SCCM Resource Library-Multisystem Inflammatory Syndrome in Children

Multisystem Inflammatory Syndrome in Children

Video Transcription

Thank you, Christina, give me two minutes to share, till then, till I pull this up. Thank you so much for having me to talk about multi-system inflammatory syndrome in children  in COVID, and it's my extreme pleasure to do this, and hopefully I will succeed in engaging my adult colleagues, so let me get started, just sort of a side note, I am actually a  pediatric intensivist by training, not a pediatric cardiologist, I do work primarily in the cardiac  ICU here at Cedars, and so I am talking from an intensivist perspective with a primary interest in cardiac intensive care, give me one second, sorry, I'm getting, I don't know  if it's only me, and I don't know if you guys can hear it, but I am getting like a notification of folks coming in, all right, so you can see my slide and hear me, okay, so I'll be  talking about multi-system inflammatory syndrome in children, and which got a lot of press last year, as you all know, and has had a lot of literature come out, this talk actually  could not be more timely, because two of the most important NEJM papers came out in July, the overcoming COVID and the BAT study, which I'll be talking about a little bit,  just got published July 1st, and I think either end of June or first week of July, so it's perfect timing to be talking about what the evidence is, as we follow this format,  let's start with the case, so 18-year-old male presented to urgent care for nausea, diarrhea, and decreased intake for four years, was known to have COVID, which was about three  weeks back, the difficulty really never improved after the COVID, he was found to be hypotensive and tachycardic to 150s, and was referred to an outside hospital emergency room,  over there he was treated for septic shock, initially with vasopressors, elevated BNP and troponin was found, and a trans thoracic echocardiogram was performed and showed an EF of  25 to 30 percent, so at that time vasopressor therapy was changed to inotrope, and to specify was on norepinephrine, and was changed to dobutamine, managed in the hospital with  immunomodulatory therapy for misc, with pediatric infectious disease and pediatric cardiology  involved, hospital stay was 10 days, and was discharged home with an acetabular and beta blocker, so what is the question, so I mentioned very discreetly that the treatment was  immunomodulatory treatment, so what is the treatment for misc, is it dexamethasone, is it  methylprednisolone, is it IVIG, or is it anikindra, or is it everything combined, or which one is  better and why, and what did the pediatric critical care community do when this happened,  so as we all started knowing about this, there is actually a CDC and a WHO definition  for this, and as I mentioned, there are the two big studies which talk about outcomes related to  therapy and the overcoming COVID and the BAT study, and they use these two definitions, which are slightly different, so I have a comparative slide here, so CDC is below  21 years of age, WHO, as I said, as it says, zero to 19 years of age, and the fever for WHO has to be more than three days, whereas for the CDC definition is more than 24 hours,  the clinical symptoms, WHO specifies it more discreetly, I mean, like, actually talks about it more, and linked to SARS-CoV-2 are pretty much similar in both the categories,  the inflammatory markers for the case CRF for CDC is much wider compared to WHO, where it's elevated ESR, CRP, and procalcitonin, and there is an exclusion criteria where it's  no alternative diagnosis and no obvious microbial causes as in the WHO definition, so when this started, just to sort of, you know, talk a little bit about what happened in the  press and what the literature showed, et cetera, when it started, it was very much,  the press was talking about Kawasaki-like disease, right? Kawasaki disease is a disease which we still don't know the causation in pediatrics yet, it's, there is a big theory  that it's viral-induced, it's because of inflammatory changes in the body, and the biggest thing, how it's related to cardiac intensive care or pediatric cardiology precisely  is that there are coronary aneurysms which are initially, either initially found or could be a  mid to late finding, and when that was found in Miss C, there was a lot of, you know, anxiety about  how is this related to Kawasaki, et cetera. We know now that it's different from Kawasaki,  you can have Kawasaki-like symptoms, and I'll come to that, come to that in a little bit and  what the differences are, and then it was like, so how is it different from basic septic shock,  right? Or how is it different from toxic shock syndrome? And there are, there's still a lot of  mechanism and pathophysiology work being done in this, however, there are some features which are  distinct from Kawasaki or TSS, and we'll come to that. So what are the key concepts? And let's start  with incidence. So this is again from the July 2021 paper, which was just out in JAMA, which talks  about the incidence of Miss C, and it, over a million person months, it's 5.1% of the incidence,  so not a lot. Now the, what's important to know is this is from the Overcoming COVID study.  It is US-based, 58 hospitals, and it is from the April to June cohort, whereas the BATS study,  which I will come to later, is an international study with 62 countries. There's one big US center,  and the cohort is over a wider period of time. So it's from October 2020 to February, sorry,  May 2020 to February 2021. So that's the biggest difference in this. So we, there is no incidence paper out yet from the BATS cohort, but this is from the Overcoming COVID cohort.  As far as our own SCCM virus goes, we have about 1,600 pediatric cases on the virus website,  which were from the last update on the pediatric part of the website was June 23rd. 29% of them  have met the case definition of MISC by CDC. So, you know, clearly it's a very good cohort  of patients where we expect a lot of good studies to come out from. So what are the key concepts about pathophysiology, et cetera? As far as cardiac  dysfunction though, because, you know, this talk is related to cardiac dysfunction of MISC,  systolic myocardial dysfunction in the mild to moderate range has been reported most commonly, though there are some reports of severely diminished ventricular function.  This is from the report from ACTION, which is a consortium of pediatric heart failure hospitals.  And they did a study of, and again, the cohort was different from what is in the other studies,  but this was related to heart failure specifically. And this is actually a little bit of mechanistics and pathophysiology about how MISC is different from toxic shock or  Kawasaki disease. What's really different most importantly is the GI symptoms in MISC. And if you recall, our patient presented with nausea and diarrhea. So that is pretty common  in MISC as compared to Kawasaki. The myocardial dysfunction in MISC has been mostly shown to be  reversible. There is an incidence of coronary aneurysms seen in MISC, but there are now studies  coming out which the coronary aneurysms actually have fully resolved. And the inflammatory markers  are clearly higher in MISC than in Kawasaki disease. So pretty different. As you see on the  screen, as you know, as I mentioned, the coronary artery dilation aneurysms are pretty transient. And then the cell markers, right? So the lymphopenia, the thrombocytopenia  is predominantly there in MISC as compared to Kawasaki. The response in IVIG and steroids is  there pretty much in all the spectrum of these diseases, like Kawasaki disease, toxic shock,  as well as MISC. And the ethnicity predominantly in Kawasaki disease is actually in Asians and  Asian ancestry, whereas in MISC, and this is an interestingly, all the US cohorts and the  studies which have come out predominantly from the overcoming COVID study, which is all over,  as well as the known data from virus, also from the New York, as well as the  Southern California cohorts, the Hispanic and Black ethnicities predominantly where we see MISC.  So this information about ethnicity is pretty much there in all the cohorts, which are under  study. This talks about the super antigen like activity for seen in MISC. And it's pretty much  like the cytokine storm you see with macrophage activation syndrome, where you see it with severe  COVID-19 and it leads to your cytokine storm. Now, what are the mechanistics and how is it different from secondary MAS, which we see in all kinds of diseases yet to be determined,  but clearly there's a association with timing of COVID. It is within four weeks. So if you have  COVID six months back and a documented infection, and you come in with a hyperinflammatory syndrome,  we recently had a patient, you cannot call it MISC. So what are the current recommendations?  And when I talk about current recommendations in the next subsequent slides, I'm going to be talking with a little bit about the immunomodulatory therapy, but I thought this  talk would be a miss without talking about thromboprophylaxis because last week we had such an interesting talk on that. So there are some recommendations actually on that because  in Kawasaki disease, there are specific recommendations about aspirin, et cetera, that we follow. So this is from the American College of Rheumatology, and this was released,  you probably can't see it with me being on the slide, but this was released in 2020, November from Jones Hospital, Philadelphia, and a whole lot of collaborators all over.  And predominantly it is IVIG as first line and methylprednisolone in addition, when there is life-threatening disease or organ-threatening disease and shock.  And if you have refractory disease, which there is the case definition in the paper, you add higher dose methylprednisolone where you intensify the therapy, and there is anakindra.  There are several cohorts of patients where different centers which have developed their own protocols and recommendations have used other immunomodulatory therapy like toxizumab,  et cetera. None of these have shown to be really beneficial. And we'll talk about even the IVIG  and methylprednisolone versus only IVIG in a little bit. So these are, you know, when this started, I think the biggest thing, because it was closely related to Kawasaki, IVIG was  tried first with reasonable success, and then methylprednisolone was added. And I apologize  because I'm blowing up the screen. So if there's anything in chat, I will definitely get back to  those questions later. So what is the missed thrombosis thromboprophylaxis management? So if the platelet count fibrin level is more than 100,000, fibrinogen is more than 100,  and there's no active bleeding, the recommendation is to start aspirin.  As far as follow-up, and I'll come to the course of the follow-up in general,  and that will sort of translate to how much time the aspirin is continued for, et cetera.  And then there are actually risk stratification with the no anticoagulation versus intermediate anticoagulation and high anticoagulation. This recommendation is in the pediatric  cardiology paper from ACTION, where I spoke about some mechanistics, and this is the heart failure cohort. So this group came up with these thromboprophylaxis management for missed  patients. The lower part talks about what you do with the follow-up in these patients, and especially if there are ongoing coronary abnormalities, the present recommendation is  actually still to go by the AHA Kawasaki disease guidelines, which talks about aspirin for how many months, et cetera, depending on what your echocardiogram results are.  So what is the evidence? Why do we do IVIG versus IVIG with methylprednisolone, and what do we know so far? And as I said, this literally came out in JAMA, in NEJM 2021.  Both these papers are out. You could review them. And the incidence paper from the overcoming COVID  group came out in JAMA in July, too. So what the overcoming COVID consortium showed, and to remind everybody, this is within the United States, 58 centers, and the cohort is  earlier, so it's a 2020 cohort, so it does not include the second wave, which may explain the different results you'll see in both these consortiums. So initial MISC treatment with  IVIG plus glucocorticoids was associated with a lower risk of cardiovascular dysfunction and initiation of vasopressors and adjunctive therapy than treatment with IVIG alone.  This is what the overcoming COVID paper said, that IVIG plus methylprednisolone  is associated with a lower risk of cardiovascular dysfunction than IVIG alone.  What did the next paper say, which is the BAT study? This is led by Michael Levine in the UK.  This was really a phenomenal collaboration. So I remember when COVID hit, Children's Hospital  Boston, Jeff Burns, who leads their unit, started this weekly meetings with all the big children's  hospitals around the country with experts, and Michael Levine came a couple of times and,  you know, talked about these efforts and how he did this. It was a fantastic collaboration effort.  So what this found was there's no statistically significant difference in the odds ratio for  endpoints of ventilation, inotropic support or death, or for improvement of a clinical severity  scale when you compare IVIG alone, a combination of IVIG and glucocorticoids, or glucocorticoids alone. So different, right? Different from the overcoming COVID consortium.  In addition to read, for those interested, in addition to reading these two papers, I think the editorial on these two papers is great. And I will, I have all the references  for you in the next couple of slides. So, and I'll put it up in chat too once I'm done talking,  but it's a high, I highly recommend reading that because it explains some of the potential reasons  for these differences in results. As I said, namely a US versus an international cohort.  The other plausible explanation is the period of inclusion for the cohort is significantly different. The BAT study includes the second and the third wave in some countries. And the  glucocorticoids included are, you know, they are not just methylprednisolone. So some of these  explanations could plausibly explain why the results are so different. Okay. There are a lot  of references. So what I did was if you scan the QR code, and I'll probably stop sharing,  sharing the regular way, and you'll also have access to this, but so that you guys can scan it,  but you, it's a list of references and I've actually highlighted the ones which, give me  one second till I can pull this up. I've actually highlighted the ones which are probably, they're  very good papers, all of them, but I've highlighted the ones which are really important in this.  Join the literature and let me stop this and reshare. And I'm sure you'll have access to the  presentation and the video also. Okay.  Okay. So it's a list of references. If you scan the QR code, you'll get it. And all the papers,  including the editorial is in there. Okay. And moving on to the next slide is one of the  conclusions. So multisystem inflammatory syndrome in children with COVID-19, it leads to a combination  of distributive and cardiogenic shock. It's likely related to an hyper-inflammatory state  with the virus, but we are still working on precisely defining what other mechanisms are  different. There are some mechanistics identified as far as, you know, immune, you know, biology  goes, for example, the chemokine CXC19 is elevated in Kawasaki disease. It's not elevated in  MIS-C, but how do you, how do you differentiate these at the bedside? And is there any other  marker, which is specific, et cetera, still needs to be defined. As far as the pathophysiology,  as I said, the coronary aneurysms, mostly with the literature coming out where these patients  have been followed for up to six months, are reversible. They've returned to normal. Like  the coronary size has returned to normal. The systolic dysfunction, the follow-up right now, is pretty similar to the Kawasaki patient guidelines, as far as the echo frequency goes,  and they definitely recommend an MRI outpatient once these patients are discharged. And the  treatment strategies include hemodynamic support, trauma prophylaxis, and immunomodulation.  As far as the mortality goes in various reports, it's around 1.6 to 2.3%.  Oral incidence is low. And if you look at the age distribution, definitely a more towards the  eight to nine years, as far as presentation goes, versus Kawasaki is below five years. 4% of the  MIS cases were found in less than one year of age. And the mortality was not significantly  different as compared to older kids. And IVIG and methylprednisolone form the mainstay of the  therapy. And with that, I end my talk. And thank you so much for the time and listening to this.  Fantastic presentation. So I see lots of links in the chat box, but no targeted questions. So  we will open it up to the group. What we've done is designated probably 10 or 15 minutes for group discussion to ask any further questions and clarifications from that.  And then we will turn the page from there to the good Dr. Bennett for Q&A with regards to the online presentation that we shared ahead of time. So questions from the group?  I guess I can... So Alex, this is... Hi. Great talk. Thank you, Pooja. Really enjoyed it.  This is a very interesting topic, not only for all our pediatric colleagues in critical care,  as well as some of those critical care physicians who also take care of young adults. But that  leads me into the next question. Any idea of differences between the MIS-C versus the MIS-A, which is what they see in the young adult population? Do they have the clinical  presentations or maybe there's not enough data yet? Yeah, that's a great question, Grace. And  you know, in fact, we were wondering, because we have a reasonable cohort and it's interesting,  right? Depends on how your institution is set up and where these patients go. For example,  we ended up taking care of this patient, but this patient was in an adult hospital initially.  And the cohort for MIS-A is not totally yet defined. And I think they're still writing those papers up. But we always wonder because we actually see more of the young adult than  pediatrics. And LA, interestingly, did not have that much, even in all the children's hospitals  combined. I mean, Southern California did with UCSD, et cetera. But interestingly, there's not  enough that I can... I don't have enough stuff to talk about that I can say reliably that that's  how it's different in MIS-C, more to come on that. And, you know, that's another thing which  Neha was asking me in one of her previous conversations is that what is, like most of the adult intensive care institutions have set up a post-COVID clinic, or what is the long-term  follow-up and is it structured? And the most data I have or recommendations I have are echo follow-up  and or a cardiac MRI follow-up with Kawasaki guidelines. But as far as, because all these  patients, I mean, a reasonable amount of them have about, you know, more about 50 to more than  50% of them do have respiratory morbidity. So it's not that it's only cardiovascular, right? And they have, you know, they are on the ventilator, et cetera. So what about, you know,  pulmonary changes and what is the follow-up for that? It isn't structured. It's really pediatric centers have not, we should learn from our adult colleagues to have this post-COVID  interdisciplinary, you know, multi-professional sort of setup. And we don't, but clearly there's  more work to be said. And if you guys look at the parameters, I mean, sorry, the references, one of them from the overcoming COVID paper group talks about how is severe COVID  different from MIS-C? Because that's another thing, right? You can present within four weeks, but what if you're in one week and why is that not severe COVID? Why is it MIS-C?  And there is, there are differences and that paper articulates it pretty well,  but it can be a diagnostic dilemma, right? Because your treatment can be pretty different, but the inflammatory markers clearly are more pronounced in MIS-C than in severe COVID,  even when you have cardiovascular complications in severe COVID. So that was sort of the  take-home message from that paper, but that paper is in there in the link I sent you. And you should  not need to do any logins for that link, by the way, it should just open a Microsoft Word document  with all the papers in there. That was awesome that you shared all the, all the links. Dong, you and I were just posting a bunch of the links as you were going through your slides.  To complicate matters a little bit more, I'm going to ask you, ask you a question where understanding is evolving quite a bit and it's probably going to become an important public  health problem for us, not just in the United States, but the world over. So long COVID,  what does MIS-C and long COVID have in common and how should we be following these children  after they've developed MIS-C? Does it increase their risk of developing long COVID? Have you  noticed anything and what are, what are some of the studies to watch out for to better understand  long COVID in, in children? Yeah, no, great question. And, you know, the, the whole concept  of that children are not really affected by COVID when this all started, and then the emergence of  the MIS-C literature, and now the emergence of the MIS-A and then its relationship, relationship  to long COVID. I think the, the key element in this is till we have that multi, multi-professional element or clinic set up to actually follow these patients  in a more structured manner.  I do think the field of pediatric critical care, there are efforts happening definitely. I don't, I think we are a couple of months  behind our adult colleagues to give you that answer, but there's definitely more work being done as we speak on that. Just a little early to comment.  So what other questions do people have?  I had put a question in the chat box with regards to the tapering of therapies. So the ACR guidelines refer to following inflammatory parameters, but there's quite a list  of elevated inflammatory parameters that you showed us during your presentation. Is there any data in terms of which inflammatory markers  are best or recommended in terms of guiding the tapering of anti-inflammatory therapy?  And so I just finished typing. So CRP and procalcitonin are the two most important ones that most centers do. Because if you look at,  if you recall this, the WHO versus CDC case definition,  the CDC one is pretty big as you mentioned, but the CRP and the procalcitonin are the two most important ones which are followed. And some of these collaborators  who are on the ACR guidelines are also from New York Presbyterian, which I used to work at previously, Columbia. So they form their own guidelines  and they actually published a couple of papers about it, but they also follow CRP procalcitonin. So most of the pediatric centers on the West Coast too,  and just some collaboration with Stanford, et cetera, and Northern California. Those two are the most important ones. Our center, we do follow ESR2.  So our pediatric ID recommends following these three before the immunomodulatory therapy could be tapered. In the patient we discussed, we actually tapered it within three days  and then sent him home on a very low dose of prednisolone, which was off in like 12 days total. So he was on steroids for a total of 12 days, including hospitalization.  Pooja, this is Grace again. One more question. And this is related to the fact that we are seeing a lot of myocardial dysfunction associated with vaccines.  Do you think there's a relation in the immune regulation that we are triggering with vaccination similar to what happens with MIS-C or those are two independent clinical scenarios?  So very, very intelligent. It's a funny thing, but I'm just going to say it. It's sometimes hard to give a talk to a group of smart people. No, just kidding.  But there is an infectious disease specialist  at our center who studies KD, Kawasaki disease. And he's actually studying this in the lab. So, you know, they do have that same question that you do, Grace.  And it's been, I'm sure it's been studied because he's collaborating with multiple centers. But, and one part of his study was also BCG vaccination  and immunomodulation and COVID related to that. So having received BCG vaccination in India, I could still participate in the study. So who knows what that did?  So, you know, that's another thing he's studying if BCG vaccination affects the immunomodulation with COVID, et cetera. So he's actually studying your exact question in the lab.  So I don't know what the preliminary data shows yet though.  Thank you. But we are seeing those two, the myocarditis with vaccination.  Yeah.  And just in teenagers, right?  Yeah, we're not seeing that in the adult population that I'm aware of. Correct. Yes. No. Yeah. Those teenagers.  Well, I think as we prepare to transition and ask the good Dr. Courtney Bennett questions, I did want to just open it up to the group. We have a number of pediatric teams  that are present on the call. If there's any other comments or discussion that they would like to lend from their experience before we turn the page and talk about  cardiovascular complications a little bit more broadly.  I don't want to speak for everyone again, but I think we have asked the questions that are right now in everyone's mind. But as Dr. Nawazi stated, we don't have answers.  I see a question in the chat, Alex, from Sarah. Yeah, go ahead. Any consideration for stratification regarding long-term aspirin similar to Kawasaki?  Pooja, any comments on that? Yeah, sorry. I was just typing it. So presently, as I said, in fact, the stratification is pretty similar to Kawasaki.  So you follow the coronary artery Z-score, and depending on that, you decide how many months, et cetera. So the AHA Kawasaki guidelines,  it's what we will follow for echo visualization. So follow up with the echo, follow up with the aspirin. And then the thromboprophylaxis, there's still really minimal data  on when to stop that, et cetera. But the aspirin is, Dr. Chalmers, sorry, very similar to the AHA Kawasaki guidelines.  Is there a potential for therapeutic plasma exchange? Yes, thank you for that question. So there are case reports actually in severe MIS-C,  where the myocardial dysfunction is severe that people have done plasma exchange. We came very close to doing it in one of our other patients.  And it depends on what institutional background you have, but if you're a plasma exchange heavy center,  everybody gets it right before, then it's really severe. So yes, there is clearly, people have done it when it's severe.  There's no RCT or any big cohort available to study the efficacy of that, but it's been done in case reports.  And Pooja, like you said, it's also the logistics of just getting plasma exchange arranged. If you're a center that does it a lot,  then you can get it done outside of the normal sort of- Right, exactly. Routine as well. And then also the timing, once you've given somebody IVIG, how soon after giving IVIG  can you actually give them plasma exchange? Otherwise you start extracting all the bound complexes of IVIG. So that's always tricky. Yeah, absolutely.  With great questions, you guys, this was really as enjoyable for me, hopefully as enjoyable it was for you. So.  Well, that was an amazing presentation and amazing discussion. So thank you very much for, that was a whole mouthful of bite-sized learning in a very short period of time.  So I guess before we pivot to Courtney, just for a second, I'd like to explain why we're doing this. I'd like to explain why we tried this little experiment.  So one of the elements of feedback that we collected from the different institution collaborating groups, as we've been asking what we could do better  over the course of the last several weeks has been leveraging different delivery styles to maximize time for discussion. Because I think we all recognize the power  and the value of this group of bright people together on a call, sharing the latest information that we have available on COVID-19 and thinking about how we can translate that  to our practice. So the suggestion came up in terms of using a flipped classroom model. And so that was where I turned to Courtney.  So Courtney was kind enough to collaborate with us to put together a summary on COVID-19 and the cardiovascular complications related to it  for a Mayo CPD presentation that we did last year. And so I thought it would be fantastic to share that presentation with the group and then invite her to come back.  And Courtney, if you don't mind, you had mentioned when we briefly discussed earlier this week, the fact that there were a few updates that were probably worth highlighting.  So maybe I'll just start with anything else that you'd like to mention in terms of updates from that presentation that I'd like to spend most of the rest of the time  just asking questions back and forth and discussing our collective opinions. So with that, I'll pass it over to you, Courtney. Yeah, thank you very much for inviting me today.  And also I've already learned so much because I'm not part of the pediatric world. So that was also very interesting and eyeopening to me as well. So some of the updates,  there's not too many, as everyone on this call knows very well that the information regarding COVID and new data is constantly coming in. I think the biggest update,  probably since I created that presentation has been more information specifically from the histopathology standpoint. There's some more recent studies, one from Dr. Eskar  that was published in European Society of Cardiology not too long ago, about 105 adult patients with COVID-19 who had myocardial biopsies.  And this has been a big question for us from the beginning. Is this direct infection with the virus in the myocardium  or is this some other histopathological process? And there's two studies. That patient, that study had 104 patients and they actually found that SARS-CoV-2 PCR  was only present in five of the 104 cases when they analyzed the myocardium. And that actually the predominant cause of myocardial injury was actually vascular,  increased vascular permeation and obstruction that was occurring in the myocardium. And so that, in addition to a small series  of 15 patients that Dr. Boyce from here at Mayo Clinic published, they had 15 patients that they also performed analysis of their myocardial biopsies  and found that they had non-inclusive fibrin in the small vessels. And so it seems that it's not actually the direct viral infection,  but more just the results of the damage to the vasculature and that prothrombotic or coagulopathy that occurs.  Otherwise, some other major findings in terms of arrhythmias that we're seeing in patients, most commonly it's still atrial fibrillation is the most common arrhythmia encountered  and other than sinus tachycardia in critically ill patients. But we're not seeing significant bradyarrhythmias either.  Those are kind of the two, I think, bigger updates. And if there's any other specific questions that you have, I might be able to add to that as well.  So let's open it up to the group. Questions for the good Dr. Bennett.  I have a question.  Tony Martinez, I can't be on video right now, but can you hear me? Yes, I can. Yeah, so do they develop what size of the vessel? And also, is it a vasculopathy?  Because you said they lay down other,  is it all thrombotic or is it vasculopathy that develops and does it kind of, is it self-limited? I can actually, what I'll try and do here, that's a very good question.  I have some more recent slides that I had creative  that I'll try and show with you. And I'm not a pathologist.  I'll give that disclaimer up front. This is the first study that I mentioned  with the 104 patients. And so it's actually, it's vascular wall damage  leading to the increased permeation in the small arteries, in the myocardium is what they found in this study. And then in the series,  this is a very small series of 15 patients here. These again, were just non-occlusive fibrin microthrombi, again, seen in the small arterioles  and capillaries on histologic examination.  So it seems to be more related to the damage that's occurring in the vessels and then the sequelae from the thrombus and the permeation.  So Courtney, this is Grace Arteaga again. I do have a question. So there was a paper that was published back in a cell, Nature Cell in 2020.  And they were talking about the immunological basis of COVID. And one of the things that got my attention from that paper was that they identified a specific auto antibody  that targets a glycoprotein that usually expressed only in endothelial cells within the artery.  That it's called endoglin. Did you guys hear about that at all? Or have you looked into that?  In full honesty, I have not. It hasn't been something that I've come across looking specifically at in the cardiology literature.  I don't know if anyone else has come across that. I'm interested, but I haven't come across that myself.  In a lot of the stroke literature, there is talk about the endotheliopathy, but not specifically to the antibody that you mentioned, Grace. And these microthrombi,  so the slides that Dr. Ben showed in looking at these microthrombosis, a similar finding. So the same question, is it the actual invasion of the brain  or the brain vasculature by the virus particles themselves, or are they triggering an inflammatory response? Or is it the formation of microthrombi? And in pathology studies,  now we've seen very, very few specimens of actual vital particles have been described, but mostly it's this inflammation and microthrombi.  Abhinav Nath and his group published in NEJM not too long ago about this endotheliopathy and the visualization of the microthrombi in the brain too. So I think that common theme  of microthrombosis of coagulopathy, I think that probably connects different organ systems, particularly the brain and the heart.  Thank you.  I see some questions here in the chat, so I can address those. From Devang, we see any thoughts on RV failure from severe ARDS? We have anecdotally a few patients with RV failure  who have severe ARDS.  How do you perform surveillance for RV failure? This is actually interesting.  Dr. Pellica, just from our echo lab here, just recently did a series analyzing the echo in COVID patients here. And most often, the most common finding  actually was RV cardiomyopathy or RV dysfunction consistently throughout the studies.  And the most predictive metric for following the RV failure was actually RV strain. And so that may be something that we add to our practice.  Actually, we subsequently, we have a COVID protocol for our echo here. And the signal was so strong and so predictive that we now on all COVID patients are performing RV strain  to try and detect earlier RV dysfunction.  What we can do with that information, I mean, it's still supportive care, but it was a predictor for worst prognosis in these patients.  Let's see. Separating bradycardia from redzivir from the association of finding with COVID.  Alex, can you expand on that a little bit for me?  So this is really a question that we argued about earlier on in the pandemic. And it seems like, at least anecdotally, we're seeing it less.  I'm not sure if that's because we're using less remdesivir now than we were before. But I mean, bradycardia is clearly an associated side effect of remdesivir.  And I was just wondering as we've analyzed the arrhythmia data more carefully, if we've been able to tease out that signal, how much of this is the drug  versus potential side effects from COVID? Yeah, that's a good question. Because from the studies that I've looked at  pertaining specifically to the arrhythmias, the bradyarrhythmias have actually been the minority of the cases, including AV blocks or even simply bradycardia.  So I'm not familiar with anything that has actually specifically looked at that drug association in the bradycardia. I'm just familiar with the literature  specifically looking at retrospectively of all the arrhythmias present in patients with COVID.  That's great, thanks.  Other questions from the group? Gautney, any thoughts on long-term thromboprophylaxis post-AFib in COVID-19 patients? Oh, yeah. So specifically for AFib,  because I know this question has also come up just about long-term prophylaxis in general. So what we typically do in our practice, so patients that have AFib  in the setting of any critical illness will typically begin, based on their risk, CHADS2VAS2 risk score, will start systemic anticoagulation.  And then typically we will continue that for three months and then outpatient follow-up, including halter monitoring to help guide the continuation of therapy.  I don't practice outpatient.  My practice is completely in the ICU, but my colleagues that do practice outpatient cardiology are using halter monitoring and a three-month assessment  to guide whether they should continue or discontinue anticoagulation for AFib.  Thank you. And other questions from the group? I'm not seeing other things in the chat. Please feel free to unmute yourself if you have a question.  I see another question from Devang just about POCUS versus SWAN, or POCUS and SWAN. Did you want to elaborate on that a little bit? So, I mean, my question,  thanks, Pratni, for talking about RV strain. My question was, so if you're getting a formal focus echo, what would be the frequency of that? And I'm talking about more so,  our patients are like ECMO and really sick referred patients from outside. So if we are concerned about that, because we found out in some of these patients  that the RV was quite impacted. And like, you know, so if you want to do a surveillance, if you're getting a focused RV, like a strain, how often should we do it?  Should it be formal? Should it just be a bedside POCUS, or could we put a SWAN? I know in ECMO it may be challenging to put a SWAN,  but just some thoughts how to mitigate this challenge so that, you know, sometimes we can do some other interventions to support RV if needed. Yeah, I mean, that's a good question.  I guess it sounds like in terms of to guide therapy, if I'm understanding correctly. I think doing the, specifically doing the RV strain  is challenging, at least on the point of care ultrasounds  that we have here.  I'm not familiar with the kind of handheld devices having the capability of doing strain analysis.  And so, but things that metrics that we could use would be evaluating, you know, the TAP-C for RV function.  And I'm really not honestly sure what the frequency of that would be. It would probably clinically driven. The other consideration for pulmonary artery catheter monitoring,  I mean, that I think would be, if you have a patient that is on ECMO and so severely ill, I do think it would be reasonable place a SWAN  for guiding therapy or monitoring PA pressures.  That is a routine part of our practice here. Most of our patients with ECMO or any mechanical support also have PA catheters for guiding therapy.  Yeah, the only glitch there, like I agree if we have a fem fem cannulation, but when IJ is involved and with the cannulation strategy, putting a SWAN or the library,  like, you know, believing the numbers become a challenge. So that's the only consideration there. Yeah, I mean, from that logistical standpoint,  I mean, left subclavian is also an option  for cannulation as well in terms of just feasibility. But that's just from a logistical standpoint.  I would say that, sorry, I didn't mean to, I would say that I would advocate for the low risk high yield from ECHO.  You know, we, very early in this pandemic, we started to panic and we created a COVID ECHO protocol in terms of actually, you know, covering the device with plastic sheath covers  and we had barriers put up for our sonographers because we didn't know what their risk of getting infected would be. And so we wanted to protect them,  but, you know, as we've learned so much more, we, you know, the risk of healthcare workers with appropriate PPE and standard precautions has been fairly low.  And so we have actually transitioned to going from a thought process where we're only going to do an ECHO on a COVID patient from our ECHO lab standpoint.  This is me wearing my ECHO hat, but we originally were saying, we're gonna do ECHO when we have discussed this with the team and it's actually gonna make a huge,  you know, change in management plans rather than doing them for surveillance. But now that we have more information and it's safe to do,  and none of our sonographers have actually contracted COVID in the workplace from scanning COVID patients. I would advocate for, you know, frequent,  maybe not frequent, but routine monitoring to help guide therapy. If you aren't able to do that with PA catheter, you can get a lot of information from ECHO and it's safe to do.  So low risk, high reward from doing the point of care ECHO or even limited trans-thoracic echocardiogram.  Thank you.  All right, we're running out of time. And I know that Dr. Bennett has a hard stop at two o'clock. Any last alibi questions? Otherwise I'm gonna take over  and just talk a few minutes about the learning community and what we have lined up for next week. Thank you.

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Infection, Crisis Management, Pediatrics, 2021

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"Update on research and evidence in multisystem inflammatory syndrome in children. This is SCCM curated COVID-19 microlearning content. Pooja Nawathe, MD, FAAP, FCCM, CHSE-A, CHSOS The Structured Team-based Optimal Patient-Centered Care for Virus COVID-19 (STOP-VIRUS) collaborative is a limited-time network of intensive care units focused on improving outcomes for patients with COVID-19. This presentation was given during a STOP-VIRUS ICU Learning Collaborative Community Session. Learn more about STOP-VIRUS at sccm.org/stopvirus. This educational activity was funded in part by a cooperative agreement with the Centers for Disease Control and Prevention (grant number 1 NU50CK000566-01-00). The Centers for Disease Control and Prevention is an agency within the Department of Health and Human Services (HHS). Its contents do not necessarily represent the policy of CDC or HHS, and should not be considered an endorsement by the Federal Government."

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Content Type Presentation

Knowledge Area Infection

Knowledge Area Crisis Management

Knowledge Area Pediatrics

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Tag COVID-19

Tag Pediatrics

Year 2021

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