The COVID Countdown: The Latest in Safeguarding Protection and Treatment for Vulnerable Populations
New Medscape live app. You can [Music] [Applause] Morning everyone. Happy windy, rainy, kind of spontaneous weather Sunday. Hope everyone had a good journey into Atlanta. We’re honored that you’re here. Show of hands. Who is an infectious disease doctor? What about working in pharmacy? Researchers, public health officials, educators. I’m missing a massive group. But regardless, I don’t think anyone in this room needs any type of call to urgency for the fact that even though CO may not be appearing in headlines every day, it is far from gone, if it ever is going to. So, thank you for joining us for this Medscape Live newsroom event as we talk about safeguarding treatment and making sure that we’re doing everything we can for vulnerable populations. It is an honor to have you all here. Do I have a clicker? Yes, I do. Is my clicker going to work? Is the second question. So, one thing I want to make sure everyone does is take a take a moment to scan the QR code and get on to Medscape’s portal. So, not only will you be able to interact directly with the slides, we want you to submit questions to try to stump our expert panelists at the end and also you’ll be able to participate in polling, password, ID week, connect to the Wi-Fi network. And just so you know, throughout this presentation, I might be jumping off stage and I might be running around in the audience with the microphone. We’re all friends now. You’ve eaten breakfast, you’ve had oatmeal, you’ve had coffee, and we want people to participate and kind of share your expertise with us as well, your experiences and what you’re seeing in your patient populations. So, with that, we’ll do one quick intro video and then we’ll start the party. Welcome to the CO countdown. The latest in safeguarding protection and treatment for vulnerable populations. SARS Kovv2 infection continues to pose a significant threat to vulnerable populations, including individuals of all ages with underlying medical conditions and those aged 50 years and older. In addition to vaccines, postexposure prophylaxis can help protect such individuals from complications of CO 19. [Music] Over the next 90 minutes, we’ll focus on the continued burden of SARS Kovv2 infection in vulnerable individuals with the aim to enhance long-term outcomes for atrisisk populations. We’ll explore emerging preventive strategies and share current evidence about the efficacy and safety of new agents. We’ll also discuss the possible clinical applications for new interventions when they become available. Join us as we navigate this important and timely topic. Right on. So, quick introduction. People are like, who is the loud person yelling from the newsroom sign? My name is Dr. Alok Patel. I am a journalist at ABC News. I work with Medscape Live and I’m a pediatric hospitalist at Stanford University. Listen, I like bash my head on the wall sometimes because I’m like, you know who else is vulnerable? Children under the age of one and with underlying medical conditions. So, I share this sentiment with all of you that we need our advocacy and our voices to be louder. But I will turn it over to the esteemed chair, Dr. Hayden, to introduce himself and his panelists. Thank you very much. And good morning to everyone. Um, I’m Fred Hayden. uh am ameritus professor at the University of Virginia and it’s my great pleasure to introduce my two faculty colleagues first Allison McGear who’s professor of laboratory uh medicine and pathobiology at the University of Toronto in Canada and Allison has experience with all the uh corona virus events over the past several decades including uh SARS which disproportionately really impacted Canada with the highest number of cases outside of the Asian countries including several deaths in healthcare workers. She’s been a consultant for World Health Organization on the the ongoing MS uh uh events and uh of course like the rest of us was heavily involved with response to COVID 19. Um Shir Shoam is a professor of clinical medicine at John’s Hopkins uh University School of Medicine and he has been involved uh with the CO 19 response as a in many ways but also as a member of the uh IDSA uh COVID guideline uh committee that helps provide guidance to uh on the use of our current interventions. So with that background, I’m just going to take you through quickly the the agenda. We’re going to hear from Allison really about uh epidemiology uh at at present with regard to SARS KV2. Uh Shmeir is going to then deal a little bit with disease pathogenesis and and start the discussion with regard to interventions in including both uh prevention as well as treatment. But uh in In the midst of that, I will talk a little bit about some emerging interventions with regard to postexposure prophylaxis and then he’ll finish with uh a discussion on on treatment updates and then finally we’ll have some interactive discussion with regard to some clinical uh scenarios. So with with that background, let me then turn it over to to Allison. Thanks very much, Fred. [Music] Okay, so here we go. Uh, so the first thing to remember about CO is how much better it is than it was at the beginning, right? So this is a CDC graph of mortality due to CO 19 from 2020 to 2025. And you can see the really dramatic decline, not unexpected with pandemics as both vaccination and uh infection have increased immunity at the population level. And if you want to think about the relative size of that, the most dramatic place to look for it is in residents of long-term care on the frailst and oldest of our subops. I couldn’t find any US data on this. So these are Canadian data in blue from Vancouver and in orange from Ontario. um looking at the case fatality rate for symptomatic COVID cases in long-term care which started at about 27% in 2020 um decline that you see the first decline before we actually had vaccines available uh and then all the way out to 25 26 um when just at the beginning of the season on the September outbreaks we’re talking about a rate just below 1%. And you think you you look at the last and you think well that’s not a dramatic decline. But if you expand it looking from 22 23 to 24 25 you can see there’s nearly been a 70% decline in case fatality over the last three years. So last year in Ontario was the first year that more residents died of influenza than died of COVID 19. Uh which is like good news and bad news. Okay. Right. because now we’ve got a disease which is not worse and maybe a little better than influenza. And the key question of course is is it going to stay like influenza where we’re really going to badly need interventions and prophylaxis uh or is it going to continue to decline over time and become something like seasonal corona viruses where decisions about treatment prophylaxis may be a little bit more difficult. And here’s now US data for the 2425 season where you can see that the number of hospitalizations and the numbers of deaths are now within the influenza range. Right? In influenza’s got a much broader range because seasons are available. Um but the estimated COVID hospitalizations and deaths are now at about the level of a active H3N2 season. our worst kind of influenza seasons. And as you might expect, uh SARS KV2 has continued to evolve. So these now are again, uh CDC data looking at the evolution of variance over time. And the great majority of isolates we’re seeing now um are XFG. Uh and here’s data from Floren Kramer’s group looking at what that means in terms of protection. on the left hand side you you can see JN1 KP2 which are the two uh the antigens in last year’s vaccine drifted a little bit the first highlighted rectangle is LP8.1 that’s what’s in the vaccine this year and then over to the right of that is XFG and you can see there’s a little bit of a drop from LP1 to XFG but not dramatic and on the antigenic cgraphy further on the right you can see that LP 8.1 and XFG are pretty close together, but at a fair distance from um the KP2 and JN1 the year before. So um this is good news that what people have chosen to put in the vaccine this year looks pretty well matched to XFG. Of course, what might happen over the next eight months during the season um still an open question. What have we seen so far this season? Um, it’s been pretty similar across all of North America and both the US and Canada. And you can see that there was a peak in activity uh in September, which has declined pretty rapidly both in test positivity uh and in hospitalizations. And what you really want to know is okay, so what does that mean for the winter? Uh, and this is what it means for the winter. I think if you’d asked any viologist in March of 2020 whether by 2025 we would have stable seasons and we would know what were going on, they probably would have said, “Yeah, they thought so.” But it’s just not true. So this spaghetti diagram is from the John’s Hopkins hub for modeling. So it’s every modeling group looking at what’s going to happen with COVID this season. And you can see um that it’s really all over the map. very hard to predict what it’s going to do. And the little gray circles are what it’s actually done so far. So, in terms of that, there are some models that looked pretty good up until September, but none of the models depicted this really sharp decline we’ve seen in September. Uh, so, you know, this is really a suggestion about hope for the best, but prepare for the worst, right? I I’m looking at that decline and dreaming that we might have a really quiet COVID season this year. Uh you know, but my rational brain is telling me that we’re probably going to have some kind of season uh sometime later in the year. Um and consequently, it it it would be silly not to be prepared for the season coming in all of our patients. Okay. So then who do we have to worry about this year? This is a standard list of people at higher risk of developing severe COVID who you need to care for. People who are old, especially those who are frail, pregnant women, anybody with significant organ system disease, and uh anybody who’s imuninompromised either by disease uh or by therapy. And of course, within all of those risk factors, there’s a range from the lowrisk green to the high-risisk red. So age imunosuppressions obviously highly variable up to stem cell transplants at the end. Uh variation in whether you’ve had no vaccines or up to eight or nine vaccines, how often you’ve been infected. Um what your organ system disease is with a very clear increase both in severity of whatever your underlying illness is and in the number of underlying illnesses you have. Uh and then finally, you’ve also got to think about what’s people’s exposure risk. Not exposed to COVID, you’re not going to get COVID. Um and it doesn’t matter. And so people who live alone, work at home, are really careful about their exposures. One category of people, people who live in large multigeneration household, work in long-term care, um have much higher risk of acquiring disease and consequently more risk of severe disease. The biggest risk um as is generally true about infectious diseases has to do with age. And so this just shows you that difference between the rate of hospitalization due to COVID and 30 to 39 year olds um is about 40fold less than in 85 plus. So really greatest increase is with increasing age. And that’s partly this is not adjusted for disease. So that’s partly just age and it’s partly that as you get older you tend to accumulate chronic organ system disease uh and that contributes to the increase as well. So first of all age uh and then organ system disease not as the highest risk but as the most common of underlying coorbidities. And this just graph just shows you the increase consistently no matter what you look at as an underlying disease. When you add coorbidities in that organ system or others, your risk tends to go up. Uh in cardiac disease does tend to have a higher risk um than others, but really they’re all relatively similar. And then there’s imunosuppression. And as we all know, imunosuppressions become a lot more complicated with the uh increase in biologics that we’re using. Uh and the easiest way to look at I find is to use the new IDSA guidelines that stratify uh higher risk, moderate risk and low risk imunocmpromised patients. uh and up at the top always recent stem cell transplant or people who have ongoing graph versus host disease after stem cell transplant hematologic malignancies lung transplants here lung transplants with COVID are a little different than solid organ other solid organ transplants and that’s different with COVID and other diseases where it really does look like lung transplants have a specific increased risk uh of severe disease with COVID. Uh and then solid organ transplants, um uh current active therapy for cancer, um HIV infection with low CD4 counts, and in the lower risk stable HIV infection, endstage renal disease on dialysis, uh solid tumor. Uh and here’s a just the range of risk. So you can see the quantitative differences in size from the UK informed study looked at a quarter of the UK population and stratified disease rates by um particular situations. So early stem cell transplants have a highest risk still lower right than age 80 to 30 but really significant. As you get further out from your transplantation the risk declines. Um next in line hematologic therapy. people with B cell therapies, um people with solid organ transplant. Interestingly, solid organ transplant risks appear to stay stable over the first four or five years. And then solid tumors with active therapy and down at the bottom significant but now moving into the same risk as other organ system disease, people with endstage kidneys disease, people with uh solid tumors who are more than a year out uh after cancer therapy. Uh so it really adds to the complications of thinking about how you’re selecting people uh for both treatment and prevention the the really wide range of increased risk um that you now have to deal with. Thank you. I think, excuse me, not only is it important to give everyone an overview and to highlight the atrisisk groups for practitioners, but also so our patients and the public know, oh, I’m high-risisk. I should probably go and get treatment, get vaccinated. So, thank you for that. We’re going to pass it over to Dr. Showum to talk about ongoing challenges with providing care for those with severe CO 19. I’ll tell you from the [Music] I was going to say from the PE side the challenge is do I call an ID consult at 2 am or do I let my colleagues sleep until 7 a.m. That’s my challenge. You can call the fellow. That’s fair. That’s fair. I can call the fellow. Take it away, sir. Great. So, uh, I’m going to talk about the challenges to providing care for severe COVID. And, uh, uh, the important things that you’re going to have to know is the epidemiology in your community. And that’s why the the things that Dr. McGear was talking about are so important. And you’re also going to need to understand the pathophysiology of COVID. Uh, and I know that half the eyes in the room just rolled when I mentioned pathophysiology, but I’ll show you why it’s so critical. Next slide. Um, so, uh, before I dive into that, I’m going to ask you guys, what are the challenges that you face in practice when providing treatment for patients with COVID who are at risk for developing severe disease related complications? ask doctor because I know someone has a challenge that they want to share with us when it comes to treating patients with severe CO this table. Does anyone have an either one of you have an opinion about challenges you run into when providing treatment for patients with severe COVID or who are high risk? Some medications are not uh um you know there are age limit for the some medications for children. Preaching to the choir homie give me a fist bump. over here. Does anyone have another barrier they run into or another challenge? Gentleman with the dapper scarf. You got a smile on. Do you have an opinion? That’s okay. Still, it’s still a dapper scarf, though. What about this table right over here? Surely when it comes to identifying patients and risk prescribing behavior what you’re doing inatient anything you could think of that might be a challenge or something difficult that’s okay I will toss it right back to my panelists I I agree with the assessment about age are there any other challenges that you feel people run into uh so for me the biggest challenge is to identify which patient is going to benefit from therapy And I’m going to show you a slide which uh will illustrate that. But I’m gonna maybe make the manufacturers of the antivirals unhappy here. But most people do not need antiviral therapy for COVID, but some do. And uh this is uh a slide looking at the right patient, right drug, right time. And I’m going to walk you through this. So you have sector one, Roman numeral one. uh and then sector three and then in the middle is sector two and this U-shaped curve is the heart and soul of the pathophysiology of COVID. So some patients like the one in sector one which right now in 2025 are those patients that Dr. McGear talked about with the bone marrow transplant and the rettoximab therapy and patients that just cannot control the virus on their own. They’re going to get a lot of damage caused by the virus. Their immune system may contribute a little bit, but they’re going to have most of the damage caused by the virus. So, the key to those patients, even if you didn’t catch them early, is to treat them with an antiviral. The earlier the better, but these patients may smolder along for a long time. Anybody in the audience have had a patient with protracted COVID, not long COVID, but protracted COVID where they’re just persistently positive and symptomatic. So, you’ve seen them and was that patient on rettoximab or some sort of uh B cell depleting agent? Almost all most that’s exactly going to be the patients that you’re going to see. So for those that didn’t hear those he he mentioned almost all those patients were on rettoximab and that’s where you’re going to need uh antiviral therapy and sometimes combination therapy uh to really knock down the virus and allow them to get better. On the other extreme are the patients that um either by the time that you got to them or maybe they were just started out that way they have a way overactive inflammatory response. An antiviral might help a little bit to if you can say um u source control the antigen that’s leading to the problem but probably not. their body is probably doing a job that’s better than most of our drugs at killing the virus. Their problem is that they’re overreacting to the virus. And then you have group two, which uh even in the worst days of COVID was most patients. They were either asymptomatic or they were moderately symptomatic. they uh never touched the emergency room or and they what they were really good at is passing COVID to the other people that are in the the the bad groups. And early on you had another problem where you had a high viral load that the body was ultimately going to control. But before the body controlled it, either because of their underlying disorders, congestive heart failure, chronic lung disease, they went out of homeostasis and had decompensated disease, or their immune system took over and shot them over into uh zone three. So, one of the most important things that remains is identifying where your patient is. And some of the things and excuse for me for this uh uh complicated slide, but the main thing I want you to take is if you’re going to treat the infection in most patients, the time to treat them is early on. And uh because by the time that uh uh their SARS Kovv RNA level is through the roof, then it uh it may be too late for those phase three people and it may be uh unnecessary for the people in group two, but uh it could trigger a response that shoots the person into group three uh where they uh have uh an hyperinflammatory response. So early uh is important but not everybody needs treatment. I’m going to go back a couple slides. So who are those patients in group two? So those patients in group two are going to be all the patients that have an intact immune system and have immunity against uh COVID. So, uh, patients that have had previous disease, patients that have been vaccinated, uh, and additionally patients that, uh, just don’t have the risk factors for progression. Uh, anybody know the story of the three bears, Goldilocks and the three bears? Raise your hand if you know it. Um, so you want the patients that are in the baby bear category in terms of those patients that you don’t need to treat. Now, interestingly, I was talking with a group from Sweden, and did you guys know that in Sweden they don’t know about the baby bear story? Because I was telling them, oh, you know, it’s the Goldilocks effect and they looked at me blank and I But so, if you have friends in Sweden, might be good to introduce them to this story. Um Um So, again, early on, that’s where you want to hit them. by the time that they’re in the orange critical illness, uh the antiviral may have a role, but the main thing you’re going for is controlling inflammation. And uh with that, I’m going to turn it over to Dr. Hayden to talk to us about how to make that group two even bigger, the people that are not going to necessarily need therapy. through just a few moments with regard to the prevention strategies. Ah, thank you. All right. I I I jumped the gun. Sorry. So, uh this is an overview in terms of uh prevention uh postexposure and intervention. So, we’re going to uh uh look at the three sectors. Uh all right. So, by the time that you’re done, there’s going to be an exit exam on all of this. So uh um no this is just to show you the huge effort between industry, between government, between public health organizations, between uh patients that volunteered for the studies uh as to uh getting the data that uh we are working with um uh and uh uh the first approach is prep uh pre-exposure prophylaxis to prevent infection. ction if exposure occurs. And uh uh the first part of pre-exposure prevention, not necessarily prophylaxis, is vaccinating people. So um who are you going to vaccinate? So repeat dosing of COVID vaccines among lower risk patients, the benefit is uncertain. I’m not saying that there isn’t the benefit, but it’s uncertain and uh you’re maybe not getting that much juice for the squeeze. We also know that the uptake of annual COVID 19 booster vaccination has been poor. I see this in my patients and I treat transplant and oncology infectious disease patients, the higher risk people and they have vaccine fatigue. Uh so uh also there’s groups uh there’s communities where vaccination is uh looked at with a little more skepticism than other communities. So it’s important uh uh when evaluating whether your patient uh should be vaccinated to know about the epidemiology to know about the pathophysiology to know about the patient type. But it’s also important to be sensitive to uh the other factors that are going on uh individually and in a community that are impacting their decision to uh vaccinate or not vaccinate and to do appropriate education and and I think we’ve all learned that appropriate education is not me doctor you patient this is what you do. It is much more nuanced than that. Um and we anticipate that future COVID 19 vaccines will be restricted to certain high-risisk groups and uh uh as the data interacts with uh culture then uh I think we’re going to learn much more about that and uh we also anticipate that study data will be required by the FDA before approving vaccines for those that are uh at uh the lower risk group 6 months to 64 uh years of age without a risk condition. Uh these are the available vaccines that are there. Uh they are all approved for people over the age of 65, 65 and older. And uh they’re all approved for younger people providing that they have uh a risk factor for severe disease or or more than one risk factor. And you can see the different uh um uh specificities of the vaccines. All right. So what does the vaccine give us in 2025? Um and this is uh uh co data is always uh it’s like giving insulin. It’s always like you’re working backwards. you’re working for the sugar that uh with the sugar that you have the information but then you’re uh trying to make extrapolations. So this is what we know about effectiveness versus hospitalization for the 2425 dose. Not yet for the 25 26. We’ll know that in the future. So 40 to 45% is pretty much what you’re going to get in terms of vaccine effectiveness. That means that if you don’t get the vaccine, whatever risk that Dr. McGear was talking about, that’s going to be your risk. If you do get the vaccine, whatever risk that Dr. Mcere talked about times 045, that’s going to be uh your risk. So, uh if you are a super low risk person for having hospitalization from COVID, you’re going to be super duper low risk. you then may decide whether that’s a uh an effort that you’re willing to make. If you’re at higher risk, then you’ll go to about half of that uh or so uh risk and it’s probably going to be worth doing. Other things that can be done but are complicated is preexposure prophylaxis with a molecule. So uh we used to have um a lot of monoconal antibodies they were available but the vaccine develops resistance to it uh at the binding site of the vaccine to the receptor and uh they’ve all become um uh either useless or very close to that. uh pivart is a monoconal antibbody that has still retained efficacy to a certain percentage of covid uh strains uh and the um percentage that it’s effective differs by the different areas uh of the world. Uh if you identify a person that has moderate to severe immune compromise either due to their underlying conditions or to the treatment that they’re having and therefore unable to mount an adequate immune response to the vaccine, you’re still going to want to vaccinate them, but uh you’re not feeling all that confident that they’re going to get a response. either they’re on uh they’ve gotten the rettoximab, they’re getting uh heavy duty u imunosuppressive medications for COVID. So you want to try to give them a little something extra and uh pivart could be that thing. Um how do they know that pivart is going to work? uh so uh there is an ongoing clinical trial but that takes a long time to recruit patients and to get the end points. So what they did is they looked at the antibbody concentration that people that got that stuff have and then they compared whether that antibbody concentration was going to be enough to control the virus. They did it both uh in in in vitro. They did it in uh uh uh different uh assays measuring the concentration of antibbody that’s achievable in the person and then they compared that concentration to other drugs that were successful when they were effective. So that’s called immune bridging and um and based on that the uh uh FDA felt that that was enough data to say okay this is going to be uh likely effective providing that the virus in the community is uh uh still sensitive in terms of toxicity. Um the most common toxicity was going to be uh infusion related reactions. uh people have different reactions. Um about uh 3.6 to 2.2% uh rate of uh uh adverse reactions from infusion. A very small but not zero percentage of patients that got pivart developed anaphylactic reactions. So um when you give this drug you can estimate that if you give it to a zillion people some of them are potentially going to have the anaphylactic reaction and that’s part of the decision tree that you make it you make in terms of whether to give it. So putting all that together, uh the IDSA recommended that in patients that are in the high risk and moderate risk group populations that this could be considered as uh a way of preventing COVID providing that the vaccine in your community is still sensitive to that. So who are those patients? There are those patients that we talked about that got the rettoximab. their patients that have lung transplant because it’s incredibly inconvenient for a lung transplant patient to have COVID both the direct effect and their the their immune system can overreact and hurt the graft. other patients you can see in the box solid organ transplants other than lungs patients with uh uh uh graph versus host disease that’s moderate patients with HIV that has a CD4 count of 200 but if I was really going to focus on the top patients to give this to it would be the ones in the top box. All right. So now a question to you guys. Does anybody use prep in this room? Where are the primary care doctors? Any in here? Family medicine, internal medicine. What does this table do? I’m curious. Right on. Okay. But you’re primary care. Oh, right on. ID. Okay, cool. this table. Are you guys practitioners? Just fans. Pharmacist. You guys are practitioners. Well, you’re indirect patient here, which counts. How about this? I just want a show of hands. When it comes to using prep in patients, who would surmise 0 to 30% of patients with underlying medical risks are getting prep? Show of hands. 0 to 30. No one. No one’s voting for 0 to 30. What about 31 to 60 middle tier? Any show of hands? You can guess like I’m not gonna I don’t know the answer. Okay, we got one person. So, the rest of this room thinks 62 to 100% of patients are getting prep. Right on. Z. What did you say? Zero. Zero to 10. Panelists, what do you think about our very interactive audience right now? For now, you guys, don’t worry. I’ll dial it up in a sec. What percentage of patients out there are actually getting prep who you feel qualify for it? Um I I think it’s approaching zero. You’re right. And I’m just going to see if I can take you back. So in the green in moderately or severely immuno compromised individuals the IDSA guideline panel suggests pre-exposure prophylaxis when predominant regional varian susceptible in many areas they’re either not susceptible or close to it conditional recommendation low certainty of evidence. So, I’m not going to say that that is a resounding recommendation. And I think that it plays out in that you see a lot of patients, you’re busy, uh, and the logistics of getting them the drug may not be straightforward and, uh, you see this recommendation, you see your patients, and it’s just hard to get very enthusiastic about it. Dan, thank you. So, now we get to pass it over to Dr. Hayden to talk about clinical evidence for emerging co 19 interventions and possibly moving from prep to PEP. So before I do that, I’d like to ask a question regarding another strategy that you didn’t mention and it’s something that we’ve embraced with influenza vaccines now with RSV vaccine in terms of cocooning and trying to protect those very very high-risisk individuals by making sure that there’s uh im immunizations been given to their all their their close contacts. Yeah. Um so um I I think that uh creating a cloud or of protection around the patient is very important. What’s the uh where are you going to get COVID? At home who’s going to bring COVID? One of the people that you live at home with. So that’s why uh the slide that uh you had that if you are living alone and uh buying all your stuff on uh Amazon, I don’t know if they have Amazon in Canada then but uh uh then you’re much less likely to get COVID than if you live in a multigenerational home. Um and so cocooning is very important. I would also add another strategy which is super important is that patients are educated that when they have the early symptoms then they get tested uh to find out what’s going on so that early treatment can be uh started and we’ll see what uh Dr. Dr. Hayden has to say, but it might make sense also that if somebody in your home has a symptom, then they get tested as well so that potentially postexposure prophylaxis can be done. Indeed. So, I’m going to try to [Music] it’s the hype music. Uh I’m going to talk to the issue of of using postexposure prophylaxis. This is something that’s been shown to be very effective uh in terms of reducing transmission to contacts in the in the household setting with influenza. We have several agents that are that have been proven to reduce that risk by 80% or more. But timing is such a critical variable here and that’s true for all the respiratory viruses. And again, a lot of this work has been done in the household setting because that’s where a lot of transmission has occurred historically and continues as is a risk situation. Uh I want to emphasize though that none of the agents that I’m going to talk about is has been approved by the regulatory agencies for postexposure prophylaxis. U there are some agents that are interesting that that are uh where there there is all fable use but we yet as yet as we speak today do not have an an agent that’s approved although one is under review currently. So this comes to a key question. What patient populations would you prioritize uh for COVID postexposure prophylact prophylaxis? Uh and how do you stratify um risk in in the practice setting? I think we’ve touched on the latter to some extent, but I’d be interested in knowing what the audience has to say about this. I’m also curious and I I’m curious on my ID squad over here with patient populations. You might be really pushing up there for co PEB I would uh look at your your IDSA guidelines and look at the group that’s in the highest risk. Retoximab for sure um probably stem cell transplant patients would be in that group but the highly immune suppressed individuals uh would probably be my key target. This staffer table, what do you all do? Not prescribed physicians. Let me ask you all a very important question though. Have you ever stepped on a nail or like cut your hand in some dirt or something like that? Did you go have to go get pro posters for a tetanus? What determined whether or not you had to get that? Right on. Did your doctor ask if you had previously gotten a tetanus vaccine or anything? Yeah. Cool. So, this is I’m This is an educated guess. Do you, this is an educated guess. Do you think that plays into whether or not people with CO 19 would need to get postexposure prophylaxis whether or not they’ve been vaccinated? Absolutely. Yeah. Right on. Cool. You all agree with that assessment? I got a great answer out of them and they said they were not practicing practicing providers. Does vaccine status play into whether or not postexposure prophylaxis would be recommended? So, in terms of vaccine status, uh how likely the person is to respond to the vaccine. that would be uh an important thing. But the other group that I would add is frailty. So uh this was a study that was done in Japan but uh it I think it is applicable to here. Um frail people they got admitted to the hospital with COVID uh had a substantially higher risk of not coming back home uh for whatever reason uh either to uh either dying or long-term care facility than people who weren’t frail. So I think that goes into the uh calculation as to uh how important it is to prevent uh COVID in an individual patient and what their values are. We don’t we don’t assess frailty routinely. So you don’t see a lot of studies looking at the assessment of frailty but in influenza frailty is as important as age. So top of the list and and it’s almost certainly true for co as well. So I’m going to add two other people. The people we really want postexposure prophylaxis for people exposed in the hospital. So people in shared rooms with somebody um with new onset COVID noscomial COVID has a very high case fatality rate. Um and long-term care homes, you know, whatever the individual level in long-term care homes may not be important, but antiviral prophylaxis for influenza has been a miracle in long-term care homes just shortens influenza outbreaks means that you know you don’t have visitors out and all sorts of chaos for as long a time and having COVID prophylaxis would be um really really helpful in that setting. And in the influenza setting, it’s that intervention in in the chronic care facilities is irrespective of their vaccine status because we know as was shown for COVID vaccine that that protection is incomplete at best. And so that uh if you’re really trying to pro protect someone with flu, you give them postexposure prophylaxis or even in some cases longer term. Um so let me uh then touch on again some of the older studies first that have uh addressed this uh question. These are all done in household settings. The first of these with was with the uh dual monoconals casariv and indiv given subcutaneously within four days of exposure to the index case in that family unit. You can see a relatively large number uh were enrolled in the study and the the risk of COVID was significantly reduced over the following 28 days because of course the antibodies have a long duration effect uh with a relative risk reduction compared to placebo of of 81%. Of course this this intervention would not work uh currently in in uh because of the the changes in susceptibility of our of our varants. There was a a study with near material vertanavir that followed on um with the standard regimen given either for five or 10 day course is is postexposure even a larger study numerically. You can see that there was a reduction. Um here there is a smaller event rate though uh in uh the placebo group. You can see just under uh 4% there. And and the overall relative risk reductions were were more modest. they didn’t reach their primary endpoint somewhat better with the 10-day course of of of postexposure prophylaxis and that’s consistent with what we think is happening within the household setting. Most of those transmission events are within that 10day period. Events later on are more likely to have been acquired in in other uh settings. Mul puree was also uh studied for postexposure prophylaxis and here the uh it was only a five-day course and it was given um it had to be done within a five-day uh uh exposure period to that initial index case. Again um the it was a more mazda effect with regard to only 24% relative risk reduction in in the events. But there were a lot of cases apparently that uh came up between five and 10 days. So that five days isn’t going to be long enough. Be interesting to of course uh see what would happen with a with a longer duration in a study like that. So those are the some of the older data. These are all studies that have been reported um in 2025. Um I’m going to start with um the uh as lasting one which uh is at not a post exposure but a pre-exposure uh and similarly and talk briefly about the interferon study which was also a pre-exposure. So as elastine is a uh antihistamine which is improved nasal spray u for treatment of of allergic rhyitis. It it does uh have potential side effects of of sedation uh as as well as apparently a bitter taste. So, it’s very difficult to actually blind a participants in a placebo control trial. But in this particular study, they used it on a three times a day uh basis for uh as you can see 56 days um uh in a in in fairly moderate sized number of of participants, many of whom were healthcare workers as it turns out. And there was a sub and they were also sampled uh on a twice a week basis to detect SARS KV2 and there was a a significant reduction overall in in in the rate of infections in in COVID was also reduced with with roughly a 70% relative risk reduction and interesting there’s also an effect on on rhinoirus infection. So this is this is intriguing result that I think certainly needs to be uh further explored in in larger numbers. uh and um there had been some rationale for this provided by uh earlier work uh that showed the potential for antiviral effects related to either viral entry and or uh possibly uh inhibition of the of the 3CL protease of of SARS COV2 and and one small treatment study suggesting an antiviral effect. So I think this is this is an agent that warrants further um study and potentially could be one that could be considered for post-exposure prophylaxis. The alpha the interferent alpha story is is is interesting in that they they they really looked at high-risisk patients. They focused on um a group with different types of malignancies about half of which uh had hematlogic malignancies and they went for a as you can see basically a three-month period using very low doses of a recominant interferon alpha 2 um and but did see some effect. uh this the dose that they use is much lower than ones that we and others had studied historically to to show reduction in uh rhinoirus coals in in when used for postexposure prophylaxis and this is an intervention that I think should be looked at but with higher doses uh going forward but again as a potential for postexposure prophylaxis so then finally let me talk about the agent that I’ve I’ve been involved with uh is a consultant to shanogi uh and and that’s in centravir which is a 3C proteiase inhibitor and I’ll show you some more information with regards to its background but in in this in this particular study u the standard treatment dose that’s currently approved uh in in Japan uh given for uh for five days uh in a large number of patients did have a significant impact uh uh with regard to preventing COVID in the household setting with a 67% % relative risk reduction. So just some background information for you with regard to treatment because again this agent has been used in Japan since 200 uh uh 22 and I think was approved in in 2024. Um it’s approved for treating mild to moderate COVID 19. It has an interesting ph coinetic profile and that it has a prolonged plasma elimination halflife between roughly 50 and and 60 hours. So this means that there’s a need for a loading dose to get adequate drug levels on board. But it also means that there even with a fiveday course of delivery, there’s protracted uh presence of uh plasma levels that would be expected to be inhibitory for at least 10 days after that five day course. Um To my knowledge, there are no clinically important differences in exposure levels between the fed and fasted states or changes with age or or any really major changes with with changes in hpatic or or renal function. uh and there’s evidence from uh an aged mouse model uh of SARS COV2 where that target plasma concentration was protective uh against disease and in fact that has now been validated when in the postexposure prophylaxis setting where that level was certainly achieved out uh past 10 days in in terms of the treatment effects um there were significant antivirus effects documented in two phase three uh outpatient trials that have now been published. The uh figure uh shows the reduction from a baseline on day one uh to day four with nearly a log difference in terms of viral RNA uh loads uh that was seen in the uh HR study. that study was supposed to be in higher risk but in fact only about a third of the patients had had risk factors. In terms of clinical benefit uh in the standard risk group there was a one day uh significant one-day reduction in the duration of five COVID symptoms whereas uh in the HR study um it was a lesser effect at but larger number of of symptoms were included uh in the analysis. of of note uh over in uh in these studies there’s been a low frequency of viral RNA rebound observed um in terms of safety um intolerability it’s it’s been good to date uh in the in the phase three treatment and prophylaxis studies I’ll show you some of those data just in in a few moments um the no u excess adverse events treatment related adverse events including disusia or study drug discontinuation has been noted compared to placebo. In terms of laboratory uh there are dose related reversible uh decreases in highdensity lipoproteins and also sometimes increases in triglyceride concentrations but again these are are reversible and have not been associated with clinical events to my knowledge. However, the the there is a potential for drug drug interactions here because it is a moderately strong uh SIP 3A4 uh inhibitor and we can get back to to that issue because it’s an important one in terms of um whether what can be used in patients that are receiving some of the classic imosuppressive agents like cycllosporin and techrolyis. Um it’s an agent which has been carefully looked at in terms of treatment emergent uh uh substitutions. The the commonest of these uh are at the methionine 49 position with to lucine or isolucine. Um and those can be associated uh with uh particularly the uh the lucine substitution with substantially reduced in vitro susceptibility as indicated um in in the um high-risk uh Scorpio trial um where there were 945 exposed to the drug. The overall frequencies of subsequently detecting u treatment emergent variants indicated there one and a half% for changes at position 49 and and less so at position 25. Um in in in that study they did notice that the higher the the baseline viral loads the the greater the likelihood that there might be treatment emergent uh resistance which is a not unsurprising result. The good news here is that um it’s a different pattern of of substitutions than have been seen for example with near metrover so that for almost all for these um rimmed desae and near would be expected to be inhibitory um and and also the the the clinical uh consequences of this are not clear at at present time and of course this depends of on the degree of viral fitness and and whether there also effects on uh replication or or transmissibility from person to person. But in the standard risk trial, the median time to recovery w was similar in in patients with or uh without these treatment emerging uh substitutions. So let me just show you a more detail with regard uh to the um trial that looked at uh incept for postexposure prophylaxis. I’m sharing slides that I presented at the Croy meeting uh earlier this year. Uh this outlines a study designed for you. This was a phase three randomized uh placebo control trial involving nearly 2400 household contacts uh who you can see were enrolled um fairly recently in terms of the the co experience. about twothirds were enrolled in the United States, a quarter in Japan and then uh South Africa, Argentina, uh also contributed along with Vietnam contributed additional patients. So it was really an international uh study. uh the index patients in these households um had to have a a local test positive for SARS COV2 and as of course as well as symptoms and and importantly the household contacts in contrast to the earlier studies which generally had to be enrolled within four to five days here it had to be within 72 hours of the onset of symptoms uh in in the uh uh index uh patients uh and of course The contacts also had to be negative at a local test as well as basically symptom free. Um they were randomized to the standard treatment dose or placebo and then monitored with frequent nasal fingial swabs as indicated by the the asterises uh through up to day uh 28. the the data I’m going to show you focus on the modified to intend to treat population. These were all the randomized household contacts who had a central laboratory confirmed uh negative test for SARS KV2 at baseline about 10% even though they had been screened with local testing 10% roughly turned out to actually be positive uh for virus uh before uh starting their uh uh postexposure prophylaxis. And the primary endpoint here was the proportion of household contacts uh who developed u COVID 19. This again was confirmed in the uh central laboratory by RTPCR testing and and they had to have at least one of 14 COVID symptoms that lasted for up at least a minimum of of 48 hours and that was within that 10day uh period uh of of risk within that the household setting. Um this is the primary uh outcome in terms of the proportion of of the household contacts who develop COVID through day 10. You’ll notice it was uh in the placebo group it was uh 9% compared to 2.9% within Septravier. So that’s a very significant uh risk ratio. Uh so that corresponds to a relative risk reduction of of 67 uh percent. In terms of the occurrence of events over time, um the inentroe group is shown in the blue uh as you can see was well protected out to uh out through day 10. uh whereas in the placebo group events started taking off within several days after exposure after initiation of of of study drug and continued to accelerate through that 10day period. Uh thereafter the the the lines look pretty paralleled uh as these individuals were exposed to a virus in other settings. But of note there was really no um rebound and that that the reduction in the in the risk was maintained out through uh day 28. Now what uh there’s also uh of course a series of of uh prespecified analyses that we looked at in terms of subgroups to see who who would benefit in in given the context of our discussion about higher risk individuals. I point out that in the higher risk group which uh cor composed about 37% of of both the placebo and active uh study groups uh there was an effect seen the the risk factors here were primarily older age 65 years and above obesity smoking and to a lesser extent diabetes uh and and heart disease but in that group the point estimate of the relative risk reduction was actually 76%. So there was good good protection observed in that group as well. Terms of safety and these again are are healthy individuals for the most part uh without baseline symptoms. Uh so it’s a different question to address than when someone who’s act is already ill with COVID. Uh there’s really no differences in terms of treatment e uh adverse events between the groups in ter in terms of frequency or type. Uh you can see a very low frequency of serious treatment uh uh u uh treatment emergent and adverse events um and low rate of discontinuation. So that uh in ter both of these interventions uh um were were well tolerated uh no real difference between incept and placebo in terms of these the clinical outcomes and and no deaths or hospitalizations were occurred during the study. So this agent um has been accepted u the NDA for it has been accepted by the food and drug administration uh for uh for review for the prophylaxis indic indication in September. Uh hopefully the the action date of of uh June 16th will will will uh be sooner than that in terms of uh uh getting access to this intervention which I think clearly does show both uh uh adequate uh tolerability and effectiveness in terms of the postexposure prophylaxis uh indication. So question, let’s be a little panel discussion on this question. Okay. I’d be curious to hear um all three of your thoughts about how you approach PEP decisions in immunocmpromised patients versus those with other high-risisk coorbidities. I mean, Dr. Shom, you alluded to this earlier, but I’d be curious to hear what you all think. Yeah. So for uh postexposure prophylaxis uh say that this drug becomes available. The key is there a way to get rid of the uh feedback? Thanks. So the the the key issue is how much of a hassle is it going to be for me and for the patient and uh let’s assume that there is efficacy. So if the patient is on tacrolymus, cycllosporin, cyrolymus and I know how to adjust the dose of those, we’re good to go. If it’s going to be a black box where the patient might come back with tacrolymus levels that are through the roof and seizures because of tacrolymus or acute kidney failure, I’m not going to want to do it. So that’s going to be up to the company and to pharmacists to be able to give us a uh a rule of thumb saying okay you start this drug you knock down the tacimus dose by x amount you measure your level and x amount. One of the problems with uh giving uh paxlovid which was near matrella uh and ratanavir together was the ratanavir that is like a force multiplier for cip 3a4 inhibition. This is not an issue with this drug. The other problem was that you couldn’t measure tacrolymus levels easily in those patients because the lab didn’t want them if they have COVID since this is pre post exposure. They don’t have COVID yet. So you could send them to Quest Lab or wherever to get labs drawn. So I think that that those are issues that are going to need to be uh ironed out. uh and uh if the patient is in the higher risk group for having a bad outcome in terms of imunosuppression, I’m on board. I just in the study that I described um there were very few imunocmpromised hosts that were included and in in in particular those who were on agents like tacimus and cycosporin were ex excluded because of the uh reasons that you you’ve alluded to. Right on. Well, on that note, we’ve gone from prep to PEP to possibly getting into some conversations about treatment. But before we go there, I know I listen, I’m not going to jump in the audience yet, but I do feel like even if you’re prescribing or not or seeing patients, people do have some type of opinions about how cost effectiveness may influence whether or not people get these interventions. So, someone just yell out how cost might influence whether or not someone gets a treatment. Someone say something. Insurance possibly maybe hospital. How much a hospital is actually able to get this medication? What What other cost variables can people think of? Someone yell one or I’ll come down through the microphone. I I can tell a story about cost over. All right. So, uh uh one of my colleagues called me and they said that they that uh she had just come back from uh uh a uh doing a uh medical mission in Uganda and now she was uh uh about a week uh coming back, fevers, chills, feels horrible. So you know you think in your mind as an infectious disease doctor about uh malaria about salmonella about uh other uh deni but uh one of the things that uh that I mentioned to her I said what about uh covid or flu so she said she was ruled out for flu somewhere and that she’s doing a home covid test and she called me back a couple hours later and she said home covid test is positive so uh u she had uh covid she was feeling horrible She is in her 40s and she said, “What do you think about paxid?” I said, “Couldn’t ho.” So, uh, so she, uh, u, so I wrote her a prescription for paxid. And then she said, well, they said it would be $1,200, so I think I’m not going to do paxid. And I said, okay, fair. I think that’s a very realistic conversation we need to have. In the interest of time, I want to hear more. I want to hear more regarding Dr. show them about contributed co 19. Um all right so we’re into the uh purple part of the uh discussion interventions after in onset and uh here are the uh different tools that we have. So moving from uh uh left to right on my uh screen uh you have the virus and the virus engages with the receptor and we can inhibit that receptor uh both by natural immunity that has already uh happened um or vaccine induced immunity or you can give them uh a uh an antibbody and that antibbody can be a monoconal antibbody or it could be a polyclonal antibbody in the form of uh convolescent plasma or potentially hyper immune serum and uh if there’s a good fit between the antibbody and the u uh the virus then you can get blockage of the uh uh uh of the interaction between the receptor and the virus and then also you can decorate the virus with antibbody that then the immune system will come and kill them. So uh the problem is uh that uh uh the virus is constantly interacting with the immune system of vaccinated and naturally infected people and uh particularly in imunocmpromised patients the virus is not being completely eradicated. So then you have uh uh variants that are resistant to the either the monoconals to the convolescent plasma or to the vaccine and then those variants from uh generally immune compromised people are passed on to the community as a whole and then the uh the vaccine needs to be updated the monocone will stop working. Um so uh that’s that uh you can do a uh this uh RDRP which is RNA dependent RNA polymerase that’s a viral polymerase and just like we do with uh the uh early drugs of HIV like ACT and the other uh nucle uh nukes uh just like we do with valet cycllovere with g valanty u and you can u uh affect the polymerase in this particular case the RNA polymerase is affected by remair and um and then this other drug called VV16 and that inhibits that uh and then you uh you can also do a uh uh an approach with u uh the uh viral uh uh protease inhibitor. So uh the virus is uh put out together as this large uh poly protein and then just like with HIV and with other uh protease inhibitors a protease comes by and snips things to the right uh place where they need to be snipped and then the virus can package itself and move on. The target in COVID is something called MRO. Uh it has another name which uh Dr. Hayden was using uh uh but uh that’s where that works. Um so what are the advantages of near metatrella and ratanavir uh sold in the US as paxlovid is that um there’s essentially no resistance to it except maybe in some very very select situations. It kills the virus, crushes the virus. It can be taken as a oral pill but it’s got the horrible drug drug interactions with the ratonavir. Some people also get disusia. There’s a mechanism as to how it affects the uh the tongue to cause that. Remesae uh given by IV um it uh was the first uh antiviral that was uh really effective. So uh there there’s still a lot of fondness in my heart for that drug. Uh and uh you can give it uh as an outpatient for three days. uh you can give it for an inpatient for longer. uh hpat toxicity can happen uh don’t see it very common but uh patients that have high LFTs to begin with we try not to give it brady cardia I have never knowingly seen it but I bet if I look back to some of the patients they got it I’ll find out that they actually had it because if you look at populations it can happen and then molure not super effective but uh you know that Crosby Stills Nash and Young if you can’t be with the one you love, love the one you’re with. So, sometimes um that’s the one that we love. Um it’s oral um and it is mutagenic. So, uh you don’t want to give it to uh pregnant uh uh people. Uh that’s the drugs that are available. Um and uh uh in addition to impacting the initial course, can it bend the curve on postcoid conditions? So the first part with that we’ll ask is how do you define postcoid conditions? So if you define it uh in in spe in different ways you may see efficacy in different ways. So postcoid conditions uh which can be um um really a range of things from kidney dysfunction, cardiovascular dysfunction to uh neuroscychiatric uh dysfunction that happens uh at at the rates that you see here 7.2% and 3.89 among older adults. This is a drug that a a a paper that was recently published in open form infectious disease which I think is very intriguing. So they looked at scads of patients that were treated versus double the number of scads of patients that were untreated all outpatients and they looked at postcoid conditions in the treated versus the untreated. So you can imagine this is a huge database that they looked at and they found that 33.7% of the patients that were treated versus a whopping 35.7% had um the postcoid conditions. Uh so you can see it’s it’s kind of hard to get super excited for the whole population, but if you go into the uh specific age groups, you may find conditions where you’re going to get uh a uh a benefit. So the teenagers not going to help them. The 18 to 49 year olds, what is that would be the millennials? I guess still some generation Z and millennials. Uh not going to make a huge difference in those as well. Once you get into people my age, 50 to 64, uh people with linebacker numbers, uh then um you get uh you can start seeing an impact in terms of uh treatment. And when you get into the older group, then you can see a treatment. I tried to find out what the uh this is just uh the overall uh numbers in terms of uh of relative uh risk reductions. I tried to find out the specific percentages to see uh if they’re more than that whopping 2% uh difference, but uh I think because of the uh shutdown uh the people that I sent the email to uh have not responded, but uh it’d be u because this data was generated by uh CDC people. Um, but I I think that what I walk away from is more of what we’ve been talking about in that if you’re going to get a benefit from treatment, then it’s going to be the higher risk groups for progression. And so that um uh 40 something year old woman that the insurance company wouldn’t pay for tax levade might not have benefited from it uh very much. On the other hand, uh somebody who is uh my father-in-law’s age, he’s uh 87. I think I’d really like to get him on Pax Levid if he uh uh doesn’t have a drug drug interaction if he had COVID. All right. So, now back to uh our baby bears. So, baby bear is good and that’s the group two. And you want people that have uh natural immunity, vaccine enhanced immunity, minimal immunosuppression, maybe got preexposure prophylaxis, maybe got postexposure prophylaxis, those are the people that are unlikely to progress. Uh perhaps in those people with preexposure and postexposure prophylaxis, you may still wish to treat them if they broke through to an active infection because they might have so many risk factors. But those are all the groups of people that I would feel uh much more comfortable that they’re not going to get a lot of damage. They’re not going to move up on that yaxis uh toward damage either from the virus or from uh an overactive immune response because they’re not going to have that much virus to drive that. Um so with that I’m going to ask you how uh do you navigate decision- making pro uh process when current treatment options have contraindications or drug interactions and high-risisk patients. So going back to uh my lady that came back from Uganda say that uh she was uh actually a uh liver transplant recipient and she called you and uh how would you navigate uh treating her knowing that if you put her on a drug combination then bad things are going to happen to her tacy but also knowing that Mulnupe is maybe not the the best antiviral out there. Yes. sometimes easily sometimes depends on your institution. I think that’s a real sweet spot there for uh Remmesir. Uh an interesting Remmesa story that happened is uh uh advocacy is so super important and uh one of my uh friends that I’ve made through COVID works for an advocacy organization and she uh she had COVID. She knew she had CO she didn’t have a positive test in her hand. Why did she know she had CO? Because her husband had COVID proven she had uh fever, COVID symptoms. She’s immune compromised. The uh um uh her home test was negative, but she’s like, I know it’s going to be positive. Uh and she could not get IV rema where she was living because she didn’t have proof that COVID was positive. So, she’s a real go-getter and she emailed and contacted the FDA and specific people at the FDA and they changed things so that it uh says a diagnosis of COVID, not a diagnosis of proven COVID. So uh if uh so when she went to if somebody like her goes to the center now and says I have COVID uh I have an exposure I have symptoms and the clinician there diagnoses them with COVID they can get from death severe because of her work to make sure that we give Dr. more than nine minutes. I’m going to turn the next question to a yes or no question for my my panelists. Yes or no? Antiviral resistance consideration as we expand the use of CO 19 therapeutics. Yes or no? Uh yes. Yes. Certainly. Always. Always. You know, as an antibiotic steward myself, I was hoping the answer was yes. Um quick polling question. I’ll be fast. When it comes to paying attention to rapidly evolving recommendations, who is paying attention based on online newsletters or online whatever it may be online recommendations? We got a couple. What about conferences? That’s offensive. You guys should all raise your hand right now because anyway, what about just talking to colleagues, too? So, this middle group, you guys just like we don’t care about rapidly following recommendations. We’re just we’re staying we’re staying put. I think it’s important. I think all of it coales together. um is is how we collectively in academia and in patient care pay attention. But Dr. Hayden, the fun part, can we please get into kind of some cases and some co clinical pearls? All right. So, first case like to ask my panelists and you all to comment on is a 72y old male who presents to your clinic for evaluation following a high-risisk COVID exposure. uh he uh resides independently but visits an adult day program three days a week. So there’s potential exposures there. Two days ago, all of a sudden uh this male turned into a she uh spent two hours in close contact with the daughter who subsequently tested positive for COVID 19. So we have a definite exposure within the last two days. You can see the history includes type two diabetes, u stage three chronic kidney disease, hypertension, some heart failure with a preserved ejection fraction and osteoporosis. So um some of the additional factors you can note here lives alone in in the senior housing complex and the daughter unfortunately even though she’s ill is the is the primary caregiver. He’s had a total of five vaccine doses uh but no current ID symptoms. So what’s your what’s your approach? I think the first approach is to see if our audience can identify some of the specific factors that might be influencing CO 19 severity risk. I see a head nod right here. What f did you hear any factors that might make you think about the increased risk in our patient? Old age. for sure. Chronic dise chronic um chronic disease, old age, putting it all together. And then on that, I think we can just do a quick polling question here. What information based on this brilliant assessment we got from the front table is most critical for your PEP decision makingaking. So show of hands supporting local EP epidemiologic data and variant circulation. Do we think that matters? What about patient specific risk factors and coorbidities? Yeah, we got a few few winners there. Drug safety profile contraindications. We got it. This is why listen I I can’t do my job without pharmacists. direct, indirect, industry, name it. Insurance coverage and cost considerations. I see some head nods and all factors are equally important. That is my vote. Just saying. Usually when you’re taking like the SATs or something and it’s like all the above, you like kind of, you know. Anyway, so in which patient, all of you, would you be most likely to consider PEP during respiratory virus season, which I think we are currently entering? And this is probably like a unfairly easy question for this crowd, but imunocmpromised patient, young athletic patient with exercise induced asthma, hospital roommates, unconfirmed cases. We have this discussion at Stanford all the time. Long-term care facility residents, none of these patients. Does anyone vote for that? Did you just come for the eggs? Or all of these patients? And he votes for I see head nods for all of these patients. Right on. And then I would I would we we we were kind of alluding to this earlier and we could probably get to this during the Q&A section, but you know considering using PEP in an institutional setting and kind of that that question about hospital roommates, any thoughts, anything new with regarding to using it in an institutional setting? You know, I think the the it’s it’s very similar to the trade-off with influence. we get antiviral prophylaxis. You’re asking whether it’s better to give something for prophylaxis or whether if you wait you can give somebody preemp you can give somebody really early therapy. And one of the with influenza because really early therapy is very effective. It’s often a more sensible choice. If you go back to the other case that said a two-hour exposure to the daughter, patients got really significant risk factors for severe disease, but two hours exposure to someone is like eh, you know, not likely to result in transmission. So that would be a setting in which if you’ve got some effective therapy, you might be more sensible to say, you know, the moment you develop symptoms, um, we start you on therapy. Uh whereas in the the setting of hospital roommates, you’re more often a setting where it might be really difficult to judge onset of therapy and people may have multiple other things going on. Sometimes it’s just um simpler and easier to say prophylaxis. So I think the the the real value of prophylaxis is probably the same as the real value of prophylaxis for flu which is going to be in institutional outbreaks whether they’re you know chronic care hospitals or long-term care acute care hospitals. Um just because if if pre if really early therapy is almost as good as prophylaxis then really early therapy is often a better and easier choice. different interpretation of the question here because I assume that this was an institutional setting where there was an outbreak ongoing and I think we covered that earlier where again the path has been trodden in terms of influenza and you definitely would want to intervene for prophylaxis of those who are apparently well in early treatment of those who have already acquired the illness. Yeah, I I agree with everything that’s been said and I I think uh it goes without saying that this would be part of a comprehensive approach toward clamping down on the outbreak or on the uh patient uh to patient transmission with uh infection control practices and the antivirals. Right on. So team, I’m going to I’m going to make an executive decision because these questions that are coming in I’m getting like hyped up about. So, if it’s okay with you, we’re going to skip the second case study and go straight to Q&A because these are great. First question that we got in, should someone with pending surgery shortly get a COVID vaccine such as heart surgery? I like I get this question all the time. Any specific thoughts there? I I I think that uh if they can get the vaccine to them uh um if they’ve not been vaccinated yet this year, it would be good to get all the ducks lined up, including vaccinations uh prior to major surgery, including flu and RSC as well. I’m glad you threw that out there. Give me a fist bump. You’re supposed to give me a fist bump, aren’t I? There we go. There we go. I was like, where’s the flu and RSV? So second question especially relevant right now and I don’t know if we have an answer but will ASIP be involved in recommending or not PEP therapies do up by ASIP uh I don’t know that that’s a immunization practice postexposure prophylaxis uh it it it’s possible though that uh um FDA and IDSA I mean it’s definite that FDA and IDSA will have opinions about it but I don’t know if AS6 It’s hard to know what’s going to happen with this ASIP going forward. I sometimes see a trickle down effect with what ASIP may say regarding the vaccine may then influence what happens with PEP, but I agree like I don’t know how to to put that in my mind. Here’s an important one. Do vaccines prevent low-risk patients from contracting and spreading COVID to high-risisk patients? There’s some semantics we could talk about in this question. who wants to take it? So, so the answer is yes, absolutely. And I think there are there are lots of low-risk patients in the same you know they they may be a minority overall but there’s still a very large number of them who would be happy to get a COVID vaccine in the same way that they get a flu vaccine because of the degree of protection it likely gives to vulnerable people around them you know father-in-laws um you know people you know or who you work with who are imunocmpromised. One of the challenges is going to be accumulating the data that demonstrate that it works. So I I have, you know, absolutely no issue with the critical importance of getting healthcare workers vaccinated against influenza because we have evidence in long-term care that when staff get vaccinated, residents are less likely to die. That’s like incontrovertible randomized control trial evidence. And so mandates for healthcare worker influenza immunization are a gimme from my perspective. Everything we know about COVID suggests that that’s probably true for CO. The question is how much evidence do we need before we say this evidence is incontrovertible? Because if we’re going to mandate influenza vaccines in some way or if we’re going to mandate co vaccines in some way for healthcare workers, then I think we’d all like a somewhat higher level of evidence we have, then this makes a lot of sense and it’s almost certainly true. So I think that that discussion is going to be ongoing complicated by the fact that of course mandates have set everybody off and everybody’s a little um anxious in general about vaccines and about control of transmission in institutions. So I think it’s going to take us some time to get there and maybe in the interim co will become a mild enough disease that we’re not willing to deal with it. Um, but I suspect that we’re going to end up with COVID vaccine mandates in the same way that we have flu vaccine mandates because it it’s likely to continue to be a significant issue in hospitalized patients and people who live in long-term care. But, you know, as with everything else with the pandemic, we’re going to find out. We’re going to find out. And that has such a so many downstream implications for public health, healthcare delivery, and access. I think that was a phenomenal kind of concluding statement. Dr. River and to all three of you. Thank you so much for taking the time and thank you all for showing up and and sharing your insights. I’m gonna gamble and just hope that we have a mild CO 19 season. I don’t even know. But with that being said, please um scan this QR code, earn some CME, earn some credit. Thank you all for hanging out. We’ll be available for autographs and pictures and selfies afterwards. And may you all have a great rest of your ID week. Thank you. [Applause] responding to questions on the platform. And yes, you can claim your educational credit at the conclusion of the program. To gain access, please use your mobile device to scan the QR code displayed on Good night. I got a feeling that tonight’s going to be a good night. Tonight’s going to be a good good night. Tonight’s going to be a good night. That tonight’s going to be a good night. That be a good good night. That good night. Tonight’s going to be a good night. Tonight’s going to be a good good night. Tonight’s going to be a good night. Tonight’s going to be a good night. Tonight’s going to be a good good night. Let’s live it up. I got my money. Let’s go out and smash it like that sofa. Let’s kick it off. Look at her danc it it I feel it tonight. [Music] Tonight’s going to be a good good night. Tonight’s going to be a good night. Tonight’s going to be a good night. Tonight’s going to be a good good night. Tonight’s the night. Let’s it up. Let’s it up. I got my money. Let’s spin it up. Let’s spin it up. Go out and smash it. Oh my god. Jump out that sofa. Come on, let’s kick it off. Look at her. Just take it off. Let’s paint the town. We’ll shut it down. Shut it down. Let’s burn the roof. And then we’ll do it again. Let’s do it. Let’s do it. Let’s do it. Let’s do it. And it come easy. Easy now we feel the shot and up and down Monday and Thursday night’s going going to be a good night. Tonight’s going to be a good night. Tonight’s going to be a good good night. Tonight’s going to be a good night. Tonight’s going to be a good night. Tonight’s going to be a good good night. [Music] You know, I was I was wondering because the force got a lot of power and it make me feel like [Music] It’s the feeling power. It happens. Get enough. I’m sensitive. [Music] Don’t you get enough up? Hallelujah. [Music] [Music] eternal etal.
