Taison Bell, MD (00:06): Our talk, Optimizing Opportunities for Vaccination, Practical Considerations for an Evolving COVID-19 Landscape. So that's what we're going to discuss. I'm your chair, Taison Bell. I'm thea Critical Care and Infectious Disease physician at the University of Virginia. And I'm very happy to have Jerika and Monique here. Jerika is coming over from California, Monique from Baltimore, Johns Hopkins, and we're going to get into it. (00:34): So here's our agenda. So we'll talk about the current guidance, the situation for COVID-19. Jerika is going to talk about an overview of the available vaccines and we'll have a discussion about children and adults. And then we'll close. And then we want to have a good amount of time for Q&A. So have your questions ready. (00:55): You guys knew this was coming. This is the, you can't sue me slide. The information for COVID-19 is rapidly evolving. We've all probably said something in this room that was later proven to be false or wrong. So send that to your lawyer. (01:10): And then it's the policy of Medscape to not mention brand names or manufacturers, but of course I'm going to violate that right away because we only know these vaccines by their brand names. So anyway, that's for your reading pleasure. (01:26): All right, so first, where are we? From this time last year, the main thing I want to know from you all is what do you want to know at this point? We've settled in with COVID at this point. We've gotten sick of it, we hate talking about it, but we're the expert so everyone still wants to ask us about it, right? That's the feeling that we have going on here, but we want to know what's on your mind. All right, so scan the QR code, send us your thoughts here. (01:53): Here are current trends. Let's look at hospitalizations. I think hospitalizations now are one of the best markers of where we are in terms of disease severity because testing, as you know, is very unreliable at this point. So we can all go back and have PTSD above these different spikes, about our Delta wave, our Omicron wave and everything here, and as a lot of us anticipated, we're seeing a little bit of a rise in hospitalizations going into the fall and early winter. Who knows if that little dip going down is going to continue, we'll just have to see. But what's really encouraging is that our deaths have trended down, and you can see there's a slight trend up, but in general there's been a little bit of divergence between our case and hospitalizations and the amount of people who are dying. (02:39): In other words, we are not at our lowest caseload that we've had in the hospital, but we are among the lowest deaths that we've had. So of course the vaccines are doing their work. There's more natural immunity, where that goes, it's going to depend a lot on variants and of ongoing vaccination, et cetera. But it is better than it has been and I'm sure you guys are aware of that. (03:01): All right, I also don't think that this slide is going to be a big surprise to people. I'm very, very happy that we're doing this conference in Boston. Jerika, you're from California doing pretty well. I'm from Virginia, we're doing relatively well. Monique from southern Louisiana, don't hold your breath for doing ID week down there the next few years. But we're seeing this trend here that there are some states that have more vaccinations per capita than others and a lot of the deaths and hospitalization that we see are going to reflect there. This is all things that we know. (03:36): Minnesota as the country's healthiest state, the lone representative of the Midwest with high vaccination rates. But we need to increase vaccination across the board. And we'll talk a little bit about that. (03:50): All right, so this is the latest graphic from uptake of the bivalent booster dose. Now as we all know, the updated vaccine is available, but it's been fairly new. There's been problems getting to it, we'll talk about that. But as far as uptake of the bivalent booster dose, which mind you is actually no longer available, the original version in the bivalent booster, you can no longer get those. It's only the new version now, but our uptake was pretty bad, pretty bad. (04:19): Now I'm sure in this room the uptake was pretty good, which makes me good about not having a mask on. But look here, we're getting a little bit better as people get older and the best uptake was 65 and older, but below that we're kind of 17 and 19%. So not that great. People just weren't really into that. (04:42): Children under five, 2 million have gotten at least one dose. They'rere at are ~22 ish million young kids in the country, which automatically makes me feel a little bit tired. And then 56 million with the updated bivalent booster dose corresponding to 17% of the population. All right, so this was a big area of improvement when it comes to thinking about a new vaccine that we're rolling out and trying to get people to take. We have a bad track record as of recently. (05:12): All right, now if any of you ran PCR gels in college or in medical school, this is starting to look like that now. This is the latest variant trend right here. And the good thing, well what is good? There's a lot going on here. There are a lot of variants. EG.5 or Eris after the Greek Ggod is in vogue now. That seems to be the one that's predominating. (05:42): And then we have FL.1.5.1, I forgot, Fornax acts or something is the name of that one. And they have a mutation of spike protein F465L. That might make it more susceptible or more able to evade your immune response. But as we've seen before, we are not seeing any game changers when it comes to variants right now, but it's still important to track them. (06:06): So we'll talk a little bit about these. We always want to know are the vaccines available, how effective are they for the variants that are circulating? Because it's going to be hard to match it up obviously. So we'll talk a little bit about that in a little bit. (06:19): And then guidance for vaccination. So obviously: get a vaccine, that's the top line recommendation. CDC recommends getting the updated COVID-19 vaccine. We are not supposed to call them boosters anymore because there's a fancy focus group that the CDC held and they determined that “booster” is so 2021, that we're going to go with “updated vaccine,” that's the 2023 and 2024 term. So that's where we're going into it. So no more boosting, we're not boosting, we're just vaccinating. (06:47): All right, anyone above five get your updated COVID-19 vaccine to protect protecting his illness. If you're moderately or severely immunocompromised, you may get additional doses of the updated vaccine. We'll talk a little bit about that. And then children six to four, they're just acknowledging here that there's not a lot of uptake when it comes to kids. And so there might need to be some extra doses that are given in those situations. And of course we'll get into that. (07:12): Now, people who are moderately or severely immunocompromised, these are often the people who are most interested in getting vaccinated and getting additional doses. There is some guidance for them, but of course at this point, three years in, there are a lot of different situations, how many doses someone's gotten, when they've gotten it, which brand they've received. So there is some guidance that the CDC has put out. (07:33): So initial vaccination, you should get three doses of the updated Moderna or the updated Pfizer BioNTech vaccine or two dose series of Novavax, which is a new vaccine. And then if you've had previous mRNA doses, it kind of depends on how many and when you've gotten them, but between one or two. And if you've got Novavax or Janssen, one of the updated vaccines. (07:55): And then again, your situation may vary depending on your patient. So they may be asking about that. But in general, just like before, we've seen that there's lower immune response in moderately and severely immunocompromised patients. So they might need a little bit more of a, I was going to say boost, but I'm not supposed to say boost. A little more doses to get where they need to be. (08:17): Okay. Children age six months through four years, I don't take care of kids, so I'm definitely going to toss this one to Monique, but you should receive at least two doses of the updated Moderna or three of the Pfizer BioNTech vaccine. And then if you've received a previous mRNA dose between one to two. What do you think about these recommendations here? Monique Soileau-Burke, MD (08:37): I think they're great recommendations. I'm all for the new vaccine. The thing that's been an issue with children is availability of vaccine across the country. So it's very difficult as we all know, to store these vaccines, to keep them in offices. So some places may have Moderna and some places may have Pfizer. The recommendations are that a child between six months and four should start and finish that initial series of three with the same vaccine. But that's not an absolute. (09:09): If you have a child that's moving around, got a Moderna say at six or eight months and now all that's available is Pfizer, then it's okay to mix them. Ideally we should stay with the same brand for that initial phase for the first two or three shots depending on what brand we're using. But if it's unavailable, it's okay to mix those up. Taison Bell, MD (09:33): All right, thank you. So actually before we kick it over to Jerika, we've got a couple of questions that have come in. So one, "What do hospitalizations look like at your respective hospitals?" Since you are in different settings of the US who's being hospitalized? Young/, old/ immunocompromised. So I also do critical care and at University of Virginia we are seeing an occasional COVID-19 case, but for the most part there's some sort of compromising condition that they have. Organ transplant, severe immunocompromised. We're not seeing the 56-year old with diabetes and hypertension, maybe history of stroke --. W we're not seeing those people anymore. There's usually something going on chemotherapy wise, tacrolimus, something like that. So they do tend to be immunocompromised. What have you heard in pediatric land? Monique Soileau-Burke, MD (10:18): So in pediatrics, there's actually been an uptick in hospitalizations during this latest, I don't know what we're calling it now, increase or slight rise. Unfortunately the thing that we really want to focus on as pediatricians is that there's been an increase in hospitalizations for children who don't have underlying medical conditions. (10:36): So of the children who were hospitalized for COVID-19 that were under the age of two, 60% of those children had no underlying medical condition. So really important for us to start thinking about immunizing the healthy kids too. Taison Bell, MD (10:52): Yeah, that's a really good point. All right, I'm going to kick it over to Jerika now. Jerika Lam, PharmD (10:57): Okay, great. Thank you Dr. Bell. Taison Bell, MD (10:59): You get the clicker of power. Jerika Lam, PharmD (11:01): All right, thank you. So before I begin talking about the COVID-19 19 vaccines, I just want to just share with everyone that there are three broad categories of vaccines available. We know that there's a protein-based vaccine and also the gene-based vaccine, mainly the mRNA vaccines. And then the third category is combination vaccine of both the protein subunit and the gene-based. And so that as an example, is the live attenuated vaccine. (11:27): So what we have here are the three currently available vaccines in the United States. So we have two mRNA vaccines that are produced by Pfizer BioNTech and Moderna. And then the only protein subunit vaccine is the Novavax. The similarities between the two mRNA vaccines are that they are monovalent, they are again derived from just the variant of the XBDB. 1.5 and they are available for children six months and older. (11:58): The difference between the two mRNA vaccines is that for the pediatric patients who are six months through four years, the vaccine vial is a multi-dose vial as compared to the single dose vials for the older children and adults. (12:13): Now in contrast, a Novavax vaccine is a little bit different. It is actually made from a protein subunit and it incorporates a spike protein as well as an adjuvant that is proprietary of Novavax. And so the adjuvant is there to enhance the uptake of the vaccine and to mount a more immune response in the person. (12:34): With regards to the Novavax vaccine, there is a series of two doses. And we see here that for adolescents 12 years and older, they have to receive the first and second dose. And usually that's separated by at least recommended by at least eight weeks. And what we also know is that for those who are not eligible to receive the mRNA vaccine, the Novavax vaccine can be a candidate for that individual. (13:01): So what we have currently here, and there has been a lot of, I think discussions about the mRNA platform and how there were concerns that maybe perhaps it can elicit an adverse response in individuals. But what we know with mRNA vaccines, they have been around since the 1990s and it's just the pandemic that highlight their efficacy as well as safety. (13:26): And what we understand here is that as illustrated in this very nice image, is that the spike protein mRNA, the genetic material is embedded into this mRNA. And we know mRNA is part of the genetic coding system. And once it translocates into the cytoplasm of the cell, it gets translated into the spike protein. And then of course the spike proteins are activated made and then activates the immune system. (13:56): And of course with the immune system being activated, the antibodies then are built and then they identify the various receptors that have this particular protein. As we know, this is how the immune system immune response is mounted and elicited. (14:15): On September 12th of this year, what Pfizer and BioNTech and Moderna companies, what they did is that they presented safety and efficacy data to the FDA. And here are just some snippets of the data that they presented. And these were cross neutralization assays that were performed in their laboratories. And as you can see on the Y axis there are neutralizing antibody titers. (14:41): And if I were to summarize the graph here, you can see that the monovalent, the updated vaccine has elicited a significant increase in antibody titers more than the bivalent vaccine. (14:57): And so the conclusion from the companies as they are presenting their data to the FDA is that there is a substantial fold increase in antibody titers that is mounted from this updated vaccine. And of course we can see that the effect is pretty consistent across the various Omicron sub variants. (15:17): And this is another cross neutralizing assay. And of course this was done by the Duke assay, but in general this data was an added on or supplement from the Moderna trials. And what they showed here is a comparison between is there enough antibody mounted for those who have no prior infection compared to those who have prior COVID-19 infection. And what we can see here across the four variants is that there is still substantial robust antibody increase from this monovalent vaccine. (15:55): And then as I've alluded to earlier, the Pfizer BioNTech vaccine also demonstrated a comparison between the bivalent, the older version of the vaccine and the updated, which is a monovalent vaccine. As you can see on the Y axis, they use a different metric. It's not the neutralizing antibody titer, rather they use a geometric mean ratio. But the take home message is the same, is that the monovalent, the updated vaccine has mounted a higher response than the bivalent vaccine. (16:29): And then this is also looking at what about a comparison between the response rate and in terms of the bivalent versus the monovalent. And we can see that the GMR ratio is also higher for the updated monovalent vaccine. (16:47): So let's shift gears a little bit and talk about the newer version of the vaccine that is not mRNA platform and it's a protein subunit vaccine. It's comprised of small nanoparticles containing that spike protein that seems to be the main target for the virus. And it is using a recombinant technology that synthesizes the spike protein, also contains antigens to stimulate the immune system as well as that adjuvant that is proprietary to the company. (17:16): So as you can see here, the graph, it's a little bit different from the mRNA graphs that I've shared with you. And what I also want to illustrate here is that the studies that Novavax presented to the FDA on October 3rd, they had studied this vaccine in macaques monkeys versus human and rats for the previous studies. But the takeaway message is very similar. As you can see, the pseudo virus neutralization as the scale on the Y axis shows that there seems to be again, an uptake in rise in response to the Novavax vaccine compared to the prototype. And this is across the various Omicron variants. (18:00): What we also found here is that the neutralizing responses in the macaque monkeys also were consistently elevated across the emerging variants that are circulating in our communities now compared to the older variants as well. (18:18): And so I'm going to hand this over to- Taison Bell, MD (18:19): Wait, before we do that. Jerika Lam, PharmD (18:22): Oh sure. Taison Bell, MD (18:22): I had a question for you. We had a couple come in about the vaccines. So one, "Given what we've seen so far, does it seem like we're moving towards an annual vaccination, do you think similar to what we do with influenza?" Jerika Lam, PharmD (18:35): Yes, definitely we are. And there is a slide towards the end of this presentation that I'm going to touch upon where the companies are looking at combination vaccines, basically combining two to three active ingredients into one shot for the individuals. And this is going to include the flu and COVID-19 plus minus RSV as well. So definitely that's going to be the trend moving forward. Taison Bell, MD (18:59): So co-administration will be a good thing obviously because there's a lot more trust in some of these other vaccines. There's actually, I looked at a Kaiser poll, there's more trust right now in the RSV vaccine than there is in the COVID -19 vaccines among vaccine hesitant people. And RSV is actually a new vaccine, it is new. So just remarkable to see that. (19:19): And now there is one, I think the CDC is recommending for RSV to space that out from your other vaccine just because it is new. But in general we do feel like co-administration would be good. So if you have that high- risk patient that you're not sure if they're going to come back for another vaccine dose in a few months, I personally think it would be fine to probably co-administer if they were in that high risk group. But the official CDC recommendation is to space out the RSV, but the other ones are able to be co-administered. Okay, thank you. Jerika Lam, PharmD (19:50): Great. Thank you Monique. Monique Soileau-Burke, MD (19:52): Well definitely as a pediatrician I'm looking forward to any combined vaccines that we can come up with. Yesterday's office visits were very loud. I'm just going to say that. (20:04): So talking a little bit about safety outcomes with these vaccines, as all of us have been saying now for I guess it's been almost two years --, almost three years -- about the safety. These are safe and effective vaccines. As a pediatrician, I spend a lot of time talking with parents who are concerned about long-term effects, about the vaccine being new. This vaccine has been highly studied. These are just a list of some of the inclusion criteria for some of the possible side effects that we've been looking for. (20:35): I'm really going to talk a little bit today mostly about myocarditis because that seems to be the one that gives people the most concerns. I am a general pediatrician, I see about 20 to 25 kids a day. About half of them are infants and toddlers and the other half are adolescents. A lot of adolescent parents who are very concerned about myocarditis. And these are patients who have had all of their other vaccines. These are patients whose parents have gotten their children the flu vaccine every year of their life and this really concerns them. (21:08): So if we look at the myocarditis after the mRNA vaccines, there was an increase in myocarditis present, especially between the first and second vaccine, because we think it's probably just having those first two vaccines so close together, it's an inflammatory --, it causes an inflammatory response., i It's more prevalent and obviously the population that seems to be most affected by it is the population that is most inaffected by myocarditis to begin with:. T those older adolescent younger male patients. There was an increased risk of myocarditis following the monovalent booster dose for some age groups. (21:48): If you look at the data, and as a pediatrician, I spend a lot of time talking about risk- benefit. The risk of getting myocarditis from the immunization is still significantly less than the risk of getting myocarditis from the COVID-19 actual virus. So we're looking anywhere depending on the study, I've seen studies that have shown it as high as eight times the risk with the virus, versus the vaccine as low as three times. So it's still pretty significant. (22:15): I also want to, just as a personal point:, I've had two cases of patients who've had myocarditis with COVID. They were both under two years old. In my patient population I realized that this is just my own observational studies. I've had one adolescent male that had an issue with myocarditis, but it resolved within a couple of days with really no significant intervention and no long-term effects. And I've had two two year olds who got myocarditis from COVID before they were old enough before the vaccine had been approved for their age group. (22:50): So talking a little bit also, I'm not as familiar with this because my patients don't generally have problems with ischemic strokes, but we've looked at this data, like I said, all in all it is a safe vaccine. It has some side effects. I know that I'm going to get my vaccine as soon as I get home. I'm running a half-marathon on Saturday, so I'm going to wait till after that but ready to go. So I think that this is something that we as physicians can feel comfortable with and I certainly do. Taison Bell, MD (23:23): I had some questions that came in. There's a correction that the Novavax vaccine is authorized for children 12 and above. Monique Soileau-Burke, MD (23:32): 12 and above. Taison Bell, MD (23:34): [inaudible 00:23:34] before. So I apologize that that information was presented else wise. Monique Soileau-Burke, MD (23:37): Yes. [inaudible 00:23:39] say that. Taison Bell, MD (23:41): "What's the best way to address the concern about long-term effects of the vaccines and that could appear years later that are difficult to say at the present time?" Anyone have thoughts there? Monique Soileau-Burke, MD (23:52): So when we talk to our patients about that, looking at vaccine data from across the last almost 100 years that we've been doing vaccinations, the majority of the effects, 90 plus percent of them occur within that first year or so that we're able to track them. So I feel comfortable talking to patients about that and explaining to them that really this science is not new. This is something that's been going on for a long time. We really have studied this very well. But that's the whole discussion about risk and benefit, right? (24:24): Obviously none of us in this room have a crystal ball and we can't see 100% of everything, but we know that our best recommendations are that this is a safe and effective vaccine and important to get, especially talking about for kids, increased hospitalizations for children, especially under the age two that don't have underlying medical problems. I think a lot of parents feel that if their children are healthy, they don't have to worry about it. Jerika Lam, PharmD (24:47): If I can add also, I mean looking at the history, just to add on to what Monique is saying, I mean we have vaccines that have almost eradicated, and I say almost, in terms of smallpox, it's because I heard recently there were some incidents coming up or emerging in other countries, but also polio. So these are great examples that vaccines do work. And this was before the pandemic, so we know vaccines do work. So it's just a matter of time and trust building. (25:18): And I think we all know that this whole pandemic has been politicized. And so I think to what Taison has said earlier, the remarkable part of the RSV vaccine is that there seems to be more trust in that. And if so we were to look at the big picture of things, the pandemic has been politicized and unfortunately the vaccines cannot speak for themselves in terms of being safe and efficacious. (25:41): And so I think we just have to really look at the conversations and discussions with our patients and giving them historical examples of success stories. And where we are going now into what Monique is saying, I mean preventable deaths are more significant than the deaths that are occurring from COVID-19. Monique Soileau-Burke, MD (26:00): And if I can say one more thing too about delivery mechanisms. We're talking about a different delivery mechanisms. My patients that I'm the most surprised that are resistant to getting the COVID vaccine for their children are the ones that have gotten all of their childhood vaccines and flu shots every single year of their life. (26:20): I had a patient of mine who, and you can always tell, we'll talk a little bit about having these conversations with patients, but asking me about the delivery mechanism. And I think it's great that the public is educating themselves, but we all had to sit with the family, including the family, and we had a laugh and I said, "This is your 35th vaccine that you're getting and I don't think we've ever had a conversation about the delivery mechanisms of the other 35 vaccines." (26:48): So it's just a thought. And I think it's great for people and parents to be very active in making decisions about their children's health and including them in that process and giving them perspective just like you were saying. Taison Bell, MD (27:01): Yeah. All right, I have a couple more questions I'll quickly get to. "How are the recommendations for fully vaccinated status evolving given the annual booster availability or annual vaccine availability and the endemic nature of SARS‑CoV‑2?" (27:15): So it's wording inand semantics really, but there'’s another fancy focus group CDC held that determined that the term “fully vaccinated” in regards to COVID-19 was confusing. Because “full” kind of implies that you're done. And it can also be confused with other terms like Aaron Rogers, the Jets quarterback, famously said that he was fully immunized against COVID-19. He is unvaccinated, he has received zero doses, but said that he was immunized because he took some herb or something that he said boosted his general antibody levels. So we don't need to dabble in that sort of stuff. (27:50): So “up to date” brings us more in line with what we use for influenza, for instance, that there's a date and by this date this is what you should have and if you don't have it by this date, then you are not up-to-date. So it changes the language a little bit to make it more in line with the language that we already use for certain conditions. (28:10): All right. And let's see. "The potential mechanism behind myocarditis induced by the mRNA vaccines could have been inappropriate vaccine administration." (28:24): So we had this discussion before we started here because we saw that, so the highest risk was in adolescent males and young males. The highest risk was with that second dose with the initial primary vaccine series. And it makes sense to me that that spacing, that close spacing with first dose in two doses, which we don't usually do with boosting a vaccine dose, usually it's more spaced out than that, induced more inflammation. (28:50): Now was that an inappropriate?, I would argue no, because we did have to study these vaccines quickly. And remember back in 2020 when this was really going on, we had to get the vaccine out quickly. And so I think the schedule that was closer together likely induced more myocarditis in a higher risk group that tends to have more myocarditis anyway because we're just not seeing it with the updated vaccine doses and subsequent doses that people are getting. (29:18): Okay. All right. I know there are more questions here. We'll get to those at the end. All right, who's got this one? Monique Soileau-Burke, MD (29:25): I do. Taison Bell, MD (29:27): Back to you. Monique Soileau-Burke, MD (29:28): Back to me. This is really just a slide talking about misinformation and disinformation. And I think that we're all highly aware of that. If you have some time later on, it's really interesting to go back and read. Some of these are related to COVID and some of them aren't. (29:44): One of the things that I thought was interesting, just as a total aside said that using birth control like pills or IUDs makes it harder for most women to get pregnant once they stop. The people that thought it was probably false was like half of the people. So there's half of the people that weren't really sure one way or the other if that was true or not. (30:05): I think that talking about vaccines is really important to focus on the data, but also talking to people about addressing their concerns. When I talk to a patient and I'm bringing up the idea of any vaccination, if I sense hesitancy or questions, I specifically say, "What questions do you have? What are your specific concerns?" Because sometimes people have things that they say that I'm like, "What?" They hear things on the internet, they see things on TikTok, their aunt told them something, really, really not valid sources of information. (30:43): So making sure that you specifically, for me at least, asking what their questions are, what their specific concerns are, and then trying to talk through that with them as a partnership, I think can be really helpful. Taison Bell, MD (31:02): And this was interesting to me. I did not know, so for a long time I thought that Pfizer and Moderna were being uptaken at the same rate, but there's been more of predominance towards the Pfizer BioNTech vaccine over Moderna, which is interesting. (31:18): And of course Novavax is new, so we'll see where that evolves. But presumably people who have some hesitation around the mRNA vaccines or just want to get a different platform, maybe mix and match, we can talk about that, might be interested in that. But I just thought that was interesting because is different than earlier on in the course of our vaccination campaign. (31:39): Okay, so questions, let's take a look. All right, "Vaccine naysayers state that both the COVID-19 infection and vaccine have caused a spike protein to remain in the system causing long COVID. Thus, some physicals… physicians are treating patients with long-term anticoagulation therapy." Comments? These are our patient's concerns. (32:02): Okay, anticoagulation, unless you need it, don't do it. As a critical care physician who does ID and takes care of a lot of people who fall and they're on anticoagulation, you're trying to figure out why were they on anticoagulation in the first place, that is something that we should discourage. (32:19): The specific population that this was found to be beneficial in was the group of people that are hospitalized with COVID-19 infection, but not in the ICU with COVID-19 infection probably because once you're in the ICU, your risk of bleeding is going to supersede your risk if there's no or active clot that's there, but there is a hyper inflammatory state that could predispose to COVID-19. (32:40): And so there has been a little bit more willingness to anticoagulate in that setting. But outpatient with COVID-19, unless there's a firm in the case for anticoagulation, I would say no to that. (32:51): And then as far as the spike protein team remaining in the system after COVID-19 vaccination or infection, I think the main thing is we're inducing a TH response in antibodies. So hard to answer some of those questions sometimes when they come out of left field and you're like, "Where'd you even get this from?" (33:15): All right. "For the flu, COVID RSV combination vaccines, how does a protein-based approach like Novavax compare to mRNA platforms? What might be the advantages, challenges, et cetera, and is it a feasible combination vaccine?" For you Jerika. Jerika Lam, PharmD (33:29): That's an excellent question. And right now Novavax is undergoing, I think phase one study, so we have yet to find out, we don't have to answer yet until the results are there. But excellent question. Taison Bell, MD (33:44): There's another question about the long-term plan boosting updated vaccine. So we're no longer saying boosting, we're saying updated vaccine. I anticipate this will be a yearly thing with the potential option that there's some game-changing variant that comes out in the middle of the summer, then luckily with the mRNA, and in some extent with the protein subunit, we can get a vaccine out in a smaller amount of time. (34:09): It might be more difficult now because there's not a big federal dollar sort of purse behind it. So that would have to be worked out. But I anticipate that this will be an annual thing that gets rolled up into your influenza vaccine, and RSV. (34:25): All right. Oh, here's an interesting one. "Are the panelists aware of postural orthostasis syndrome related to COVID vaccination? Cardiologists I know report that they see it." So have you guys heard of this? Jerika Lam, PharmD (34:39): No, I haven't. No, I haven’t Monique Soileau-Burke, MD (34:44): I have a couple of patients who have long COVID. That they've been diagnosed with it and also are having some postural orthostasis. These children actually had COVID disease before they were old enough to get the vaccine. So this is going back, but certainly we see that. I see that a lot in young adolescent females. (35:06): For me personally, I haven't seen an increased diagnosis of that or increased presentation of that in my office. It's pretty constant and consistent over the last 10 or 15 years. Taison Bell, MD (35:19): And honestly, my first thought here was that there's an overlap in risk factors here. So going to a cardiologist, you're more likely to be a person who has orthostasis. Being an older person, and likely, and wanting to get vaccinated, you're more likely to have orthostasis. And then if you're all of a sudden thinking about this and someone gets orthostatic, you say, "Oh, maybe this was related to the vaccine." When in reality people just get orthostatic all the time because they're living their life and they're older. (35:45): So I don't know much about this, and I'll look into it just to make sure, but I've gotten a lot of sort of things from specialists over the last couple of years, like, "I'm starting to see this more with the COVID-19 vaccine." It's really that the incidentincidence hasn't changed if you look at the vaccine symptom tracker, but it's more that we're noticing it and trying to find a connection more. Whereas before we weren't necessarily trying to do that. (36:14): All right. "Some of my patients and friends don't want to get the new vaccine stating that they had arthralgias flare up of underlying conditions. How do I tackle that question?" That's a difficult one because it gets to the risk and benefit question. And I do think it's different now than it was before and early on in the pandemic. (36:36): So I think if someone, most people who are asking this question have probably gotten their primary series, they've probably gotten COVID once or twice. Maybe they've gotten their booster that's no longer available and they're asking, "What's in it for me at this point?" And I put it in different categories. I would say if it's a younger person, younger meaning less than 65 and no serious comorbidities, I might say, You know what? If you really don't want to get this, I think it's probably fine." But if that person does have some of these more severe comorbidities, more of like the population I'm seeing that's still going to the hospital with severe COVID, they fit that criteria, then I would push and say, "You really should get this." (37:14): But I do think we're at a point now with combination of more natural immunity, more vaccine induced immunity, et cetera, we're seeing the trends generally go down as far as death and hospitalization, there can be a little bit more parsing out in customization for people who have a lot of hesitancy. (37:31): Now, not everyone agrees with me on that, but I do think that in general the vaccines have done their job and so we can think about it a little bit differently for some patients. "With fluvid..." Fluvid. "COVID, flu and now RSV vaccinations- Monique Soileau-Burke, MD (37:48): That's a good name. Taison Bell, MD (37:48): Maybe I'll trademark that. Monique Soileau-Burke, MD (37:48): I like that. Taison Bell, MD (37:48): "What do you advise children and adults to receive? And what priority?" Monique Soileau-Burke, MD (37:57): Oh, my answer is all of them. And then we usually go parse it out. Once again, it's by the child's risk factors, at least for me. Are they in daycare? Are they not in daycare? Do they have older siblings? Do they not have older siblings? Are there immunocompromised people or older people in the house? (38:18): Clearly this time of year pediatricians, are all very excited about the RSV vaccine, especially after last season. So it's hard for me to make a choice and sometimes I'll tell my patients that, they'll say, "Well, you get to pick two." (38:33): But I think as long as you have a relationship with the family and you have a plan for follow-up, if I know the family well and I know that they're going to come back if I tell them to come back in a week or whatever, I feel a little bit more comfortable talking through that with them and making a decision about what to do first. (38:53): Certainly right now with RSV, because we can give the RSV vaccine, we're hoping ideally to give that in their first seven days of life. That's an opportunity there because they're not eligible for COVID or flu yet, so just getting the RSV vaccine in them as soon as we can. Taison Bell, MD (39:08): Okay. There was a question earlier, I'm back to you, Monique, about potential imprinting with children who get the vaccine. And imprinting referring to potentially suppressing your ability to generate a de novo response to infection after getting vaccination. Has that been a conversation in your circles at all? Monique Soileau-Burke, MD (39:28): Not really. Taison Bell, MD (39:28): Okay. Good to know. [38:19] All right, now we have a poll here because we know you guys are seeing different scenarios here, weigh in on what do you want to discuss in a little bit more detail? Number one, the unvaccinated pediatric patient. Two, an adult who completed the primary vaccination series and is seeing you. And then three, an unvaccinated, presumably adult patient who is hesitant. (40:23): All right, let's see what we've got. The unvaccinated patient who is hesitant. All right. Presumably an adult patient. So Monique, maybe you're off the hook here. (40:42): So the unvaccinated patient now is different than the unvaccinated patient from two years ago. The unvaccinated patient now has seen lots of people around them probably get vaccinated. They've probably gotten COVID at this point and there is some reason that they are just holding out for a long time. And there's probably an argument that, "I've had COVID, it's only like the flu. My cousin got it and they were fine, or my aunt got the vaccine and then she got COVID right afterward and went to the hospital." But these are people who are super, super dug in. This is a different person than it was two years ago. (41:28): So my approach to people who are still unvaccinated at this point, there are not a lot of people in my community who are unvaccinated, but I want to find out why. And that's a simple question to ask, but it's a hard answer to get to because a lot of folks who are unvaccinated at this point have inherent mistrust in the healthcare system. And you represent the healthcare system. You're not representing just their doctor who's giving them advice. Now you're rolled into the medical experts and the people who are trying to push vaccines into our arms and things like that. (42:06): So I really try to start with the standing and it is hard for me to do this without sounding judgmental. I'll be very honest. I'm human and I've been living this, and I think people who are unvaccinated are making a wrong decision. Nevertheless, what I try to do is figure out what exactly are the levers that I could potentially pull to get that person to get vaccinated. (42:29): And I also think of this in the long term. When I was a resident, I used to think every one interaction I had was a super high- risk sort of thing and I had to convince this person to change the goals of care status and to take this medicine. But now I view it, especially if it's someone that I'm going to have ongoing contact with, that is someone that I can chip away at over time. (42:50): We were just talking about kids advocating for cell phones. I have a five and a nine-year-old and my nine-year-old wants a cell phone, but he knows he's going to chip away at me at it each time. He asked me like every week, "Can I get a cell phone? Can I get a cell phone?" The answer’s still, no. But he's still chipping away at it at the hopes that I'm going to relent and just one day give up and just say, "You know what? Just take the [40:47] damn phone." (43:12): That's kind of what we have to do with people who remain unvaccinated, especially if we have a good relationship with them. It's really chipping away and trying to find out exactly what are the underlying reasons, and then introduce this concept, that concept, and try to get to it over the longterm. (43:29): We do know just some organizational psychology, the Rogers adoption lifecycle, that the natural human nature is that some people are going to jump in line for things first and then a lot of people are going to be laggards and not uptake. And some are not going to take it up at all. But we really need to think of this over the long-term, over the years now, because like I said, we're in a different spot with COVID at this point. (43:49): So the person I'm really going to press is really that person who's severely immunocompromised and still for some reason vaccine hesitant, unvaccinated. That's the person I'm almost not going to let out of my office. But most other people I could say, "We can have another conversation." Just chip away and eventually get them to take the cell phone, or I mean that vaccine. Okay. (44:14): Oh, anything to add there? Jerika Lam, PharmD (44:15): No, you said it perfectly. Taison Bell, MD (44:16): Okay, thank you. Monique Soileau-Burke, MD (44:17): I think that's a perfect segueway into talking about communicating with families about vaccine confidence. One of the things that I like to draw back to, especially when I'm teaching with my medical students and residents, and exactly what you were saying, we remember our motivational interviewing skills, right? The pre-contemplative stage. And a lot of the families or your patients might be at this stage where your job really, I feel is just to provide them with information, say, "This is what I think and this is what's going on. And why don't you just think about it." (44:49): Talking about there's some good recommendations here from AAP. ABAP AAP has a ton of resources about talking to families, patients about vaccines. As a pediatrician, we've been dealing with vaccine hesitancy for a really long time. So we had the whole MMR debacle back in the early 2000s. There's been concerns about aluminum, there's been concerns about lead, live vaccines. So we've actually gotten some pretty good resources. If you're ever bored one night when you're on call or something, you can take a look at these. (45:23): But really talking about the common good, sometimes that helps. But the most important thing is to know the people that you're talking to so that just like Taison was saying, so that you can appeal, know where they're coming from so that you can figure out why this is concerning to them. (45:41): I was saying earlier, before we started, I absolutely love what I do. I have the best job in the world. I get to watch kids and families grow up from the time that they're born until they're 22 years old. Those relationships are very helpful. And I know other doctors may not have the luxury of having that confidence and that interaction with the family, but it really is important. (46:03): Also using just some simple metaphors, things like, "We're just updating the vaccine. Like you got a new Apple iPhone, you wouldn't want it to be still using the iPhone three, would you?" We all have to have the iPhone 15. Taison Bell, MD (46:17): I don't need the 15. Monique Soileau-Burke, MD (46:20): But your child needs the 15. Taison Bell, MD (46:22): That's true, that's true. Monique Soileau-Burke, MD (46:23): But we all need the iPhone 15. I have to tell you, that has worked so well with my adolescents telling them when I'm telling them they're getting the new vaccine, it's because it's like the new updated iPhone. (46:34): So thinking about that, talking about families, talking about importance. As we were saying, originally I'm from New Orleans and during COVID I had this shirt that said, "They all masked for you." It's the a play outon a New Orleans song about, "They all ask for you." And I think that's just another thing to talk about, appealing to the community, appealing to people, saying this is the best thing to do for them. But once again, just really getting on that communications level. (47:04): We talk about the big strategies, trust and support. Obviously I've talked about that in terms of patients and families, information, making sure that we're getting good information to the right people at the right time. There is a distrust of the medical profession, but if you look at the studies about that, the distrust of the medical profession is about the medical profession. If you ask them about their own physician, it's different. (47:32): So making sure that you are being a good source of information, advocating for good information and against disinformation, knowing the resources, that's really important. And I think that's been very difficult for all of us. We had that slide at the beginning about what we're saying now, may not be right in a week. Man, resources, we've all been there, we've learned that, but making sure that we can have that. (47:56): And accessibility. Accessibility is a big issue and a big concern of mine. I will tell you that right now in my office we have COVID-19 vaccine for private insurers. We've had that for two weeks. We still have zero VFC vaccine. The Vaccines for Children program, I'm sure most of you're familiar with it. It provides free vaccines to children who are uninsured or underinsured. So that to me is, I'm going to say unacceptable. (48:27): We're also seeing the same thing with RSV. I have private stock of RSV vaccine that I've had for two weeks and still don't have any from the VFC. So making vaccine accessible, being where the patients are, where the families are and really going out to them. Jerika Lam, PharmD (48:47): So where are we going? What are the future directions that we're taking? And what we know in May of this year, the government has ended the whole sponsorship of the vaccines for our communities. And so the monovalent, the updated vaccine, now they are available for private insurers and also they are available through the Affordable Care Act. (49:09): Also, the updated [47:30] vaccine, the Novavax vaccine is authorized by the FDA as of October 3rd. And what we know is that the original Novavax monovalent vaccine is no longer available just like the bivalent mRNA vaccines. (49:28): As we mentioned earlier in this presentation, there are combination vaccines that are coming down the pipeline. Pfizer BioNTech, Moderna, and Novavax are all coming up with their own products. Now Moderna, based on the studies I've read, is pretty far ahead in terms of combination of the flu and COVID-19. They're in phase two and three trials now. Pfizer is second and Novavax is actually doing a three-pronged approach where they're doing the COVID-19 with the flu, COVID-19 flu plus RSV and something else that may be on the horizon soon. (50:03): So we have yet to find out, but it's also exciting times for us to know. So we hope to hear by the end of this year what's going on with the Moderna trials. And then probably in 2024 we'll have more data from the Pfizer and the Novavax clinical trials on the combination vaccines. Monique Soileau-Burke, MD (50:22): Talking about commercialization of the COVID-19 vaccines, from somebody who orders vaccines every day, having them provided for us for free from the government was a real luxury. It was wonderful. So this has been a big change. They transitioned the federal, they will no longer provide us with free vaccines. We're now going ahead and ordering vaccines from the companies. (50:46): They have come up with some pretty nice returns policies for most of us. As Jerika was saying earlier, everything is a single dose vial except for the six months to four year olds, which is really difficult because it comes in a three dose vial. The vaccines can be very expensive, so they are going to allow us to return them any unused portions. So making sure that we tell people still it's okay to open that vial even if it's only to give one shot, because we have to get the shots in the arms. (51:16): What's not going to change is we're still going to be following all those evidence-based vaccination programs, we're still going to be reporting, we're still monitoring safety. And obviously we're going to continue to focus on development of new COVID-19 vaccines and continue to follow the ones that are already out there. But I will say as an aside, as a private pediatrician, it's been a lot more difficult since the government is no longer doing it. Jerika Lam, PharmD (51:44): Oh, I think this is... Oh. So we've all heard on the news that the federal contracts have been modified to allow hastened delivery. And many of us speaking as a pharmacist myself in infectious diseases, many of my colleagues in the retail pharmacies do have the vaccines available. My clinic is an underserved clinic and we have not had the vaccine yet, which is unfortunate because of the communities that we serve, which are marginalized, underserved people. (52:12): But what we also know is that the contracts with participating retail pharmacies are also modified and expanded. And this is through the Bridge Access Program. And this is allowing, again, private and commercial insurance to have these vaccines covered. (52:28): I was sharing with my colleagues here before the presentation is that a couple of my friends who are eager to get the vaccine before they attended this trip and other conferences, they actually told me that they have to pay out of pocket for the vaccines. And Monique told me that recently that the vaccines are finally covered. So normally the price will be $120 to $130 per dose, but hopefully with our insurance that that would be covered without any copay. (52:57): Now the commercial insurance is expected to be available at the same time and hopefully into the spring for all the vaccines, including COVID-19 vaccines. And what we know is that the insurance plans will cover these vaccines technically, immediately, hopefully after this conference. And people with Medicare and Medicaid will also have access to the vaccines at no cost. (53:20): Now to what Monique is saying in terms of Vaccines for Children program, they should be available as well as for those who are American Indians and American Native Alaskans as well as for those who are underinsured. And so that is something that I'll probably have to follow up with my clinic when I return from Boston to California and see if our patients do have the vaccines available for them. (53:48): As we are going to wrap up very soon, what I want to address with all of you here is that when we're talking about vaccines and access to these vaccines, we also need to mention, if possible, break down the language, the hard, heavy scientific language to illustrate to them that these vaccines are safe, they are effective, and they are susceptible to combating against COVID-19 infection, as well as preventing severity if one were to get sick or infected. (54:18): And we need to also address the risk and benefits as all healthcare providers are, whether they're nurses, pharmacists, and physicians. And I like the point that Monique made earlier. There is still a prevalence of mistrust in the medical community and also among our patients. But I like her analogies that it takes only that one pharmacist, that one physician, that one nurse, to really have that rapport with the patient to change their mind. (54:44): So perhaps we do represent the establishment per se in terms of the medical institution, but we are seen differently with patients that we know and we interact with on a daily basis. (54:56): The other thing to also note is that there are logistical concerns and challenges with making appointments for people to come in for the vaccines. So if there is a possibility and opportunity to give the COVID-19 plus a flu vaccine at the same time, why not one in each arm if possible. And then maybe, hopefully they can come back for the RSV, again, depending on the risk factors and their underlying comorbid conditions. (55:22): And the vaccine norms in their community, these are the sort of things that we have to address, especially about vaccine equity and also for the accessibility for these various communities. Taison Bell, MD (55:35): All right, I'll close this out. We only have a few more minutes. Short and sweet. Vaccines are good. Vaccines are effective. People should get them. You guys know that. (55:44): All right, now what we're fighting though is misinformation disinformation, which isare still very rampant. It circulates just as virally as it was earlier on. And in addition, we're fighting COVID fatigue. We're tired of this, they're tired of this; and people that are vaccinated hesitant have always been tired of this. And so we're fighting all this and we're trying to find new methods to try to get people to get vaccinated. But we do have to keep trying because for the sake of our patients and encourage vaccination because we know what the devastating effects are. (56:10): And it reminds me of a funny story of a resident who was trying to get someone who was vaccine hesitant to get vaccinated. The resident actually taped a styrofoam spike to their chest and it came out of their shirt and walked into the clinic as if nothing was going on. Like everything was normal. And the patient was like, "Why do you have a spike coming out of your chest?" And the resident said, "Oh, I just got the updated vaccine and the spike came out in my chest." I don't know, the patient started to laugh like hilarious, right? And the resident said, no, but serious, "Can I give you this [54:10] damn vaccine today?" The patient said no on that visit, but on the next visit they got the vaccine. (56:45): So anything you can try, maybe not everyone try that, but all right, a couple more questions before we end. "The patient status post stem cell transplant, three to six months is a three dose or four dose mRNA series favored. CDC gave an option to add one more dose, but wondering if the four dose series is favored overall?" (57:05): This reminds me of when I was rounding with the immunocompromised physician, ID physician who saw a patient had this exact same question, "Should I get this updated booster?" Whatever, it was a booster back then. And he said, "You sir, whatever vaccine dose is available for you, you should get that." So whatever you can get, you should get. (57:24): And so for this person, who I would say of the patients that I'm seeing is the patient that I'm seeing in the hospital still with severe COVID-19, stem cell transplant, solid organ transplant, if there's a vaccine dose that I could legally give to them or by the guidelines give to them, I'm going to try to get it to them. So for that person I would say if a fourth dose is available and it's within guidelines to try to get that dose to them. (57:48): Well thank you guys for your insights. This was a really illuminating conversation. And thank you all for coming. And please give us your feedback. I'll be here for a few more minutes afterwards if there are any more questions. So thank you. Monique Soileau-Burke, MD (58:02): Thank you.