Ask the Expert: Omicron and the Next Phase of the Pandemic
By Brian Hiro
When a new pathogen called the coronavirus first began to take root in America in early March of 2020, we turned for answers – and some comfort – to Cal State San Marcos immunologist Bianca Mothé, who (with her biological sciences colleague James Jancovich) helped place the emerging threat into context.
That was when the number of confirmed U.S. cases was only in the hundreds, and the number of deaths was fewer than 25. Almost two years later, of course, more than 900,000 Americans have perished from COVID-19, and the cases total is roughly a quarter of the U.S. population.
With the latest variant, Omicron, clearly on the wane and daily life returning to some version of normalcy, we decided to check in again with Mothé to talk about where the pandemic stands now and the endemic phase that could soon be our reality.
Question: What do you think about the current situation with Omicron? Case numbers are declining rapidly, though hospitalizations and deaths remain distressingly high.
Bianca Mothé: The overall numbers will continue to decrease. But I think there's a cautionary tale in that there are still lot of unvaccinated individuals. In the U.S., we have about 35% of the population who are still unvaccinated, but that doesn't represent what's happening internationally. In African countries, there still are places where only one in 10 people have been vaccinated. Those are places where a variant like Omicron can really take hold. Unvaccinated adults have a 15 times higher risk of dying from COVID than those who are vaccinated. We have all the tools, but we haven't distributed them equally. So while we may take comfort that, in San Diego, we've definitely hit the peak and are coming out on the other side, there's still potential for this particular variant to take hold in other places, and lead to much more death, because there's greater unvaccinated rates in some of these countries.
Q: And that can also go for parts of the U.S. where the vaccination rate remains low?
BM: Correct. I think we're pretty lucky here in California with the vaccination rates that we have, close to 70%. That definitely doesn't represent the entire country. We're probably going to continue to see, even with Omicron, these outbreaks that are regionally-serving just based on vaccination rates, or lack thereof.
Q: You mentioned countries where only one of 10 people is vaccinated. What is the specific threat to the U.S. of vaccines still not achieving a global spread?
BM: I think Omicron is a cautionary tale of that. It emerged in Botswana, but it was really detected in South Africa, where it was first reported. Then it progressed super quickly in terms of being able to spread to other countries. So I think what you're creating in these countries that have low vaccination rates is an opportunity for this particular virus to continue to create variants that might have an even more rapid rate of transmission. We can't take comfort in the U.S., even though we may have higher rates of vaccination. We might be threatened by a new variant that is emerging from somewhere that has a low rate of vaccination.
Q: When you first heard about Omicron late last year, could you have imagined that it would turn into the beast that it has?
BM: It was interesting because, at that point, we were all really concerned about Delta. Delta is much more dangerous in its ability to cause disease. When Omicron first emerged, we didn't know a whole lot. Scientists were sequencing it and identifying which mutations it had. The Omicron variant has over 60 mutations compared to some of the original strains, and it was surprising at that time to realize there was a specific variant that could carry as many mutations as it had and still be fit. When I say fit, I mean it's a virus that can still infect effectively and transmit, because ultimately that's what the virus wants. The virus wants to be able to go through a replication cycle in a new host. Omicron is unique in that it multiplies 70 times faster than what we were worried about, Delta, and especially in the upper airways. The way it does this is it has specific mutations at a cleavage site that allows for this particular SARS-CoV-2 variant to get swallowed up by the cell instead of having to fuse in a step-by-step manner. This variant can effectively infect cells in the upper airways. We had seen other variants with other mutations, but in the spike protein, which is what it uses to attach and get into the cell. That was new. Omicron also has additional mutations that allow it to escape immunity created by previous infection and/or vaccination. So that's what was surprising about Omicron, that you could have a variant with as many mutations that gave it an ability to become more fit.
Q: What new information do you think scientists have learned about COVID and its many variations from the encounter with Omicron that will help us going forward?
BM: I think Omicron was a great tale of international collaborations. South Africa was very forthcoming in saying they had identified a new variant. And while they didn't know all the details, they were able to share with the international community information about the virus and give it to people who would be able to model and see, based on these mutations, that this was what we would predict would happen. I think that's a real evolution, countries deciding that collaboration is going to be one of the best ways to deal with this. Now there's heightened surveillance in most countries so that as a new variant emerges, it's rapidly detected and the international scientific community can tackle it and determine the situation with those specific mutations. Is it leading to something that's more infectious or can transmit better? We're probably going to continue to see new variants coming from some of these countries that don't have the vaccination rates of others. But we have gotten better at surveying those and distributing that information internationally.
Q: What is your perspective on the variants out there right now? How would you sum it up?
BM: When we talk about Omicron, everybody is thinking about the original Omicron sequence, which is called BA.1 and has been studied pretty intensely at this point. There are two more variations of Omicron. One of them is called BA.2, and then there's another new one that's emerging that's BA.3. BA.2 is less prolific, but in some countries, it has overtaken BA.1. The specific countries that we can point to are Denmark, Nepal and the Philippines, and it has a minor presence in India. If you look at India, for example, with its lower vaccination rates, that is a place where BA.2 could continue to mutate into a new strand. The third one, BA.3, has yet to take off; there are only a few hundred cases where it's been detected. But that's something where people are beginning to monitor and look at the sequence to see how different it is from BA.1 and BA.2 and whether it’s giving the virus any additional advantage based on mutations.
Q: BA.2 has been discovered in California, right?
BM: Yes, we already have BA.2 here. But it hasn't taken over BA.1, which is the original Omicron.
Q: Is it too early to say how BA.2 might affect the population here?
BM: There's a lot of investigation right now to determine the extent that people can get reinfected. Can someone who has had the original Omicron get reinfected with the original Omicron or BA.2? If someone has been infected with BA.1, the original Omicron, can they even catch BA.2 or BA.3? There's some indication that reinfection can occur, but we don't know what these additional variants will represent in terms of reinfection. I think that's one of the big questions right now: Can you keep getting it over and over and over again, because the immune response that you'd get from infection maybe isn't that strong or that durable.
Q: What about the question of whether vaccines and boosters are as protective against BA.2 and BA.3 as BA.1?
BM: That's still to be determined. We're still working on getting more booster shots into people. You don't want to have a false sense of security just because you've had two shots. That booster shot really does help your immunity, even in the context of something like Omicron that isn't as severe. We have a tool out there in vaccination, and that will protect you from severe disease.
Q: We’ve been discussing two new variants in the Omicron family. Could something still come along that's entirely different?
BM: Yes. Omicron has taken over in terms of numbers, but Delta is still out there. There's still a possibility of going back to some of those original sequences, like Alpha or Delta, and something mutating from that. Given the ability that Omicron has to infect new people, most of the infections are coming from Omicron, but that doesn't mean you still couldn't get mutations from Delta.
Q: There was a time not too ago when the general public didn't think about the word “pandemic” and maybe didn't even know what it means. Now, of course, it's fundamental to daily discourse. These days, we’re beginning to hear the word “endemic” more and more often, and some people might not have a clear grasp of it. How do you define it, and how does it differ from pandemic?
BM: Pandemic is the introduction of something new, a new pathogen into the population and the ability that it has to spike and get a lot of infections. Once something becomes endemic, it is really in our population. A good analogy is that influenza is endemic, but in a seasonal way, meaning that we can all anticipate that there's going to be a flu season and roughly how many individuals are going to get infected and how the flu is spreading throughout regions based on the time of year. I think what we’ll get with COVID-19 is that it's going to be around and we have the tools now to control it more effectively. We've got vaccines, we know that masks are protective. We're going to have to learn how to deal with it, and hopefully we’ll see in the next couple of months that some of the indoor mask mandates might go away. But we're introducing new public health tools like sewer water testing that will determine regional locations where there might be increases in numbers of infection. And then some of the usual public health tools can be reintroduced. So when we think of it being endemic, it's going to be around. It's not going to go away tomorrow or next month or even in six months or a year. But now we have the tools to better control it and even predict what's going to happen next.
Q: Will it go away in our lifetimes?
BM: Well, coronaviruses have been around. Some of them are responsible for common colds. So I don't think so. This has really taken hold, and I don't see it going away. I think the way that we're going to be able to interact with it, we probably won't go back to our previous normal. We'll just be using public health tools more effectively to be able to monitor it.
Q: Regarding the comparison to influenza, do you think COVID will turn into a seasonal thing?
BM: The goal originally was that it would be seasonal. In the winter, people are indoors, and that would lead to increased transmission rates. That didn't happen in our first two seasons with COVID, though there were some peaks. I think it’s still to be determined whether there will be increases and decreases in infection based on season. I haven't seen any data that will clarify that for us at this point.
Q: What do you think about the increasingly expressed idea of learning to live with COVID and how our society might deal with that?
BM: In thinking of how to live with COVID, there's a flu vaccine that is available to everyone every year, and it's pretty successful at preventing severe flu outbreaks. That's a tool we now have with COVID, and we've had to implement booster shots, so it could turn into something where you're just going to have to get a vaccine periodically. I think that's one way we're going to live with it, by boosting our immune system with a periodic COVID vaccine. And if we can, as a society, increase those vaccination rates, hopefully we would hit herd immunity and protect those individuals who can't be vaccinated. That would ultimately be the goal. Are we headed in that direction? Well, we're seeing a moderate increase in vaccination rates. If we can continue with that philosophy, these vaccines are what we’re going to need to continue to live with COVID.
Q: Reflecting on when we first talked in March 2020 to where we are now, what has surprised you most about the arc of COVID?
BM: This virus has thrown out all the models that anybody would have had for a new virus being introduced into the human population. But as several of my colleagues have said, this has really tested scientists. And ultimately, it's probably going to go down in history as one of the greatest accomplishments of science and medicine in being able to introduce a vaccine in nine or 10 months after the discovery of a new pathogen. So while it has really tested us in terms of not being able to predict what was going to happen next, it did provide an opportunity for a new vaccine generation. And now taking those tools that have come through in terms of COVID and applying them to other pathogens that we’ve been dealing with for a long time, like HIV, that's exciting.
I think this is also an opportunity for us to realize that, as scientists, we have to do much better in terms of communicating with the public and utilizing platforms that are much more accessible. For me, it's exciting to have a whole science Twitter section that I can go to where there are multiple papers every day in peer-reviewed and non-peer-reviewed literature that are really moving science forward. Even for scientists, you can't keep up with all the new information that's coming through.
What surprised me most is that there was a pathogen that was introduced into the human population that no one could have predicted would have taken hold and replicated so effectively, and from an optimistic perspective, scientists were able to respond to it in a way that has never happened before. I think if this was 10 or 15 years ago, we still wouldn't have a vaccine for it; we wouldn't have had the platforms that we have now to generate new vaccines. And that's really exciting to see. The virus evolved, and our tools to deal with it had to evolve even faster.
Brian Hiro, Communications Specialist
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