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.
When SARS-CoV-2 first arrived, it was as if a raging wildfire had been blown by a strong wind through dry, flammable timber. So says Ali Ellebedy, PhD, an immunologist at Washington University School of Medicine in St. Louis. As a population, he says, we were completely vulnerable to the virus because no one’s immune system had seen it before. In the two years since the virus first appeared, millions of infections and vaccinations have been able to tamp down some of the flames, and Ellebedy says that process should continue in the coming weeks and months. He’s looking forward to new vaccines being tested that are designed specifically to fight the omicron variant. He says if society wants to return to a more normal way of living, it’s important to vaccinate as many people as possible, as soon as possible, throughout the country and the world. But it’s also important to update vaccines to make them more effective. Ellebedy says that although he has no idea whether omicron will be the last of the major COVID-19 variants, he is confident that if another variant does arise, it will be more similar to omicron than to former variants, so he says omicron-derived vaccines should be beneficial even as the virus continues to evolve.
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 discuss the unprecedented wave of omicron infections, how to make vaccines more effective, and how long it may be before we finally can return to something resembling normality. Ali Ellebedy is a scientist in the Department of Pathology & Immunology at Washington University School of Medicine. He says the current wave of infections shows that we were lucky other strains of the virus arrived before omicron did.
Ali Ellebedy, PhD: We are fortunate that omicron was not the first variant of the original virus, because that would have made it really hard for even those who have been recently infected to have any resistance. That’s what actually we are seeing now. Those who were infected early in the pandemic and haven’t been vaccinated, they are being reinfected again.
Dryden: Ellebedy says he’s excited about the fact that it may not be too long before there is an updated vaccine available that’s more specific to the omicron variant of the SARS-CoV-2 virus. Clinical trials on that vaccine already have begun. And he says even if the omicron wave ends before such a vaccine is available, it’s still likely to be useful, because it’s likely future variants will keep some of the mutations that made omicron so very infectious. Ellebedy says almost two years of COVID-19 infections and a year of vaccinations have left the population of our country and our world with partial immunity. Otherwise, he says, the current omicron wave could have been even worse and made those infected a lot sicker.
Ellebedy: The difference now is that we are partially immune against this virus, and I’m talking about we, here, as the population. Because when we (were) first exposed to that virus in early 2020, we did not have any previous exposure to that virus, either in the form of infection or in the form of vaccination, and it was infecting freely. Now, the difference is we have partial immunity because of vaccination, so the virus doesn’t have all doors open. There are closed doors now, and that makes it much harder for the virus to achieve the same level of pathogenesis or make it more deadly compared to what we had in the beginning. So you can think of it as a virus that — when the virus as a wildfire (is) being introduced to a place that is completely dry with some wind, that’s really perfect conditions for the fire to spread. What vaccination does is make this place partially wet. Even if it’s not completely wet, it’s partially wet. That makes, really, the spread of the fire much slower.
Dryden: As I understand it, there’s some evidence that omicron is as infectious as it is because it’s really good at evading some pre-existing immunity. So would this have been even worse if omicron had come first?
Ellebedy: This is an important question. We cannot really do the experiment in real life. The only thing we can really think about is that we are fortunate that omicron was not the first variant of the original virus because they are very different, and that would have made it really hard for even those who have been recently infected to have any resistance. And that’s what actually we are seeing now. Those who were infected early in the pandemic and haven’t been vaccinated, they are being reinfected again. Now, the omicron variant is a different level of change, a very significant one, and that’s allowed the virus the chance to really escape (the) pre-existing antibodies that we form from that vaccination, and that allows the virus the upper hand in terms of just establishing the infection. The good news is that if you have some immunity, then you can mount a memory response. So those are the cells that we formed from that initial exposure, they can start producing antibodies that can, in a way, partially limit how omicron can spread. And that explains why we are seeing a milder form because we have this partial immunity. So yes, omicron is as infectious as we are seeing now. This is the biggest wave so far. Every one of us knows a lot of people that got affected by this, even including my household.
Dryden: I was going to ask you about that. So you spent the winter break with some sick folks at home.
Ellebedy: Yes. It was an interesting experience given that a virus that I personally spent the big part of the last two years either thinking, talking or writing or working on it, that you finally had — unfortunately had — the chance to see it very closely. … Actually (I) came home and this is, my wife actually tested positive the day before Christmas, and this is when we are just about to start our winter break. And that’s something that we really didn’t plan for, obviously. The good news is that we actually canceled all our travels for the winter break because omicron was on the rise. We realized that it’s not a really good time to travel, so in a way, it didn’t affect our plans, except that we had to stay home for more than eight or nine days until she tested negative. Fortunately, she was vaccinated and had the typical symptoms, relatively mild, but she was symptomatic. Again, we were fortunate because all of my three children are in the 5 to 12 age range, so they were also vaccinated, so they have (been) twice vaccinated. So that also made me more relaxed about the whole process because I knew that we have some sort of partial immunity that we discussed, and we couldn’t really isolate inside the house. We isolated from outside, but we couldn’t really efficiently isolate inside the house. I know for sure, given how infectious omicron is and given how short the incubation period we’ve seen, there is increased likelihood. I mean, obviously nothing certain because none of us in the household, other than my wife, tested positive. We had the exposure, and I like to believe that it’s our vaccines that make us really — it made me much more relaxed over that period, although at the end of the day, we stayed home for 10 straight days.
Dryden: Now your wife was not boosted. She hadn’t gotten around to getting the shot when she tested positive. There is a new booster on the way. Clinical trials have started on a booster that is specific to omicron. Is that something that could be available sometime soon?
Ellebedy: Oh, again, that’s a very important question, and I get this question all the time about this. We know that the big pharmaceutical companies already started right away from the first early days after the first sequences were published that a vaccine was being made. We know that that vaccine actually made its way to animal models already, as you mentioned the clinical trials to test it. The question becomes, when will be the time and what would be the FDA requirements for this vaccine to be approved? But if everything goes according to what we have seen in the past, then we are talking something around the spring, probably.
Dryden: And will it make a difference by the spring? In other words, is it possible that by the spring, omicron will have evolved into some other variant that has more mutations that won’t be as responsive even to the updated vaccine? And is this going to be years of a Whac-A-Mole game where we try to — just as we hit the mole on the head it springs up someplace else?
Ellebedy: It’s likely, very likely, that when this vaccine becomes available for the general public, that then the numbers will be on the low end and at least we will be way past the peak of the viral infection. But that doesn’t mean that having that vaccine will not be useful from an immunological standpoint. The reason is, let’s say, that the estimates will be like 40% of the U.S. population will be exposed to the omicron. There is still a lot of people who will thankfully actually escape that. But we will still want to have our immune system in a way updated. You can think of it as having your software, which is in that case, our immune system updated with the latest version of it. And we want to update our immune system with what’s the latest version of this virus to keep the pressure on the virus itself and make sure that the virus doesn’t have an easy chance to spread. And I’m talking about whatever virus that will come after the omicron. There is a chance, a big chance, although, again, no one can say for certain, that the next virus or the next variant of concern will be more similar to omicron than to the original strain. It’s hard to make predictions with this virus. It’s truly unpredictable, especially with the massive change that we saw between the delta and the omicron.
Dryden: As you said at the very beginning, there’s some at least background immunity in the population now that wasn’t there when this first appeared. And one of your early papers in this whole pandemic talked about how people who had been infected had some protection against reinfection. Not necessarily guaranteed that they wouldn’t get reinfected, but that they had some antibodies that were made in response to being infected after they recovered. That paper is still being used by some folks to say, “I had it. I don’t need to get a shot.” Why is that wrong?
Ellebedy: That was a really a lesson for me personally about how communicating science to your fellow scientists is different from communicating using science to the general public, because our paper just briefly showed, really, that when you get infected with a mild infection with SARS-CoV-2, you would produce what we call immune memory, which is an advantage. And it is something that we as a species, we depend on this to really build immunity over time. Whenever you get infected as a child with any virus, you have some sort of immune memory made against that particular virus, so when you get exposed to it again, then you are much better prepared. The trick here is you get exposed to the same virus again. Some people misinterpreted or miscommunicated our findings in saying that, “Oh, you are infected with SARS-CoV-2, then you are protected for life.” That could be true if SARS-CoV-2 itself didn’t change. If SARS-CoV-2 was a virus similar to the smallpox virus or similar to the polio viruses. So, those viruses did not have these different variants. That protection is completely now changed the moment the virus changes. Because now whatever you trained your immune system — or whatever features our immune system trained to recognize in the original strain, these features have changed, and that’s the big difference. There is a significant similarity in those features between the delta variant and the original variant, but that goes all away now with omicron because that’s a virus that is significantly different from the original strain. So if you have been infected a year and a half ago and you have that immune memory, the virus itself is completely different, and the virus that you made immune memory against with that initial infection is no longer circulating in humans. If the virus changed like influenza, like SARS-CoV-2 now, then you have to keep updating your immune system to keep track of the virus.
Dryden: You’ve spent years and years studying influenza. We get a shot for influenza every year. Is this eventually what we’re looking at with SARS-CoV-2, that we’ll get regular immunization, whether it be something that’s omicron-specific or the next variant-specific? How does this end?
Ellebedy: I would say I would start from the end. I don’t think we will need to be social distancing forever. Masking, to be honest, in places like airports and other places, it could have a benefit even after the pandemic ends. But I don’t think also that we will need this forever. The main goal for these important interventions is to really slow the spread of the virus. Days like when we are living now, where we have overwhelming numbers of patients that need to be cared (for) in our health-care facilities and you have overrun facilities, that’s the danger. And that’s where these interventions can really slow the spread of the virus. And that’s a very, very important aspect of our response to the pandemic that shouldn’t be ignored. The road to the virus to be endemic is to have what we call herd immunity, is that we don’t have this dry land anymore for the virus. We don’t have these easy open doors for the virus anymore. We have collectively, as a population, we have some resistance for the spread, so wherever the virus will show up, it will be a small outbreak, and within that outbreak, the cases will be milder and milder. The hospitalization will not be needed. Going back to that point, is it going to be an annual vaccination? I don’t know. At this stage, it could be. There is a chance that, yes, we will need to be updated, but also, unfortunately, we’ll have to wait to see what the data will bring and what the virus — what’s the next step for the virus. So yes, it’s a bit frustrating for us, even scientists before anyone else. There is a lot of unknowns, and there is a lot of uncertainty about what’s next. But I think there is really no other way other than just really keep monitoring, keep sequencing the virus, keep tracking the surveillance efforts that we do worldwide. One of the things that are amazingly impressive is that when this variant started showing in South Africa and before that in Botswana, it was very, very early detection. Thanks to the scientists in South Africa that really quickly sequenced the virus and shared it with the global scientific community, we were able to realize right away that this is different. Seeing a very different sequence that’s spreading very fast raised the red flag very early on. And despite all our efforts, we know that the virus continued to spread. But at least we started making the vaccine, and we started preparing ourselves for it. So I think continuing these efforts would allow us to keep track with the virus, keep track with its evolution and trying to make sure that we are prepared. I am optimistic that we will be able to prevail, and we will prevail. We will actually be able to limit the virus back to regularly, like other coronaviruses that we have. It will be eventually a common cold virus, where really there are no need to even test for it at a certain point. This is what I’m hoping for. One day we will not be tested. You will be sick for a couple of days, but no one is dying from it. That’s important. No health-care system is being overrun because of it. Whether this will happen after omicron or after the next variant or after the variant after that, this is something we don’t know. The other advantage we have is we have now a tool that we are impressively able to adapt very quickly and produce in a large scale. The next phase is to be able to produce that tool or produce that vaccine in a large enough amount to share it worldwide. Because what delta has taught us, and now omicron also taught us, that you can vaccinate your population or your surroundings. But the problem is if a variant that evolves thousands of thousands of miles away, it will in no time reach your shores, and it will in no time go everywhere and cause the trouble. So it’s always great to be able to make sure that the virus doesn’t have that free or open doors anywhere. Limiting the ability of the virus to replicate and divide freely and infect people freely in communities where there is no access to vaccines and no access to proper health care, that will give the chance (to) the virus to continue to mutate and produce the next variant. So I think we have reason to be optimistic about moving forward, whether we will need a new vaccine, annual vaccines, that will always have to wait for the data.
Dryden: And Ellebedy says he’ll be one of those scientists gathering and analyzing that data. And he says he stopped trying to predict how the pandemic may change moving forward. But he does remain optimistic that there will be a day in the not too distant future when we should be able to start transitioning to whatever normal life will look like in the future.
“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.