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The Round Barn: Will COVID Go Away?

  In this week's episode of The Round Barn podcast, Dr. Ashley Mitek and Dr. Jim Lowe talk about
the Omicron variant, and what it could mean for COVID and humans going forward.
Dr. Lowe digs into his animal infectious disease background to explain why this virus keeps mutating;
why vaccines for it might need semi-annual boosters, instead of being good for years or decades like other vaccines;
and what it means that COVID is now endemic in the population.
Tune in to learn more.


released January 11, 2022

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Dr. Ashley Mitek: Happy New Year to everybody! Did you have a good new year?

Dr. Jim Lowe: I did. How was your break?

Dr. Mitek: It was awesome. What did you do?

Dr. Lowe: Nothing, which was the goal.

Dr. Mitek: Do you watch Netflix, Amazon Prime? Is there sports on you watch?

Dr. Lowe: No. I piddled around the house and did holiday things and didn't do email, which was a win, a big win.

Dr. Mitek: Did you do your wife's to-do list?

Dr. Lowe: I have my own to-do list. I like making my own to-do list.

I'm Dr. Jim Lowe.

Dr. Mitek: And I'm Dr. Ashley Mitek.

Dr. Lowe: And welcome to The Round Barn.

Dr. Mitek: Alright, well, we're gonna need coffee to get through today's topic, because there's a whole lot of stuff going on in the infectious disease world right now. Why don't we talk about what is on everybody's mind, this Omicron variant? It seems like all of my friends are getting COVID right now,everybody's getting COVID. Why is that happening?

Dr. Lowe: Well, everybody's doing it, it's popular.

Dr. Mitek: [LAUGHS]

Dr. Lowe: No, no. So, it's an interesting bit, right, as we think about infectious disease, and these viruses. We've chatted about this before, these RNA viruses have got, we call it a plastic genome, so they-

Dr. Mitek: Whoa, whoa. I'm an anesthesiologist, you used a word that is not in my vocabulary.

Dr. Lowe: So, they change rapidly. They're highly variable. So, they're not... conserved is the fancy word. And so, the genes change a lot. And that's how they adapt. And that's their survival strategy. And so, this is expected, right? We've got a lot of RNA viruses out there - flu, and in the animal world, PRRS and BVD and other things. So, we've got these RNA viruses that change very, very rapidly. This happens all the time. And so, this thing got introduced to humans, and it's just figuring out how to transmit in humans better. Disease ecologists and those of us who pretend to be disease ecologists said, "Yep, this is how it works."

Dr. Mitek: So, you're not surprised by, is it fair to say, the evolution of the virus? That has evolved into a virus that it's easier to spread?

Dr. Lowe: No, not surprised at all. In fact, if you just had to start with a hypothesis and say, what's going to happen? Evolutionarily, this is exactly what you'd expect to happen. It's going to get better at doing its job, and a virus's job is to jump to the next host.

Dr. Mitek: So when is this going to end, then?

Dr. Lowe: End is a silly word. It's not going to end. It's now endemic, right? I don't know if the WHO has finally admitted that or not, but this virus has basically been endemic, continuous transmission in the population, right, shortly after it was introduced. This is like influenza and every other virus we have that floats around now. It's there. We've stomped out a few viruses, right? We got rid of smallpox. We've, by and large, kind of gotten rid of polio. There's a few pockets of polio still in Asia, I think some in Pakistan, some areas where they haven't had good vaccination rates. But by and large, those are two viruses we've had kind of big wins on. Those are both DNA viruses. They don't change genetically, pretty easy to vaccinate against.

Dr. Mitek: And is that why you can stomp out those viruses, versus it can be harder to stomp out something like COVID or even the flu virus?

Dr. Lowe: Yeah, there's differences, in those in terms of both their change, i.e. their ability to evade the immune response; plus, they're not as transmissible. Really deadly effects, but they don't transmit as easily. It takes a lot more contact than these respiratory viruses that are shed in the upper respiratory tract - flu, coronavirus, we've got PRRS in pigs, porcine reproductive and respiratory virus. These things shift.

PRRS is a really interesting discussion. It's a pig virus, it's not related to COVID at all. It's an RNA virus and it's in pigs. But, that virus really started primarily as a reproductive virus, and it transmitted reproductively. So, it was sexual transmission of that virus. But it also infected the lungs. And as we stopped sexual transmission, we stopped infected boars. So, it could be transmitted in the semen. So, when we tested all the boars and removed the virus from the boars, the thing just became a respiratory virus.

Dr. Mitek: So now you have PRRS in pigs as a respiratory virus.

Dr. Lowe: Yeah, it's primarily a respiratory virus today. And the transmission thing is, is - Scott D did this work, we thought there was no aerosol transmission of the virus because they used some of these original viruses from the 90s, and they couldn't create respiratory transmission, aerosol transmission, small droplet transmission. And now, that's probably the dominant route of transmission, is small droplet, upper respiratory secretion transmission of the virus.

Dr. Mitek: So, the virus changed how it's transmitted, essentially.

Dr. Lowe: Yeah, the virus changed how it transmitted, because it said, I can't transmit the way I used to. It used to produce a lot of virus in semen, it was a reproductive thing. And it said, okay, I can't do that; well, I'm going to now transmit respiratory. And so, they documented that very clearly, that the new strains preferentially reproduce in the upper respiratory tract, or are shed that way.

Dr. Mitek: How is a virus like PRRS or COVID smart enough to figure out that they need to spread via respiratory transmission, or that it's better to spread a lot and only make people a little bit sick, so then those people don't die, they just keep spreading it?

Dr. Lowe: It goes right back to the core of evolutionary theory. First of all, a virus isn't smart. These RNA viruses are clever, or they have a unique adaptation - I just said to not call them smart. They have a unique adaptation. They don't exist as a single virus. Because they have so much mutation rate and substitution rate in their replication, they actually exist as what we call a quasi species. If a pig has PRRS - let's use that as an example - it doesn't have one virus. It has many, many viruses. And the strain that it has, the sequence that it has, is what we call the consensus sequence. It's the most common sequence that we see. And so, it's the most common strain, but there's a lot more there. And what we know is - we did some of that work here with Tony Goldberg years ago, to prove that PRRS existed as a quasi species, as does influenza, and as probably does, I've not seen the work but I presume, COVID does. I mean, these things, that's how they work. What it really means is, is that in endemically infected populations, there's a lot more variation in an individual animal, an individual pig in this case with PRRS. And in acutely infected populations or acutely infected animals, there's a lot less variation. So, we get a lot of virus variation.

And then, the virus, its evolutionary trick - when we think about evolution, and we think about evolutionary theory, fitness means you're more likely to pass your genes on to the next generation, or an individual gene onto the next generation. We think about fitness not really as a whole host, but individual genes. So, I'm more likely to pass an individual gene to the next generation. And so, what defines fitness is the ability to do that. And with a virus, I can't replicate without a host. So, if I use my host resources, quickly, I kill my host, then I have to transmit to the next host before I kill my first host. So, RNA viruses, this is where they've worked out - they've evolved to exist as this quasi species. They don't have very many genes. It's a really, really small bit of genetic material. A virus is really, really small. And so, because they don't have very many genes, their adaptation... in a mammal, in us, we have lots of genes, and there's duplicate pathways, so I can do the same thing multiple ways. Well, a virus only has one way to do it. So, instead of having multiple pathways within the same host, they just have lots of pathways within the same population. And so, as you cut off one - in this case, let's think about PRRS and sexual transmission - those viruses that replicated in the seminal vesicles and ended up in the semen at high rates, all of a sudden weren't as preferred, they weren't as likely to be passed on to the host as those that passed in the respiratory tract. And so, we selected for those viruses that wanted to live in the upper respiratory tract.

And that initially is pretty slow, right? We thought we were winning. We cut off semen transmission. We tested and stopped semen transmission. So it looked like we really, really reduced the rate of PRRS transmission. Okay, we're winning. Because there weren't very many of the viruses in the population that were respiratory preference. But as those viruses started to become more common, whoop! We saw a big change in the outcome, and now we've got rapid spread.

Dr. Mitek: So, to answer the question of when is this going to end, it's not going to end. We're going to have COVID in our life for the rest of our lives, probably. Hopefully we will all have vaccines and our boosters, or get immunity to it from having it. Speaking of boosters, how's your arm?

Dr. Lowe: Oh, I got boosted about an hour ago, so I'm super-proof now.

Dr. Mitek: Still here and with us. Awesome.

Dr. Lowe: Yeah, I haven't died.

Dr. Mitek: Hopefully you will have, what is it going to take your immune system, a few days to respond to that?

Dr. Lowe: 7 to 10, probably, yes.

Dr. Mitek: And then you're superpowered Dr. Lowe.

Dr. Lowe: Yes.

Dr. Mitek: And why exactly - I feel like there are some vaccines my kids get or I get, that we got as kids, and you get boostered, and then you're good to go the rest of your life, you're good for 10 years. What was the impetus for various agencies coming out and saying, "We highly recommend everybody who got vaccinated to get another booster?"

Dr. Lowe: It's the joys of the immune system. These RNA viruses - particularly coronaviruses, all the coronaviruses - actually don't produce very good immunity. So it's interesting, right, when we think about COVID, the disease appears to be primarily driven by a poor immune response. It's an over-reactive immune response, I guess, is the best way to put it. When we think about an immune response, we think about two pieces. One, there's the kill-it phase. And then there's the healing phase. And every immunologist that ever listens to this, don't be offended with my simplification of the immune response. But it's kind of that simple. And it's really complicated, how that works, but that's kind of the gist for the layman.

And so, with this COVID thing, it appears that we've got the killing phase going crazy, and it kind of forgets to turn on the healing phase and turn off the killing phase. So it quits playing offense. It just keeps playing defense and forgets to play offense and fix it back up. And so, that's the thing with with COVID.

But at the same time, it doesn't produce an immune response that's very deep. We think about immune responses in two ways. We think about them in broad breadths, so, how wide a variation will it protect? And this one appears it's pretty good, right? The original vaccine is protecting pretty well against these new variants. Okay, so, breadth appears to be okay. But depth isn't very good. It doesn't last very long.

I don't think we know, we haven't had this around long enough to really understand, but if we look at the other coronaviruses - there's coronaviruses in every species. There's certainly ones in humans, and we call those colds. And we look at that in pigs, and there's two or three or four enteric coronaviruses in pigs. There's coronavirus in cattle. Those animals are pretty susceptible to... like 6, 7, 8 months after they've had natural infection, really good natural infection, in 6, 7, 8 months, they're susceptible again. Now, they don't get as sick, but they're susceptible again to be infected. So, they've got this really short window where they're completely protected, at least from clinical signs. But then, 6, 7, 8 months later, they can start to have clinical signs again.

Dr. Mitek: And I feel like we're seeing that with people with COVID. People who have had COVID 8 months ago, some of those people are getting COVID again. Knock on wood, the ones that I know, they're not in a hospital deadly sick. But there's still a potential that you could get COVID again, if you had it.

Dr. Lowe: Yeah. And I think that's going to be our reality. Trying to extrapolate too broadly between species or too broadly between other viruses, but we all know we can get the common cold every year. We certainly know, if we look at cattle, if we look at pigs, if we look at other diseases, right, we can see reinfection. The good part is that it's not nearly as severe, and that's really what marks an endemic disease. This transition from pandemic, where we're having infections of naive people, to an endemic disease where everybody's had it. It doesn't mean that we won't have sick people. But hopefully, what we'll have is maybe a bad version of the cold. Maybe it looks like flu. Maybe it's slightly worse than that, or significantly better than that. Who knows. But, you're going to see this sustained transmission with much less severe consequences for the vast majority of people.

Now, we still have a lot of people that die every year from influenza. When you've got other disease conditions, preexisting conditions, infectious disease doesn't always go very good. It can result in death. Again, if you've got pre-existing conditions, this on/off switch of the immune system doesn't work quite right. The immune system is really complicated. We don't really understand how it works. I mean, we understand a lot more than we did five years ago, and astronomically compared to 20 years ago. But when we start to think we understand, we don't understand the next thing.One of the huge benefits of COVID is, we're going to understand a lot about the immune system. So, that's good.

So, I think, you've got these balances going here. Hopefully this thing evolves to endemic. Hopefully we don't have to have boosters every year. But, who knows? We might have boosters every six months.

Dr. Mitek: That was going to be my next question. Are we going to have to get a booster every six months?

Dr. Lowe: I think what we'll figure out is... I could see us saying, okay, for healthy adults, we're going to need a booster once a year for three or four years, and then the frequency of transmission decreases and, okay. But I can also see, given what this thing has done, we could certainly have high-risk populations. Think about people in nursing homes. That's pretty high-risk. You've got marginally effective immune systems, a lot of density. If you get virus in there, a lot of transmission. Influenza is a disaster in nursing homes. So, you could start to see where, okay, we're going to booster people in those spots. I could see, people would have to go to the hospital, they'd say, hey, we're going  to booster those people before they go into these intensive, high-density scenarios.

The good news is, if this thing caused serious disease in little kids, you'd be really nervous because you've always got little kids, and they would have been exposed. And so the good news is that probably, little kids are not very severely infected. And so, putting a vaccination campaign together with our other childhood immunizations, we can probably keep it from being a mess in little kids.

But, if I knew what the vaccine schedule was going to look like, I wouldn't be here. I'd be in the Bahamas drinking drinks with umbrellas in them, right, because that'd be wealthy.

Dr. Mitek: Do we need to talk about anything else before we wrap up? That was a lot.

Dr. Lowe: As an infectious disease guy, as a disease ecologist, this has just been fascinating to watch and understand. And unfortunately, it's playing out a lot like what we've seen with animal health diseases, particularly as we look at these RNA viruses in livestock. I mean, it's not dissimilar in its patterns, right? It gets endemic, it's everywhere. I think this Omicron was really interesting to me, because we were trying to think about, oh, it's only in South Africa; crap, it's in France; oh, it's in Belgium; oh, maybe it's in the U.S. I think one of the things we've learned over time in my day job is that if you think you know where emerging diseases are, you're kidding yourself, because they move way faster, and you've got this lag between infection and detection, and people move all over the world today, and livestock moves all over the world today. And so, you're always chasing your tail. And so, when you hear of something - I think that's maybe one of the lessons hopefully we learn. When disease is detected anywhere, it's probably everywhere.

We've had a lot of discussion about African swine fever in the pig world. And I think the general fear is that we're going to pull out the 1970s playbook for a 2021 or '22 or '23 year hopefully 2030 disease. And, are we smart enough to learn our lessons here, watching what's happened with coronavirus? We had a coronavirus outbreak in pigs in the U.S. and we didn't manage that very well. And so, can we shape our thinking and revise our thinking, and how do we take lessons away from this to improve what we do, and maybe deal with reality, and not create so much collateral damage that none of us wants to see?

Dr. Mitek: Well, that was very well spoken. We've got a lot of challenges ahead, but we have a lot of smart people working on them. Thank you for joining us on The Round Barn.

Dr. Lowe: Thanks, everybody.

Dr. Mitek: Thanks for joining us. We hope you enjoyed listening. We'd love to hear from you, too. Find us on Twitter. Our handle is @TheRoundBarn1. We may even share your comments on our next show. Please subscribe and tell your friends about the show. It's available on iTunes or the podcatcher of your choice.

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