. Interestingly, and Eva Cheung alluded to this, well everyone is doing testing for SARS-CoV-2 propriety of tests, usually PCR or antibody, and most had in their definition for meeting criteria, not all are necessarily requiring the known link for positive test. Insert hotspot area some centers are working that every committee is exposed and has seen somebody in the last four weeks that has COVID-19. They are waving this requirement at least for diagnostic purposes. 

As part of the workup for the child who is under suspicion of possible MIS-C, there is a common blood work looking for inflammatory markers, CMP and CBC to the hospital. Many centers start with that as a first-tier looking for evidence of inflammation to see whether these children would potentially meet criteria. If they do, many would move on to second-tier testing such as troponin, BNP or BNP Pro BNP coagulation test and others looking for other potential causes of illnesses in children including blood culture respiratory panel. Not excluding based on that but doing a complete workup of the child with multiple days of fever. 

As part of the investigation, almost all places are doing echocardiograms. Many doing it in all question -- patients have MIS-C. Similarly, for electric cartogram and chest x-ray. Other testing such as abdominal imaging or chest CT seems to be very patient-driven and only done in some patients. The light blue represents some patients on the slide in the next slide. 

For consultants almost all children or institutions have consulting infectious disease is part of particle for all cases. Similarly, hematology (Indiscernible) and rheumatology is (Indiscernible) nephrology seems to be consulted for some patients as an unneeded basis. I will talk about some of the treatment by 39 of the centers. IVIG seems to be a hallmark most centers with more than half of the centers giving IVIG regardless of the severity. I should mention that we did ask how different centers to find severity. You heard Eva Cheung talk about how this was defined at her institution. 

This varied widely. Anywhere from looking at (Indiscernible) scores, to presence of shock, presence of cardiac involvement or location with the patient in the hospital in ICU. Of those centers that used IVIG, 22 did have particle to recommend a second dose if it was refractory. There were a few other drugs mentioned by some institutions to be given regardless of severity. Most commonly used with aspirin. With the dosing amount changing depending on the severity and course of illness. Corticosteroids especially in severe cases. Similarly, heparin was across the board where most are using some sort of heparin in moderate and severe cases, with a few giving in all cases. 

Two drugs that are commonly used, but really restricted to the moderate and severe cases, include in anakinra and vasopressors with more than half institutions as part of their protocols. And we also asked about a number of different drugs as you see here fewer than 20 centers reported the use of each of these drugs. Some of them being more commonly used in acute COVID-19, potentially playing a role in the treatment of MIS-C as well. 

When it comes to follow-up, we asked whether people were following the Kawasaki guidelines or doing something else? Of those who reported follow-up guidelines, about have said that they were following the standard AHA Kawasaki guidelines, which includes cardiology with an echo two weeks in six weeks. Then based on coronary findings. Number mentioned they are doing some sort of hybrid type of follow-up based on the particular patient condition. Some following standard institutions protocol and others doing more of the Kawasaki protocol. 

For the clinic visits, all included a cardiology visit. The one group and the other down below is for Kawasaki which includes a combination of cardiology and infectious disease. Infectious disease and rheumatology are also a part of standard article at half of the centers. A review includes standard hematology follow-up. A nephrology follow-up was not standard for institutions but certainly on and as needed basis. 

In conclusion, there is a lot of variability in the evaluation and management of these patients. Not all institutions are treating these children the same way. There are some common themes that emerge. As we heard today, it takes a team approach. Infectious disease, mythology, nephrology, a lot of people are helping out these patients. When it comes to treatment, IVIG and aspirin are common, regardless of severity. Steroids are very common in severe cases. It will be interesting to see during the course of the surveys, many of you know they were results regarding the use of steroids in acute COVID-19 and adults. I am anxious to see whether this trickles down to management of this publishing as well. 

For follow-up, currently many are following things similar to the Kawasaki guidelines. Certainly, that can be tailored to individual patients. A final important to remember is protocols are changing often. People are learning as we go. There is a lot being published on COVID-19 now and we are learning more about these patients every day. Regardless of protocol, care can be individualized. 

I would just like to acknowledge and thank all the collaborators at Children's Healthcare of Atlanta and Emory, who helped with this project. Would like to thank participants at the collaborating centers who contributed to this. We do hope to get this published soon online so many of the hospitals preparing for patients coming will have this information available to them. Is a very much. With that, I will turn this over to Adriana Tremoulet, to talk about some recent guidelines that have come out regarding the syndrome. 
>> ADRIANA: Thank you. I and Adriana Tremoulet. I am a pediatric infectious disease physician at University of California San Diego and the Chavez hospital and associate director of Kawasaki disease research center. It is my privilege to present to you guys today, the clinical guidance for pediatric patients with MIS-C associated with SARS-CoV-2, as well as those with the hyper inflammatory state during the respiratory illness of COVID-19. This is guidance that was put together by a test with the American College of Rheumatology. 

My disclosure is the ACR did provide a stipend to participants but otherwise no other involvement. There is no corporate involvement in the decision of these guidelines. Where is this document I will go through this relatively quickly and I wanted to share with you if you click to the next slide, where you can actually find this yourself. On the ACR, on (Indiscernible), it is the ACR website. If you go to practice and quality there in the middle of the screen and click on clinical support, that will take you to the next page which is clinical guidance for pediatric patients. 

On the bottom of that page, you see the clinical guidance summary for pediatric patients with MIS-C. That's what I believe reviewing today. If you would like to look at the actual document, you are welcome to do so at that website. The purpose of methods of what led to this guidance that I will review here, the goals of the group were to identify the most appropriate diagnostic and therapeutic steps for MIS-C, as well as recommendations for children with the hyper inflammatory syndrome due to the COVID-19 respiratory illness. We were tasked with looking not only at MIS-C, but also children with the respiratory illness. We did mostly focus on MIS-C. The ACR task force is felt was composed of nine Pietro rheumatologist, a couple adult rheumatologist, pediatric cardiologist, a couple specialists including myself, and one pediatric critical care physician. 

We do acknowledge there were people involved in the care of these patients that aren't represented here, but we thought this was a good place to start at the time when this task force was created. This is done over a couple rounds of anonymous voting. We used definitions of MIS-C and not the intent of the task force to create a new case definition we went with what was from the WHO and CDC. It does reflect evidence to relate May 2020. This is an evolving field and what we had at the time that the task force met and you can note that it's six weeks later and (Indiscernible) speakers have noted. Will present to you today what we came up with based on the data we had when the task force was meeting. 

Probably the key piece of this guidance is this chart here, which is also an evolution. We are currently working on (Indiscernible) submitted for publication. I can tell you that between what I will show you here and what will make it into the eventual publication will also be different and evolving as well. At the time you put this together, we wanted to provide some guidance for people that are evaluating these patients. This takes into the account the existing CDC and WHO case definitions for MIS-C. Starting with the child having fever, epidemiological link to the SARS-CoV-2 infection, as well as clinical features. 

From there, you go on to whether a child has shock and needs a full diagnostic evaluation for MIS-C, whether you can have on the right-hand side as he moved down, tier 1 screening evaluation which involves some laboratories that may show some significant inflammation, which then leads you to possibly doing a tier 2 of significant enough involvement of inflammation. 

Many have asked and posted in the questions and I have heard from colleagues, how do we know to evaluate and what the emergency room should do, and who should go on should be admitted. I think this starts in early start of the guidance of demonstrating that it's only a significant inflammatory process as others have pointed out, that really lead to the diagnosis of MIS-C. We hope this provides some guidance on the diagnostic evaluation of these patients. This too is alive document. 

Now, I will go through more of the specific information that was presented by the task force for diagnostic evaluation. The outpatient valuation is appropriate if there are stable vitals. A reassuring exam in close follow-up. It may be certainly, if one of these is not present as Eva Cheung pointed out, there is an emergency room evaluation or admission may be warranted. 

Consideration of admission has been pointed out and include abnormal vitals. It's key to know that a lot the children have a level of tachycardia that exists even in the absence of fever. It is quite notable. It may be due to the left ventricular systolic dysfunction that is showing up in many children. There may be neurological deficits, status, renal hepatic's injury and inflammatory markers are key. I would say and elevated CRP on (Indiscernible) pretest amount that is greater than 10 is something that we hear locally and many colleagues have seen. Certainly, a presence of elevation of inflammatory. 

(Indiscernible) That seems to be one of the most common on an EKG with signs of arrhythmia or issues of repolarization on the EKG, elevated BNP or troponin that reflect the strain of the left ventricular dysfunction that exists. As he mentioned, this is certainly a multidisciplinary approach that needs to happen as reflected by the task force makeup. 

One of the things that we evaluated as part of the task force is doing a comparing and contrasting of the features of MIS-C and KD. I was called into the discussions of MIS-C with my KD background but it has become clear over time that these are different diseases in several ways. There may be overlap, but there are certainly differences and we thought we wanted to call attention as part of the task force. 

Patients continue to present and continue to require evaluation and treatment. As I can tell you from local experience, we are still seeing those patients. There certainly appears to be an ethnic and racial difference that occurs. I think it's quite interesting how much of Asia that has seen SARS-CoV-2 infection, has really not reported much in terms of MIS-C cases. It may be that there is a genetic predisposition that's -- that might be between these two diseases. Trauma patients tend to be older. They have more prominent G.I. neurological symptoms. Mort left ventricular systolic cardiac dysfunction, and certainly, aneurysms are being seen in the MIS-C patients, but the reports of giant aneurysms seem to be more specific to Kawasaki disease. 

In terms of evaluation of MIS-C patients and how they seem to differ from KD patients in terms of laboratory evaluation, MIS-C patients tend to have lower platelet count. They tend to have lower lymphocyte counts, and higher CRP's as well. I want to touch upon the cardiac management of MIS-C. The task force addresses this. The consensus was that an animal BNP and troponin on admission should be trended until normal. 

And EKG should be followed every 48 hours while hospitalized. As already discussed, follow-up outpatient should happen at two and six weeks. There is also discussion about whether there should be follow-up later on in the course like at one year or six months as is been suggested by Dr. Cheung. 

And, if abnormal (Indiscernible) is key. I think Dr. Cheung's point about standardization of echoes in the hospital is very important. These patients require full cardiac and echo including ventricular function both systolic and function. Also, coronary artery measurements that are evaluated by capitals the scores. We can make assessments about whether there is coronary involvement are not these patients. 

Echoes should be done in the hospital and more increasing frequency. If there is change in the patient or increase in BNP that reflects that, certainly the task force (Indiscernible) it was discussed by the task force about a year follow-up visit and is this process evolves, there will be more specific follow-up. Love to keep in mind that this disease has only been around for a couple months. Finally, we did have a discussion it to in six months if it is less than 50%. 

There are more cardiac evaluations that need to be done. As longitudinal follow-up becomes evident, we will have stronger recommendations and guidance. So, (Indiscernible) to a treatment in MIS-C, I'll start by saying we really have not had a study that defines what we should do in these patients. Much of this therapy has been based on our own local expenses with what we have done for Kawasaki disease or a site that is more guided by the rheumatologists for other disorders and really but has dominated the guidance. Certainly, randomized trials are still needing to be done to provide better information about the true treatments. What we went on was mostly the experience of what is out there. 

Progression of therapies is certainly reasonable. First tier should include steroids or IVIG which most people have done as standard of care. Consider cardiac function and fluid status. IVIG is quite a bit of fluids. Most of the children that were early on that had the need for cardiovascular support because of left ventricular systolic dysfunction, really needed to have fluids done in a very cautious manner. 

It was not uncommon in many patients in the ICU for the IVIG to be given for more than just 12 hours. You need to consider that (Indiscernible). It was given (Indiscernible) per kilo but then you saw the experience there from the Columbia group with using higher dose steroids in the sicker patients as well. Other therapies that we included in the guidance include things like in anakinra and higher dose steroids. There has been experience at a number of using (Indiscernible) although that is not mentioned in the guidance simply because there wasn't really any affirmation out there that has been published. 

I will say that Detroit Children's has had quite good experience with (Indiscernible). We need to as a community, keep an open mind about treatment regimens and what the future holds for the treatment of MIS-C. In regards to antiplatelet and anticoagulation therapy in MIS-C, the standard appears to be low-dose aspirin and a Max of 81 mg and that isn't antiplatelet. This should be continued until you have (Indiscernible). Anywhere in the midst of that 2 to 6-week period that the task force was suggesting about two weeks of treatment. 

Depending on your site and what your hematologist used, there may be a threshold below which your platelet count may be for your patient or suggested by the task force was less than 80,000. At which aspirin therapy maybe discontinued for a bit. Many children to become (Indiscernible). In terms of coronary artery anticoagulation, certainly for a Z score of 10 (Indiscernible). I would say that the task force recommended the hematologist be involved in terms of the TE prophylactics depending on what the risk factors are for your patient. 

Generally, for MIS-C, the thought was low-dose aspirin. Certainly, if the injection fraction was 35% the task force fell in those patients that there may be consideration of enoxaparin. That is under the guidance of the hematologist fully understanding that we still know very little about the need for anticoagulation in these MIS-C patients. It is certainly not to the level of patients or adults with the acute COVID-19 ARDS illness. 

I will switch gears very briefly at the very end which is (Indiscernible) in children with the respiratory illness of COVID-19. What I discussed up until now is symmetry illness of MIS-C which is what the task force focused on. Thought we couldn't leave this topic untouched which is children with acute COVID-19 respiratory illness. This is following on the heels of recommendations from the adult literature looking at adults with ARDS that are also ill and develop hyper inflammatory response. 

The task force left vague but (Indiscernible) therapy. What has been tried although certainly in few patients has been steroids. In the hyper inflamed patients, and anakinra. Tocilizumab was discussed as part of the task force but there is data to suggest there is fungal infection so there is a caveat in warning about use of this in these patients with that, I will turn this back to Ibad Khan. Thank you very much. 
>> IBAD: Thank you for providing audience with such useful information. We will now go into the Q&A session. Audience, please remember, submit questions to the webinar system by clicking the Q&A button at the bottom of the screen and typing your question. Due to the limited amount of time, we can only take two questions. The first question is with recent spikes in COVID-19 cases, should we expect to see spikes and MIS-C cases as well? 
>> ERMIAS: Just to briefly answer that question, unfortunately, the brief answer is yes. Particularly with a number of COVID-19 infections in the West and South East, and particularly among the younger populations, we expect to potentially see an increase in MIS-C. Basically, that is need to continue to monitor MIS-C going forward. Already, we have seen some anecdotal data that states jurisdictions that have not reported MIS-C cases, or reported small numbers in the past. We started to report cases with MIS-C. 

We are not yet at the same level as what was reported (Indiscernible) MIS-C has a delayed of several weeks from acute COVID-19 infection. It's a good possibility that MIS-C -- you may see an increase in the future. 
>> IBAD: Thank you. The next question asked the American College of Rheumatology guidelines mentioned MIS-C as well as hyper inflammation in COVID-19. What is the difference in how do we know which one we are dealing with? 
>> ADRIANA: The COVID-19 hyper inflammatory syndrome is really (Indiscernible) quite similar to what is seen in adult patients, although the ARDS seems to be less severe. That is the acute period with respiratory illness. MIS-C is a hyper limitary syndrome that is presenting as Ermias presented early on, after a month after acute illness. Many patients have either SARS-CoV-2 embodied -- body positive or epidemiological link to either a front-line worker, or someone else in their immediate family or circle that has been positive previously. That is a post infectious response. 
>> IBAD: Thank you. On behalf of COCA, I would like to thank everyone for joining us today and sharing this hour with us. With a special thank you to presenters. Close caption video for this COCA probably posted on COCA's webpage shortly after the call at emergency.cdc.gov/coca. Please continue to visit emergency.cdc.gov/coca over the next several days as we intend to host COCA calls to keep you involved of the latest COVID-19. In addition to the webpage, COCA announcements for upcoming calls will be sent via email. Please remember to subscribe to receive notifications by going to emergency.cdc.gov/coca /subscribe. Please join on Tuesday, July 28, at 2 PM Eastern for another COCA call where the topic will be coronavirus disease 2019 COVID-19 and diabetes, importance of prevention management and support. 

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