Cardiologist Clifton Watt, MD, explores what’s now known about the SARS-CoV-2 variants as well as COVID-related multisystem inflammatory disorders, explains COVID’s potential for residual effects on the heart, and offers help with identifying COVID “long haulers.” Bonus: update on outpatient therapeutics.
I today? I'm planning to talk a little bit about cardiology updates in Cove in 19. I do understand that all of us have gotten a lot of information about Kobe 19 because, you know, the literature and the evidence base is very dynamic. Um, so I am by no means an expert in the field, of course. But certainly I can provide some some of my cardiology slant. And hopefully it's the talk. Today is going to be practical and, you know, incorporate some pretty, pretty recent developments in cardiology and Kobe 19. So I'll go ahead and get started. Okay, great. So I have no relevant disclosures for this talk. Eso I'm I'm just going to go over some of the learning objectives here. I think one of the topics that we are hearing a lot about is the new variants of the stars. Kobe to virus. So, um, even though it's not a cardiology topic per se, I'll give a given update because I think it's very relevant. Thio, you know what's going on in current events? Um ah, one topic that was also recommended for me to go over his multi system inflammatory disorders in Covina 19, Um, and another third topic, I'll go over very briefly is, um, Kobe. 19 outpatient therapeutics, specifically the outpatient treatments that are you? A. And then finally, we'll talk a little bit about the chronic cove in 19 syndrome or, as it's been termed, in the media, the long haulers. Um, so there's not a lot of information about that, but certainly I can talk a little bit about that. Eso just first as an introduction. I know we've all heard about stars Kobe, too, and the cardiac manifestations. But I'll just go over these very briefly, Um, just as an introduction. So So we know that, you know, stars Kobe to can affect many different organ systems, including the heart. And so what? We don't know exactly the path a physiology off stars Kobe to on the heart. But some speculation is that there certainly is a direct myocardial injury that we see when the virus actually enters the mile cardio self, either through fusion of the membrane or through endo psychosis. Um, so that's that's one way we've actually seen that the virus can actually cause injury to the cardiac Maya site. Um, there clearly is lots of data coming in about how, uh, SARS Kobe to can cause a side, a kind storm and inflammatory sort of milieu and that can cause, you know, inflammatory effects on multiple organ systems, including the heart in another, Certainly in another model of myocardial injury is demand ischemia from, you know, uh, illnesses such as a RBS acute respiratory distress syndrome, respiratory failure, leading toe hypoxia and and myocardial injury. Indirectly, uh, this is a flow chart or algorithm from the American College of Cardiology website. Um, this is I know it's a busy slide. I don't mean for you to, like, take a look at each box, but certainly just to show that in general, viral infections here at the top can cause many different. Well, at least it's proposed that our own fiction infections can cause multiple different pathways of injury to the heart anywhere from as well. I mentioned, you know, direct, um, injury to the heart to vascular injury to micro thrown by two vascular hyper coagulate bility to inflammation to increase sympathetic stimulation. So and then ultimately, what we see as clinicians is, you know, increased risk for heart failure, myocardial infarction and arrhythmia. and coded 19 or stars. Kobe to is no different. So that was a little bit of an introduction. Now, kind of moving on to Mawr mawr. Some newer topics and these were the new variants that we've that we've heard about in the news. Um, so I actually recently heard, uh, one of the epidemiologists from U. C. Berkeley. Um, talk about how naturally viruses, um, you tend to mutate at least several times a month. So it's not surprising to this epidemiologist, and, you know, us in general, that SARS Kobe to has, um, variants and mutations s. So this is something obviously, that the lots lots in the scientific community are paying close attention to. So this variant and there's a lot of different ways of, apparently of naming these viruses. And obviously this is not a virology. Talk about, um, this variant, which I've seen named as b 0.1 dot 1.7. This is the variant. That's probably one of the making the news. We hear it as the UK variant, um, the one that has kind of taken taking a stronghold in the United Kingdom. Andi has gone into the United States and I'll show you. So this variant was first identified in the UK in September. Um, it has a serious of mutations. Again. This is not a virology talk, but I just put this slide up to show you that there are about, you know, 20 mutations in this particular variant, at least on a point. Some of them out on DSO. You know, it was you know, these this variant definitely, you know, started to come into play. You know, last month in December. Now it's in 36 countries, including the United States. As of the writing of this, uh, this talk, Andi, as of a few days ago, Um, I'm sorry that it shouldn't be eight. It's 88 cases identified in the United States across 10 different states. Um, and so what? What is relevant for the virologist, Aziz? Well, is that this variant has multiple mutations in the spike protein that s being the spike protein, which is the main way that the virus binds to the receptor of the cell. Um, and that's how it gets into the cell. And there's this deletion called the 69 slash 70 delusion. Um and and that's one of the mutations and these mutations in the spike protein potentially affect the confirmation of the receptor binding domain and may increase theme transmissibility of the virus. And that's why it's getting a lot of news. Andi, this news or sorry, this data this, um, evidence of increased transmissibility comes from the UK contact tracing data from a few months ago showing that the infectivity rate for this variant was 14.7% Um, compared with 11% of the wild type or the original. Um, sorry. Is Kobe to virus? True. So this is a map of how be this variant 117 has spread across the United States. And, you know, you can see this is a map from the CDC. I think data from a few days ago. The states in blue are the states where this variant has been identified. Um, and in California, a zoo of the writing of this talk, there have been 40 cases. Most of them have been in Southern California. Okay, so this, um, this is actually an interesting, um, slide of a model from the CDC again from the CDC. So let me explain. Um, so the CDC has put together models off the this strain as well as all other variants of SARS. Cov too. And this thes models look at, you know, going forward in time. How many cases will be present in the United States moving forward in time and so you can see in this slide on the left? Um, this is again, this is a model thing. This is modeling. And so this is assuming a reproductive number of 1.1 are not of 1.1 a z. We know, you know, um, are not of 1.0 means that, you know, it's a virus transmitted transmissibility is neither. You know, you know, it's basically a 1 to 1 transmission. Um, whereas less than one or not is a transmission that's decreasing, Andi greater than one. This is increasing in scope. And so, assuming on the left side, assuming are not of 1.1. And this is also assuming that no vaccine, we're not assuming any, um, you know, assuming that there is no impact of the vaccine on DSO, you can see that this dark purple bar represents the current stars Kobe two variants and then the lighter purple bar or curve represents the UK variant, if you will. Andi, you can see over time that, you know, at around Middlemarch Onda March you can see how the UK variant or the B 117 variant kind of overtakes all the other variants in the United States. Um, and you can see so that's on the left. And you can see similar, um, curves on the right, except for the only difference is that are not is 0.9, and so that is reflected in the the you know, the shape of the curves. But you still see that, um, the B 117 variant will be the predominant variant in the United States around with mid or late March. And so that Z you know where the thing is, the data where the, you know the CDC is you know, saying Dr Fauci from the H is saying that things new variant will probably be the you know, the new new major variants around March. April. This is this is the day that the modeling data where he's getting this from, um, now this is the same model, um, except with vaccine in place and I include this for a reason. Eso again are not at 1.1 on the left. Um, you can see still, you can see still, you know that be 117 variant will still overtake all the other variants United States around mid late march. But you can. The shapes of the curves are flatter if you will. Um, but the key, you know, you know, we would love to see this. This graph on the right side, where you have an are not of 0.9 and the modeling is taking into account vaccine vaccination. And you could see how, even though you know, the new variant, um, still, you know, becomes the most prevalent one in April, March, April. You know, you can see how flat these curves are, so it's it's so important. This is why you know, we are emphasizing her patients. Andi, Essentially everyone thio get vaccinated if if if possible, whenever it's available. Because it really will affect, um the you know, these curves and Aziz we've heard and I didn't mention this yet in the bullet points, but we don't have any evidence to believe that the this variant will not be affected by the vaccination just due to, you know, different epic tops. Um, with the vaccination. So we think that the vaccine will still be effective, effective against this this period. Eso a little bit about the other stars. Kobe Two variants. Um, so this one of the B 151 variant. So I think I've read, um that this is called the South Africa variant. You know, even though we try not toe, you know, name them as as from their country of origin, so to speak. The B 13 51 variant was first detected in South Africa in October. Um, we don't have any data to show that this this variant is mawr, uh, causes more severe disease. However, it does have a mutation. Um, in terms of the 484 k, that does potentially reduce the binding potential of antibodies targeting targeting the receptor binding domain. And this this is from, you know, X view. Oh, studies of patients who you have this variant basically blood samples taken out of coated patients and looking at antibody studies on on on those samples. Another variant that's making the headlines is this you know, be 11 28 or p one variant. I've seen this, as you know, variant from Brazil. I've seen that described that way. It was first detected, um, in four travelers from Brazil who had entered the jab in an airport in Japan, Tokyo, Japan, during a routine screen. This was also a few months ago. This variant also has the e 484 k mutation, which potentially could affect again could affect, um, the binding of antibodies. And so we certainly do not know about the vaccine for either this variant or the B 1351 variant. We don't know how these variants will, um, respond with the vaccination, but there is concern because of because of the mutation. In addition, um, what we've seen with the Brazil variant, if you will, is that we've seen well early on that Brazil had a very high prevalence of Kobe 19 infection. Um, and more recently we've seen a surge and hot Moreover, high rates of reinfection in Brazil on board folks are thinking the virologists are thinking that this may be because this variant can lead to re infection because it could potentially have an impact on on neutralizing antibodies, basically making them ineffective or less less defective. So there's obviously concern with these two variants. At this point in time, we have not detected either of these variants in the United States. Okay, now, this is actually very, very recent. This variant, the l 45 to our variant this I think this article was from over the weekend. Um um you know, obviously there are, you know, these sometimes the news headlines. They're a little bit dramatic, but but you can see how, um, this variant is actually a variant that was first discovered in California, Um, in the United States. Andi. Actually, I don't know if some of us have heard about the, um, you know, one of the local hospitals. I won't. It's listed. It's written down here. But one of the local hospitals did have an outbreak Where there was a person, um, dressed during Christmas as a costume in an air inflated costume, and that was thought lead to multiple infections. I think close to 100 infections, I believe. And that that actual outbreak was this particular variant. Um, so in December of 2020 this variant was s O. Obviously, UCSF has been doing lots of sequencing of variants, um, in their in their stars. Kobe. Two cases. And in December, this variant was detected in 3.8% of samples. But by January, by this month, this variant was detected in a little over 25% of samples. So this this prevalence, we believe that this variant is increasing. We don't We don't know too much about this variant yet about its transmissibility or or severity of disease. So more to come. Okay, so now I'll just bring up a case. This is a case that was not, um, not my patient, but it was actually from a case report published in the Journal of the American College of Cardiology. So Oh, i'll go over this one. Eso switching, switching gears. This was a 15 year old a teenager who presented female teenager who presented to the emergency room, um, in Southern California with fevers, malaise, abdominal pain and diarrhea. Eso in. I'm sorry I didn't mention this was around. I think may march or April of 2020. Um, s O. Obviously coded 19 was definitely a big issue then. And so in the emergency room patients. T max was 38.7 degrees Celsius. Her abnormal examine her Chest X ray were benign. Um, And what what was done was in the emergency room, They discharged her with you, or I risk Pretoria. Viral infection. Um, she was, you know, she was tactic Arctic, but well, otherwise, well appearing. And so they discharged her. But, you know, before they discharged her, they did a SARS Kobe to PCR, which did turn out to be negative. However, the patient or the teenager returned to the emergency room three days later because she had continued to have fever. And then she developed. You know, uh, you know, these I findings that she saw in the mirror, and then she also noticed a rash on both of her homes. Um, in the emergency room that day, her white count was a little over 11,000. Her s r and her AARP were both elevated. Aziz, you see here. So this is a picture from that article of this this particular patient of her palm. Um So you can see this, um on her palm. You can see this, you know, Arafeh Metis, you know, you know, to regularly shaped rash here, Andi, I would say polymorphous, you know, different. You know, this. This may be some central clearing here, but here's here's different areas of rash on her palm. So based on her fever, her rash, um, as well as her inflammatory markers and the fact that you know she, you know, she had a mild Luke, Luke. Oh, psychosis. But no, no other. Um, you know, evidence of infection. Um, she was diagnosed with presumed multi system inflammatory syndrome in Children or abbreviated as m. I s Dash C. Um And so at that point, she was transferred to a local pediatric hospital. She was given I, V i, g and aspirin. She did get a SARS Kobe to a I G. That turned out to be positive. And eventually, during your hospitalization, she had an echocardiogram that showed a mild a delegation of her left main coronary artery. Um, a repeat echo three days later showed slight worsening of this delegation of her left main coronary, as well as a newly identified right coronary artery aneurysm or civilization of her right coronary artery. And so, at that point in time after she had been given i V i g as well as aspirin. She was then started on a prednisone taper and eventually discharged. And at that point in time, the team had seen that her inflammatory markers had been improving and she was clinically improving as well. Come eso eso. This was a case report One of the earlier case reports of multi system and fun toys syndrome in Children or m i S C. And this is a topic, um, that I don't I don't know if we see Children, but this is certainly a topic that has been, you know, reported Not too, and frequently, even though we know that disease Kobe 19 disease in Children, you know, maybe less virulent. You know, sometimes patients do have this inflammatory storm or side of kind of storm. That can be very you know, very uh uh can can cause increased morbidity mortality eso thio just to go over the definition. And this this definition is from the C. D. C. As well as the I think it's the American College of Rheumatology. Um, defining M I s C. As an individual less than younger than 21 years old, with and they have to have all three of the following. They have to have a fever greater than 38 degrees Celsius for at least 24 hours or a subjective fever for greater than 24 hours on dso. That's 12 is they have to have evidence of abnormal inflammatory markers. Way already went over some of them C r p e s saw vibrant age and fair written V dime er. A lot of these, of course, are very non specific. Um, but, you know, certainly they can be used for for assessment of general inflammation. L D h elevated neutrophils reduced lymphocytes on low albumin. And then finally, the third piece of the definition is is multi organ at least two organ system involvement. So, um, this patient had Dermot a logic, involvement and cardiac involvement. But of course, we see you know, this inflammatory syndrome, you know, in the lungs a r d s, you know, we can see kidney injury way obviously could see him. Ato Logic evidence of inflammation. Um gmg I and even neurologic involvement. Um, you definitely have to have no alternative, plausible, plausible diagnoses, you know? So you have to rule out a bacterial infection, you have to rule out of P E. You have to rule out, you know, all other alternative, um, diagnoses. And then finally, um, part of the definition is patient has toe have been positive for, ah, current or recent stars Kobe to infection, or at least an exposure to a case of Kobe, Kobe 19 within four weeks prior to onset of symptoms. And I'll show you part of what we've seen with my SC is that, you know, we can see presentation this presentation, you know, weeks or, you know, even over over a month after the acute initial infection. Um, and s Oh, this is this is what I'll show you in a subsequent slide is that we've seen a delay. You know, compared to the initial co bid, uh, 19 acute infection of the SC, this inflammatory storm Uhh. And so in these patients, you know, given, you know, obviously this is a cardiac cardiology talk. You know, their cardiac manifestations are certainly very frequent. So, you know, these patients typically do get, you know, e k g echo, troponin, bnp, and sometimes even an m r. I, uh, cardiac m r i. This is a slide from the C d. C. A graphic, if you will showing some data off M I s C cases from March to May of 2020. Andi, uh, you can see. You know, first a Z I alluded to earlier You can see in this, um, sort of lower left panel. Um, this is a graph of Kobe Kobe, 19 cases as well as M I s C cases over. You know, during the period of march, Thio May you could see this. This green line being the cove, it numbers. Um uh, in I'm sorry. And these air in pediatric pediatric population, you could see how, during this period of time, you could see this peak of covert infection around April, and then this started to come down. But then, on the other hand, you could see these dark green bars, vertical bars being the M I S C cases. They they actually peaked. Um, you know, well, well, after the peak of Kobe, 19 cases again alluding to the fact that M I s C tends to be, you know, a post infectious, you know, inflammatory syndrome that can manifest you know, weeks later, Um, there was a a male predominance Seen, um, here. You could see. You know, m I s c um, in illness all the way up. You know, you know, from from toddlers all the way up to teenagers. Um, and and we'll soon see an adult's. I'll bring that up. I mean it there. It seems to affect all ethnicities fairly equally. Um, but also, what I'll bring up is on the lower right. A z I mentioned. You know, cardio cardiac manifestations are quite frequent in M I s c. So you can see you know, in this a study of these patients, um um you know, 55% of thes m I s C patients had ejection fractions on on echocardiogram of less than 30%. Andi, actually, 40 Looks like 48% of them needed Veysel pressers support. And we're quite ill. And then 4% of them required ECMO. So So this is not certainly not a benign, uh, disease. What eso now you know, certainly, uh, m I s c um is an inflammatory syndrome that can be, um, can that can affect multiple different organ systems. Um, it has some overlap overlap that we've seen with Kawasaki's disease, which, which I'll talk about because, you know, this certainly is relevant to us in cardiology. Andi, you could see here on the right. Uh, it's relevant because of the prevalence of coronary artery aneurysms. Eso these air thes air. You know, this is the right coronary artery with, you know, clearly you could tell very abnormal, you know, fuse of form, vilification of the right coronary air here on the top and the left, main and left, anterior descending coronary artery here eso a little bit of to compare the that these two syndromes, if you will so on. Abbreviating Kawasaki's disease is K d. Kawasaki's disease. You know, we know this as a systemic vasculitis, typically affecting the small and medium sized arteries, most notably the coronary arteries. We don't know the path of e guess. I guess the pathogenesis of this, but potentially it could be related to an initial infectious insult. Um, the diagnosis of Kawasaki's disease does require persistent fever and four of the five following for the following five criteria, Not just a review. So, uh, conductive itis Orel Fangio Because membrane changes cervical in fan apathy. We typically see extremity changes like Palmer or soul exclamation skin changes. Onda polymorphous rash. Andi, That's actually what I thought about when I saw the this sort of the palm's of our case report patient, um, another classic finding his strawberry tongue where, you know, the tongue is cracked and red and inflamed. I mean, so why I'm bringing Kawasaki's disease up is that there is some overlap, as you could tell, between M i S e and Katie. So, um, but there also are some differences. So Kawasaki's disease does typically affect, um, or more often affect Children of Asian descent. Whereas M I see, as I showed, tried to show you affect Children of multiple different racial backgrounds. Um, my Children with my SC typically are older, um, patients with Kawasaki's disease, you know, on average, are younger than four years old. Um, less than half of Children with them, and I see do exhibit, um, you know, do kind of fit this diagnoses diagnostic criteria for for Kawasaki's disease. Um, and Children with them, I see, tend to have high rates of cardiac involvement. Um, I've seen, you know, I think rates of as high as 30% of of coronary artery aneurysms. Yeah, okay, s So that was a little bit about ah little comparison of Kawasaki's and my C in terms of treatment. Well, obviously we don't. You know, this is a fairly data free zone. We don't we don't. We don't have a lot of data in terms of treatment. But what we do is, we've, you know, taken the our treatments of Kawasaki's disease and kind of empirically used it for M I s e so the You know, the first thing we way, you know, do is think about supportive treatment. So I v fluids patient, you know, is way feel like needs resuscitation. Um, you know, blood pressure monitoring, heart rate monitoring and basil. Presser of support if necessary. Yeah, s o I v i g. And this patient case report patient didn't receive this. Um, I've i g has been shown in research to prevent the developer lower the risk of development of coronary artery aneurysms in Kawasaki's disease. And so this is something that's in this CDC and the American College of Rheumatology literature in terms of treatment for M sc. So you to use I d i g um, Aspirin is something that's typically used as an anti inflammatory for Kawasaki's and also m I s e um, there is language in the American College of Rheumatology literature about using cortical steroids, either moderate dose or high dose corticosteroids for patients who are resistant to i v i g So e there they're getting They've got an I D i G but they're you know, they're clinical course is worsening. You know, that's where steroids potentially can come in. Andi, actually, uh, this is a agent that is also in the rheumatology literature as a gentle recommendation in aisle one antagonist called Anakin Ra, which is used in patients who, you know, have evidence of cytokine storm. Um, you know, macrophage activation syndrome, you know, doing very poorly. Despite I v i g and steroids, you know, there is some literature about I should say there's some language in the American College of Rheumatology about using Anakin ra um, an Aisle six antagonist, um, has been studied. Actually, I've seen this literature in in the Chinese literature when they were treating, um, these inflammatory syndromes with total is a mob in aisle six, antagonistic that's not typically recommended by, um, um, experts in the United States, but it has been used in in China. Onda. Finally, anti coagulation is a big topic. You know, we know that thes patients probably are at higher risk of thrombosis. Certainly they if they're hospitalized, they should be on, um, pharmacologic, um, anti coagulation. I should say prophylactic pharmacologic, antic regulation. Um, even if they certainly, if they haven't had a diagnosis of promised, they should be on prophylaxis. And, you know, I've actually seen some, uh, providers actually put these patients on therapeutic anti coagulation empirically so that there's I don't I haven't seen any data for that. But certainly this is, as I said, a data free. So Okay, so that was a lot about kids. And, you know, I I'll bring up the adults because we'll probably most of us take care of more of it. More adults than Children. Um, but there's a lot applies, I believe to the adults. Compared to Children, there's just less data on the adults. I'm not sure the reason for that, but but, you know, this is from the CDC. A report direct from their website from October um, you know, writing up a case Siris of multi system inflammatory syndromes. And adults associate with Kobe. 19 infection. So this was again, this was from October. And this case, Siri's brought up 27 patients. Um, and, you know, I thought that was, you know, very, very small number, even even as recent as October. And I'm sure there's there's more patients than that. But in any case, you know these patients, um um, were diagnosed with this multi system inflammatory syndrome, they were greater than 21 years of age and really the diagnosis. Uh, sorry. The diagnostic criteria, um, are the same. You know, they have toe have inflammatory markers. They have to have fever, and they have toe. Have, you know, a recent, um, or recently positive stars Kobe to testing within the prior 12 weeks without alternative diagnosis? S o. I would There's actually not a lot of data or recommendation. Um, about these patients, these m i s a patient's, but, you know, I would suspect that, uh, you know, in terms of treatment, you're you're looking at the same type of diagnostics and treatments. Aziz, you were with the Children. Eso We'll learn more about these patients. Um, it's 5. 14. I'll go over this next series of slides fairly quickly for the sake of time. This I'm switching years now and talking a little bit about, ah, persistent cardiovascular effects of Kobe 19 after recovery. And so way know about patients with persistent symptoms. Um, you know, including chest pain, shortness of breath. You know, what do we know about how? What the residual effects of the infection are on the heart? And this There was a study of German study looking at that. So this was a observation ULS study of 100 patients from the hospital system in Germany who were positive fork over 19. Um, And for the study, they were eligible after a minimum of two weeks after their original diagnosis. If they no longer had symptoms and we're isolated. Andi recovered and subsequently had a negative repeat PCR test eso out of these 100 patients, 67 of them recovered at home. So you know, you know, outpatients. Um, certainly not. The 67 probably didn't have severe infection, but, you know, for the study for the purpose of the study, they all underwent cardiac memory and high sensitivity troponin t and both healthy controls and respect. Her match controls were used. Okay, so, um, in terms of results, you know what? What they found was that the mean duration between the positive of it 19 test and the memory was 71 days. So so over two months, eso to give you an idea, you know, that's you would you know, when I see that number of 71 days, I think, Gosh, I mean, that's well out from their initial cardiac Sorry Koven test. You know the patient, typically, you would imagine, would have recovered clinically by them. But what they found also was that the high sensitivity troponin t was elevated in 71% of these 100 patients and significantly elevated 5% of these patients. Um, and moreover, out of these 100 patients, 78 of them had abnormal cardiac Ameri findings, and this included a decrease in their left ventricular ejection fraction and increase in their left ventricular size or volume. And there are for the radiologist in the room. There are, you know, these, um um factors or metrics that we look at on cardiac m R I, t one t two and l g, which stands for late Carolinian Enhancement t one and T two. Just to keep it brief. Can suggest myocardial for fibrosis or Dema um, injury to the to the my cardio and LG can suggest a scar scar of the my cardio. So you could see that, you know, a very large proportion. Almost 80% of these patients had abnormal cardiac Marie findings, you know, you know, well, out in recovery phase. So So the we're still learning more about this, But these findings do suggest that there may be ongoing cardiac involvement even after a recovery of the clinical acute clinical infection. Um, I will skip over this for the sake of time. Just it's just data from that study. Um, okay, we're second. The last topic, I think, Um, now I'll talk a little bit about outpatient. Kobe 19 therapeutics on. I thought this was important or relevant because, you know, we all see outpatients, and, you know, sometimes we do have a patient that has Kobe 19, and and this is something that we think about. What do we do for these patients who don't have severe infection don't need to be hospitalized, but we're trying to minimize their risk of being hospitalized. Eso There are two treatments that are so I should say there are no FDA approved treatments for outpatient therapy for Kobe. 19. However, these are there to, um, emergency use authorization treatments. Um, so that means they're not approved, but they can be certainly considered under and have been considered for emergency use while the investigational studies are ongoing. So this first, uh, drug is called bam land in a band land near the mob, which is a monoclonal antibody that binds to the receptor binding domain of despite protein of SARS. Cov too. And potentially it can Brock block the despite proteins attachment to the human ace two receptor, which is how the the virus binds to the self. Um, eso it was granted emergency use authorization on November 9, a z we know and I think this language is fairly important is recommended or granted you a for treatment of recently diagnosed mild to moderate cove in 19 infection in patients who are greater than 12 years old. Way at least 40. I'm sorry. That's 40 kg, not 40 years old. way at least 40 kg and are at high risk for progressing to severe disease or hospitalization and so high risk, you know. What does that mean? Um, that, you know, there's I won't go through too much detail. You can look at the the the F D. A. Website thio obtain this information but high risk. You know, patients who are have a higher B m I. They have ckd. They have diabetes there, even suppressed. And, you know they're greater than 65 years are of age or older and other other high risk, um, features again. I don't I won't bore you. But you know some of these your patients greater than 55 years old and have cardiovascular disease, hypertension or COPD s O. This is a lot of patients. Um and I'm sure we have patients like this. So this is something that you know? Certainly. I just wanted to make the audience aware of if if we're not already that there there are these monoclonal antibodies out, um, and so very briefly to go over the data that this you way was based on this'll was based on a non going face to trialing called the blaze one trial, looking at 452 patients again outpatients Onley mild to moderate disease. And they were randomized to one of three investigational investigational drug doses or placebo. And the primary endpoint was a decrease in the viral load from baseline. And you know, there was one dose the middle dose, where the decrease in viral load was significantly different but not in the other two doses. However, you know, what was observed was that most patients, including the placebo recipients, had already cleared the virus by Day 11, which was when the viral load was looked at. I think what the you know the way was really more based on was the secondary in point, which was the rate of hospitalization, um, or er, visits by day 21 day 29. And so in the antibody recipients, that rate was 1.6% versus 6.3% in the placebo. Um, and so you know, that's that's the data that the CEO way was based on. There is another trial called the Active three Trial, which is evaluating investigational treatments and hospitalized Kobe, 19 patients, and this trial stopped random izing patients to treatment with Band Land near the mob because there was lack of efficacy. So again, just to clarify this monoclonal antibody treatment is not for hospitalized patients. It's on Lee for outpatients. At this point in time, just as an f y I. It's given as an i V infusion over 60 minutes. And patients need to be monitored for at least an hour after the infusion because there have been And if lactic reactions reported, um, just as a Masai it you know, I did have I have had a patient who did receive this family and neighbor Mab monoclonal antibody treatment. Um, and you know, he received it several days after his initial diagnosis. He received it in a I believe in infectious disease clinic locally, and he said that he felt symptomatically better afterwards for what it's worth. So, you know there are clinics that are administering thinness. Um, I'll go over this very briefly. These this combination of monoclonal antibody, Cassa Rhythm AB and dip in Devon Mob also are very similar, um, to the other monoclonal antibody in that they also affect the spike protein. Also granted the EU A in November. Um also based on the EU A was based on phase one and Phase two clinical trial data. Um showing that there was a decrease in viral load, um compared to placebo in the experimental group as well as the decrease in the proportion of medically attended visits within 28 days of treatment, 2.8% versus 6.5%. So this is also a treatment that has e way by the FDA. Alright. Eso were at 5 25 almost done here. So second case, this is actually a patient of mine eso this waas 33 33 year old female who was referred to my clinic for chest pain. So in March of last year, she developed cough, sore throat, shortness of breath, subjective fever in my al just her partner actually had similar symptoms. Evernote She did say that she had had some contacts from friends from Japan prior to developing symptoms. So she went at that time she went to the urgent care and she did have a SARS could be two PCR that was negative. She was diagnosed with a wry Andi then subsequently many of her symptoms did improve on their own eso it. Fevers, biologist cough and sore throat did improve. However, afterwards, she did continue to have intermittent chest discomfort and shortness of breath. She went to see her primary care provider. Um, she waas uh, pericarditis was Was then suspected. Essentially you are. I related pericarditis. The patient was then put on high dose ibuprofen, but that did not improve her symptoms. She at that point she was then referred to me eso this patient was again a 33 year old female. She did have ah remote history of an intracranial a b m and had a craniotomy for that in the past she took she was taking a limo. Tra jean nickel for seizures In terms of social history, she had previously worked in the Obama administration. She doesn't do any. She didn't have any bad habits. Eso this when she came to my clinic, this was her e k g. Which a zoo we can see really looks fairly benign. You see some a little bit of a Sinus arrhythmia, but no SD changes. No PR, no clear PR depressions. S t segments really look quite normal. You might you might notice a little bit of S T elevation diffuse Lee, but it's very slight on DNA. Not sure if that's related to the baseline. Wander. Um, s o I ultimately did have her undergoing echocardiogram. This is not a moving image, but I just took a snapshot of it, uh, on. But suffice it to say, her left, um left ventricular and right ventricle sizes were normal, and her function l B and R B function was normal. Basically, it was a normal echocardiogram. She continued to have symptoms, and, you know, I did. Then eventually send her for cardiac Emery. Um, and essentially, eso go very briefly on this, But this is the short access off the left ventricle here. The right ventricle here. Anterior to this. This is sort of ah, short access view. Um, cutting trans verse. Onda, Uh, basically, there was no evidence of any late Catalonian enhancement. Um, you know, the function was normal. This was a normal cardiac emery that she had. Okay, so she you know, again she continued to have Internet and chest discomfort. Um, you know, she winter primary care who ordered a antibody stars Kobe to serology for her. I g was negative, but then she you know? Yeah. She continued to have a waxing waning symptoms of chest pain. And moreover, she did note that her heart rate periodically would go to the as high as the 100 fifties. After just a short period of walking up a slight hill. Before this illness, she was regularly, physically active, exercising, and so she thought that this was a very abnormal finding her her this technique cardio response. She also noted that her resting heart rate was in the eighties during this period time, whereas before her illness, it was typically in the sixties. Eso this is, you know, I I use this case as a segue into this topic called Cove in 19 long haulers. And, uh, some of us may have encountered these types of patients, you know, these is chronic, you know, it's turned chronic Kogan 19 or post viral, um, you know, syndrome, um, in these patients where they continue to have symptoms long after recovery of their acute infection. Um, it's in. It's really unclear what this is from way. Really? Don't know. You know, I'm reading articles just from a few days ago, you know, postulating whether this is Is this related to a direct effect of the virus that is long lasting, even though the patient is potentially no longer contagious? Is it an autoimmune response that's persistent? Um, way Don't know. Um, but what we What I have read is that it's not clearly related to the severity of the initial Kobe 19 infection. So I have read there's there was this JAMA article from from Recent talking about how this patient who had Kobe 19, had very mild symptoms. Um, but then you know her. She continued to have symptoms that lasted and continue. Thio persist to this day, Um, even though her initial infection was very mild, I've heard, um, you know, symptoms described as brain fog fatigue. Um, chest, chest pain and shortness of breath certainly are very common. Um, you know, I mentioned in my patient tachycardia. And actually, even autonomic dysfunction has been postulated as as a as a component of this illness. Um, you know, patients. Um, with prior infections, for example, the SARS infection or the mirrors infection, you know, have been have been known toe have post viral infections that were grouped into this category called, you know, my al GIC and self LaMotte encephalomyelitis slash chronic fatigue. Chronic fatigue syndrome was a mouthful. Um, and so, you know, this is currently being studied thes chronic fatigue. You know, my al GIC, uh, and Cephalon myelitis patients where Potentially, you know, this can have an effect on the central nervous system and automatic, uh, system. Um, and so what? What? All I'm close to ending on is that, you know, we know about these staggering numbers of the cove in 19 infections. But, you know, we really don't know what the long term toll on the health care system will be with respect to these long haulers these patients on did. It may be really tremendous is what I'm worried about.