Mayo Clinic experts discuss the latest information on the SARS-CoV-2 delta variant's impact on vaccine recommendations for the general population and for solid organ transplant recipients. Additional topics include breakthrough infections in typical versus immunocompromised hosts and the most current vaccine updates.
Moderator: Claudia R. Libertin, M.D., consultant, Division of Infectious Diseases; professor of medicine
Gregory A. Poland, M.D., emeritus consultant, Division of General Internal Medicine; Mary Lowell Leary Emeritus Professor of Medicine; director, Mayo Vaccine Research Group Featured Expert:
Sadia Z. Shah, M.D., M.B.A., consultant, Division of Pulmonary Medicine; interim medical director, Lung Transplant Program; assistant 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.
welcome on behalf of the Mayo Clinic School of continuous Professional development. I'd like to welcome you to the Mayo clinic Covid 19 webinar series. I'm dr William palmer. Associate Dean for the school and your host for today's webinar update on SARS Kobe. Two variants of concern and vaccines implications for solid organ transplant recipients. Webinar, This webinar is accredited for 1.5 am a pr a category one credit record of attendance will be provided to all other health care professionals. This webinar is supported by an educational grant from Pfizer Incorporated. Here are the disclosures for this activity before we get started. We'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 edu slash Covid 10 12 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 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 we will facilitate questions. You'll see at the bottom of your screen the chat and Q and a function. If you have any questions during the webinar for today's presenters. It's important that you drop them into the Q and A channel rather than the chat box. This will help ensure the panel can see your questions. There's also a helpful up vote button. So be sure to up both the questions that you would like to see answered. If you're experiencing any technical issues during the webinar, please use the chat feature to share so that our support team can assist here are today's learning objectives that will be covered throughout the webinar. I'd like to introduce today's moderator Dr claudia libertine. Dr libertine graduated from the University of Toledo Medical School and completed internal medicine, infectious disease and medical microbiology training at Mayo Clinic in Rochester. She had been on staff at Loyola University in Chicago and Yale University Until she rejoined us at Mayo Clinic in 2014. She is professor of medicine, director of infectious disease and consulted of infectious disease at Mayo Clinic in florida. During the COVID-19 pandemic. She's led the Covid I'd multidisciplinary team is a member of the treatment review panel for Covid And his p. I on five randomized control trials including active five. Today's panelists will be personally introduced throughout the webinar with that I'd like to turn things over to our moderator dr libertine. Thank you dr calmer and welcome to the first of six Covid 19 webinars that we're going to be having today, we're going to be discussing solid organ transplants but subsequent ones will include global health in kenya Ghana and India post Covid syndromes and the life cycle of SARS Cov a tube and drug discovery methodologies but before I introduce the distinguished panelists, I want to personally thank each and every one of you who have rendered tremendous care to our patients in an unprecedented capacity. Our health system has been markedly disrupted and the core ingredient needed by all of us has been compassionate care and I am very deeply um indebted and grateful for what you and your families have sacrificed during this time now. It's my great honor to introduce dr Saadia shaw. She is a lung transplant pulmonologist here at Mayo Clinic florida. She trained at Stanford University and lung and heart lung transplantation program in ex vivo lung perfusion at Toronto General Hospital and obtained an NBA from the University of massachusetts. Since the emergence of the covid pandemic has involved been involved in daily multidisciplinary covid rounds as well as being active in clinical trials and involved in the covid treatment review panel here at Mayo Clinic florida. She was pivotal and piloting piloting a project for the first lung transplantation here at Mayo Clinic florida and then the subsequent multiple other patients that have been transplanted for covid related lung diseases. We are delighted to have her insights of covid 19 in solid organ transplants. Our next speaker and Panelist is Dr Greg Poland. He is a physician scientist and current director of the Mayo Clinic vaccine research. He has been awarded over 200 million dollars in competitive research. Extra mural funding and has published over 650 publications and book chapters. He is the mary leary um emeritus professor in medicine. He holds the rank of a professor of medicine and infectious disease. He's a distinguished investigator at Mayo Clinic and is the editor in chief of the journal vaccine. First. Our first Panelist is dr shaw, it's over to you Saudia. Thank you so much Dr libertine for that introduction and thank you so much for inviting me to discuss this topic which is so near and dear to my heart and for the honor of having this talk along with Dr Poland who is that? You know, one of the geniuses in this talk. Um so I'm going to start with uh my disclosure site first. Um so I do not have any disclosures unfortunately, hopefully in the future. Uh so today, but we will be doing is we'll be discussing the different kinds of covid variants that are out there. And despite the impact of covid on the solid organ transplant, how has the process changed since the start of the pandemic and the infection? How do the solid organ transplant patients fear after being diagnosed with covid infection and the fact of covid vaccinations on solid organ transplant recipients. So, with regards to the COVID-19 global impact, we have already had about 235 million confirmed cases of COVID around the globe. So, and this is a very scary number as you can imagine because not all patients report that their COVID infection and not all cases are diagnosed and it has already resulted in about 4.8 million deaths globally. On a positive note, we have already had about 6.1 billion COVID charts already given, which is fantastic and a phenomenal accomplishment globally. But we still have a long base to go now. Uh as you can imagine globally, we have several different team members in agencies trying to combat this covid infection and in order to make sure that the left hand knows what the right hand is doing. The U. S. Department of Human Health and Human Services established what they call the SARS Covid two integrity group and this was done to in order to improve the coordination amongst the CDC NIH F. D. A, the biomedical Advanced Research and Development Authority and the Department of Defense. The this integrity group is basically involved interpret characterization of emerging variants to determine what the severity of the disease, the ability to transmit in fashion from person to person and also to monitor the impact of critical stars could be to countermeasures which includes the treatment regiments, the vaccination and diagnostic testing. It also analyzes the defend variants on an international level as well as the regional level. So we know exactly which vary and is where, so that may be, can interact with a countermeasure it accordingly. Now based on the different variants which are available. The CDC did come up with a formal classification of different variants of clothing. So it's divided into four categories and the first one is the variants which are being currently monitored by CC. So this is a list of different variants which are currently being monitored by CDC. And as just as you can see, we're here in the orange color, we have the delta variant which is the most prominent variant across the globe and definitely in us. Um And speaking to most of the hospitalizations currently in the United States, the other different categories if you have is the variance of interest variants of concern and variants of high consequences. And they really, in terms of, you know, in terms of how severe the disease processes they're just disability and the impact on their covid on the different company measures that we have with variant of high consequence is being the one which have failure diagnostic test targets decreasing efficacy of the vaccination, increased breakthrough cases as well as hospitalization and and that's the same kind of variant. That's thought to be the one which would have reduced susceptibility to emergency use batteries. A therapeutic options that we have currently the good news is that you don't have any vaccines uh experience of interest or very supplied consequences. But we do have variants of concerns which are your alpha, beta, gamma and delta variant. And if you're currently managing now, how does courage pandemic has impacted the process of transplantation in solid organs. Um So the first thing that came to light was what happens when you have different donors. And how do you process these patients who have different uh donors that are being uh sent your way? So because of that the american society of transplantation um they discussed with the transplant community as well as the different organ procurement communities. And they came up with a joint statement in A. Q. And A. That we have here and they go over, how do you potentially slap those different kinds of donors? So before that, all of us were attempting to figure out how exactly to do this on their own. And this is a study that was done recently in which different people were looking at the different kinds of categories. Um So that was based on the risk exposure as well as the clinical aspects of the donor. Whether they were exposed, did they have a positive test or not? And whether they have any radiographic finding. So based on that, what they were doing is that they were giving a risk at risk or to these donors. And then those risk scores were much more stringent for lung donors as opposed to the heart, liver and kidney donors. So, based on all of this information, the american Society of transplantation came up with this current guidelines. It says that if you have a potential donor, which you always have to make sure that you look at the upper recipe track for possible possible covenant fashion within the last 50-72 hours. All potential lung donors should be tested for covid infection of the lower respiratory tract. If you're looking for a lung donor. And we also are supposed to look at the chest imaging to ensure that there is no clinical evidence of covid infection. Then the next question came, What about the patients or donors we already know have a history of korean faction. How do we evaluate those donors? When are they going to get transplanted? So for those donors documentations are that we have to ensure that the SARS covid PcR testing is negative, especially from the lower SPD track for long donors. And there's and they have no known symptoms at the time of donor transplantation And 21 days that already laughed since the time they were actually diagnosed with COVID. And the whole idea behind doing that is to ensure that the likelihood of transmissibility is very, very low. Obviously we have very, very limited data available on these organs. So I think as we transplant more and more patients using these organs will probably have more information. The other important thing to keep in mind is that the reason fashion can still happen. So if you have a potential donor who's you know, who did get infected and there are more than 90 days out, you should always ask questions that it had any recent exposure or potential reinfection risk before moving forward for transplantation. And it's also important, especially when you have living donors that you do ask them questions about possible exposure history because you can always wait and transplanted more than 20 days out. Um to ensure that there's no transmissibility to your potential recipient. Now, how do we assess the recipients who are coming to get their lung transplant or any other solid organ transplant for that matter? So for those patients, what we do is that being asked to bring them over to the hospital? We go where their clinical symptoms or potential exposure history, especially within the last 14 days or so. You always want to make sure that they have a negative differential school for Covid. And then we also ensure that the chest X ray is not consistent with any covid infection. And if those things are negative, then we go ahead and proceed with transplantation. What about the patients who are in a weightless? And what happens if they get infected with covid? When would you consider transplant for those patients? And that's one of the questions we get asked all the time. And our patients are you know, always scared that if they get in fashion, they will no longer be getting their transplant, which is not true. So for patients who are diagnosed with Covid and they are on a wait list. If they have an interesting exposure to COVID-19, then you can potentially just wait for 14 days And having these a friend whose fault done to ensure that there is no active infection. Um and if it's negative repeated 24-48 hours later and you have two negative tests and you can go ahead and proceed to transplant 14, you know for seven days later. But if you have patients who have an active symptomatic covid in fashion, That's always very important to ensure that you wait for 28 days after the initial diagnosis of the infection. And you have to have two negative covid tests 24 to 48 hours apart to ensure that they are not actively infected before you perceive a transplantation. Now obviously we would have patients who would be really, really sick and we can potentially wait for that long in such cases we have actually waited for at least 14 days after the initial infection. Um What about the asymptomatic patient? And they just had a positive covid test And those patients can only wait for about 14 days or so. And if they're covid topples negative over two days, then we go ahead and we list them and release them for the transplant. Now, what about if you have a patient who have started organ transplant who got infected with covid. So how do we manage those patients in those patients? We've seen that the majority of these patients tend to have a much more severe disease. So here what we have done is that we have looked at the different case. Your code in case series. Um and comparing lung transplant patients and also in solid organ transplant recipients. And you've looked at what's the difference between those in the general population over here. And we saw that most of the patients who have a history of solid organ transplant, they tend to have a war's outcome of tend to have a much more severe disease. So they have higher likelihood of being ICU setting or higher likelihood of pipa Ksenia and even a their case mortality rates are much much higher as compared to general population. So these are very, very sick patients with very, very severe disease. It's very very crucial that we engaged the transplant physicians taking care of these patients earlier in the course rather than not. Now. What about the testing? So the diagnostic testing for solid organ transplant is quite similar to what we would do for non transplant patients. Um But the more important thing is to be more cautious and we normally tend to evaluate these patients far more frequently than not transplant population. What about the immune suppression? So this was a survey done by the guilty. That's the International Society of heart and lung transplantation. Just that's what most centers are doing when they are patients are diagnosed with covid infection. So we saw that majority of the transplant community was actually stopping the anti medical lights and or reducing the dose of the antibiotic, intimate rights based on how to stick their patient population was there's actually really, really important to have the transplant physician taking care of those patients um to weigh in on the management of those patients. Now having said that, that can vary. So for example if you do have a patient who has pretty bad history of antibody rejection, you need to be mindful of that and you're assessing those patients. Hence the reason why the transplant physicians need to be involved in this care. Now. What about the treatment guidelines for this patient population? So NIH currently has the treatment guidelines and they mentioned that for the transplant patients as well as the patients who have solar therapy recipients, they should be managed the same way like the non transplant patient population. But it's very important that the physicians taking care of this group of patients are involved in the cure. So that way they're immune suppression can be adjusted as well as because it could potentially be drug drug interaction that we need to be mindful about. Now this is the current NIH Covid 19 treatment guidelines. And um I'm not going to go where the details of those but we basically follow the same algorithm. In fact we have our Mayo clinic's own treatment algorithm for Covid 19 and we we meet on a regular basis to go where the current uh guidelines that are out there and then change it accordingly. As you can all imagine it's a fluid situation and more and more data comes in on a usual daily basis and then we evaluate that and make decisions accordingly. Now what about COVID-19 and hospital to hospital transfers. So we get a lot of calls about, you know, certain patients who could potentially be candidates for transplant or for that matter as a bridge to recovery. So I think it's very very important for us to analyze those patients sooner rather than later because if there are patients who can potentially recover from these modalities like asthma or lung transplant, you want to be able to get them to that respective center sooner rather than later because that's the only way you have the highest chances of success in this patient population. Obviously the indication and contraindications for use of abnormal for covid 19. The disease uh is available. And these are the current guidelines that economic tend to use for this patient population. Having said that the way different variants have worked have been very different. So for example, in the alpha variant we were seeing a lot of patients coming in with pulmonary embolism or even arterial thrombosis. Whereas in the delta variant we saw a lot of patients with new member the S and M our new Matar IX. So we have now been getting a lot of calls with you know, patients with persistent bronco player fistulas and they are needing possible ECMO and need a potential transplant. So based on the different variants, it can actually vary. So you have to be mindful of that? So we actually have an algorithm in which we actually figure out who would potentially be a candidate and then I want to redeem a patient is a potential candidate. We want to be able to get those patients into our center sooner rather than later. So we can potentially develop them for possible transplant. Having said that you know, given the you know hospital capacities, the ICU capacities and the actual capacities is very, very important that you have a multidisciplinary team was actively involved in the management of these patients and you collaborate and know exactly what your capabilities are before you accept transfers. So now since this side of the pandemic we have had several patients who have been transplanted globally for the actual diagnosis of COVID-19-related ideas and um we like to regular to report that Mayo clinic is also has done that as well. So we are one of those centers who have been able to transplant patients with covid related lung disease. And this was our first lung transplant here in florida for covid related lung disease was done very, very well. So very very proud of them. But I would like to say it literally takes a village to take care of these patients. So I think it's very very important that their right place and they're being evaluated to ensure a good successful outcome. So what about vaccination status? So covid 19. 1 of the most important thing that has come to life has been that what what how do we go about evaluating patients who refuse to get vaccination for covid 19? And this is one of the news club thing that I have up here where our hospital actually deny transplanting a patient who would refuse to get a covid vaccination. I think that's one of the hot topics of discussion these days. How do you go about managing those patient population? Because it's the ethical question. So if you transplant that patient and they they have covid in the end, they don't make it, then you spend a lot of resources and organ for that matter um to transplant somebody who may not make it in the end. So we all have to have hospital policies to ensure that patients are being taken care of both before and after transplantation. So there's a joint statement by american Society of Transportation as well as the International Society for Heart and lung transplantation, addressing just that. And uh and they're recommending all sorts of organ transplant recipients to undergo vaccination for COVID-19 along with their households and close contacts and recommending that the vaccination prior to transplantation ideally be a minimum of two weeks prior to the actual transplantation. And now they're also recommending the third dose of covid vaccination as well from now. How effective is this vaccination? So this is a study that was done by Brzeski and john Hopkins and as you can see uh in this from the step today, only 46% percent of their total solid organ transplant patients actually mounted a covid like they did not have a covid antibody response at all. And that was after two doses of the covid vaccination. So more so that's about half of the patient population not wanting any the body response. So we have to be very very mindful of this patient population. And this has led to to determine what kind of patients would not mount a covid response. And they found that patients who have had who have been on medications which are anti medicalized for the one which were lower had a lower likelihood of actually mounting a good response. Since then now we have a booster vaccinations. And this was a study that was done to evaluate that further in this solid organ transplant recipient population. And they saw that most of the patients who under about 44% of patients who were initially seronegative did actually mount a good response after the third dose of COVID vaccine. And they also saw that the people who already had antibodies, they actually had a huge boost in their antibody typewriters after the booster vaccination. The ones who did not actually have a good response where the older population more than 65. The ones who are in a higher degree of innocent passion and the ones who had lower g. f. r. s. Now since then we have another study that came out from and that's our colleague from Canada. And they looked at the three doses of Moderna vaccine and they found that in solid organ transplant recipients and they found that in about 1 20 recipients that they did have a very good response not only just a human neural response but they also noticed that the SARS cov especially T. Cell and actually also increased. So it was not just the antibody but also the T cells increased after the booster vaccination. Um Now that's been a potential question that a lot of people tend to ask. Uh and their questions have been that okay what about antibody response versus cell response? Post vaccination. And this was a study that was done too well with just that. And they saw that a lot of these patients it's not just the antibody response but the T cells are also um impacted and they are increased which is a good sign. But in solid organ transplant it can vary. So the two may not be linked to each other. So in some patients you can just have a cellular response and have no anti production whatsoever in other patients. You can potentially have antibody production and no solar response. Now how those two things interplay is yet to be known unfortunately do not have those answers as yet. So what does CDC say what the CDC says that all sort of organ transplants should be immunized along with there is another team or you know, other patients who have certain medical conditions and they have recommendations for those patients to ensure that those patients are also fascinated as well. Yeah. Um, now, what about one of the questions that I ask get asked a lot is, what about can patients get covid vaccine, flu vaccines together? And this was one of the study that was done by bristol University in the UK is called a conclude uh cove study and in which they found that most of the patients who were, who got the vaccination together in in England and Wales with the fighter and the Astrazeneca vaccine um, actually had minimal side effects and they were able to tolerate that very well. So, so, good news for everybody out there. They can get both their shots and we can. What about the risk of fracturing fashion. So, one of the things that came up and that has been a major concern. And a lot of people have been asking about, should I be getting one vaccine versus the other. And what about the different variants and how do they impact the outcomes? So, you'll see in the study of about 16 patients, they saw that most irrespective of the vaccine, about half the people did have mild disease, some of the people did have severe disease. Majority of these patients actually did have a pretty high water load irrespective of how bad the disease was. So as you see over here is like, the mean is about 19 and it didn't matter whether they had mild disease, severe disease, it could be anything. And the patients who were solid organ transplant patients tend to have a much more severe disease and a much more poor outcome irrespective of the vaccination. Um Which vaccine that God. So I think it's very, very important for a solid organ transplant population to ensure that they are still masking. There's still social distancing and taking all these precautions from CDC because as you can imagine, even if somebody has a little milder disease, they can still have a very high viral load. And you can potentially catching fashion from such a patient. So with that um I would like to thank everybody for joining in. We really appreciate that. And I'll hand over the mic to uh to dr Poland thank you. Sorry, a boy that was a beautifully organized uh discussion of what is a complex topic. So thank you. I want to reinforce something that dr libertine said at the beginning of our time together and that was how hard everybody's worked. And certainly we've all observed that that's what our lives have been like and what our colleagues, one of the things that's sometimes hard on me is colleagues and patients ask questions that they would like black and white answers to and of course that's not always possible. Not always possible in all of medicine, but I want to commend an article to you that you may want to send to colleagues and to patients that ask questions that you can't give a black and white answer to. It was published just recently in the atlantic and it's called the Covid serenity. Prayer actually has nothing to do with prayer. But I thought a very good discussion of how we operate under conditions of uncertainty. Uh so what I'm going to talk about is the covid pandemic and immunocompromised persons. What have we learned? In reality? I'm going to kind of give a potpourri of uh data related to this topic. All right, let's see if I can get the first slide to advance just disclosures which have already been done. Let's start with a discussion about infection and breakthrough infection, which I define as a documented infection that occurs 14 or more days after completion of a full vaccination series. Whatever that is. And we distinguish between primary failure, which is that a protective immune response did not result from vaccination and the secondary failure, which is what most of the press means. When they talk about breakthrough infection, they're talking about a infection due to waning of protective response. So in this case a protective response developed but waned below a protective level over time or due to a change in the host immune system. Note that a substantial change in the virus actually a new variant might be better defined as a part of re infection which occurs after a previous documented infection. This is something that people, particularly patients do not understand. Well, is that even after so called natural immunity, They are at risk for reinfection and in fact at least in one observational study done in Kentucky, published by CDC. That risk if they did not get immunized compared to that, if they did get immunized after recovery was 2.3-fold higher. Now, I also want to talk about this risk of breakthrough infection. This is a paper I published in 1990 for regarding the most infectious virus that we know about, which is measles. And I want to I want to explain what is an apparent paradox to people because you hear them saying there's more and more breakthrough infections. Absolutely right. They falsely conclude that all of those are due to the vaccine doesn't work. And that's that's a that's misinformation. So let's just take a school of 2000 students When none of them are immunized, none of them are immune and the number of students susceptible who will get disease when exposed is all 2000 of them. So 100% of them got disease. But none of them by definition occurred in immunized students When you immunize all 2000 with a vaccine that has a 95% efficacy, 1900 of the students will be immune because of vaccine, But upon exposure, the 100 who were not who did not respond to the vaccine, those 100 will get disease. But note that 100 of those cases occur in somebody who was previously immunized zero versus 100% 2000 who get disease and are susceptible versus 100. So you can conclude nothing from hearing about the percent that are immunized and in cases that have occurred in people who have immunized until you have this piece of data which of course doesn't get reported. All right. There's a complex interplay here. Saadia alluded to it. Um, when she talked about human role and cellular immunity, we have the host characteristics, things like age, race and gender genetics and comorbidities that come into play with breakthrough infections. We have viral characteristics like variance in Oculus size portal of entry, that differences in vaccine type and efficacy time since vaccination. So we certainly see cases that occur right after vaccination and cases that occur distantly when waning has occurred. And of course there are differences by geography. These are just some of the factors that interplay one with another to create the picture that we see. Now. Susthrough cases reported to CDC as of 21 September so 183 million fully immunized and you know, these are representations. I don't think anybody thinks we know about every single case, but it gives you an order of magnitude. So roughly equally divided between males and and females. Um but overrepresented in people aged 65 and older, they were 69% of the fatal cases. So, death was occurring about one out of every 35,000 Fully immunized and hospitalization in about one up around a little bit, one out of 11,000. Now in Minnesota of the three million fully vaccinated minnesotans, fewer than one Have experienced a known breakthrough COVID-19 infection. Hospitalizations occurred in .47%,, Death and .004%. And other studies have shown rates varying from breakthrough infections occurring one in 100. And some studies in Israel to as few as one in 5000. So quite a range. Again, it relates to in these studies confounding due to lack of control over these complex this complex interplay of risk factors. Now, if you look at rates of New COVID-19 hospital admissions and deaths and try to compare them. This is the hospitalization rate per 1000 people comparing vaccinated and unvaccinated people across as many states as I could fit on this slide. And you see that that rate of hospitalization Is anywhere from 17 times higher to 161 times higher, depending on geography, which is really a proxy for burden of community transmission and variant. If you look at death rate per 100,000. And again, information not well appreciated by the lay public and by the vaccine hesitant and those who have rejected vaccines, the risk of dying if you are unvaccinated went from a low of seven times higher To a high of 87 times higher. As I always say, pick which risk you want. There is no choice without risk. There are risks to vaccination that are very, very low with very high benefits. There are risks to disease, very low benefit to getting disease. Very high risk. Which risk do you want? You have to assume one or the other. Now there's also a gradient of vaccine efficacy. People toss around the term of vaccine efficacy. Well, in fact, it is a gradient. We get very high efficacy with prevention of death prevention of severe disease prevention of hospitalization. Then we see a drop with prevention of mild to moderate disease, then we see another drop with prevention of asymptomatic infection. Yet another drop in prevention of transmission. So vaccine advocacy is complicated. It is a gradient of protection. The vaccines we have, whether we're talking about covid or any of the other vaccines are much better at if you will disease blocking rather than infection blocking depends a lot on the health of the underlying immune system. Whether we're talking about the innate arm, the adaptive hue, mural or the adaptive cellular arm depends on predominant circulating variants. Time since vaccination and the population or individual being studied. And so if I can show you the top part of the graph, this is a vaccine that is disease blocking you note that there's this one unfairly characterizes that there's just as much in the way of infection there isn't. But the point I want to make is you reduce severe, moderate and mild and therefore the surge demand on the medical system and the morbidity and mortality experience of those patients that do end up with disease that requires hospitalization. And what you expand is the amount of asymptomatic disease as opposed on the bottom part to a vaccine that prevents disease and infection. And this is more like what we have where you still have a symptomatic disease. You've dropped the rate of disease, but you you severely decrease in a beneficial way. The amount of severe, moderate and mild infections. So my point here is that the headlines obscure What you saw was modern and fighter 95% vaccine efficacy. Well, the headlines lie, that's one part of it. But let's just look at Moderna and I'm going to pick The age group over 65 the age group that I now fit into. So the point estimate Was not 95. In fact, it was 86%. And the truth lies between the 95% confidence intervals from 61-95. So by definition, there are going to be people who get immunized who will get disease. Now, generally speaking, they're going to get a far less severe case than they would have had they not been vaccinated. But this again is a point not well understood by providers and patients. Now, if you look at back covid 19 vaccine effectiveness against covid 19 associated hospitalization. This happens to be adults who do not have immuno compromising conditions. I want to show you something this is getting at vaccine efficacy against hospitalization with time. So moderna on top after full vaccination, even 120 or more days after immunization, 92% efficacy for fighter. That dropped to 77% efficacy for Johnson and Johnson. It dropped to 68% efficacy. So again in this complex interplay vaccine product and type and time matter. So if we can generally summarize this is vaccine efficacy against illness and hospitalization against Delta by geography Against illness, 88% in the UK87% in Canada. And what we have repeatedly seen as discrepancy data in Israel only 64 Against hospitalization much higher. There's the gradient of protection again in the UK 96% Canada. 100%. Israel 93%. What about breakthrough disease? Well, this is looking in blue at the unvaccinated and in green, the vaccinated, 88% reduction in illness. If you got vaccinated hospitalization, 96% reduction. Death, 96% reduction. Which risk do you want? Now, when we get to the immuno compromised hosts? We've dramatically complicated the picture. This is extremely heterogeneous. Are we talking about primary versus secondary reasons for immuno compromise. What disease type? What treatment type combinations of the above And when we get to disease And treatment is the effect on B cells, plasma cells, t cells on downstream signaling receptors on cytokines, chemokines or combinations of these. That's why it has not been possible to give black and white answers even on something as basic as what level of protection can we expect? What level of vaccine efficacy? It depends and depends. It's spelled in capital letters, italics sized and bold because there's so many factors involved. So if you look at hospitalized breakthrough infections, About 40-40% of those are occurring in people immuno compromised, even though there are only about 3% of the population, They are also more likely to transmit to household contacts compared to those who are not immuno compromised but yet have breakthrough disease. They have higher death and complication rates and they are at higher risk for prolonged evidence of infection and shedding, which leads to a higher risk for mutation and recombination viral events. So if you look now at healthy health care providers versus the immuno compromised, this is a pre print that was put out there in the end of june I believe it was and we're looking at the percent who have evidence of protection very high in the healthy. Really surprisingly high in HIV though they're treated solid organ transplant, quite a reduction. Only about 40 autoimmune or chronic inflammatory treated conditions. Really pretty good in the 80%. Same with solid tumors. Uh pharmacologic malignancy less. So we do see less ah immunogenicity. If you will in solid organ transplants and those with him a geologic malignancy compared to other states of immuno compromise. I'm gonna go buy this because that was shown already. If you look at percent of subjects with antibody response after two M. RNA vaccine doses and again, kind of grossly lumping by immuno compromising condition, small numbers and that's been one of the problems in all of the studies. And you look at people who are considered to have an antibody response. Dark blue is Hema to logic cancers much lower though some do as well as other people with cancer, hemodialysis. Really pretty good organ transplant. Quite a gradient from people who do really pretty well to moderately well to poorly. And then a variety of people who have immunosuppressive therapies depending on what that therapy is. Now, if you compare a third dose of covid mRNA vaccine, if you look at zero positives after a second dose, you're talking about 40% with solid organ to as low as 20% in one smaller series. And in patients on hemodialysis, that same range of response between 40- 80%. What does that look like after a third dose. Well it does bump up now. This particular slide I think underplays it. I think we get a response more than a 4% bump, more than a 10% bump. These were early, small sample sizes and I think we do better than that were the third dose overall. In fact Saadia showed this. But let me just reinforce this. If you look at prevalence and the A panel and actual antibody tigers in the B panel, if you look before the third dose, the prevalence of uh Detectable antibodies around 40% a month after the third dose upwards of 60 65% which fits with that same bump in actual antibody tighter that scene. So he's a third dose worth giving. Yes. Now variants waning and boosters as you know that for the three vaccines we have in the US the final common pathway is the development of anti spike antibody which binds to Spike which prevents binding to the trans membrane ace two receptor. Now this is a problem because what the press and what the patients and what some providers are doing is worshiping at the altar of neutralizing antibody and that's a mistake. Without knowing a correlative protection. It pretends that the only thing that leads to memory is neutralizing antibody out of this hole part of the immune system. When in fact we get activation of T cells the development from naive t cells of cd foreign cd eight cells Cd eight are critical in disease severity and clearance of viral infection activation of B cells with CD four help leads to antibody but also memory B cells. So looking at one little part of that is just that one little part of the picture which does not explain the full realm of protection that immunization offers. Now that's an issue. When you get to the delta bearing, this is extraordinarily transmissible. We went from the ancestral Wuhan virus with an R. Nought of two ish to a virus that probably more fairly has an R naught of about six. It leads to significantly higher viral loads in some of the studies about 1000 to 12 times higher. Which has allowed for some mild to moderate evasion of vaccine induced and convalescent induced immunity. So if you graph and I commend the Corey paper from Nature medicine this year to you, if you look at neutralization level by protective efficacy, you can see a gradient and they're attempting to model a correlate of protection. We see very high rates with Novavax which is not yet approved. And the two mRNA vaccines and lower rates with the adenovirus vectored vaccines. Mm. In addition, we see a gradient in antibody levels simply by age. So this is a graph of SARS Kobe to specific antibody levels By age. Really high levels in young people much lower levels as you get down into your 60s and 80s. In addition we see that same phenomenon not only by age but by variants. So they happen to take the P one variant against the uh Washington uh strain or variant. And you see that with age you see a decline but you also see this decline From the Washington Strain to the P one variant. So variant matters age matters. Time matters. When you look at protection from symptomatic versus severe disease. I think this helps people to visualize and explain. So let's take the M. RNA vaccines overall efficacy against severe infection in that 90 to 95. So what's the efficacy? And they fit a black line here against any symptomatic disease where you go from 95%. Protection against severe disease to 70 75%. Protection against any symptomatic disease doesn't mean it's not a good vaccine. It means that like all vaccines, it has its limits. Similarly with waning neutralization tighter the time till a booster is required. They tried to model. So if you take an initial efficacy of say 90 Well you still have 70% efficacy by about 200 days. You have 50% efficacy way out here past 250 days. So you're asking yourself, why are we giving a booster? What's the outcome we're looking at? And that can that answer can differ by outcome. So the consequences of the viral mutation we've seen have been that in virtually every case. In virtually every variant we have reduced neutralizing activity with perhaps the exception being the Moderna and J and J vaccine against the alpha variant. Now neutralizing responses. After 2 to 3 doses, I again want to show you on the left side, these are 18 to 55 year olds on the right side, 65 to 85 year olds. Now, what I want to point out here is to correct a misperception that the elderly don't respond to booster doses. That is not correct. While they prior to dose three may have uh antibody levels that are half that of people who are younger. Nonetheless, after a booster dose in there, getting up into the 2000 and high 1000s whereas younger people are getting up a little bit higher but these are not highly significant differences. So the whole idea that we as vaccine, ologists used as the construct for how we think are of boosters. When you're in a situation where you need to build immunity quickly, you give two doses and get at a population level and hopefully at the individual level protective immunity that like every vaccine we has wanes with time, coronavirus vaccines wayne faster than other vaccines. Just like natural immunity to seasonal coronavirus is wanes quickly. That's why we repeatedly get reinfected and so we give a booster dose. What will eventually happen if we can't convince people to get vaccines are mandated is that there will arise a viral variant with sufficient ability to evade immunity that we may have to refocus immunity by using variant specific boosters. So in terms of routine boosters, a lot of data needed. Now as you know that recommendation has already been uh made. There's disagreement I would say over the need for those routine boosters that the EU a now has been extended as dr shaw showed there were two should recommendations and to may offer recommendations. I won't go over those. Those are easily findable on the C. D. C. Site. Note that this is only for Pfizer vaccine. Only if it's been six or more months And only in those 18 or older. The third dose has already been recommended for those who are immuno compromised. It's about 3 4 the U. S. Population and meant only for those who are moderately to severely immuno compromised. Now for the immuno compromised, I want to start with first principles just to say we take a multi layered approach. Number one is getting fully vaccinated. You and the people around you. Number two wearing a proper mask properly. You and those around you responsible distancing and hand hygiene. Eventually I hope we will be able to measure a correlate of protection but we are not there yet and I don't want to forget about other vaccines for the immuno compromised. They need an influenza vaccine. pneumococcal plural vaccines T death and shingles vaccine. Now on the 14th just a couple of days. The the EU way will come before FDA to look at booster doses of moderna the next day. They'll look at booster doses of J. And J. And the mix and match studies. I have seen all these data. I'm under confidentiality but what I can tell you about this is they all work and they all work well. I hope we'll have the wisdom to say it doesn't really matter what vaccine. Any vaccine you can get, any vaccine you can be boosted with october 26. Then there may have been a change to the 29th. I have to double check that they're going to look at extending the Eu A two Children 5 to 11 with the Pfizer vaccine giving a third of the dose. That is not 30 micrograms like people 12 and older but 10 micrograms. So I will end there and I'm sure we're going to have lots of questions. Thank you Greg and Saudia for phenomenal talks and you are absolutely right. Dr Poland we have a lot of questions for all of us here. The most popular one is and follow up of the pediatric group for vaccinations. What are your thoughts from Mayo about immunizing Children? Less than 12 years of age? That was the most popular question. Well, I'll take a first stab at that. I think let's see the data which will be coming out over this week. Um so that we can actually make reasoned decisions. One of the things that's going to be important is do we see less or more adverse or serious adverse effects such as myocarditis with the MRNA vaccines. I would commend you an article published in mmwr. That laid out in a very nice table. The risks of myocardial itis and the risks of not getting vaccinated and develop how many cases if you do vaccinate of disease hospitalization, I see you admission and death that you prevent as you go younger. That risks and benefits that teeter totter looks like this as opposed to adults or that teeter totter looks like that. So, you know, I think it is. I think reasonable people will have disagreements in the younger people. But what we can say is that the delta variant, unlike what we saw with the ancestral Wuhan strain As no question uh, affected Children out of proportion led to hospitalizations. We've had somewhere under 600 deaths now in Children due to delta variant. Um, and so for me as a parent, it would be an easy decision. I recognize that might not be so for other parents, but I would encourage you to look at those risks and benefits. Again, there's no escaping risk. It's a matter of what magnitude of risk do you want for the benefit that you get? And Greg, Could you comment as to the rationale for the european and UK where they currently are not recommending immunization of Children. Did you address that for that population listening to us? It's a great question. Claudia and I think number one, they're trying to use as much vaccine and people at higher risk than younger Children generally are. And get that that group uh, immunized. The second thing is there are variations and how people think about side effects by geography. Um, myocarditis has spooked them. Um, it spooks some of us to and we need more data. I will say for the fighter vaccine license. The FADA is requiring long term safety studies after somebody's developed myocarditis that go out to 2025. So we will have more and more information. Let me remind you. Covid cause is much more in the way of myocarditis than the vaccines do. influenza causes mild card itis, lots of drugs and other autoimmune conditions cause myocarditis. It's just that the public hasn't heard about that and many providers are unfamiliar with that. The vast majority of this is asymptomatic. A tip of the iceberg is symptomatic. Most of those resolves spontaneously and rarely to our knowledge do we see any long term effect of that? So while it sounds scary, I would say, let's look at the data, it gets less scary. The more data that we look at. And um dr shaw, there is a question regarding a question of how frequently transplants are occurring for those who have post covid. And can you comment on your experience here at mail? Yes, definitely think here doctor routine. So we have currently transplanted about four patients who have underlying covid related lung disease at florida. Uh, as you can imagine, it is on a case by case basis, You have to make sure that the patient and has an underlying lung condition that is irreversible or um and that's the patients that you would want to proceed with possible lung transplant. Is this something that? And I get asked about this a lot of times people say, oh, how about I skip the vaccine and just wait for the transplant to happen and tell a lot of people that it's not as easy as you may think that is, it's not the case. And the life in transplantation is a 10 times much more tougher life as opposed to just getting one single shot. It's a lot more poking. Uh It is involved in transplant as opposed to just with the covid vaccination and also with the covid vaccination itself that you will get scot free will still ask you to get the covid vaccination afterwards. So it's just better to get it then it will not cause all that habits than not. So, I think it's very, very important that people get the vaccination from the transplant perspective I mentioned about how we have done here and we are already currently evaluating five more patients as we see for possible lung transplant for covid. There are only very select centers across the globe that have actually transplanted patients for covid related lung disease. So not every center knows how to do that and the outcomes of these patients. We are yet to determine how these patients will do in the future. Uh they will have more infections for that matter if they'll have more complications for that matter. So I think this is something that we still need to have agency as more and more data comes in. But one thing I can tell everybody please get the vaccination because end of the day we tend to see a lot of the tail end of these patients and it's heartbreaking to watch that really maybe one other thing to add and Salyan and claudia. You will have a more informed perspective on this than me but I am unaware of any evidence of organ rejection. Um as a result of vaccination, correct. In fact, thank you so much for bringing this up dr Poland. I'm actually writing you know about to submit a manuscript on that. So what we did was we evaluated patients who underwent covid vaccination and looked at all our solid organ transplant, not just along transplant and see whether or not they had any rejection and they did not. So and also not just that, but also antibody mediated rejection to see if they're developing new donor specific antibodies to reject their organs and patients or not. So I think it's very very important to do that infection on the other hand is a very well known thing that can potentially trigger possible rejections in the future and can potentially to graft dysfunction. Um so the covid infection itself can potentially trigger some rejection. So we have to be very mindful of that dr shaw since you've been talking about that there are several questions I'm going to combine as to how do you time giving vaccinations if a person is on immunosuppression instance for example, one question was, how long do you wait after somebody takes a course of predniSONE? What do you do to optimize immunization in your solid organ transplant patients before they go? Okay. That's a very very good question. In fact we're about to start that trial that the Dr. Fallon was talking about soon too. So um I can tell you is that most patients who have undergone transplant you have to wait for at least 90 days after the initial transplant episode. The reason for that is because a lot of these patients undergo induction at the time of the transplantation, which decreases the likelihood of actually getting a good antibody response or immune response for that matter. That includes both human role. That's antibodies as well as the T cell response. And so after trust, 90 days post transplant would be a good time whether or not you can actually do a reduction immune suppression. Um That's something that your transplant physician is the best person to get in touch with, who can go over that because just like you mentioned somebody just had a rejection. That's the wrong time to be decreasing their immune suppression because the likelihood of rejection is gonna be more so timing it. Uh in a way that you have a higher likelihood of having a good antibody response or t cell immunity. And at the same time not causing harm to your graph is going to be the most important thing. And the transplant physician to help you. There are clinical trials that are we're talking about doing and that will answer that very specific question. But we have definitely transplant physicians are going to be very intricately involved in those trials to ensure that the craft is being looked after and ensure that there is no rejection happening. Once we do modify the ministry faction. Now dr Poland there's uh an immuno compromised group. Probably not. So much. So the pregnant population. Could you please address the antibody response that occurs with vaccines and pregnant women? And also on what your recommendations are for backs and then as a as a follow up fertility because that's also always an issue. Sure. In fact, I'm going to move from a recommendation to a desperate and I mean it a desperate plea for women who are going to get pregnant or women who are currently pregnant to please get immunized not only with covid vaccine but uh pertussis vaccine and influenza vaccine if they have not received The data are clear here. Women who are pregnant who get COVID have a are you ready for this? It stuns you to see this have a death rate that's 70 times higher. 7070 times higher than women age matched who are not pregnant. There's additional benefits. You not only protect that pregnant woman and the risk is greatest in that 2nd and 3rd trimester to the woman. You protect the unborn and then born baby. And you pass you pass maternal antibody to that baby to protect that baby at least for some weeks to months until such time as we can immunize them. And if you breastfeed you further give secret torrey antibodies to that baby. There have been no increases in still uh still births in congenital birth defects in any measurable way there have been no evidences of harm done. So again more than a recommendation a plea C. D. C. Having seen this data moved from one can offer to one should offer vaccine to these to these women. And I would actually dr Poland just mentioned because we get to see you know the other end uh and we get called a lot you know uh you know 30 year old lady just give birth you know had bad covid infection premature baby need a potential lung transplant evaluation. So we're seeing unfortunately the other end of it. So you know I would I would share the same sentiment and say please please please get vaccinated and the other reason why you know and to to talk about this is like when would be a good time to get vaccinated? That's pre transplant. So that's why all this teller with the patients please get vaccinated to likelihood of developing those antibodies are very much much higher. Before you start getting all those immuno suppression than not. So please please please get vaccinated and claudia. You mentioned fertility to let me take both of those no evidence of decreased fertility in women. There may be some evidence of temporary disruption in the menstrual cycle that spontaneously results. Probably just due to inflammation. Low grade fever. Just like any other vaccine or low grade disease might be in males. There have been a couple of studies done and interestingly enough those studies show an increase in sperm count in semen quality. I think it's just a statistical aberration but the point is there was no detriment or harm done. Thank you. Now dr shaw. Um there's a question on what is the utility of doing antibody. I presume anti spike I. G. Testing and a solid organ transplant who is doing well. And on the flip side of that um to follow up dr Poland would be what is the consensus on the level of neutralizing antibody to be considered enough for Unity? Doctor shall have you go first. So I would say right now we don't have enough data to be able to tell what is a good tighter at which you would have a good immunity or for that matter severity of the disease. If you do get a breakthrough infection. I think a lot of this information once we are collecting this data we will know in the future that oh you know patients who had antibody level beyond X number feared veil of patients who had antibody levels below a specific number had less chances of having a severe disease. Having said that in solid rock and transplant population is just not the antibody levels that are protecting you against the code infection is also your T cells CD four CD 8. How much of the several immunities also helping those patient populations and how was the interplay between the two is yet to be known. So I think there's so much that we still need to discover and it humbles you every single time and you're managing these patients. So I think it's you know, a Nobel virus and we're all learning as together as a team. So I think it's important to have the data and then once you have the data is important to then see who feared well or not. I absolutely agree. Couldn't say it better. You said it better than I did. I absolutely agree. I think we will get that correlate of protection at some point neutralizing antibody tighter czar somewhat tedious to run. I do them in my lab and the the T and B cell essays are also tedious and not well standardized. That's changing and I think the practice of the future, we may well be able to do that. One of the ways we're going to get that correlate of protection earlier is in the UK. I don't believe they've started yet, but they've been approved for challenge studies. So they'll take younger people who are immunized, measure their antibody levels. They will be arranged, challenge them with the live virus and see who develops disease or complications of any sort so that those data are coming. But I absolutely agree with Saudi. We just don't know now. Obviously if somebody came to me and they had a anti spike I G G E R B D and a body that was really high. We know at the population level. Well, we see that when we see the range of the antibody levels across the population, we know that 95% of those people are protected and if they're at the 95th%ile of the antibody range, we can presume. But you know, it gets real dicey after that. Yeah. And in our compromised host has received the third dose of vaccine already as part of their primary immunization series? I'm going to presume they must be older since that would be part of their primary Maybe you could comment on that? When would you give the subsequent does things where do you anticipate that to occur? Dr Poland? Not a lot of clarity on that yet. So you're right claudia in saying that for the immuno compromised. So it's not age based for the immuno compromise? They really have a three dose primary theories we play around with semantics and we call it to uh initial doses and a late additional it's a three dose primary series and then a booster um typically six months or more later. Now you asked specifically about the immuno compromised and when you get to solid organ transplant, sal you can comment whether there are any guidelines from those societies. But I don't I don't think we have data yet that tell us, correct me if I'm wrong, Saudia. I don't think we have any data that would tell us gee maybe we better do that at three or four months and not six. Yes, you're absolutely correct. We currently don't have that data available. Obviously we are currently recommending all our solar dog and transplant population to be getting the booster vaccines which they are having said that we do have a recent article that was just published in New England Journal of Medicine in october 5th doctor livin in which they studied the Pfizer vaccine and that that the antibody response does decline at the six month mark. And I think that's probably where a lot of this information about the six months target timeline. Um and I think in the future that's going to be vital than we are assessing these patient populations for another booster. I think it's going to be crucial to determine you know what timeline we should be looking at and do the other t so you know response, does that go down faster or not. Um And should we be talking about when we're doing the vaccinations, should we just go with the three series of the same, you know, back to back a month apart versus not? So I think and should we be doing mix and match like dr Poland mentioning the slides because that data will be coming out soon too. It doesn't make sense to have a different vaccination to have a better response to an uh an antibody production. So I think as the time goes on we'll probably have a lot more answers to these questions. But these are all very good questions. Now in terms of the transplant population, there's a question here is what is the risk to the recipient if the deceased donor is covid positive? Are you accepting covid positive patients? Um and then address it? Yeah. Yes, definitely. So we are not accepting covid positive patients, donors at all. In fact, the the guideline says you're supposed to check for a covid vaccine. Covid covid testing. And these are friends of swab in the upper respiratory track. And then especially lung transplant donors, you're actually supposed to get a sample from their lower respiratory tract to ensure that they are covid negative prior to proceeding with transplantation. And we say normally that testing should be done with the 72 hours of actual transplantation. So and we do the same for our recipients to so we have recipes are coming for transplantation. We do a thorough analysis of whether they had any exposures. Uh they have if they have any symptoms of actual code infraction. And then we actually test them with another friend just called to ensure they don't have any covid infection before proceeding with transportation. Because obviously, as you can imagine at the time of transportation, that's the time when the patients would be the most immune compromise with a lot of induction agents being given and you don't want to be have this complication, which you have a corporate infection that happens at the same time. So there are currently gun lines and uh that you talked about that. It's important to ensure that the testing is done before proceeding forward. We do have some data in which, you know, these agencies are saying that we can let's say what if somebody had a history of a covid infection three months ago, can you take those organs or not and in those organs, it's very important that we have. Again, they're testing done to ensure that they don't currently have any infection and to ensure that they currently don't have any evidence of organ dysfunction. But the imaging that we have and also to ensure they don't have any current symptoms before the patient passed away before the organ donation. To ensure that we are not transplanting organs from anybody who has an active infection and dr Poland does natural exposure to covid and vaccinated patients. I present the persons vaccinated and then they get covid or breakthrough infection, increased lasting antibody response that they have. You know, we don't want this for anybody but the combination of vaccine and infection is really superior immunity. Um In fact this has been looked at. If you fully vaccinated you can see you can see antibody levels up in the thousands. They've done some studies on people who were infected and then gotten Two doses of vaccine and they can measure antibody levels in the 20-30,000 range. So it's really superior immunity now, does that protect them against a variant that would evade that immunity? Not necessarily. So so that's why we we really do push people that have gotten previously infected to get at least one dose of vaccine and I would echo what dr Poland just mentioned about the transplant patient that I mentioned who had the covid and ended up getting a transplant. Some of them they were like no I'm not to leave the hospital before I get my covert both directly because they were they were so scared from what has happened. And as the time goes by, I mean you know after a few months those antibody tigers may go down. So it's important for you for those patients to be able to get their vaccinations before you know before they go out to the community. This is very important question. I think we need to then possibly clarify this point is do you recommend a half dose booster or a third full dose of Moderna for immuno compromised people? I'm not aware that any of you recommended not giving the full dose booster vaccine. Could you both, could you both clarify that the three dose series that an immunocompromised person gets his full dose? What the questioner might be confusing is when Moderna comes forward on thursday with their eu a packet to FDA Moderna's coming with a request for that booster for non immuno compromised people to be a half dose. That's a different situation than the three dose primary series and immuno compromised people. Thank you for making that more clear. Did you want to say something dr shaw? Yes I was just going to add that. We recently had this article published in doing the Journal of Medicine in which in Canada they actually did look at Moderna 1st 1 $20 Robin transplant patients and they got the three series of vaccination and those patients had a good antibody response. But they also had a good T cell specific to SARS cov two response. So I think you know for solid organ transplant population or framing suppressed population. I think it's important to get the full benefit of these vaccinations. Now dr Poland there's a couple of questions about immigrants or people coming in from other countries that have been vaccinated. Would you be recommending that they get a booster vaccine when they arrived here in the United States? That's probably a big depend but I'll defer to you. Yeah Claudia. This is a really good and obviously with afghani refugees coming into the country Pressing one. We've seen evidences of measles and mumps outbreaks undoubtedly we'll see some malaria. Um what to do about covid 19. Well if they were immunized there's likely no record of it. And so we would probably start a fresh if they were immunized and had a record. They they're highly it's highly likely that they got a vaccine that is not approved in the US. And where if we do have data suggests that it's a much lower efficacy. Um and so I personally would probably start a new with it. But but I will say I will say there's been no official guidance in that regard yet that will be coming given the current political situation. During our I. D. Week conference, you bring up a very important point that other countries are seeing escalation of HIV TB and malaria because of the covid pandemic. And we'll probably be hearing more about that on our next webinar. There's an interesting question here for specifically for Minnesota. But I think it's a proposed for everybody is what is your recommendations for upcoming holidays? Um there's a concern about the high rate of delta that you're seeing currently right now in Minnesota but could you both comment as to what precautions you would recommend to families for the holidays. You want to go first or do you want me to? I can go first. So I will say, I think it's extremely, extremely important to take precautions. One of the last slides that I showed was that even in patients who have milder disease, you can potentially have pretty high wild count. So I think it's important to ensure that you are still taking precautions wearing your mask and doing social distancing. And um, I would say from my own experience and I know dr liberty, you would, you know, echo the same thing in our covered ground to be the most disciplined rounds that we have, uh, solid organ transplant population. I saw a big jump. They got their vaccination and we started seeing some patients come in and they will tell us the same exact story. Oh, I got my vaccine. I thought is I'm totally okay meeting with my family members and you know, going out for dinners and going out and the second they give away those precautions. You saw a huge influx of hospitalization. Whereas in the first initial half and I remember talking to dr Pauling monday like it's actually pretty interesting. We're not having much admissions for solid organ transplant, which I thought in my head that would be the first group of patients showing up on our doors and we didn't see that. So it tells us how good those measures can help you So please police fees. You know it's important that you spend time with your family. But the same time it's important to make sure that you're protecting your loved ones and you're taking all the precautions to make sure that you continue to have multiple multiple more holidays together. And you know in florida in florida you guys can have your holidays outside Minnesota that's a little a little harder. But and you know again it's not just covid 19 that's the more dangerous one. But you know imagine in immuno compromised or solid organ transplant patients having to deal with prosthesis or influenza. Um you know last year in the us there were only 2400 documented cases we've already seen more than that this year. Because, yeah because people are pretending the pandemic is over. So as you know overall in the US cases have decreased hospitalizations have decreased thus far are limited. History with this virus suggests that as the colder weather comes and as people abandon precautions that the history suggests that we will see yet another surge because of that. So absolutely agree with dr shaw that distancing masks and vaccinations are the key to trying to do this safely. It's that layering of protection. And if somebody is symptomatic they unfortunately should protect them protect other people by not commingling or keeping their distance they go to their room or symptom they go to their room and think about why they got in fact so dr Poland er doctor shot. Do you want to make any summary statements at this time? Dr pol and I'll let you go first. Okay well you know I think we're going to see a lot of data about Moderna and J. And J. I didn't mention it in my remarks but a lot of concern among my patients who did get J. And J. Worried that you know I got an inferior vaccine. How come there's no booster for me. You know type type of thing. We will have those data. You will see those data. You will see the mix and match data this week and I think people will be impressed. Let me put it that way. You're going to be very very impressed overall. You're going to be impressed with the safety. You're going to be very impressed with the immunogenicity. Um And and Claudia again I didn't mention it. I'm very thankful you did for the woman planning pregnancy or who is pregnant. There's there's a series of vaccines you need not be afraid of. We have good data. We never have perfect data but you incur a far far higher risk not getting vaccinated than by getting vaccinated. And that's true for everybody who has not yet been fully vaccinated. Thank you so much. So I would echo a doctor Poland just mentioned. I think there's a lot of new data that's coming up and hopefully we'll be able to have more answers for you. But I think it's very very important that you do get vaccinated and you do protect your loved ones, especially with the holidays coming up and together as a team as your providers and physicians and and we'll be able to, you know, be able to get a control over this virus. So until then we thank the panelists and we thank you very much for attending and we look forward to having your participation in our future webinars. Thank you. Thank you. Thank you. Be safe, everyone be safe. Yeah.