President Ruth Watkins: Welcome to the U Rising Podcast. I'm the president of the University of Utah, Ruth Watkins. And today I have a remarkable special guest. I know we're all hopeful that the pandemic will come to an end and that the vaccine is around the corner. Today, we're going to talk about how the coronavirus vaccine will be rolled out across the U.S. with an expert, my guest today—Dr. Andy Pavia, chief of the Division of Pediatric Infectious Disease at the University of Utah. Welcome, Dr. Pavia.
Dr. Andy Pavia: Thank you, President Watkins, it’s a pleasure to be here.
President Watkins: Well, I have no doubt that this is going to be a very popular podcast because this is a topic on everyone's mind right now. I think it would be helpful for listeners to have a little bit of background about the Pfizer messenger RNA vaccine. What does that mean? And how does it work? Especially the messenger RNA part.
Dr. Pavia: Well, those who remember their basic biology will remember the messenger RNA is the template that cells use to follow the design, it's the jig that a carpenter might use, to make a protein. And it is quickly degraded after it's used to make a protein. And so what this vaccine does that's really remarkable is that it creates a structure in which a message to make a part of the virus protein is taken up by a cell. It then makes that protein and it expresses it on the outside of the immune cell so the immune system can recognize it, but it does it without putting any DNA in the body, it can't be part of your genetic material. It doesn't stick around for a long time. There's no live virus. It's really just a question of inserting some computer code, in this case it's like the Mission Impossible code because it self-destructs after it's been used.
President Watkins: I think many might question the process, given that it went so rapidly. So, I think your voice of expertise on who participated in these trials and your own sense of confidence in these vaccines, it would be very helpful for listeners to hear.
Dr. Pavia: I think early on we all had some distrust as how the process was going to play out. We saw politics potentially entering into this, but I've been really pleased that the FDA has done a spectacular job of being really transparent, of waiting until the data were pretty complete before reviewing it. And to make sure that outside experts had a voice, people who had no commercial ties, no political ties whatsoever. So, anybody who wants to can see all of the data that was reviewed on the FDA website. And I think that's the sort of thing that gives me confidence and gives other people confidence. So, hundreds of vaccine experts have been pouring over these data and coming to the same conclusions.
The other thing that we worried about early on was that the vaccine wouldn't be studied in the people most at risk, but pretty strong efforts were made to do that. And if you look at who was in the trials was 50% women, there was 28% of the participants were Hispanic or Latino, 10% were African American. So, there was good representation from the communities most at risk. There are few communities that were not well represented. Our Native American populations only contributed about 200 participants overall. And that's probably because most of the study centers were in bigger cities and not close to reservations or other population groups. And there weren't a huge number of Pacific Islanders or native Hawaiians involved. That's a shortcoming, but I think we do have good representation of communities of color and also of people of lower socioeconomic status who have been hit particularly hard. I do feel good that these results can be interpreted for everybody, whether you're rich, white and urban, poor, Latino and rural. We have data to say that the vaccine works and there was no big difference in efficacy or safety in any population, which is really important and kind of remarkable, too.
President Watkins: It sounds also like you are assured by the openness and transparency of the data and the fact that the vaccine trials and the outcomes have been widely and openly shared, which seems quite important to me.
Dr. Pavia: Yes, absolutely. Transparency in science is everything. We share our data, we invite criticism of it, and that's what's been done here. And I think that's incredibly helpful.
President Watkins: So, what do we know about this vaccine in terms of effectiveness?
Dr. Pavia: Well, this vaccine, the one from Pfizer, which is the first one that will probably receive an EUA has shown 95% efficacy. Now in the vaccine world, that's pretty remarkable. There are only a handful of vaccines that are that effective. The measles vaccine, the shingles, the new shingles vaccine, not many others. That means that your risk is reduced by 95%. There's often a misunderstanding that means, only 5% of people will get disease. It means that whatever your risk is, whether it's extremely high, because you're going to dance parties or whether it's very low, because you're very careful, it's reduced by 95% by 20-fold. The second vaccine that's coming along from Moderna, which we only have seen the preliminary results of, looks every bit as good. So, this is really staggeringly good news. We didn't hope for anything nearly this good, we were hoping for 60% efficacy, willing to take 50%.
President Watkins: I think that is really stunning, particularly the timescale at which this work has happened. I think you mentioned EUA and I believe that stands for Emergency Use Authorization, you can correct me if I'm wrong on that. I know listeners will be interested in your perspective on the safety of this vaccine.
Dr. Pavia: Yes. So, Emergency Use Authorization is a standard that was developed to respond to emergencies, to bio threats, particularly the pandemics or biologic attacks. And it allows the FDA to give temporary authorization to a product that's needed for a health emergency when there's evidence that it's more likely than not to be effective, and that the risks outweigh the benefits. So that's the minimum standard. And for some of the EUAs this year that have been a little bit controversial, their products barely met the minimum standard. In this case, we're seeing terrific efficacy and from a well-done study that is only different in how quickly cases accrued. Everything about the study was done the way a normal vaccine study would be done, but because it was in the midst of a pandemic, instead of taking two years to see roughly 200 cases, it took four months. It's bad news for us, but good news for getting the vaccine developed quickly. And the safety data, which I've stayed up for the last two nights reviewing because FDA has been very transparent and put all of the data on their website, it looks really good.
And I want to make a slight distinction between safety and side effects, because all vaccines have some side effects. Everyone remembers sore arms or muscle aches. But when we think about safety, we also think about, could it do anything more serious? And knowing that we only know what we know and not what we don't know, this vaccine has not had any serious safety signals at all. The only thing is there were four cases of Bell's palsy—that's a facial paralysis—in vaccine recipients and two in people who got the placebo. This is a common condition, everyone probably knows somebody who had facial droop. And this is within the range that you would expect in 44,000 people.
One of the things about starting to use the vaccine more broadly once it's approved is you start to see things happen to people that you're not sure about the relationship. And we just learned that two people in the UK, once they started broad vaccination, had anaphylactic-like responses. So, we're trying to figure out what that means. These two folks had histories of having had anaphylactic reactions before, they carried EpiPens, so they were severely allergic people, but with only two cases, we don't yet know how much of a risk this is and what the best approach is to that. We'll wait for the FDA's advice, but probably people who've had severe anaphylaxis before—and you know who you are because you carry your EpiPen—should be vaccinated in a place where there is a chance to administer epinephrin and take care of you, if you do have that kind of reaction. But we probably should talk about side effects because that's pretty important.
President Watkins: Yes, it would be great. Listeners will want to know, are there side effects to these messenger RNA vaccines?
Dr. Pavia: Well, there are, and the side effects are those that you would expect with something that's a very potent stimulator of your immune response. Those in the audience who are over 55 who had the shingles vaccine, the side effects are very, very similar. In fact, shingles vaccine is perhaps a little bit worse, but 8 to 10% of people had at least a moderate sore arm. The other side effects included fever, which was present overall in about 7% and was high in about 2 or 3%, muscle aches, fatigue, and some joint pains. So, this is very similar to what you would expect with certain vaccines which cause slightly higher side effects—the tetanus vaccine, the shingles vaccine—but not in some of the milder vaccines, like flu vaccine where most people only get a sore arm and even that can be almost hard to notice.
President Watkins: Well, let me express my gratitude to you for spending the last couple of nights reviewing these data so carefully. That's very helpful for our listeners to hear the voice of an expert, our own expert at the University of Utah Health, with that analysis of data. So, when do we anticipate that U of U Health will receive the first shipment of vaccines and do you have any idea how many we will receive?
Dr. Pavia: So, we know that we'll receive it within a day of the FDA giving an authorization, the VRBPAC, that's the advisory committee of outside experts, has voted in favor of the FDA giving an authorization. And so now the internal FDA deliberations are ongoing. We expect that to happen sometime this weekend or perhaps Monday, maybe as soon as tomorrow. And then U Health will get their first shipment within probably 24 hours. The size of the shipment is still a little bit up in the air. You may have seen on the news the way this vaccine has to be transported—with 60 pounds of dry ice, in specially constructed pizza boxes, fairly large batches in each one of these pizza boxes, and then you have 60 seconds to take it out of the special box with dry ice to get it into a minus 80 research-type freezer. So, the handling is going to be pretty complicated, but through it is tremendous teamwork at the University Hospital led by Jeanmarie Mayer and with tremendous input from Pharmacy and many others, they're set to hit the ground running pretty much the next morning after we get vaccine.
President Watkins: Really extraordinary work. So, let's talk about the distribution plan. How are we prioritizing vaccinations? And knowing that for a while supply will certainly exceed demand as rollout happens of these vaccines.
Dr. Pavia: Prioritization is something that requires a lot of thought in advance. And there have been really extensive efforts to think about [this], the National Academy of Science has put out a report on this, the Advisory Committee on Immunization Practices developed a prioritization scheme, and what we're doing here at the university follows those recommendations and those of the Utah Department of Health. What that means is that there's three early phases and they're calling them 1A, 1B, 1C.
1A is people who live in long-term healthcare facilities and healthcare workers broadly defined. Everyone who works with patients or who may have contact with infectious materials, so it's not just doctors and nurses. It's also our environmental service workers who are in the rooms cleaning up after the patients, it's the engineers who have to go in and fix the ventilator while the patient is there. And so that's phase 1A and that's who's going to receive it first.
Phase 1B will come fairly soon afterwards. It is going to depend a lot on vaccine supply. And that's going to be essential workers. The state of Utah is refining the list of who are essential workers based on both their risk and their real need to keep working, to keep our society and our state going. And then 1C will be people with increased medical risks, people over 65, people with underlying health conditions and the like. After that, there'll be more general distribution in phase two, but it's going to take a while before we get to phase two. So, if you're a healthy person who is able to work from home and isn't in an essential occupation, like police, fire, EMS, education, it's going to be several months before you get a chance at vaccine. If you're an emergency room nurse or an environmental service worker a cleaning up in the ICU, you're going to be first in line.
President Watkins: And that just seems so wise and so appropriate. I want to thank all the people who've spent hours working on that plan. So, Dr. Pavia, what can you tell me about children and vaccines? Particularly the messenger RNA vaccines.
Dr. Pavia: We really haven't done a lot of vaccination of children yet in these studies. The Pfizer study included children 15 and up, but they were very few who are enrolled. In the 15-to 17-year-old age group, there were a modest number of children, 16 to 17, about 140 enrolled. And the reason that we move slowly in children is, of course, they're not little adults, but more importantly, there are a couple of other things that make them different. They can't give informed consent, so when they enter a trial, teenagers have a pretty good idea of what they're doing, but the younger the child, the more they're not really agreeing to participate. And the other is the immune system of younger children is different. Sometimes they need three doses instead of two, sometimes they need smaller doses to reduce the side effects. So, the studies are just getting underway in adolescents and will be stepping down in the age groups.
As a pediatrician and epidemiologist, I'm a little bit disappointed that we didn't move faster in the teenagers because there's so much transmission of disease in the high schools. And because although high school aged students don't generally end up in the ICU, there's some pretty nasty disease effects that do impact kids in that age group, including inflammation of the heart, the prolonged fatigue, so-called long-hauler syndrome, and we'd like to get those people of that age group vaccinated as soon as we know it's safe and effective. It's going to be harder to figure out the right way to vaccinate the younger children. And I think that research is going to take a lot of the next year.
President Watkins: So, the research will continue as we are then able to better answer some of these yet unknown questions.
Dr. Pavia: And you asked also about mRNA vaccines in children and we don't have a lot of experience with mRNA vaccines. There's no licensed products. A lot of their research has been done in cancer vaccines with mRNA, which obviously hasn't included a lot of children. But the process is pretty similar for all vaccines. You need to figure out what's the right dose in children? What are the measurements of immunity that you're going to use to see that it's working? And what does the safety profile look like? So, you're going to move cautiously, not just with these two mRNA vaccines, but also with the other COVID-19 vaccines that are coming along afterwards.
And it's important to remember that we're probably going to end up with three, four or five effective vaccines that we're going to use in different settings in order to be able to get enough vaccine for everybody. If you think about it, a vaccine that needs to be stored in a minus 70 below zero freezer is not going to be very helpful in a small office or in a remote Native American community. We need more practical vaccines for many of these other settings.
President Watkins: Very helpful. So, of course, our big hope is that we build immunity in the community. Can you speak to how community immunity is built and when we might begin to see that happening around us.
Dr. Pavia: That's a really important issue. And there's been a lot of, I think, misleading discussions about the idea of herd immunity because some have said we can just let everyone get infected and then we'll have community immunity and transmission will stop. And that might happen, but the bodies will be stacked high in the street if we go that route. What we want to do is get community immunity through vaccination so that the virus has no place to go. What herd immunity means is that when one person is infected, they don't have a good chance of passing it on because the majority of the people that come in contact with will be immune.
We have formulas we've used in epidemiology, really since my training, which was 30-odd years ago, that are pretty good predictors, but they're not perfect. And for a disease as transmissible, as COVID-19, we think that about 60% of the community needs to be immune before we see a major drop in transmission.
It's not a magic number and our estimates are imperfect. We may see an impact at 50%, may not see it until 70%. So right now, from the Utah HERO Project, this joint project from the David Eccles School of Business and University Health, we know that something in the range of 5% of Utahns have had COVID-19, at least along the Wasatch Front. So that means we have to get up to 60%. So, we have to get another 50 to 55% of the population vaccinated. Hopefully, the number of people infected isn't going to rise too rapidly this winter, although I'm afraid it will. So perhaps 50% of people need to get vaccines to really cut this epidemic off at the knees and let us get back to whatever the new normal is going to be.
President Watkins: So, when you described that Dr. Pavia, I would say that tells me the vaccine is one tool, but we need to stay vigilant on the other tools that we have to reduce the spread of coronavirus. And maybe you'd comment just a little bit on that because we do have many things that we know are helping a lot and we probably need to keep, well, maybe I should change that and say, we must keep doing those things that we know are making a difference. I'd let you, the expert, give some advice on that.
Dr. Pavia: Well, I think you've really said it all. We know that community mitigation—masking, social distancing, hand washing—really can decrease the spread of disease dramatically, almost as well as a vaccine can. We haven't been doing that great a job, to be perfectly honest, in Utah. I'd give us a failing grade on how we'd done overall as a state. And in order to get to that point where the vaccine has done its job in the spring or summer, we've really got to double down on our efforts to stop the spread. And that really means, you know, now that we see the light at the end of the tunnel, we see the goal. Maybe we should use a more Utah analogy. We can see the summit, but we've really got to keep climbing. And there's another four to six months of hard work before we get there. Just because you can see the summit doesn't mean you can sit down in the snow. You're going to die if you do that.
President Watkins: Well, what we know is we can do this. We have the tools with masks, with physical distancing, with hand washing and with keeping our group sizes small, really only gathering with immediate family under your roof, those are the best tools for us, and I think everyone that I know wants to help do their part. S,o reminding people that, yes, it's a bit of a long tunnel right now, the really fabulous news about the vaccine, but we also have to stay vigilant now. I'm wondering about people who've had COVID-19, do they also need to get a vaccine? Or what is your advice on that?
Dr. Pavia: We don't know everything we'd like to know about that. We do know that immunity from natural infection isn't perfect. In the vaccine trial that Pfizer did it, they tested everyone at the beginning, they let everyone get vaccinated before they knew the test results, and of the people who been previously infected about 10 of those in the placebo group got infected again. So, we know that natural immunity doesn't last forever and isn't perfect. So, using the vaccine as a booster is probably going to be important. The question that we don't know the answer to is when do you need that booster? If you were infected in November and you were a healthcare worker, should get vaccinated in December? We don't think so. CDC has suggested that you're probably protected for at least 90 days so you should probably wait at least 90 days after infection, but after that, at least based on what we know today, we think you should get vaccinated to get that long lasting and much closer to complete immunity.
President Watkins: Really helpful. My guest today, Dr. Andy Pavia, infectious disease expert at the University of Utah. What a pleasure to visit with you. I'm so grateful for your time and your help, particularly when, I'm sure you, are very, very busy right now.
Dr. Pavia: Thank you very much. We've been busy, but this busy of getting prepared to start the end of the beginning, to start rolling out the vaccine, is one of the more exciting times and one of the more hopeful times we've seen in the last 12 months. So, it's really a pleasure to be able to share that information. I know everyone has had lots of questions about this. We don't have all the answers yet. One of the major things that we try and do is say what we know when we know it and what we don't know.
President Watkins: Well, and please know that we are all very grateful to you. Listeners, I think this may be one of your favorite podcasts because it's been so informative. Thanks for joining us today and I hope you'll tune in to the next edition of U Rising Podcast.