What You Should Know about the COVID-19 Vaccine

0:00:04 Narrator: Hello and welcome to Population Healthy, a podcast from the University of Michigan School of Public Health. This episode is part of a series of special editions of our podcast, focusing on the ongoing coronavirus pandemic. Join infectious disease experts, Dr. Arnold Monto and Dr. Emily Martin, in a virtual discussion about what everyone should know about the COVID-19 vaccine. Dr. Monto is a professor of Epidemiology and Global Public Health at the University of Michigan School of Public Health. He also serves as acting chair of the Vaccines and Related Biological Products Advisory Committee, which provides advice to the Food and Drug Administration on the authorization and licensure of vaccines to prevent COVID-19.

Emily Martin is an Associate Professor of Epidemiology at the University of Michigan School of Public Health. Her research focuses on respiratory virus epidemiology, hospital epidemiology, infection prevention and molecular epidemiology. Dr. Monto and Dr. Martin co-lead the Michigan Influenza Center, one of five centers across the country that collects data for the Centers for Disease Control and Prevention.

0:01:10 Monto: Since we last had a webinar, a little more than a month ago, we've had two vaccines approved. The vaccines have been rolled out, and there have been a number of developments in the overall epidemiology. I recall that in the past flu pandemics, we've had discussions about who should be vaccinated at first. With flu, as you know Emily, school age children are the vectors in the population. They spread it in the population. Should we prioritize them because then we can really bring an epidemic under control more rapidly? That's a discussion we haven’t had here because we haven't seen that much asymptomatic infection in young individuals. But boy, the asymptomatic infection is playing a much bigger world than we ever thought with this weird virus.

0:02:01 Martin: Right. And this alludes to another question that we've gotten a lot of comments about is learning more about how the ACIP process worked, the committee at the CDC that decides vaccine priorities, like how did we get to where we are with prioritization? Because there are a couple of different ways to approach it. You can approach it by vaccinating the people spreading the disease, but may not be that impacted themselves, as severely. You can vaccinate your people that are most likely to get severely ill first. Or you can, as they did to some degree in ACIP, focus on your critical infrastructure. You don't want mass amounts of your healthcare workers calling in sick in the middle of a pandemic. And so it's kind of a mix of number two and three. You're getting your infrastructure and then in your frontline workers, and then you're getting some each aged based strata to try to do it by risk as well. And so it's sort of a hybrid of two different strategies, which is complex operationally, but it does kind of meet two needs at once, which there are benefits to doing that as well.

0:03:03 Monto: The FDA basically says, who can get the vaccine and doesn't go into any detail. It's ACIP, (Narrator: ACIP, The Advisory Committee on Immunization Practices) that really says how the vaccine should be used and makes recommendations based on evidence and then goes into details. The question in my mind is whether there is not too much detail in terms of who should get the vaccine here in terms of our healthcare system and their ability to deal with the roll-out. How do people recognize who has underlying conditions? With the flu recommendations they used to have a recommendation for people with underlying conditions. They found it was unworkable and they basically went by age. So you've got all of those logistic problems in addition to trying to get things moving and our healthcare system is fragmented as we know, our state health departments and especially our local health departments are under resourced.

0:04:14 Martin: There’s a lot of people that have asked related questions about how to find out where we are in the vaccine distribution process, how to get instructions on where to get a vaccine, who to call. The way the US healthcare system works, is that it lives with your primary care provider, or it lives with your county health department. The healthcare system, the primary care providers, are still getting up to speed on how to mobilize at that level. And so, for the best source of information to go to is gonna be the website for your county health department. I think Michigan's decisions to start changing their prioritization structure to expand things is gonna move things faster here too.

0:04:49 Monto: And we have a lot of people who now are authorized to get the vaccine going down to age 65 rather than age 75.

0:04:56 Martin: Yeah, and then one of the tricky things will be to balance the needs of communities that have got big health systems or big infrastructures, and then the needs of communities that are further out that have more infrastructure challenges.

0:05:10 Martin: There's so much to talk about how fast the whole process happened, because “warp speed” makes it sound like you're just hurdling through space to qualify vaccines at the same time. It kind of leaves behind in my mind the fact that these are vaccinology strategies that have been around for a while and have been in development for a while. What do you think about speed, whether there's been a kind of a speed versus safety tradeoff?

0:05:35 Monto: I don't think there's safety concerns that we really have to be worried about when we know we have a 95% vaccine efficacy. There is always a possibility of infrequent side effects. We typically don't figure them out until we have the roll out of the vaccine and the vaccine being used in millions and millions of people. As long as those side effects are not severe, this is not really a concern because we need to deal with risk benefit and if there were much of a risk, we’d know it as the vaccine gets rolled out. We usually don't see those because of the numbers in the clinical trials. The one thing that there was a slight signal about was Bell’s Palsy in both of the trials, maybe one more in the vaccine than the placebo group. The problem there is this is something which occurs naturally in the population, in the unvaccinated. There may be a slight excess, but again, it's so rare that you need to get millions of people vaccinated in order to be able to show there is a slight access, which means that really the benefits so far outweigh the risk. In the face of what we've got going on, people should get vaccinated without concern.

0:07:10 Martin: I'm impressed by the fact that I think modern technology and mobile technology, and the fact that there's the V-safe program now where everybody that got vaccines is doing regular reporting on their side effects and any effect they've had from the vaccine for weeks after they get it, and we're getting that data in real time now. For every other vaccine we’ve rolled out we wait to find out if we're hearing reports from doctors or hospitals about there being a problem. Doing it at this granular level with this amount of data collection, if there are any safety issues we’re going to see them really, really fast compared to where we would have been years ago.

0:07:45 Monto: They had to choose the right interval between the two doses and how much to put in the vaccine quickly. This usually would take quite some time, dose finding, and looking at different intervals. They just picked intervals and were really locked in, and appropriately so, with the dose and the intervals that we've got right now, because that's all we've got data on. In parallel, there probably will be studies to see whether we can spare doses and allow more people to be vaccinated, but that has to be done in parallel and in small groups where you have an efficacy endpoint, because we really don't have curative protection yet. We can’t just use antibody as a surrogate for protection. And then we have the duration issue, and that's gonna take a while to figure out.

0:08:43 Martin: It's interesting that a lot of the dosing schedules for other vaccines have evolved over time as we've seen them be used and see what works in the population. And we're not used to tackling that question. We’re used to tackling that question after a vaccine’s been out for two or three years, that you’d be changing the dose or changing the schedule.

0:09:00 Monto: And one of the problems we have with the rapid roll out of these vaccines is the fact we spent less time in trying to figure out exactly what the appropriate dose would be, and the timin. If we weren’t under the gun in terms of rolling out vaccines in the face of a severe pandemic, this would have taken a lot more time. The positive is, we've got the vaccines. The negative is, we probably may want to tinker a little bit with the dose, but you can't beat 90 odd percent effectiveness. So the consensus right now from FDA is we go with what we've proven and we continue to use what we have approved.

0:09:53 Martin: Alright, switching topics, let's talk a little bit about the new variants of the virus. So there's the B117 variant in the UK, there is a similarly structured variant reported in South Africa. One thing I wanna make sure everybody understands is that viruses, especially these kinds of viruses, are always mutating and changing. The changes for these particular variants, they seem to be operating in a way where they make it more transmissible. We can see it in the epidemiology data and you can see it and the molecular data now, it makes it so that the virus is particularly good at sticking to the cells that it needs to replicate and infect other people. And so it probably makes it spread faster because it makes infection more efficient, but it doesn't change the way, at least so far, these two, doesn't change the proteins of the virus in a way that makes our body react differently to them. To our body, they look similar to the proteins that come out of the vaccine process, they look similar to other versions of SARS-COV-2. And so at this point, there's not any concern on the table about the vaccine not working, or various treatments not working. It also doesn't look like they're more severe, they're causing deaths at a higher rate, I think they are just spreading faster. So I think it's going to mean we've gotta be more careful with our public health mitigation.

0:11:14 Monto: And if there is any issue in terms of vaccine efficacy, we'll probably hear about it first from the UK. They're rolling out the AstraZeneca vaccine along with the Pfizer vaccine. And they've got domination of the new variant which actually emerged there in September. It's not really anything that just recently came out.

0:11:35 Martin: It really seemed to take it hold right as they were coming out of their restrictions period. A lot of people don't realize we already have a huge kind of plan and infrastructure, an existing way to look at this because we're so used to watching this for flu. We were used to watching changes for flu throughout the year and looking to see if it changes who's getting infected, depending on who's getting vaccinated, and so we’re used to watching it and figuring out what it means for the vaccine. The US does such a good job of all the monitoring of vaccines that are already around. So how long does protection last? Are we gonna need booster doses after a year or something like that? Or is the virus changing enough that we're gonna need to update it? We can use the same methods that we use for the flu vaccine.

Based on what you saw in the FDA meetings, what do you think about waning and how long immunity is gonna last? 

0:12:26 Monto: In our household study we’ve got since 2010, data on the seasonal coronaviruses - four viruses that cause in most people common colds, occasionally more severe disease. And we know there are re-infections. We even have one individual who had three infections with that virus and was one of the first people in the group of households that got SARS-COV-2. This would suggest that antibody is not gonna be long-term, that we are gonna need booster inoculations. But also a re-infection once you've got antibodies is not as severe. So there's, again, no downside to be vaccinated. As a matter of fact, there's an upside, because if there is waning of immunity, you're likely to have a more mild disease, if you do get infected.

0:13:22 Martin: If the vaccine is preventing disease in a person, is it also preventing them from transmitting? And just to kind of clarify where this question comes from from people, before I bump into Arnold is, you might be able to have an infection that's very mild and asymptomatic that you're able to spread and that wouldn't necessarily show up in the initial trials of the vaccines because those were measuring to see who got sick. This is an incredibly effective vaccine. It is way more effective than I expected to see coming out of the trials, and so I'm very hopeful that it can prevent transmission. At the same time, we've already seen how well this virus works asymptomatically. I do wanna wait for the data to see whether a transmission is possible post-vaccination.

0:14:06 Monto: We've had to change our thinking totally about the asymptomatic transmission since this virus emerged. There was little evidence with the original SARS virus that there was asymptomatic transmission. This virus is much more efficient. Well, less efficient in causing severe disease, so there are more asymptomatic cases and those cases seem to transmit, but not regularly and we don't know why some people transmit more than others, and I think we're not gonna be able to figure this out until we get more data.

What I think is going to be very interesting is what happens with the other products. What we've heard from AstraZeneca is a bit confusing. We've heard estimates of efficacy anywhere from 60 odd percent with the standard dose to 90 odd percent with half dose, which is not what's in their protocol. And that's one of the reasons why the AstraZeneca vaccine, which was supposed to come up for review in February is probably gonna be delayed to April because things are a bit confused in terms of some of the results of the trial. I think the Janssen or J&J vaccine, it's gonna be very interesting with the one dose and they do have in their protocol that a second dose will be given three or four months later.

0:15:30 Martin: The US is notable from the fact that we are solidly on these two MRNA vaccines for now, and we're starting to see a broader range of other vaccine technologies being used in other countries, but these two vaccines are both coming out with these efficacy numbers that are definitely in the higher echelons that we see with vaccines. 

0:15:48 Monto: Well it's gonna be interesting to see how the traditional vaccines fair, the NovaVax. One of the problems they're gonna have in the US is they're not gonna be able to run the NovaVax trial in the US for older individuals, and that was a requirement for the two vaccines that are currently under emergency use authorization. They're gonna have to go outside the US, because would you, if you're over age 65, wanna be in a placebo group when you can get one of the vaccines that's already licensed. As you know, they've done RSV vaccines in various countries in the world. They're gonna go back to those countries in order to test older individuals, so they can maintain the placebo group. And we're gonna have even more problems going forward if we start changing dosage and things like that. It’s gonna have to be against an active comparative, vaccine against vaccine. Because we're not gonna be able to do a placebo trial in the US, ethically.

We're a polarized country in so many ways, one of the things that were polarized about is getting this vaccine. Some of us, including me, are eager to get the vaccine, and then there are some people who don't wanna get the vaccine. And it's really a paradox because those that wanted an in bad. 

0:17:13 Martin: Yeah, it's interesting, the results from the trials about how striking the effect was and how fast it was. I think we're gonna start seeing the vaccine working, and I think that's gonna mean a lot to people once they start to see that it really does prevent deaths. 

0:17:34 Narrator: This has been a special edition of Population Healthy, a podcast from the University of Michigan School of Public Health. During the ongoing coronavirus pandemic, we’ll work to bring you analysis from our community of experts to help you understand what this public health crisis means for you. To stay up-to-date in between special edition episodes, be sure to check out our website publichealth.umich.edu, subscribe to our Population Healthy newsletter at publichealth.umich.edu/news/newsletter and follow us on Twitter, Instagram, and Facebook @umichsph.