Mayo Clinic and other experts discuss the latest information on the impact of SARS-CoV-2 variants, vaccine and treatment updates, and implications for long-haulers.
Moderator: Claudia R. Libertin, M.D., consultant, Division of Infectious Diseases; professor of medicine
Featured expert: Isabel C. Mira-Avendano, M.D., associate professor of medicine, divisions of Critical Care, Pulmonary and Sleep, The University of Texas Health Science Center at Houston-McGovern Medical School; director, Post-COVID Center of Excellence; co-director, Interstitial Lung Disease Center, UT Health
Abinash Virk, M.D., consultant, Division of Infectious Diseases; professor of medicine
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The views and perspectives shared in these resources are presented based on information available at the time of recording.
All right. Welcome on behalf of the Mayo Clinic School of continuous professional development. I would like to welcome you to Mayo Clinic's Covid 19 live webinar series. I'm dr William palmer, Associate Dean of the school and your host for today's webinar entitled updates on Covid 19 variants of concern vaccines and long haulers. This webinar is accredited for one a.m. a p R a. Category one credit and a record of attendance will be provided for all other health care professionals. This webinar is supported by an educational grant from Fizer. Here are the associated disclosures for this activity before we get started. I'll cover a few points. The first is how to claim credit. If you'd like to claim credit after the webinar please visit ce dot mayo dot e d u forward slash covid 0111. You'll need to log into the site and if this is your first time visiting, you'll need to create an account profile after you've done this and logged in, you will be able to access the course, complete a short evaluation and then you'll have the ability to download or save your certificate. This link will be dropped into the chat box throughout today's webinar. The second item is how will be facilitating questions, you'll see at the bottom of the screen, the chat and Q and a functions. If you have any questions during today's webinar for our presenters. It's important that you dropped them into the Q and A channel. There's also a helpful up vote button so be sure about the questions that you would like to see answered here are today's learning objectives which will be covered throughout the webinar review variants of concern in the U. S. And globally including omicron, compare the delta and omicron variants and transmissibility infectivity and clinical manifestations. Update the effectiveness of the Covid vaccines against omicron variant review prevalence clinical presentation and distinguished characteristics of long haulers of covid and update the management of long term complications of covid. With that I'd like to introduce today's moderator, our own dr claudia libertine. Dr libertine is an infectious disease specialist, certified certified physician executive and licensed professional coach as professor of medicine with over 100 peer reviewed publications. She has led the covid service and multiple clinical research trials at Mayo clinic in florida. She graduated from the University of Toledo Medical School and completed Internal Medicine infectious disease and medical microbiology training at Mayo clinic in Rochester. So with that I'd like to turn things over to dr libertine to introduce today's panelists. Claudia. Thank you dr palmer and thank you everybody for being with us today on this webinar. We at Mayo clinic first want to extend our gratitude to you for the care and dedication that you render to our patients and colleagues on a daily basis. We have fantastic presentations from two of my highly respected colleagues. The first um session will be by dr Isabel Mira who completed medical school in Colombia where she completed an internal medicine residency program at the University of Antakya. After moving to the United States, she completed a second internal medicine residency program at university hospitals at Case Western Reserve University in Cleveland Ohio. A pulmonary and critical care fellowship followed which she completed at the Cleveland clinic in Ohio. She then became one of our colleagues here as a consultant at Mayo clinic florida from 2012 to 2020 where she was co director of the pulmonary rheumatology clinic and created our interstitial lung disease program. In July of 2020 she joined the University of Texas McGovern Medical School in the Department of Pulmonary and Critical Care. She is an associate professor of medicine, importantly, she is the co director of the interstitial lung disease clinic there and director of the Center of Excellence for care of patients with post covid disease. She will be discussing long Covid, Our next distinguished colleague of mine is dr robert Mashberg. She is a professor of medicine at the Mayo Clinic College of Medicine and Science and a consultant in the division of infectious disease in Rochester Since 1997. Currently she is co chair of the COVID-19 vaccine allocation and distribution workgroup at Mayo Clinic. She has a physician chair of the Mayo Clinic enterprise antimicrobial stewardship program and outpatient parental antimicrobial therapy program. Previously, she served as the Acting Chair of the Infectious Disease Division from 2016 through 2017 and was the Vice Chair and Practice Chair from 2010 to 2016. She established the Mayo clinics, Travel and tropical medicine clinic in 1999 and directed it for over 17 years. She has been actively involved in education and internal medicine residency program and in the I. D. Division and has received innumerable number of awards for teaching and mentorship. She served as the educational chair and the I. D. Fellowship program director From 2000 and 2 to 2010. She has numerous peer reviewed publications and book chapters related to her areas of interest in antimicrobial stewardship, COVID-19 vaccines, orthopedic infections and travel and tropical medicine. DR received her medical degree from ASAN Medical College in India, graduating in the top five in her class. She completed internal medicine residency and chief residency at Prince George Medical Center in Maryland, followed by an infectious disease fellowship at Mayo clinic. She will be discussing variants and specifically omicron variant. So first we invite dr mira to address us on long haulers. Covid. Okay thank you thanks for the introduction. Um It's my honor to be present during this webinar. Thank you so much for the invitation and let me share my screen. Okay I think it's working. Um Yes as um we will be talking during all this time. Let me start saying something really sure about the the video that has been affecting us during the last two years when I say affecting us is the whole world As we know. This was initially detected as a aggressive pneumonia in people from Wuhan China back in December, 2019 and later on this was recognized as a disease SARS infection Uh, and was considered COVID-19 because the first cases were diagnosed at that moment. Since then these statistics are changing and unfortunately increasing the number of deaths and affected people. But this is at this point about six million of deaths in the whole world. But I want to concentrate with our country this when I initially created or work on this presentation A couple of months ago, these were the statistics, we have 45 million of cases deaths about 700,000 and then this amount of people recovered. So the last statistics are showing increased numbers. Now the deaths are almost 900,000 and then we have about 42 million people recovery. So that is the people or the thin I'm going to talk during these 20 minutes is what is going on or what is will happen basically with the people that have recovered from covid. Even before this moment at the after the first search we had tweets and I mean in the social media started talking about not only the acute episodes but symptoms that were persistently active in patients who survived or recover from um mild or severe covid infection. So then the question was we still need to learn a lot about this virus. Then publications like this one started being around and again this is in the media in the in the newspapers. So then the the the term about landholders started being common between all of us. And it's All these amount of symptoms they say for instance in this paper nearly a 100 symptoms For more than 100 days present after recovering from the infection. So I called this conference the heritage of Covid 19 and I will summarize in this way. So first definition of post covid syndrome. Then how we classify the post covid syndrome. What part of physiology has been recognized so far? Which ones are the main risk factors, visions are the critical manifestations and I will be able to be concentrated on the chronic long manifestation. The post Covid I. L. D. Or lung fibrosis or post chronic lung disease. Um first the definition there are different names but we refer to the same thing. This post Covid syndrome. Long Covid. Post acute covid syndrome all the long coolers. Okay the time is um still is still with with discussed exactly when to define acute and since one moment we say this is a chronic covid process. The cute post covid are symptoms present in the first weeks, which ones are those few weeks, especially the first 4 to 8 weeks. This period of time between the 8 to 12 weeks is probably naturally clear. But if symptoms are persistent after 12 weeks, basically three months after recovery is when we consider the case as a chronic covid syndrome Now faces who are hospitalized and are hospitalized for a long time. A long time. In more than three weeks, we consider more than 12 weeks. We consider that passing that time, even they're still at the hospital recovering. You know, they'll tag the all these, they're considered chronic syndrome. So this is this graphic is trying to summarize that short covid. This patient that has symptoms for less than 23 weeks prosecute covid goes probably until 8 to 10 weeks. But chronic covid includes those patients will past 12 weeks of symptoms. This is as well like to summarize what is happening in terms of the viral load. When the patients are in this period of time, we know during this first two weeks we have positive test. Then these tests start being a negative, but then patients start having other manifestations, especially up to The three months post infection wishes are the risk factors definitely. There is increased risk for post covid symptoms in patients with more severe initial disease. However, in our Center of excellence for post covid patients, we have a lot of patients that were that have been um self referred because they were diagnosed not hospitalized, no severe disease, but they still have some symptoms. So this varies. But in general for most of the publications is considered higher risk in patients with more severe initial manifestations that is correlated with the presence of more than 55 symptoms at the time of the diagnosis and as well related with the complicated cases is more common in patients with older patients with prior medical history of diabetes, hypertension, obesity and mental illness now. Um the minority ethnic groups is question mark. You know, this is a big debate but definitely um probably related with prior medical conditions. Some racial groups have been affected most as we know. Uh the risk. In terms of statistics, we have about 10-35% of patients when they are not hospitalized but symptoms can be persistent for patients in up to 80% of patients who required to be hospitalized at the time of the diagnosis. What is the explanation for these chronic symptoms? So there are different theories. I would say that the direct viral toxicity, the we know the stimulation of the inflammatory state. In fact, we think that this cytokine syndrome explain aggressive presentation in many cases. So we don't know how much of this still explain the chronic symptom, Atala ji, there is endothelial damage and microvascular injury that as well explained some of the manifestations of the acute setting as a hyper caligula ability. The man adaptation of the angiotensin converting and sign to pathway that we know as well has significant impact in the compromise of the lung tissue. The different manifestations if we go for rheumatology manifestations. Again, it related with the production of cytokines. There is this amount of patients that have developing kind of immune related conditions following covid or at least perhaps prior diseases X. A. Survey or are finally diagnosed. Then there is this additional theory about the formation of a notified extra cellular traps of netto sis that could be related with the antibody information and at the same time with chronic inflammatory response. Some of these patients have been documented with anti forcefully syndrome and anti antibodies and and some of them associated with the hyper calcula ability has been considered with anti forcefully syndrome. The positive prevalence of A. N. A. is up to 30% as well. So then the third is is really covid induce these changes for the patient. Well I mean the person had the process and the covid exacerbated cultivated the final response. Other manifestations have been seen like a hemolytic anemia. I myself treated a couple of patients with refractory severe hemolytic anemia associated with Covid immune aromatherapy nia, cutaneous vascular injuries or even inflammatory miniseries. And my algebra three classic symptoms of patients. Even with my covid syndrome. This multi systemic inflammatory syndrome has been even recognized as a possible Kawasaki Kawasaki disease in Children is equivalent in in in in adult patients as these severe again cytokine syndrome as has been recognized by many physicians and we even in the in the I. C. U. We recognize especially with cytokine syndrome where they have this kind of chalk presentation and again or private diagnosed or immune diseases are common during this acute setting. Now. More in the post covid saying. What about the hematologist quella. So we know about this industrial damage and the hyper popular ability. But there is a disproportionate in relation between the traumatic state during the acute phase versus what happened in the chronic cases Chronically. I mean after 12 weeks the risk for traumatic events are much lower. So in fact we don't consider needed to keep the patient Atlantic population passing that time. Cardiovascular Sekula is very common with patients again after 12 weeks still to complain on some degree of chest pain. Again, prevalence about 20% palpitations could be present up to six months following the infection. The we know from cardiac M. R. I. Stone in the acute setting that the the degree of um Possible myocarditis could be up to 60% no clinically established or money or clearly diagnose. But if we do a marine or patients the degree of myocarditis could be at this This level is really high as well. There have been increased episodes of a stress induced myopathy is pretty common. Um It's probably one of the more more common complaints of the patients Post covid is fatigue. The complaint of chronic malaise still diffuse my elijah's multiple sleep disorders have been associated a present in these patients as well. And then it's all this is associated with cognitive impairment. Uh the famous the term of brain fog is probably the more common thing we are seeing patients post covid and this will be linked with depression and anxiety given all these manifestations. And I will be honest say that it's it's hard to approach these patients initially the the the idea now is compare it is like to create different groups of syndromes on them. So when you initially see the patient, you can characterize what is the more um the the the the more important complaint of the patient and then try to get a syndrome for the patient. And in that way you can approach to better their care, the head of his care. So then we can classify as a fatigue syndrome as the name says, profound profound fatigue. It's important in this case is be sure you're not missing something else. Be sure there is not any other chronic disease that can explain the symptoms. It could be more cardio respiratory syndrome characterized by cough, Disney, a chest pain the same. Be sure you're not missing another diagnosis as as established heart failure or coronary syndrome or something like that. The other group is the neuropsychiatry process. The patient that complains mostly of headache, the persistent um a nose mia, neurocognitive difficulties and depression. The gastrointestinal syndrome. I linked this with the high plateau billiards syndrome that is pretty, I'm pretty sure the the decisions that are seeing this specimen, the intensive care unit are familiarized, familiarized. We have many patients with this post um call static process when they when they stay in the ICU or in the hospital for a long time. So we see when they go out from the hospital they still can deal with issues especially from the cold static biliary process. The Moscow psychological syndrome is characterized by muscle pain, weakness. Our travel just to be sure if the patient is posed. I see you this is not related with the myopathy associated with long I. C. U. S. State. The human body syndrome I already mentioned that is real after three months to have acute metabolic events. But if the patient had during the event of course is just be sure it's safe to stop anti population of math. Some dermatologic symptoms have been as well described like Suraj in different kind of um kind of arctic Korea pictorial symptoms, the covid toe as well. But this is more than the acute setting. The janitorial mary syndromes with protecting a real high material or renal disease and in general the multi systemic inflammatory syndrome with persistent episodes of fever symptoms, writes like a more general symptom Atala ji talking about the loan itself. I mentioned already some idea about the path of physiology but going deeper basically there is we know there is this damage inside Al Viola that is character or characterizes the what happened in all kinds of acute respiratory distress syndrome. So E. R. D. S. With the breakdown of the end of Chilean and they will tell you about the membrane. So this happens as well in prior in other E. R. D. S. That has happened in the past with H. One N. One for instance. But we see in the same in in in covid but it's not clear why some of these processes are persistent. And do we see patients with severe fiber optic process just 23 weeks after the initial diagnosis of covid. Um the the severity of the Anatolian injury can again affect the complete membrane and seems to be worse in some cases of covid than the damage that was similar similarly seen in places with influencer in the past. Then because of this law damage, We see of course we explain these multiple deaths. But for the patients who survived then we don't know yet how many of them will develop Corona five process. Then these terms about how to call this colonic this long disease are now on the discussion. We say post inflammatory pulmonary fibrosis, post viral promoting fibrosis, post viral interstitial lung disease, post covid interstitial lung disease, post covid pulmonary fibrosis. I can tell you that my fellows are asking me dr Mida really we can call I. L. D. L. D. Patients post covid six months post covid that are still showing abnormal findings in the city and a normal pulmonary function. Test to be honest at this time. We are not completely sure because we don't know if we ended up having another classification among all the interstitial lung diseases that we already know or these patients will improve as it happened with more or the most of the patients positive one in one or definitely we are dealing in one or two years with more chronic fibrosis just related with um covid and then it would be like a new class of I. L. D. The reason could be related. I mean the chronic process could be related with the angiotensin converting enzyme two pathway as I mentioned, because this is down regulated and this pathway is protective for fibrosis. The increased production of the inflammatory cytokines as well. And in cases of the places with the VR. DC that were on the ventilator, we had the ventilatory associated injury and the oxygen toxicity as well. So where we are, so as we mentioned, there are millions of people affected. Now. Majority we go by statistics majority of cases have been mine, But 10% develop severe disease. And for that group of patients, we count the millions that are as well, millions that were affected and survived And then 20% of them will eventually develop chronic lung disease. If we look at numbers by percentage, it sounds Low. But if we go by the 20% of millions of patients then we will have definitely a lot of chronic lung problems in these patients. So they will present. Then with corona Disney to decrease diffusion capacity as expected for chronic fibrosis or interstitial lung disease. Then we are dealing with the need for supplementary ocean therapy. And we have noticed that many of these patients are diagnosed with new process as I sleep apnea, with the need for positive ventilatory presser. And then the next three slides are showing images of patients with recovered pneumonia and how the different different courses we have seen in this. This is a case of patient who has severe er DS that even required ECMO for treatment and is seen later on in our clinic. You can see in the in the here in october 20 the classic findings related with covid that is characterized characterized by patchy areas of consolidation in peripheral distribution. So this obviously was severe affecting the whole loves in both lungs. But these political distributional lesions are the ones that make you feel pretty confident that the the diagnosis is covid and probably there is not anything that that is affecting the patient. These patients even after ECMO unfortunately is doing really well as is seen in the in the posterior city and clinically he is as well. He's even of oxygen doing really well on during his rehabilitation. This patient you see is less amount of fibrosis. This is December 20 when she presented initially and we compare with six months later and definitely the city's better. The pulmonary function tests are better but she was not feeling better with multiple um general symptoms, significant weakness, developed diabetes following the steroid used during the acute phase. So she's dealing with a lot of different symptoms. Despite of the fact that the lungs look better. This is a particular case that is really touching to me. I took care of this patient when she was initially admitted to the intensive care unit pregnant. The baby was born emergency because of the severe hypoxia. The baby recovered, but the mom died almost six months after being unable to read the unit with all the consequence related with the lower state and Covid. Um, basically I really wanted to show you is the different aspects. Some patients develop severe disease and recover some patients loans are better. But they are dealing with all these additional syndromes, honest as we know many patients die. So then how we approach the patient who comes to a clinic and we know have Covid before. So first it's important categorized the kind of post Covid syndrome and that's all the different syndromes I mentioned is really important because there are different symptoms to have a multidisciplinary team. So, the covid clinics that are around the country are basically formed by different specialties because it's necessary given the multiple manifestations of these patients, we need to start analyzing and publish the data that has been collected because this will be again a long process from now and we don't offer how many more years we will be dealing with the sequel of Covid now with medications we can use. Um basically asking about antibiotic therapy for lung diseases. There are many trials now and if I hope we will have some answers based on the results of those trials. These patients as well require aggressive rehabilitation. This is the list of the trial that has been that are now running in University of Texas. When I am we are one of the sides for the bio 300, that is one of the antifreeze proteins that we are analyzing in patients post hospitalization with evidence of intersectional and damaged. Yeah, this is a publication chest that basically was talking about the need for this um covid clinics and basically about is mentioned, it is mentioned the groups that need to be part of the clinic. So we need knowledge pulmonologist but we need psychiatrists, we need um the pharmacist who helps. We need a really good PM and our physicians, cardiologist depends on what is the syndrome that is affecting the patient the most. So in in you think we have established the clinic uh that was the start of the status is May 2020. We have four terminologies that we are initially evaluated patients but then we have the the collaboration of cardiology, infectious diseases neurology, psychiatry, p. m. and R nephrology and rheumatology, we can do our own testing, we have a dedicated nurse practitioner and registered nurses and medical assistance. So the whole team to cooperate to the multidisciplinary care of these patients. This is the statistics of how many patients I'm talking about before omicron. So about 500 patients in 30. We offer telemedicine. Now for instance we are doing more telemedicine given the the new outbreak. Um 60% of our questions have been self referred. Of course half of them are post hospitalization. We have noticed 70% of evidence of interstitial lung damage in the first three months post hospitalization. But after that most of the patients improved not totally but improved. So again we are started to using some of the antibiotics. I mean Ecuadorian antibiotic on those patients. Um We are collecting all the data along with the group for the MD Anderson as well. So in summary we need still to learn a lot about this virus is definitely an aggressive viral pneumonia. The survivors of the severe disease developed chronic symptoms in up to 80% of the cases. Majority of them improved in the first six months. But we have again a significant amount of patients is still that we will be that will be treated. Interstitial lung disease is expected to develop them in many of these posts, especially post hospitalization cases. Um We need to look for how to treat these patients and collect data to improve the care. Thank you so much. I think this instead of say the end is to be continued, I'm pretty sure we will be talking and dealing with this disease still for a long time. Thank you so much. Good afternoon. This is Avinash work sharing my slides. I hope you can see them. And um so as the as the previous speaker just said we have much to learn. That's the same thing with just SARS Cov two and all the variants. We have a lot to learn yet. So I will cover oh macron and what's next and see what, what we know about the macron so far discuss where we are in terms of the variants, where they are globally and also in the US and list what we know about symptoms, diagnosis, prevention and management so far. So as we know these cases globally, uh covid 19 cases have continued to increase. This slide was made last week. You can see that it's already um obsolete because the number of cases have increased, both for mortality as well as overall cases. Ah And when we look at the U. S. This slide again was made last week and you can see that um the cases last week, particularly since the week of christmas, we have had a large number of new cases all over the country uh and essentially at this 0.95% or more of the variants that we have in the United States is omicron and I will go into the details of omicron in a in a few seconds. So I just wanna level set in regards to variants because I think people do get confused about variants and essentially if you have the schematic of SARS COv two which has the genetic material which includes includes the gene for the S protein and the receptor binding protein and also um has a nuclear capsule proteins etcetera. Uh it's the spike protein as we know, which is critical for causing the infection. It's a receptor binding protein that domain that essentially attaches to the angiotensin converting enzyme two and requires this special protein is called temporaries to essentially enter the cell. So this has been found to be critical for the pathogenesis City of SARS COv two. And this this work came from MARS and the initial stars. That's how we know that the spike protein is critical for this infection. What we also know is that these viruses tend to replicate really fast that they have a high yield once they replicate. And as they do that they also have mutation allow abnormalities. I sort of equate that to having a photocopier and you are making 100 copies of a page and you'll have some of them that are going to be smudged, You can work with them, you can read what you need to but some of them are going to be really messed up. So a lot of these mutations are non meaningful mutations and don't really impact the pathogenesis itty of the virus. Whereas some of them do in fact change transmissibility pathogenesis city um maybe even impact the diagnosis and treatment but have a limited expands globally. Or even in a country such that they are they need to be watched but they're not at the level where they're going to cause a global event variants of concern on the other hand have significant mutation, a lab formalities. And in this case of course we're talking about SARS cov two. We're talking about mutations within the receptor binding domain and the spike protein uh that these changes certainly increased increased transmissibility and increased pathogenesis city and may or may not have an impact on treatment and prevention. And these when they have spread beyond just a local region, become variants of concern. Um And thus far as of today, we have five variants of concern. And you've heard all of them alpha Which originally came from UK Beta that was isolated back in May 2020, in South Africa gamma. And then of course most recently we've been dealing with Delta which originally was identified in India. What we knew about these earlier variants was that alpha did not have much impact on um effectivity of vaccine or treatments. Uh and but beta gamma and Delta did show reduced effectivity against uh the vaccine effectiveness as well as potentially some degree of decrease in monoclonal antibodies. Whereas what we are learning about omicron is that it does seem to have more impact on both of those. And we'll go into more details in a second in the U. S. There is also another definition called the variant of high consequence. This is when you have a variant of concern that is causing increased transmissibility, increased pathogenesis. Itty but you're also now beginning to have impact on your health care system such that healthcare employees are out ill and your infrastructure cannot handle the volume of patients that are coming in. So you're not able to really treat these patients and the consequences of kind of maintaining normal system is getting eroded. Those are variants of high consequence and thus far we don't have a an official variant of high consequence. However uh this is being reviewed so switching over to omicron, what we know is that and this uh this is from the next train dot org where they're uh they're categorizing all of the variants that have been identified since the very start of the pandemic. Uh This slide just essentially shows you the variants since january 2021 all the way through january of 2022. And what we see is that the alpha was um you know um pushed out as the predominant variant. Uh alpha took over essentially as the predominant variant uh since essentially middle of 2021 it seems like now omicron is beginning to uh is uh delta out essentially globally and we'll have to see uh you know how how many um how high and how what the caseload is going to be, What I want to show you is that from the very beginning of the end of the pandemic these individual variants have um have added mutations over time. And if you look at the left uh the Y axis shows you the increasing number of mutations and the Y axis X axis is time. And what you're seeing here is that over time every virus that we are identifying whether it's a variant of concern etcetera is accumulating more and more mutations. For example. This is a slide from the world health organization. What you see here is that the mutations are shown in these different rectangles. What you see here is that between alpha and omicron which is shown here in the dash line, There is a significant increase in the number of mutations. Some of these mutations. For example the D614 is in all of them. And this was one of the early ones that was associated with increased transmissibility. And more recently the 84 84 is associated with some resistance to antibodies and treatment. So you know, so we know that these mutations are going to have some impact on transmissibility um treatment response uh and we will have to uh learn more about these variants. So what do we know about the transmissibility of omicron? So based on the mutations that we see with within omicron, these have increased ace two binding and are known to potentially increase transmission. Uh and there are a number of those mutations that we see in omicron. And there is that scientific rationale uh that omicron is going to transmissible be more transmissible. Although there are some mutations that may decrease ace binding but it seems that more of them are increasing the ace two binding and therefore transmission. This is also substantiated by the rapid increase globally of cases. There were a couple of new studies that came out recently in both of these are helpful in understanding another aspect of why transmission maybe increasing uh there seems to be higher viral loads within the respiratory tract and therefore the environment. And also there may be some possible um change in the transmission pattern in terms of being more aerosolized as opposed to just drop lead like we knew for the previous variants. And this is one study that came out of Hong kong that showed that um depending on how the doors across the hall in the hotel were open, uh there was risk of infection in the in the room across the across the hall and it's not really possible with droplet but more so with a revitalization. So when we look at omicron, you know since november 9th which was the first confirmed case in South africa essentially within three weeks or less, 80% of South africa. Uh SARS-cov-2 was omicron and on november 26th it was declared as the variant of concern and by then a number of countries already had it In the us. We had the first travel associated case on December one and on December two We had the first um case that was not associated with international travel. This was an individual that had traveled only to New York City indicating that a comic Ron was already here in the United States. And when you compare the Delta versus oh macron the 0 to 95 you know not the 0 to 60 as a car but 0 to 95%. Um uh the proportion of the infections in the country in the United States, what we saw was that Delta took about 12 weeks for it to go from 0 to 95%. But when we look at omicron it only took six weeks for it to become 95% of infections in the United States. And so it's no surprise that a number of countries already have macron present. Many of them are reporting rapid increases and some may not have detected omicron specifically but need to be continued under you know monitoring in terms of diagnosis. I think it's important to take home that the pcr tests that we have will diagnose uh omicron very easily. Um There are some tests that may have decreased sensitivity and those have been uh you know identified and pulled off the clinical use at least in the United States in terms of the antigen tests because of the mutations that are present in the um spike protein. There is a possibility that the sum of the antigen tests will have lower sensitivity. That lower sensitivity is more likely to occur when the viral load is low. Um So example when the symptoms are either asymptomatic or early part of the syndrome where the viral load may be low and therefore you can have false negative testing. If antigen is being used to identify infection, Then a recommendation is to repeat that antigen test in about 24-48 hours. So the way I kind of look at the antigen test is that if it's positive it's great. It tells you that you have covid or tells us as a provider that you that the patient has covid? It's very specific and you can rely on that result if it's negative and there has been a known exposure um or there's concern that somebody may have omicron and it's negative. Then there is repeat testing required whether it's the antigen or it's the pcr to confirm whether somebody has uh the has omicron. Some of the antigen tests have been identified to have possibly slightly higher um sensitivity compared to others. Currently in the us there are 43 Eu a antigen tests that are approved but a few are possibly better than others. What about symptoms of what the symptoms Range. Uh now this is a very illustrative case. This is one of the index cases that we had in the us, the individual had previously had an infection came back home and had six household members, all six of the household members got infected. Two of them had never had an infection before. So this was the first infection, but the other four had had prior infection and one of them had had a vaccination as well. So in what this study looked at was time to symptoms. In the secondary cases and the onset of symptoms was 73 hours to the range of 33-75 hours. Patients who did not previously have an infection had slightly more intense symptoms and those were cough, joint pain, congestion, fever, and chills, those that were previously infected, even those that one that had the vaccination, the symptoms of overall milder. Um, and these patients did not have any loss of smell or taste. What we learned from this particular. Um, uh, study was that number one, the incubation compared to Delta is shorter. So it's three days versus four days and five days. Was what the original one was. Uh, it seems to have high transmissibility. So all of them, All of the household members got it previous infection or vaccination does provide some protection. It may not completely prevent an infection, but it confer some degree of protection uh, and causes a milder infection. And I think that's a really good important point and substantiated with additional studies. What about severity. So what we know about severity is that the the hospitalization and death data tends to lag behind a little bit. However, all the studies, all the information that we are hearing from the United States as well as from other countries, shows that the rates of hospitalization is lower than what we noticed in the previous waves. In terms of the ratio of patients who are hospitalized or have died from omicron compared to say Delta or others. A study from the UK showed that hospitalization was approximately half of what the delta hospitalization rate was. And for those that were vaccinated, the risk of hospitalization was decreased 81% if they'd had three doses and 65% if they had two doses. And this is what we see in the U. S. So the orange line is hospitalizations for uh the seven day average of new patients admitted to the hospital hospital. And the red line is the average number of cases in the US in the seven day. And what you see is that hospitalizations are increasing. But you know, compared to where we were with dealt with the previous wave back in january, the proportion is lower than what it was before. This is what we are seeing. Also from the various uh epic curves that we're seeing from other countries. This is data from our world in data and also from the UK public publication. What you see is that when you compare to the previous waves of cases, the the the number of hospitalizations are much lower. So the green is the United Kingdom purple is the United States and the pink here is South africa. And you can see that the south africa, the covid decrease very rapidly and hopefully that will happen in our country as well. Uh There are other preliminary information that suggests that severity maybe lower with omicron. So, this is an in vitro study that showed that omicron replicates much more uh efficiently and at a higher rate in the broncos in the upper respiratory tract Compared to what they saw in the lung. That in the lung itself omicron replicated 10 times lower compared to delta. Another study, another set of studies looked at animal models and what they found in the animal models was that the infection was less severe. So it was an attenuated infection and these animals had a lower viral burden. They didn't die as much and they had less weight loss. So suggesting a less severe illness. Another study and more recently shows that the another pre print study looked at replication within the nasal passages and they showed that omicron replicates quite a bit more than delta. So that could be another reason why there's higher transmissibility. Um also that uh this is interesting that omicron may not necessarily require the proteus. The temporaries proteus for entry into the cells. So suggesting that it could have another way of causing infection in the rest of the cells which then also suggests that there could be higher transmissibility and potentially infection of the local tissues. And what they also showed was that these viruses, the omicron related infections tend to have less census year formation in the tissues. What about vaccine effectiveness, vaccine effectiveness? So this is a study from the UK. Uh it's also pre print but I just want to share with you what they showed was that there is overall reduction in protection against the omicron symptomatic disease after two doses. So what I want you to focus is on the salmon color bar. So this is the the astrazeneca vaccine ah and this is Delta compared to omicron. They did not have enough cases in the omicron and the astrazeneca. So so please ignore that. But basically what they showed was for Delta and Astrazeneca, it was only about 48 Uh vaccine effectiveness in about 15 to 19 weeks. But when you compare Fizer so fighter was at 72% at that 15-92% for delta. However, the vaccine effectiveness was only about 34% at that same time in Turbo. They compared these patients to those that had boosters. So they looked at those that had the booster and they showed that the booster substantially increased the vaccine effectiveness both for the astrazeneca vaccine and also for the omicron. Although the omicron a booster vaccine effectiveness was a little bit lower Than it was for Delta, but it was 75% effective. This is also shown in this in vitro study where they were able to show that the antibody levels uh in people who who had three who had only two doses of the Pfizer vaccine against the omicron had very low uh neutralized virus neutralization titles. But they increased substantially after the booster. And even in patients who had an infection before when they got a booster, that law of virus neutralization really improved quite a bit after the booster that they received. So what this really shows is that prior infection is not going to protect enough in terms of prevention of infection. But the booster even in vaccinated, primary to those vaccination or a prior infected person would improve a protection. Another similar study that looked at neutralization essay. This is green lines are those that had two doses of the Pfizer vaccine plus prior infection although compared to the original strain, oh Macron virus utilization is lower significantly lower. But it was much better than if if somebody just had two doses of the Pfizer vaccine. So again, giving you some evidence that another dose or an infection is going to help in addition to the two doses as the primary similar studies have. This is all press release that we have seen from moderna and Pfizer's that have indicated substantial increases in neutralizing antibodies and a study uh specifically looking at J and J booster 6 to 8 months after the single dose showed that the vaccine effectiveness preventing against hospitalization caused by omicron was 85 84 to 85%. A really good uh efficacy in regards to hospitalization. Um Well here what I want to show you this is data from new york state where they've been um monitoring the breakthrough infections. Um And looking at the vaccine effectiveness um particularly in the gray zone which is the omicron. What you see is that overall in In terms of infection vaccine effectiveness it's a little lower than 80%. But the risk is much higher in the unvaccinated compared to the vaccinated And in terms of hospitalization protection that has stayed very very high between 90-95%. Uh But again risk is the risk of hospitalization is higher and unvaccinated compared to the vaccinated. What about the fourth dose? We've heard about the fourth dose from Israel? Um You know I think this is something that we are going to yet learned more about. Uh Certainly giving the fourth dose seems to have increased the antibody level five fold and we'll have to see how this how this relates in terms of monoclonal uh antibody effectiveness. What we have learned is that um the bamboo linen made bob and uh the region Dickov both have not been uh they're not effective against omicron convenience and plasma partially decreases the uh neutralization. However the shorter of the mob and the new ever shield both have retained neutralization efficacy against the omicron. What what is the future after omicron? I think the one thing that we have to take away is that there will be more variants and what they will look like and what they what they're transmissibility or pathogenic city is I think it's unknown. The one thing that seems to be emerging is that now the SARS cov two variants seem to have adapted enough so that they can actually go back into animals and come back into humans again. More recently, the data showed that the virus has been identified in mice where it's attaches very well to the ace two receptor. And the question is will this uh will there be a new cycle between humans and animals just like we have for avian influenza? And what does that, what will that do? And so one can only conjecture that hopefully over time as people develop more immunity and infections become less severe, it will go away. But I don't know if it will ever go away, it's more likely that it will become more like influenza where we develop immunity but there will be some degree of changing variants. Uh and we will always have people who don't have immunity whether it's because they're not vaccinated or because they are uh immune compromised hosts etcetera. And particularly if they does develop an animal reservoir then that will become a kind of a source of ongoing epidemics. Hopefully this won't be a worst case scenario where the virus also becomes more lethal, which hopefully it will not happen. Um we're at times so I will stop here just to say that the aim of vaccination is to obviously reduce all aspects of infection. However, um uh currently most of our vaccine prevention is against the severe disease and the spectrum of transmission is what we are seeing right now. And with that I will end to say that omicron is more transmissible, highly infectious causes milder disease boosters are needed for protection and hopefully we will not see too many more serious variants in the future. Thank you doctor for work for a superb talk and we will ask dr mira to join us for our panel discussion. But while you were talking a couple of things arose from all the questions that we have. I think we're up to about 65 questions is um first of all, could you comment on the availability of monoclonal For treatment of COVID-19 I know that there are available but with markedly restricted supply. Yes. So monoclonal antibodies are very restricted supply in the United States. They are particularly of the shield is very, very restricted and is being limited to severely immuno compromised individuals. Um and um sort of the map is a little bit more available but certainly you know will be challenging over the next few weeks and then dr work, can you refine a bit about the fourth dose of vaccines and specifically? I think the place to address that would be among the immuno compromised hosts are transplant patients if you could comment. Yes. So I think that's a really important point that we are finding that patients and providers are a little bit confused about the doses that immuno compromised individuals received back in august. So I want to highlight that four immune compromised individuals. The dose that was approved in august was an additional dose. It was those number three. And the reason why it looked like a booster looked like a booster is because by the time it was approved in august many of the immune compromised individuals had had the vaccine many months ago. So it seemed like oh that was a booster. That's actually the number three does in a series of three primary series in immune compromised individuals. All immune compromised individuals should now receive the booster five months after that last dose in august. So essentially all immune compromised individuals should be getting four doses as opposed to the non immune compromised. Our three for the third as the booster. And then just in that vein, are you aware, I am not of an agreed upon protective anti spike level. That one could test to see whether or not they are protective. I I believe we don't know that but dr mirror or dr burke. Are you aware of any breakpoints? No, we we don't and that that is unfortunately uh an issue that hopefully we'll have some answers to. We still don't have a proper correlate correlate of protection in relation to the antibodies. Now, Dr mira, there are quite a few questions on post covid syndrome. Um two of them were one. How do you separate steroid withdrawal from those individuals who are hospitalized and are having post I see you syndromes and then possibly steroid withdrawal involvement. And then another question was, could you refine a bit if you have any character characteristics that you use in your designation medical center for anti fi broderick agents? Yeah, I was just I was answering some of the questions and I was ready to answer that one in the past. I mean it's one of the more important differential diagnosis. Um So first for the physicians that have been taken care of these patients. So in general, trying to prevent that, we should not use steroids more than 10 days on these patients first. So we use the six mg per day based on the initial trial in patients who are not intubated, The patient who requires mechanical ventilation, we go to 20 mg daily for five days and 10 mg daily for five days. Following the Meta analysis that was published in summer after we were using for six months and six mg. But we don't do above that even if the patient is receiving the this high higher dose of asteroids then we we don't use or I mean any other medication that cannot be more than one of the the the immune condition. Because what we've seen is that the I mean when they stay longer in the in the intensive care unit, these patients are dying after a resistant infections and many other problems related with the use of high doses of asteroids. So that's this one message. But unfortunately I think probably even mostly in the first search, we have many patients that were treated for a long time with asteroids and they're coming to the clinic with the findings suggestive of um asteroid in this problem. How I recognize that I mean patients, one of the first patients I had was the one I showed the city the second city she came with not new diagnosis of diabetes that she didn't have before she came unable to walk for severe muscle weakness. And when we reviewed the city we saw improvement in the city and the permanent function tests were consistent more with chest weakness more than really a damage of the of the gas exchange. So we can recognize that as a pulmonologist. So all these findings are consistent more with the myopathy related with the long term long use of asteroids. So it it's basically the same approach that we do with any patient that is using high doses of steroids for any reason. And it's the thing that we we need to apply in the post covid if that's the case. The first thing is slow down there. I mean paper of the steroids and um sometimes I need to talk to the endocrinology is to help the help because some places I receive so high doses that they can develop a journalist adrenal insufficiency, otherwise this and start aggressive rehabilitation. The PM in our doctors I think they're playing a really important role in post covid patients because they can approach not only the physical part but they can help with the mental part as well. And the rehabilitation is is really important. We haven't haven't seen patients now for more than a year and most of them after like six months of aggressive rehabilitation, they start finally feeling better. But the way to to differentiate is the history of course or how long the patient wasn't destroyed. And then physically there is a clear myopathy. This is more likely related with the steroids. Now there are many primary care individuals who are asking questions. Can you address? What type of work do you think should be done prior to sending a patient to a long call or a long covid Post covid type of center. What type of basic work ups should be done post hospitalization before referral to you? Oh that's a pretty good question. Yes. Um First is the time, I mean the patient is um many places come like within the first three months of the diagnosis if it's if it's too close to the initial diagnosis um I think probably still the primary care can watch the patient if it's after three months and it's still the patient is complaining a specific symptom. Again we go to the syndromes if it's more related with a brain like a headache, lack of concentration. So so then I mean I don't know if it's basic but the the neurologists are in agreement in these cases do a brain M. R. I do all these kind of tests so probably refer the patient um If it's more related with muscle disease then be sure that we're not missing some connective tissue disorder. So order the best the A. N. A. D. N. A. The C. K. So all these kind of differential diagnosis. If it's more like a fibromyalgia picture so then look out for rule out connective tissue disorder and then um definitely send the patient. If it's a persistent shortness of breath echocardiogram just be sure that the patient developed pulmonary emboli. Be sure there's no developing pulmonary hypertension or is a new dinosaur heart failure. I would do always pulmonary function test and if it's possible a chastity just to see there is definitely establishment of chronic lung disease. Um That would be like those those are the more common symptoms. But I will say mostly it's the period of time many of these patients after three months they even don't come back because they feel fine they say I find find I don't I don't want you don't need to combine them. I don't need to do more tests. So I would say that. And then there there's questions as to the difference between delta and oh, Macron in the incidence of long covid And I think it may be too early for us to say we know the answer to that by your definition of 12 months. But there were several questions on that. So could you also address that? It's early. I haven't probably seen yet patients with I mean established an instant of post covid now because we are just having the acute episodes. But I can see because one of the questions in the in the panel was what is the difference in what is the risk for post covid if the patient is fully vaccinated. I had because now we have many many of us, many of the of the medical I mean the the health system providers are having positive tests or possibly sick and we are full vaccinated in my institution for instance is we cannot worry we are not full vaccinated. So it's is there is no option. Um, we I mean I haven't seen but I don't I don't I'm not sure about any publication. I have but I haven't seen too many patients with significant symptoms if they were vaccinated. But there was a publication that showed a lower risk of post covid infection in vaccinated individuals. And I think the other thing I would suggest is that I agree with dr mira, that it's too early for us to really know about the post covid and omicron, but but we also know that post covid is a little bit more common in patients who had severe covid. And and so if we, if we think of it from that perspective that most of these patients are having not in and it's not everybody, but many of these patients are having milder shorter duration of symptoms. Perhaps their risk of long covid is also going to be lower with omicron. But again, this is yet to be seen. Mhm. Um Dr burke. Can you comment on, you mentioned the possibility that oh, Macron maybe aerosolized. Can you comment on aerosolization versus droplets for omicron and the type of masks that should be used during this time period? Um So that was the one study that I showed you that was from a Hong kong hotel study where they looked at possible a revitalization. So there is some um there's that one study and I think, you know, we don't know yet fully uh it hasn't been replicated at other places or with other methodologies to see if it truly does arrest elicits a theory. Um but what we're also seeing is that a surgical masks uh seem to be very protective against omicron or delta. And thus far we are recommending surgical masks for all of our staff. Um and the the N- 95 if they're doing um, you know, some areas realizing producing procedures. I think the one thing that I would say is that cloth masks, especially those that are only to layer our gators that tend to be knitted shouldn't really not. I mean they're not going to be as effective. So I would not recommend those currently with the omicron. There's a question here as to whether or not vaccination improves long covid syndrome. And the way I would reframe that is that vaccination very clearly decreases the likelihood of one getting severe covid disease and it's more prevalent among those that have severe covid disease to develop long Covid. Would you agree with that? Dr mira? Yes. I think I think Dr Burke already mentioned that. So, I think that's the explanation. We are not seeing too many patients who at least know with the severe post covid that was described after the first. Even the second search because after the second search in in in in the summer, we started having more vaccinated patients. And now we see that because the disease is less severe because it's through 80% of patients that are hospitalized are the ones who develop chronic disease. Our patient is only about 35% of them. So definitely with vaccination, the risk will be much lower. But I think the question, I'm wondering if the question was asked that if somebody has post Covid syndrome already and they were not nominated and if they get a vaccine, would they post covid symptoms go down? I don't know that. I some I seem to remember something about it, but I I can't go to you on a paper right now on that, but I think there was there was some paper on that specific question. Yeah. I don't know if that would be. Can both of you comment on the pediatric population? We are seeing more. Oh, Macron in the younger age group. Um, can you comment as to why? And we don't see pediatrics here at Mayo clinic florida. But there's a question as, what is the prevalence of long covid in the pediatric population? Doctor for, Do you want to go first? Yes. So I think the number of cases right now when we look at uh Children compared to earlier last year and now there does seem to be a slightly higher rate of Children are getting the infection of Macron and also getting hospitalized with Macron. And uh, I think part part of it is related to the fact that the percent of the Children of you know, 5 to 15 that have been vaccinated are not that high. So between 11 to 15, it's about 50% and between five to 11, it's only about 25, So a they're susceptible. So the larger number of kids that are more susceptible compared to the adults. And secondly, they, you know, they are they have been back in school uh you know, for the last weeks etcetera. And there have been a lot of social activities. So I think that those are kind of multiple reasons why we may be seeing slightly higher rates of infection in Children. Dr mira. Yes. No, to be honest, I don't have experience with kids. I know about the statistics but we don't I don't see any any Children. So the the texas Children is totally different from what it's like. I don't want to say anything because I don't have experience. Yeah. Okay. I do want to comment that mmwr this week did report That among among those under the age of 18 have a significantly increased risk of diabetes of which is um important for us to be able to monitor for. And they also show that it does occur in higher age groups. But it was predominantly in those under the age of 18. And I think the window of time was 1-2 months post on having COVID. Now, both of you are like me are very familiar with influenza. There are questions regarding the combination of flu oona. Is it worse than that of covid alone? The combination of influenza and Covid, you're giggling dr burke. So yes, I've actually done a few uh yeah, I've had a few discussions about this. So Firstly at the winter of 2020 and 20, So last winter we had very little influence because everyone was masking, everyone was social distancing and uh there was limited social gathering etcetera. So we saw very little influence that this year, influenza is already increasing in many states in the United States and I'm sure at other in other countries as well, there's increasing seasonal influenza because we are masking less and we have more social activities etcetera. We have already seen patients that have had both influenza and Covid and you know, uh the question is whether co infection is going to be more severe or not. We we have not seen that so far, but it's early in the influenza season. I do think that for the immune compromised host or the elderly patients who are already more susceptible to all people with chronic lung disease etcetera who already more susceptible to severe lung disease with these viruses are probably going to have a more severe infection. The other thing that we've noticed in the United States this this season is that The influence of vaccination is about 7% behind last year. So people are more susceptible this year because they are also less vaccinated. So I think we will see both of those. And the third thing that the final thing I wanted to say about this is that here at Mayo Clinic are testing strategy last year as well as this year for the winter. Was that if anybody presents with influenza like illness, fever chills, headache, etcetera, We are testing them for influenza and um uh covid 19 and if they have the risk factors for rsv meaning that their immune compromised etcetera. We're testing them for all three of them. If they're coming in with those because it has implications for treatment. It has implications for isolation and um you know, so those are just a few points that wanted me. Yes. We are doing the same here at Mayo clinic florida as you just described. And we are very much strongly encouraging not just covid vaccination but influenza vaccination. Dr mirror. Did you want to comment? What university of texas may be doing? No, it's the same. We have the same rule the same for the for the for us we are the same. We don't we don't have the vaccine. We cannot work. And that was that the campaign that started in september it was even sooner than normally for the vaccination. Ah And I'm not aware either about combined. I mean at least not in our units like a case of like crts or severe associated with both at the same time. We are testing everybody with the whole viral panel. Yes. Plus the covid but I haven't seen cases or combination um dr for can you comment a bit more about natural immunity versus that of vaccination. There is a question regarding if somebody has adequate antibody levels. Do they need to get the boosters. I believe that we already alluded to the fact that we don't know what antibodies are protective and I would be recommending that they do get quote the booster or if they are immuno compromised, they've completed the third dose series. But maybe you could reiterate that to avoid any confusion. That may still exist right? So well, as I showed in the slides that especially against Macron uh just natural infection itself is not enough in terms of protection. And we also know that natural infection related protection does not last long term. Uh So three months, maybe six months but no more than that. And also based on the studies that I just showed you in terms of just the increase in the antibody levels. But also for the fact that clinically we're seeing better protection and people who have had the thought those uh that infection itself alone without your boosters is not going to be enough to protect against Macron. There's a question as does a recipient who receives monoclonal antibody have a decreased inmate antibody response because of the presence of those antibodies. Um so um you know, this is not very well studied when the vaccines were originally approved automatically. We had v as in uh you know the whole country and others globally had recommended to wait 90 days before we vaccinated for the concern that there may be some interaction there. However, more recently because also looking at the end of the half life of some of these medications, It is reasonable that maybe we should be doing vaccinations less than 90 days. Uh and that's one of the reasons Why CDC recently changed the recommendation that if you're giving Monoclonal antibody on a kind of a prophylactic basis versus treatment basis, uh then you could give the vaccine a month after prophylaxis. Whereas you still want to keep the 90 days after the monoclonal when it's given for treatment. And the other rationale for waiting the 90 days is that we know that the natural immunity is also going to protect people for the 1st 90 days. So, so, you know, so there isn't much of a concern that if somebody had an infection that they have to wait for 90 days to get the vaccine, it's also um stressed that the innate immunity or even vaccinations Have more to do than just antibody levels. That involves the CD 45 and T cells. And that's they play a very critical role involved in this. Um and and to add to what you just said, I think there's, you know, as we know, the immune system is so complex, you know, there's the T cells, there's priming there's uh you know, long term memory cells. Uh there is more data that's coming out suggesting that the booster, you know, again, based on what we know from other vaccines as well, is helpful in increasing that T cell immunity as well? There's a question regarding vaccination in those individuals who have long covid. Do you hesitate doing that dr mira? Is there any reason that you're seeing somebody that is, let's say 90 days out post hospitalization meets the criteria for long Covid. Is there a reason that you would hold off giving them the influenza vaccine? No, no, no, no. We always recommend. We always ask respectfully and everything has to be vaccinated because you know, it's still some patients don't want but we always encourage them for vaccination for the whole. Yeah, I mean, influenza and Covid. Okay, mm hmm. Give me a moment. I is there any reason to be giving nasal vaccines or nasal treatments? I'm not aware of a nasal vaccine that's FDA approved for use in the United States. And I'm not aware of any treatment that is nasal oriented. I know that. Mm hmm. I have not seen the study but I know that individuals may use steroids nasal steroids for people who have lost smell during the acute phase of disease. But that's not trial tested as a recommendation? Or are you know any of you want to comment on that? No. No. Okay. Um And then how long does the fighter and Moderna confer their duration of efficacy? Are we aware of that information? When does the vaccine wait in a normal host? Um So um what we are learning is that it when we talk about vain ng immunity. It is vain ng against protecting infection. Just getting an infection many mild symptoms but it's still holding its protection against Hospitalization and severe disease that has continued. Now we are a year into the vaccination since December of 2020. That that protection against hospitalization and severe disease is holding in that um you know 80 now with the omicron around 80% 90% in that in that frame uh and based on the previous studies that were done including studies from here um that the about 67 months is when your immunity does go down. But you know and that's where the hopefully the booster will help with the longevity of these of this protection as well. Dr mira. Would you like to comment on that at all? You totally agree. Okay. Um there's another question in regards to the path of physiology of pulmonary long covid and stopping anti coagulation. Could you re address um the path of physiology and the use of anticoagulants. Yes. The anti population was highly um used and recommended especially the first and the second search uh following that we didn't have or we don't have enough evidence that definitely helps with inflammatory process. Except the patient who clearly have indication for clear episode. Now passing that event when the patient comes to a clinic after three months, they say that the patient requires to be anti coagulated for pulmonary emboli or DVT during hospitalization. Basically we are following the same rules for pulmonary emboli. Like it was provoked emboli associated with the disease. Three months of anti calculation could consider it is considered enough. You can probably consider six months of some patients. But if you are, if we are considering concern, continue the anti calculation because of the post covid itself. No, there is not evidence of that and if it's related with the risk for long fire process either. So basically, no, there is not indication that continue anti population will decrease that or they are clearly indicated now the other point and I know because even some pulmonologist have been doing that is the not not only for the long disease but the inflammatory estate that they offer maybe low dose of aspirin or even anti coagulation for these patients. Uh, there is no clear evidence. I never used more than three months when the patients were started on it after hospitalization. I don't know if DR burke has any other. I agree with what you said, I'm going to give each of you one minute for a summation of what you want. Our wonderful audience to walk away with. I'll Let You Go 1st. Dr. Burke. Well, uh, I think omicron unfortunately, just one of the many variants that we've had so far. Um I think unfortunately none of us can look at the crystal ball and say what the future is gonna hold except to say that we will have more variants and hopefully um there will be less severe as we go into the future, particularly if people are more and more protected with vaccination. Hopefully this will become a mylar and unimportant disease. For my part, I think it's for the we don't know what else is coming, I hope it's with the incidence or the prevalence of the amount of vaccinated people. We have less chronic damage. But still I think we need to learn how we will work with the chronic si quella related with the disease. And in general I think we all of us we are doing a great job working against this and we need to continue encourage the people to get vaccinated. I agree. I want to thank both you dr burke and dr mira for phenomenal talks. I want to thank everybody for being present with us today and again Mayo clinic and all of us extend our gratitude to you for the care and dedication that you are rendering to your patients as well as to your colleagues daily Again, thank you and please entertain joining us on the future of webinars. Thank you. Thank you. Thank you. Thank you