released March 03, 2020

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Dr. Ashley Mitek: Hey, Jim?

Dr. Jim Lowe: Yes, Ashley?

Mitek: Did you know that zoonotic diseases are responsible for an estimated 2.7 million deaths worldwide each year?

Lowe: I didn't know that. Hey, Ashley?

Mitek: Yes, Jim?

Lowe: What does zoonotic mean?

Mitek: It means a disease transmitted from animals to humans, and researchers believe that the coronavirus outbreak started the same way.

Lowe: Hi, I'm Jim Lowe, and today we're going to discuss the novel coronavirus, how viruses spread from animals to people. Joining me is my colleague Ashley Mitek, who's also a veterinarian here at the University of Illinois. We're going to talk about this novel coronavirus outbreak, how government health organizations are responding, and really what you need to know.

Welcome to the Round Barn.

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Mitek: Jim, can you talk to us a little bit about what is a zoonotic disease, and how common are they?

Lowe: Ashley, when we think about zoonotic diseases, we're really talking about diseases that cross between species, and specifically cross from animals into humans. They're actually quite common. Most of what we think are the major human pathogens probably started in animals, and that's just because there's a lot more animal species than there are one human species.

The most common ones we would think about are things like influenza. Influenza is zoonosis and what we call reverse zoonosis. It passes from humans to animals and back to humans, in multiple species and between multiple species. Influenza is really interesting. We know that's been around a long time. We can think about not just zoonotic disease, but then what we call pandemic disease, where disease goes from animals to humans and then spreads very rapidly within humans. That happened in 1918 with flu, and it happened in 2009 with flu.

The other big virus group that tends to transmit between species is really these coronaviruses. We've got this COVID-19, or what the fancy name is. This is this novel coronavirus that's appeared in China. But you've heard the news talk about prior viruses that are coronaviruses -- the SARS outbreak, which was Severe Acute Respiratory Syndrome; and then this Middle East Respiratory Syndrome. Both of those were also coronaviruses, maybe not that different than this current COVID outbreak.

These things happen quite frequently. Most of the time we have zoonotic disease transmission, nothing happens. They're very normal kind of events. It doesn't work very well in the human; it doesn't spread within humans. And so, when we get excited about these things, it's that we didn't just have transmission from animal to human; we had sustained transmission within humans. That's when everybody gets excited, and that's what's happened with this novel coronavirus.

Mitek: Is there something unique about the coronavirus in that ... I guess, can all viruses go from animal to human, human to animal, and back and forth, and have this zoonotic potential? Or is there something unique about coronaviruses that's making everybody get excited about the animal part of it?

Lowe: Most viruses tend to be very species-specific. You work with small animals a lot, so let's think about distemper in dogs. That virus only infects dogs -- it won't even infect cats, and it doesn't transmit to humans -- because viruses have to infect a cell and then replicate inside that cell and then get out. They don't have their own mechanism to make themselves. That's an important bit. So, viruses tend to be very species-specific. We don't think about cross-species transmission. Why coronaviruses are interesting is that coronaviruses -- and there's a huge number of coronaviruses -- infect a tremendous number of species.

Also, there's two types of genetic material, RNA and DNA. RNA is single-stranded, so it has a lot more mutation errors; so, it's more easy to adapt. Coronaviruses are RNA viruses, just like flu is an RNA virus. And there happens to be flu that infects every species in the world that we know of. When you have a virus that infects lots of different species, and it's really likely to change, they're just more likely to be zoonotic. We have an African swine fever outbreak going on as well. That's probably the biggest virus we know of. It's a DNA virus, there's a big chunk of genetic material. It's pretty hard for that to change because if one bit changes, it's not likely to be very successful. But these little-bitty viruses that have a lot of error in their replication all the time are more likely to transmit, particularly when they infect a lot of species. So, that's kind of what makes coronavirus an interesting bit, that there's coronavirus that infects dogs and cats and pigs and cattle, and those are all separate.

And then, there's this big reservoir, we think, in bats. That's probably where this virus came from, although we don't know. But, that's certainly where SARS came from. But there's coronaviruses that infect camels, and that's where the MERS virus came from. So, you've got a lot of species infected, they mutate at a higher rate so they can adapt. A little error in the replication might make them successful in humans and not in bats. So, yeah, that's what makes coronavirus kind of special.

Mitek: One of the things they've talked about in the media is this virus's potential to kill somebody and its ability to be ... what's the right word? Virulent?

Lowe: Virulent, yeah.

Mitek: Is that a reflection of the fact that it can shift and do mutations as it goes from species to species? We have millions of viruses in the world, and not all of them are going to kill us. But it seems like this one is a little bit concerning because it does have a higher mortality rate. So, I guess, does the fact that it can go to different animals make it more virulent in and of itself?

Lowe: There's two things when we think about zoonosis that scare people when it becomes what we would call host-adapted, when it can now replicate in a new species. One of those is, there's no background immunity. When we think about infectious disease, right, we're always thinking about the contact between infecteds and susceptibles and what part of the population is resistant. There's only those three bits in any population -- infected things, susceptible things that could be infected, or those that have been infected and are now resistant. When you have a novel disease introduced, or a novel agent or pathogen introduced, there's no resistant population, so everybody's susceptible. That makes it move fairly quickly.

And then, the other thing that becomes a challenge is, if it can cross and it becomes host-adapted enough to move from one species to another, they tend to be more aggressive. They replicate. When we think about viruses that are more severe, more lethal, they replicate very quickly. So, they infect and kill more cells. The basic mechanism of a virus is, it infects a cell, replicates inside the cell, and then kills the cell to release itself. That's kind of the basic mechanism of pathology. So, the viruses that are new and can spread rapidly, and the only way it does that is to kill a lot of cells, you tend to see those things be more virulent, at least initially. And then, as they get more adapted to human beings, they tend to resolve their level of virulence down to something that's more sustainable.

I think when these things cross, we think about them tending to be very virulent. Now, what I find interesting about this COVID-19 is that it's actually not very virulent. The case fatality rate -- so, those the die of those that are infected -- is somewhere in the 1% range outside of China. That's the most recent estimate. Maybe it's a little higher, a little lower; the point is, it's quite low. Flu is, like, 0.002% or something, two-hundredths of one percent. But flu's been around for a long time, and flu infects a lot of people. So, it's higher than flu, but it's not like if you get coronavirus, you're going to die. I mean, 1% of the people will die.

Mitek: Sure, yeah.

Lowe: The other thing is, as we think about this, that's probably going to reduce over time. If we look at compared to SARS, the case fatality rate, I think, was something like -- don't quote me -- 10% or something. It was a lot higher. If you got infected, you were relatively likely to die. But that virus didn't transmit very well. It died out fairly quickly.

I think why everybody's scared about this one is, yes, there's some deaths, and those aren't to be taken lightly, but we're in the thousand deaths range at this point. Relative to the total number of cases, it's quite low. So, this one is more likely to spread very widely, because we have a lot of people who are infected and not sick.

Mitek: Why do you say the death rate is going to decrease over time? Why do you think it'll start to go down?

Lowe: That's some fascinating work by Paul Ewald that was really looking at dysentery in people. They worked out this hypothesis -- which, you know, it's always tough to prove that it's true, but when they worked out, there's certainly strong evidence that it is -- that when a pathogen is really, really virulent, virulence means that it's consuming host resources very quickly. So, it's using up the host. A pathogen, right, can't live without the host. So, it's consuming the host's resources. The whole theory of evolution is to pass your genes on to the next generation, so, if I'm a pathogen or a bacteria or a virus, that means I don't have to pass them just to the next generation; I have to pass them to the next host. So, if I'm going to consume host resources, i.e. have high virulence very quickly and disable my host, I have to have a high rate of spread. Conversely, if I consume my host resources very slowly, i.e. I'm infectious for a long time, the potential to spread is longer, then I don't have to spread as quickly.

There's been some strategies saying, "We can reduce the severity of disease." And they did that with dysentery by saying, "Listen, let's just block contaminated water." So, dysentery went from high virulence to low virulence because it couldn't kill people quickly and be transmitted in water. That generally works with all of these pathogens. As we have pathogens which are lower virulence, they shed longer, and they're more likely to be transmitted. That also means that low virulence is preferred from passing yourself to the next host.

Mitek: So, the viruses are a little smart.

Lowe: Yeah! It's evolution, right? I mean, I'm fascinated with infectious disease because it's evolution on steroids, right? We can talk about, what are we doing to genetics, and what can we do to shift and select -- I mean, I've grown up in agriculture, and we've tried to select the right pig or the right calf. But even a pig is over a year generation interval. Humans are on a 20-year generation interval. So, thinking about, how do we change things, a virus is on an hour's generation interval. Bacteria is on hours. So, they change generations very quickly. So, you can shift evolution either for or against what you need.

If you look at the efforts that the public health community has made with this virus, what they've really tried to do is stop transmission. Now, have they been successful? Absolutely not, because we've continued to get cases. I mean, we've got cases in Europe, we have cases in Iran, blah, blah, blah. But, what they have done is is slow the transmission, which is therefore selecting the viral population for, actually, lower-virulence organisms, if you follow Ewald's hypothesis.

So, the strategy hasn't stopped it, hasn't made it go away; but it's selecting for what are probably non-apparent infections. It's becoming the common cold, and that's great, as opposed to some superbug that's going to kill us.

Mitek: On that note, with containing the virus, we typically have seen situations in the past where one of the things that the public health community and medical community resort to is creating a vaccine. Can you talk a little bit about if you think there's a vaccine in the future for this, and other strategies to contain the virus?

Lowe: That gets back to this SIR triangle. The population is susceptible, infected, or resistant. One of the core tools of infectious disease has been vaccines. I can increase the number of resistants in the population, those that aren't eligible to be infected -- which means, if I just think about, if I've got a percentage that's infected, you've got 90% resistant and 10% infected, the probability of an infected animal bumping into a susceptible one is one out of 10. If it's the other way around, if it's only 10% resistant and 90% susceptible, it's nine out of 10 I'm going to bump. So, I'd have transmission. So, the idea of vaccines is, how do I shift the population to being more resistant?

Will we have a vaccine for this? Absolutely. Will it work is another question.

Mitek: [laughs] OK. How quickly can you recognize a virus and then give it to somebody who can make a vaccine, and they make a vaccine that has a reasonable chance of working?

Lowe: I mean, best-case scenario is 18 months. Realistically, it's probably three to five years. There's a couple of reasons. One, coronaviruses are, as we talked about, are itty-bitty viruses, and they mutate. So, there'll be a fair amount of genetic variation. I have to get the right virus or the right viruses in the vaccine to get the right immunity. As you said, viruses are smart. If I build immunity to virus 1 or type/strain 1, and strain 2 is there, strain 2 will emerge when there's more resistance to strain 1. So, we'll have to work out the bits of which strains do we need. That's the challenge with flu vaccine. You hear them talking about, "The flu vaccine didn't work very well this year because they picked the wrong strains," because there's lots of strains of the virus. The same will be true with these coronavirus. And so, they'll have to get the right strain and kind of sort out what they're going to do. It's not as complicated as flu, but there'll be a fair amount of work on that.

And then the bigger bit is, the first rule of medicine is do no harm, whether that's human medicine or animal medicine. So, just a lot of safety testing is required, because you don't want to put a vaccine out there that actually hurts people. They'll be killed, so it won't make people sick, but we don't know what happens when you put it with an adjuvant. There are a lot of smart people that are working on this, and they're working very hard, and they have some very good estimates. That's way out of my league; I don't do vaccine development. They'll know what's going on. But, it still doesn't mean that I don't have to do all the safety steps, etc., etc. And then, once I get the safety testing done, then I have to go to the efficacy testing. It's just not a fast process. And we don't want it to be a fast process, you know?

Mitek: Sure.

Lowe: We don't want to screw it up. So, yeah, we'll have a vaccine. I don't know when we'll have it.

Mitek: In the media, they've talked a lot about pandemics and endemics. Can you talk a little bit about if this new coronavirus is going to reach those levels, and what those terms mean?

Lowe: Those are big fancy science words. I'm not sure any of us really know what they mean. But the definition of a pandemic as defined by the World Health Organization -- the people who do this -- is sustained transmission on multiple continents. They don't believe we're at pandemic. They don't believe it's met the criteria yet. We'll let them make that call because that's their job.

Is there transmission on multiple continents? Absolutely, but it's not huge. It's not really transmitting broadly. I mean, there's a cluster in Italy right now; there's a cluster in Iran; there's probably some other clusters that are going to happen in Spain based upon some travel to Italy; we've seen cases now in Brazil; there's maybe some reports of some transmission that's not associated with travel in China in the U.S. So, certainly, yeah, there's a lot of transmission going on. But pandemic is a word that obviously has a lot of connotations in the media that would say, "This is awful and terrible." Is it transmitting everywhere? Yes.

The other word you used is endemic, which means that that disease is here and it's not going away; there's sustained transmission of that. I think there's every evidence today that that's what's happened. It's become endemic. It's going to be endemic. We're not going to stomp this out. But, as we chatted about a little earlier, the heroic efforts that have really been undertaken by health authorities with quarantine and some of that stuff sounded not very good in the media, right? Like, we locked up cruise ships and yada yada. But those things have gone on in China, and really, their efforts to try to contain that, and what's happened in these other outbreak centers -- I think everybody up front knew that stomping it out was going to be really hard. It's really hard to control the disease when there's 3 million, 4 million, 5 million people in one spot, or animals, whatever it is, right? You get that many things that could be infected in one spot, controlling that or storming out is almost impossible.

But forcing it to be endemic and not epidemic or pandemic -- epidemic means it's spreading very rapidly. This is clearly epidemic. Pandemic means it's broader than that. But, forcing it to endemic instead of really pandemic is their goal, I think. And I think those efforts have largely been successful. I mean, we've got transmission, but the transmission generally is mild, and the vast majority of people infected probably don't even have signs. We've reported several tens of thousands of cases now. That's probably a gross underestimate of the number of infected people because we know we have people who are infected and don't have clinical signs at all. They test positive, but they're not clinically diseased; so, the host isn't sick, the person isn't sick. And so, we know the number of infections is grossly underestimated. That's good. We're turning this into the common cold. And if that's what happens, that's OK. That's not a crisis.

Mitek: Jim, it's really interesting that you mentioned that somebody can be exposed to the virus and test essentially positive for it, or we can detect in their bloodstream that they were exposed to it; but yet they may not be sick from it, or they may not be clinical for the virus just yet. Can you talk about what exactly is going on in that time period and what that means?

Lowe: Oh, now you're getting me on some long-term rant.

Mitek: [laughs]

Lowe: This is a long-term passion I have.

Mitek: OK!

Lowe: It's a really critical point. When we think about infectious disease, we mean disease in the host -- in this case, the person. I tend to think about animals, but in this case, the person. So, what that really means is is that a pathogen has infected the host, and then the host responded to that and probably couldn't control the infection. That's when we get disease. We can have infection without disease. That's a really important bit to understand when we think about that. As medical people, right, we tend to see things that are sick. But you can be sick and infected, or you can be infected and not be sick; you could also be sick and not infected, right, because it could be something else. And so, when we think about that, it's really, if the person sees the COVID-19, and their immune system says, "I got this," and they clear it, they can be infected and never have disease. That's actually what happens every day of the week.

Mitek: Can those people still spread it?

Lowe: Absolutely.

Mitek: Wow.

Lowe: They're infectious but not diseased. We do that with the common cold. At our house now, my wife is sick, has the cold. I probably had a runny nose for 24 hours.

Mitek: So now I'm going to get it, because I'm sitting next to you.

Lowe: No! I mean, I'm perfectly healthy, I'm not shedding!

Mitek: [laughs] OK.

Lowe: Because I cleared it up, right? We think about that all the time. You've got little kids, right? They may get sick, and you don't get sick. You were probably infected, but your immune system saw it and said, "Got it. Get rid of it."

Mitek: What makes an individual, whether a human or animal, be able to clear it versus somebody who gets exposed to it and becomes actually clinically ill?

Lowe: That's a really complicated question. Let's try to sum that up in a little bit, that there's kind of two parts to your immune system, the innate and the adaptive. The adaptive is specific, so it's specific for a specific disease. That happens when this first part of the immune system, or the innate immune system, doesn't work. Every day, we are exposed to billions of bacteria and viruses, like, just walking around. Every time we breathe air in, there's bacteria and viruses that we inhale. Our body's natural defense is, this innate immune system sees those things, says, "No, not me," and kicks them out.

Growing up, your mom probably told you, "Don't go outside without a hat on your head when it's cold," or, "Bundle up when it's cold." Well, that's because they're saying, if you're stressed -- if you're cold-stressed -- that innate immune response doesn't work as well. And so, if you're a little bit stressed today, and you get exposed to the virus -- whether that's cold stress, or emotional stress, or you're just tired, you didn't sleep enough -- that innate immune system may not work as well. And now, bingo, bango, bongo, that exposure causes you to get sick, get diseased. If I slept normally and ate and wasn't stressed and wore my hat outside -- bald head, you've got to wear a hat all the time. It's a bugger. It's a real burden on society because if I don't have a hat on, it's either sunburn or freezing.

Mitek: [laughs] Is there a future study that bald guys are more likely to get viral diseases?

Lowe: Bald guys who refuse to wear hats. I mean, that's one of the conversations. But, it's this stress thing, right? If I'm not as stressed, my immune system sees it and says, "No big deal." It's that kind of balance. And certainly, every human being going through every day has varying levels of stress and what's going on -- how much sleep did you get, how good were the meals yesterday, those things. So, when we think about this shedding, you really worry about it shedding in stressed environments. In our livestock world, that means I didn't do a good job taking care of things. We think about, I put people in an airport. Well, I don't care what you say, there's contact in an airport; but there's also some stress. I'm getting put on this plane, and all this stuff goes on. That also lowers my immune response.

Why you get infections is a really complicated answer. But the easiest way to say it is, if I do things that lower my innate immunity -- which fluctuates minute by minute throughout the day -- then I'm more likely to get infected.

Mitek: That's really interesting. Well, thanks for joining us.

Lowe: Well, and thanks for joining us, Ashley. We should do this again. This has been a lot of fun.

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