A new episode of our podcast, “Show Me the Science,” has been posted. At present, these podcast episodes are highlighting research and patient care on the Washington University Medical Campus as our scientists and clinicians confront the COVID-19 pandemic.
A few weeks ago, no one had heard of the omicron variant of SARS-CoV-2. Since its recent discovery by scientists in South Africa, infections with the variant have been found in dozens of U.S. states and countries around the world. Scientists are scrambling to understand whether the new variant, which houses several mutations on the spike protein that infects cells, might be able to evade protection from current vaccines. Virologist and researcher Larissa B. Thackray, PhD, an associate professor of medicine, recently completed experiments in mice in which her team tested the efficacy of vaccines against an earlier SARS-CoV-2 variant, the beta variant. She plans to use the same strategy to test the vaccines against omicron. Meanwhile, Steven J. Lawrence, MD, an associate professor of medicine in the Division of Infectious Diseases, says omicron is likely not the last worrisome variant that will be discovered. But he says old, reliable mitigation techniques — such as wearing a mask, avoiding big crowds and staying home from work when you don’t feel well — will remain effective, no matter how infectious omicron turns out to be and no matter how many new viral mutations appear.
The podcast, “Show Me the Science,” is produced by the Office of Medical Public Affairs at Washington University School of Medicine in St. Louis.
Jim Dryden (host): Hello and welcome to “Show Me the Science,” conversations about science and health with the people of Washington University School of Medicine in St. Louis, Missouri … the Show-Me State. As we continue to detail Washington University’s response to the COVID-19 pandemic, in this episode, we move several letters forward in the Greek alphabet to discuss what the arrival of the omicron variant might mean.
Steven Lawrence, MD: There’s a real chance this may be somewhat of a new normal for us and, at least in the next few years, where there may be times of increased coronavirus transmission, perhaps from a new variant, that will require more mitigation measures to be able to make sure that there are environments that our kids can go to school, that people can go to work.
Dryden: That’s Dr. Steve Lawrence, a Washington University infectious diseases specialist. He says it’s important to continue to use tried-and-true mitigation strategies like masking while scientists in the laboratory learn how the new omicron variant might influence the course of the pandemic. Meanwhile, a team of Washington University virologists has published findings in the journal Science showing that when mice were fully vaccinated, they were fairly well-protected from an earlier viral variant called beta that also had properties that made it look as if it might be able to evade some antibodies. The scientists also found, not surprisingly, that vaccines that had been tweaked to address beta in particular were a little more effective than standard vaccines. Washington University virologist Larissa Thackray and her colleagues now are set to study how vaccines work against omicron in mice. She’s part of a large group of scientists called the SARS-CoV-2 Assessment of Viral Evolution, or SAVE, Consortium organized by the National Institutes of Health. She’s also launched a podcast called “Let’s Meet the Virologists,” where she talks about the state of things with others who study viruses.
Larissa Thackray, PhD: We’re part of a larger SAVE Consortium that the NIH put together at the beginning of this year. And the whole, sort of, purpose behind this consortium is to actually be scanning out, looking for sequences of variant viruses. And then when essentially that pops up, just like it’s happened for omicron, the idea is that you then take a look at it, see based on the sequence whether it looks problematic. Our group is actually part of an in vivo group, and so we basically set up mouse models to kind of look at how the vaccines — and, in particular, our group partners with Moderna to look at their vaccine — and so we have these mice that are vaccinated with, sort of, various vaccines, and we look at, OK, if there’s a new variant that’s coming along. So in this paper, it was actually the beta variant. So this is actually quite a while ago, but this is now sort of a template that we’re currently using for omicron. We look at how much virus is in different parts of the mouse, so in the nose, in a way, in the lungs. And then we also look at how the vaccine is still responding.
Dryden: So as you just said, you were looking primarily at the beta variant, which, as I understand it, is sort of resistant to the vaccines, but for whatever reason has not become a problem in humans. And I’m wondering when you talk about the template, if we’re all keeping our fingers crossed, that omicron is going to be the same thing.
Thackray: When you’re looking at a new variant that’s coming up, it may have changed itself so that it’s not as fit. So, for example, it can’t transmit as well between people. So that’s sort of like with the beta variant. That one actually in in vitro and neutralization assays, we were actually quite concerned about that one. But it never really took off. We were worried about it enough so that we actually started doing studies, but then it kind of died down. And in fact, what took over was, in fact, delta. And so that variant actually, sort of, was both more transmissible, although in at least in in vitro studies, it was not as escaping as beta actually was. And so omicron has many, many amino acid substitutions in the spike. And so it’s predicted that it will actually be more like beta in that it is, at least for neutralization, problematic. But how that actually will, sort of, behave in a vaccinated mouse, in our case, or individual — based on our study with beta, the study sort of suggests if you’re well-vaccinated, you will probably do OK against something like beta and maybe even something like omicron for severe disease. And then, as has been shown in the press, a lot of the manufacturers are now considering, should we actually make a new vaccine? So a vaccine directly targeted against, say, omicron. And that’s what we also studied in our paper. And not surprisingly, if you have vaccine and the, sort of, the challenge virus being the same, in that case, we actually had better protection. But still, for when you’re well-boosted, when you have lots of, sort of, antibody out there, even in our mouse model with sort of a different variant, even delta, you were protected. It was more when you had sort of lower levels of antibody. And in humans, that’s sort of analogous to a waning immunity or, unfortunately, people that, for whatever reason — underlying conditions, drugs that they’re taking, medications — they don’t raise a good antibody response to begin with.
Dryden: I have heard it said about the vaccines that we have all gotten that really they were a three-dose vaccine from the beginning, and that maybe after boosting, immunity won’t wane. Is that something that your group will be looking at, not related to omicron or beta or any of those other things?
Thackray: Some of our studies now, we actually have cohorts of mice. And this is, once again, some of the initiative from the SAVE Consortium is for essentially us to have mice almost sitting around that basically got the primary series. So they got sort of the initial vaccine and then the second one. And essentially, they’ve been sitting around for a couple of months. And so now we actually can look at if we boost them, how much better are they now protected? And then we can even look at, for example, if we boost them with a new variant vaccine, so against omicron, is that better than the original vaccine? I think part of the issues with the vaccines before was that a single dose, especially of the mRNA vaccines, really didn’t do much. And so you had to bring a second dose on very quickly in order to get a decent response. If you are not in a pandemic — so if you think about your childhood vaccination scheme, you’re not in a pandemic situation. You can actually space out the vaccines and bring on protection over years, essentially, right? But we really didn’t have the time to do that. And so in the beginning, I believe that a lot of the studies, sort of, in the preclinical models suggested two doses for the mRNA vaccines would give you good enough protection. And so that’s what we went with. I do believe that now some of the idea is “Should we revisit this?” But even then, clearly in all of those cases, there’s still waning. And so the idea is just like a lot of other — MMR or some other vaccine series — you probably need a third dose to really kind of boost the levels up and to kind of broaden your immune response to leave you more protected against, sort of, different variants.
Dryden: You said you’re working with one of the companies right now, with Moderna, and I’m assuming that other groups in the consortium are working with other vaccine makers, so as the work goes on, you’ll know how protective all of the vaccines are.
Thackray: Yeah, so part of the consortium was basically to pair people with different in vivo models. And so, as part of that group, there are people like ourselves that do mouse work. But then there are other people that do, say, hamster work. There are other people that do nonhuman primate studies. And so for all of these different models, there are, sort of, groups of animals that essentially have been vaccinated. And in our case, it was vaccinated with Moderna and then also our version of the adenovirus vaccine. So this is something that Mike Diamond’s group had worked on earlier.
Dryden: Mike Diamond is the Herbert. S Gasser Professor of Medicine, and he specializes in the study of new and emerging viruses. Diamond began studying the virus that causes COVID-19 even before the first case was reported in the United States, and his group has been working on an intranasal vaccine.
Thackray: So we have some mice that have been vaccinated with that, and that’s an intranasal vaccine. So we will look at how does that protect against omicron. But other people partnered with Pfizer. Other people partnered with Johnson & Johnson and AstraZeneca. And so basically, we have all of the major vaccines that are licensed in, sort of, Europe and the U.S. that are part of the consortium.
Dryden: You mentioned the intranasal vaccine that’s been developed here. My understanding is that the idea is that what we’re getting now is boosting a systemic response whereas something that we got in our nose might block the infection from entering the body to begin with. Is that correct?
Thackray: Even the mRNA companies are starting to investigate this. And so we are definitely, I think in general as a team or as scientists, looking at whether you could boost with one of those. And potentially that would actually limit the amount of replication in the nose and really try and sort of reduce transmission.
Dryden: You’re part of this huge SAVE Consortium. You’re also a podcaster. So you’ve been talking to virologists from all over the world. What’s the consensus? Is this a virus that we’re going to be living with forever as it mutates? Is 2022 going to be the year that we finally get past this? Is there a consensus with the people you talk to and work with?
Thackray: I would say it’s still not clear. I think it depends on the virus and our behavior. If we are successful at bringing some more of the, sort of, mitigation strategy, so there’s less transmission, people are more vaccinated, then essentially there’s less sort of variant viruses that arise. But what’s a little bit of concern is that, for example, in the United States, there’s now a lot of evidence to suggest the virus has gone into white-tailed deer. And so we may actually have animal reservoirs of the virus. And once you have that, it becomes very difficult to eradicate a virus.
Dryden: Meanwhile …
Lawrence: I’m Dr. Steven Lawrence, professor of medicine, the Division of Infectious Diseases.
Dryden: … Lawrence says despite so much of the news being focused on omicron, currently the vast majority of cases in the United States and in the St. Louis area — where cases have been rising a lot since Thanksgiving — are still the delta variant. And he says it’s pretty clear that the spread of delta was not the result of society collectively lowering our guard.
Lawrence: It was going to emerge anyway, regardless of the level of mitigation in a particular country. Once a new variant that has a competitive advantage and, in this case, with delta, it was twice as transmissible as our prior variants. And that gives it a distinct competitive advantage, so much so that it outcompeted all of the other variants and nearly all of the virus in the world in the last couple of months has been delta. When that happens, there is going to be a surge of cases whenever it is introduced into an area. And while the mitigation measures are certainly important to blunt the effects of that surge, having some relative relaxation of those mitigation efforts, in almost all certainty, wasn’t the reason why we had delta emerge and surge in the United States. But I do think that there’s a real chance this may be somewhat of a new normal for us, at least in the next few years, where there may be times of increased coronavirus transmission, perhaps from a new variant, that will require more mitigation measures to be able to, first and foremost, protect the health-care systems, but secondly, to make sure that kids can go to school, that people can go to work. Because what we found, especially in the era of vaccines, is that even during a surge, we can put some mitigation measures in place that can be successful at preventing overwhelming the health-care systems and keeping people working and in school if we use some of these common-sense mitigations, particularly masking when indoors, having indoor spaces that are well-ventilated, procedures in place so that people aren’t coming to school or to work when they have symptoms, and adequate testing capacity so that we can certainly test everybody with symptoms. But then on certain occasions where it might make sense, to even do some asymptomatic testing when that may be called for.
Dryden: So aside from vaccines, in many ways, what you’re talking about with those mitigation strategies are the same strategies that we had in 1918 with the flu. I mean, they didn’t have a vaccine, and it didn’t exactly go away, but the pandemic did end. Is the same sort of pattern eventually going to happen with this virus?
Lawrence: Well, it’s hard to know for sure what the future of this coronavirus is going to be, but there’s a reasonable chance — and I think many of us who have studied pandemics and viral infections do believe — that we will eventually get through what we would call a pandemic phase, which is really defined by a new virus with an antigen on it that people haven’t seen before so that most of the population is susceptible to it, that circulates very widely, it’s easily transmitted from person to person and that it’s global. We are getting to a point, as we go through this, where there are enough people becoming vaccinated and infected to provide at least some partial immunity such that we would anticipate at some point, in the hopefully not too distant future, we won’t be at high risk for huge surges of infections. When we get to that point, we would have started the process of converting with our language from calling this a “pandemic” to this being an “endemic” virus. It’s very likely that SARS-CoV-2 will be with us for the rest of our lives, and it may be part of the respiratory virus landscape that we experience on an annual basis. And interestingly, the same measures that are effective at reducing the impact of COVID really haven’t changed, as you mentioned, since 1918. Masking, avoiding large crowds coming together, being outdoors instead of indoors. These types of things — not being around people who are sick — these types of things are the basic fundamental infectious disease epidemiology principles that haven’t changed. They’re not fancy. They’re not exciting, but they’re effective. We do have the advantage of vaccines now, which give us a huge upper hand.
Dryden: So I’m guessing that regardless of what we learn in the next few weeks and months about omicron, it’s probably not going to be the last variant we encounter.
Lawrence: Well, almost certainly, omicron is not going to be the last variant that we encounter, even if we do run out of letters in the Greek alphabet to call these variants. Variants occur all of the time. This is the way that RNA viruses work. When they replicate within human cells, there are mutations that occur that lead to potential variants all of the time in many, many people. But what sometimes happens is that there are enough mutations that occur that can confer an advantage to the resulting virus, either make it more transmissible, to make it more virulent so it causes more severe disease, or to make it able to evade immunity from either the existing vaccines or prior infection. When one of those three instances occurs as a result of mutations is where we get a variant that is considered a variant of concern.
Dryden: A moment ago, you mentioned passing from pandemic to endemic, but the first SARS went away altogether. Is there any hope that that might happen here?
Lawrence: I wish there were, but I don’t think so. There is a huge difference between SARS-CoV-1 and SARS-CoV-2, which is the reason why the first one caused 8,000 cases and about 1,000 deaths, but then disappeared because of the ability to use infection-control measures that would prevent spread from person to person because there was no significant amount of transmission prior to people having symptoms. So nobody was contagious unless they looked sick. That cannot work and is not going to work for SARS-CoV-2. And we’ve already demonstrated this through almost two years of this, and the major reason why is because significant amounts of transmission occur prior to people having symptoms.
Dryden: You and I, we both wear glasses. I don’t know about you, but I am so sick of foggy glasses, I can’t tell you. That’s the worst part of masking as far as I’m concerned. You’re doing work with actual patients who are sick, and I know that. But just the bother of this for you, how has it changed your life?
Lawrence: Well, it definitely is a hassle. It’s something that is tough to get used to, even after all this time. But it’s also a relatively small inconvenience when thinking about the impact of patients who have been infected with this. I’ve seen patients — watched them struggle for air, watched them die from this virus. And while the risk for that happening, for those of us who don’t have severe underlying compromised immune systems and are fully vaccinated, while that risk is very low, it’s still something that stays in your mind. And the inconvenience even of wearing a mask is pretty small in comparison to the inconvenience of say, if you become infected and don’t become sick. That missing 10 days of work or 10 days of school or 10 days of doing things with your family, 10 days is a lot of time right now. Even those who have had mild infection, there’s still some that have had long-term symptoms that we still don’t totally understand. So I think that that’s what keeps me motivated to not be too frustrated with the inconvenience of masking indoors pretty much at all occasions.
Dryden: Lawrence says while the scientists, like Thackray, are working to better understand omicron, cases involving delta continue to be on the upswing, a trend that is expected to continue as people gather for the holidays and spend more time indoors during cold weather. “Show Me the Science” is a production of the Office of Medical Public Affairs at Washington University School of Medicine in St. Louis. The goal of this project is to keep you informed and maybe teach you some things that will give you hope. If you’ve enjoyed what you’ve heard, please remember to subscribe and tell your friends. Thanks for tuning in. I’m Jim Dryden. Stay safe.