Karie Dozer [00:00:05] I'm Karie Dozer, and this is TGen Talks. For our final episode of 2021, we are back at TGen North in Flagstaff. TGen North is home to the pathogen and microbiome division and is the hub for research into the ever changing coronavirus. I sat down with Dr. David Engelthaler, who has been directing TGen’s research into COVID since day one and who appeared on TGen Talks in the first episode of this year as the rollout of the first COVID vaccines was getting underway. We asked Dr. Engelthaler to look back on the year's work and reflect on the good findings and successes so far in fighting this pandemic and to reflect on what needs to be done to take on the new variants of COVID 19.
Dr. David Engelthaler [00:00:48] Well, it's good to be here with you, Karie. It is, you know, good to be able to continue to track the progress of this pandemic in this virus and starting to see the direction things are going, especially when we have additional variants popping up that were probably unexpected.
Karie Dozer [00:01:06] OK, so that's topic number one. Is it Om-i-cron or Omah-Cron? Because it's obviously the variant of the moment.
Dr. David Engelthaler [00:01:14] I think the correct pronunciation is Om-i-cron , but we're hearing people pronounce it in many different ways.
Karie Dozer [00:01:21] So what is your take now? What do we know about Omicron after knowing about it for a couple of months? What do we know and what's left to find out?
Dr. David Engelthaler [00:01:31] Well, really, we the world just first heard about this on Thanksgiving Day, so it's still fairly new to us and we are continuing to learn more and more the some of the initial information we heard is bearing out to be true. We think one that this particular variant seems to spread even faster than Delta, which we didn't think that was possible. Pretty remarkably so. However, we are not seeing more severe cases. In fact, we're starting to think that we might be seeing even milder cases than we would normally expect with Delta or any of the previous variants. So those are two pieces of news that are somewhat conflicting one not so good at spread so fast, but one that might be very good, that it's mild and we don't have as many serious outcomes. There's three theories as to why we get these new variants. With all these new mutations in Omicron is the king of this one now. I mean, 50 new mutations all at once is pretty remarkable. So the first theory, and probably the most likely, is that you have somebody who's chronically long term infected and the virus just replicates over and over inside them. And then by the time it comes out of them, it's picked up enough mutations that it looks like she's got a whole bunch at once. And those are typically an immune suppressed individuals that we see this long term chronic type of an infection. South Africa has, you know, enormous problems with HIV, but it's also could be somebody who's going through cancer or some other reason why they'd be immune suppressed. That's now the leading theory. We think that's happened with the previous variants. The second one, which is really intriguing, is the possibility of what we call a reverse spillover, where we actually may infect animals and animal. It may replicate, and for some reason, the virus is being selected for in a different way. New mutations show up. So it's possible that a different animal could cause the virus to evolve in a slightly different way and then have to have spillover back into human. That's a possibility. It's a little bit more of a stretch, but it's a … it's a favored theory by some. And then our last theory is that you may have had recombination, so somebody who infected by more than one strain of the SARS-CoV-2 and then you had a lot of genetic exchange between those, then you get some kind of what we'd say, like a Frankenstein version of this virus that happens with influenza and other viruses. It can happen with coronavirus, but it seems less likely that's the case here, just looking at the genetic signatures.
Karie Dozer [00:04:06] We're starting to see it here in Arizona. What do we know about when it may have come here? How many cases you think we will have and what is the data showing you?
Dr. David Engelthaler [00:04:15] Yeah, right now it's it really is too early for us to even guess as to where Omicron is going to go in Arizona. In the U.S., we have different populations in other parts of the world where this really first emerged, like South Africa, we have a much more highly vaccinated and immunized population, which means that there's less ability for the virus to move, although we're seeing the virus can still be transmitted between people that have been vaccinated if their immunity starts to wane. It probably doesn't matter what variants it is. And so we don't really know how it's going to really play out in the U.S., but it fits following the trends that we're seeing. It could replace Delta as the most important variant we have to deal with. That might not be a terrible thing if this one, in fact, is actually much more mild in our … like the other human coronaviruses.
Karie Dozer [00:05:06] Yeah. You talk about immunity starting to wane if this virus is in fact so different from the ones we've seen before. Doesn't immunity have to lay in a bed at least and how ready it is for this variant?
Dr. David Engelthaler [00:05:18] Well, there's no doubt that our immunity to a particular pathogen has to evolve with the pathogen. And if a pathogen picks up a number of mutations that can start to evade the antibodies that we already have, even if we if we have good strong immunity. But what's also happening at a time now that we've had a lot of vaccination, say, 10 months ago, nine months ago, the immunity that we got from that, the antibodies that we got, those are really definitely dropping off and dropping off faster than we anticipated or wanted. But we still have that strong cellular immunity, which is why we don't get most people don't get really sick and die if they if they've been fully vaccinated. So we have the waning antibodies. We have a new variant that might evade some antibodies. So theoretically, it should. When we look at where the all those mutations are, which just means I think we're going to continue to have transmission of this virus, probably the al-Muqrin variant, and it could become the dominant one. But again, like I said, most people who have been immunized, whether from previous infection or vaccine, they're going to have protection from getting that serious illness and dying the ones that are most at risk, the especially the elderly. We want them to get their booster shot because they just don't have a stronger immune response. And that's why we're still seeing deaths.
Karie Dozer [00:06:40] How much do we have to work to keep our vaccines up to date? How do we how do we keep up? Yeah.
Dr. David Engelthaler [00:06:46] Well, there's two ways that we can evolve or evolve our immunity to match the virus. One is we're just going to get re-exposed and then we're going to get probably a minor infection, a cold like illness, and now we've got some immunity towards the most recent strain. But one way to bypass that is to get an updated vaccine for whatever new variant if it's Omicron, but maybe it's the next one after that so that we're prepared our immune system is better prepared to respond to that one. So most likely, we'll continue to see adaptation of these vaccines. The good news about the many vaccines they're really easy to update is just essentially like a little piece of code that just needs to be rewritten a little bit. And the rest of the vaccine is the same, and they're already developing those within a matter of weeks to come up with a new vaccine. Then they have to trial it again, but not as much as they did before. So we'll probably have updated vaccines in 2022. And it's not a terrible thing. We do this for influenza every year. I just want to point out there's been a lot of discussion about like, well, now there's they're going to make us do another booster and then what another booster after that? Well, that's what we do for influenza. The reason is that we don't want people who are at high risk to die from influenza. So and we don't want to get knocked out with influenza for a week or so on an annual basis. So a lot of us get the influenza booster every year. Our bodies may need it maybe every couple of years, but it keeps that immunity level high and keeps us off of our backs and in in working or in school. So getting your COVID booster should be thought of is like getting your annual flu shot, and that's probably what it's going to come down to.
Karie Dozer [00:08:29] Could there be a silver lining to the fact that the Omicron variant is spreading more quickly to more people but is less deadly, more survivable? Is that a good thing?
Dr. David Engelthaler [00:08:40] Yeah, I think that that is the silver lining here is we are all going to be immunized, whether or not you know, it's from vaccine or from natural infection or from both. And most likely from both. As the virus moves around, we're going to continue to get exposed. And if you have pretty strong immunity, you may not even know it, but your immune system does, and it'll get reinvigorated. And hopefully, if it's a milder virus, that's great. But with a silver lining, there's also a dark cloud. The dark cloud is that there's still going to be high risk. People were hoping that we're going to have new medications out to help prevent those deaths were getting better at treating and managing patients early on to prevent those deaths. So the number of deaths are going to continue to drop, but we're still having them. So we don't want people to think that if they got vaccinated 10 months ago and they're 75 years old, they're good. They're not. They still need to get that booster and we still need to might have to do some medical management if they get exposed because the virus is still deadly to them.
Karie Dozer [00:09:44] Characterize for me, if you would, the size of your staff up here in Flagstaff and your day to day as far as COVID research is concerned, what are you doing?
Dr. David Engelthaler [00:09:53] Yeah. So, you know, up here in TGen North, where this is the infectious disease wing of the Translational Genomics Research Institute, which means that we do all the great things that TGen does. But we. Really focus on microbes, especially those that are considered pathogens that infect humans. We also study the microbiome, which is these microbes interacting with each other and that that ecosystem. So we have a lot of the same type of research that the rest of the region does where we're developing new diagnostic tests. We're assisting in the development of new drugs or therapeutics. But we also have something a little bit different where we're doing things to support public health. So new analytical tools are actively being part of investigations of outbreaks or even helping with surveillance to look for outbreaks. So all of that clearly came to bear during this pandemic, and we were able to jump in, as we've talked about before, this kind of genomic first responder moniker that we have really quickly in use these tools. So one, we developed a new diagnostic test really quickly and then got FDA authorization for that. We got we stood up a diagnostic lab so we could test patient samples here and get the results back to doctors, something you really hadn't done before. But one of the first labs in Arizona to do that. But maybe the biggest thing we've been able to do is sequence this virus. Since the beginning of this pandemic, we've really been closely monitoring and tracking the evolution of the virus in all its different strains and variants here in Arizona, more largely throughout the Southwest, and then working with local health departments, tribal health departments, hospitals, places like long term care facilities, jails, shelters, others to help them understand what's going on if they're seeing an outbreak or are they just seeing a number of new cases just coming in from the community? We've been doing this really since the beginning and it really wasn't until probably the beginning of 2020 when people started, excuse me, 2021, when people started talking about these variants, the alpha variant that came out of the U.K. and the one out of South Africa, the one out of out of Brazil and others. And so we've just been watching those variants, but we didn't call them variants early on. We call them different strains or lineages. But now we're able to continue to do that. We're still doing the sequencing, providing a lot of background information and helping track those first cases of al-Muqrin as they move into Arizona.
Karie Dozer [00:12:24] That's an important distinction is that Omicron and Delta aren't the only two variants, they're the two that got the most attention.
Dr. David Engelthaler [00:12:30] Yeah, well, these two before Omicron, we really identified Delta as being the winner or winning that survival of the fittest race. Really, it out competed all the other variants. We had a number of really successful variants before that, and especially the one that came out of the U.K., the California variant also very important here in Arizona. But the next the next one to come up typically had an ability to spread even faster, replicate it gets into you, replicates faster in your cells and gets out faster. And that's definitely what Delta did. And now I'm a crown, which is picked up even more mutations seems to be able to really fit inside that lock that's necessary to get inside of human cells very quickly. It's like a perfect fit, almost. And then it's got some mechanisms that allow it to replicate faster, and then we haven't fully understood how then it could get out of out of the body faster. So Delta did this and outcompete it. Everything else. Al-Muqrin may do this to Delta. It may just be just a little bit better, which in the end might mean just a little bit better for us, too, because it may be more mild.
Karie Dozer [00:13:35] Does this give you any information about who the next, what the next variant in this reality show competition might be?
Dr. David Engelthaler [00:13:43] Yeah. When we saw Delta and I'll admit, I thought, Wow, we've seen the winner of this because it was just so superior in its efficiency to replicate and spread faster. And we'll see if Omicron really kind of holds up in the trends that it has now in our competing delta is unexpected. Which to me means that we're just going to have to expect the unexpected. And we don't know. There will likely be versions of Delta and Omicron for some time. It's quite possible a whole another variant pops out because of one of these mechanisms we were talking about maybe some long term chronic infection or maybe a reverse spillover from animals. We just don't know. It's hard to tell, but we're getting better and better at dealing with this are immune. Now we're developing immunity. Now we're getting drugs pretty soon. Here, too, to help treat cases to keep people out of the hospitals. So while we can't get rid of this virus, we can at least adjust to it and now deal with it in a very endemic level.
Karie Dozer [00:14:47] Do you hypothesize is this what you think about at night?
Dr. David Engelthaler [00:14:50] Oh, it's probably not what I think about at night, but it's definitely what I think about during the day. More importantly, we try to stay on top of what's happening now. It's what we do know. It's impossible to model. You know, we can come up with some pretty advanced mathematical. Modeling and understand which mutations have been more prevalent and which ones might be more important. But no one predicted Omicron. There's a whole layer of randomness to what we would say stochastic effect of mother nature that we can't predict and we don't know what the what's going to be the next one. However, the one thing that we do know is that all of the coronaviruses that have become human coronaviruses essentially evolved towards this being easily transmitted, but being mostly mild and just causing the common cold. It's an effective strategy. It allows the virus to continue to find the next person and the next person, but it doesn't really wipe out populations. And hopefully we'll be able to move away from seeing this millions of cases of year a year in the world and get back to maybe more like a regular infectious disease where this can be some at risk groups, but the vast majority of us will be able to deal with it just fine.
Karie Dozer [00:16:04] How is Arizona doing overall? You guys see data from every county. Small towns, big towns. How are we doing?
Dr. David Engelthaler [00:16:10] Yeah, yeah. Well, there's been a lot made about looking at different states. And the problem is that this virus typically moves in waves in different segments of the country. So a few months ago, we were talking about how horrible the South was doing, and they were just, you know, just getting pummeled by this virus. And there was a lot put into, well, it's obviously it's the policies there versus the other parts. Well, they got through that wave and now other places are getting pummeled by this virus as we move further into winter. And so in in like Florida and other places in the south, they're really not seen a whole lot of virus right now. But that'll change again. So we do know that this virus moves in waves. Arizona's been in that. Interestingly enough, we've had a fairly high level of cases occurring for a fairly long period of time in Arizona. But most of those cases are mild. Most of them are not showing up in hospitals, and definitely most of them are not dying. And that's because we have a reasonable I have a perfect level of immunity, but we have a reasonable level of immunity that I think is protecting most of our at risk people. But not all of them are and is limiting the amount of serious cases that's occurring. But we're pretty effective at continuing to move this virus around. So we're still seeing a lot of cases and we see those numbers every day.
Karie Dozer [00:17:33] Thanks again for your time for all your work this year.
Dr. David Engelthaler [00:17:35] Yeah, you bet, Karie. Thank you.
Karie Dozer [00:17:37] For more on TGen’s COVID research go to TGen Talks slash News. TGen, an affiliate of City of Hope, is an Arizona based nonprofit medical research institute dedicated to conducting groundbreaking research with life changing results. You can find more of these podcasts at TGen dot org slash TGen Talks or on Apple Podcasts. For TGen Talks, I'm Karie Dozier.
