Host:

Hello, and welcome to the podcast. In the coming weeks, we'll be learning more about coronavirus, not just about the virus itself, but of the response to the global pandemic that has shut down cities, forced people into their homes, and started a race to find effective treatments and therapeutics.

In today's episode, we'll talk about spillover events. What are they, and how can a disease in an animal spread to humans? To that, we turn to Rita Rio. She's a biology professor at West Virginia University's Eberly College of Arts and Sciences. COVID-19 has spread to every continent except for Antarctica. But where did it get its start? You might assume that it came from Wuhan, the capital of China's Hubei Province. But, really, it's complicated.

Rita Rio is a biology professor at West Virginia University. She's an expert in how infectious diseases emerge, spread, and evolve. And as she explains, scientists have identified the sequence of RNA that makes up the SARS-CoV-2 virus. It's the virus that causes COVID-19. That RNA sequence revealed an intricate story, and that story begins ... with a bat.

Rita Rio:

What's amazing about this particular event is that there's been so much sequencing that's been involved, and so sequencing's become really cheap. It's become very readily accessible, and we're gathering a lot of sequencing data as infections are being confirmed throughout the world. This has been really important towards our understanding of how SARS-CoV-2 originated.

Rita Rio:

We know that it's a member of the Coronaviridae family and that it harbors very high genome similarities to another virus that was originally isolated from bats and, specifically, Chinese horseshoe bats. But what's intriguing is that these bats, although they were isolated from China, these are bats that were distantly located from Wuhan.

Host:

If the virus originated in bats that didn't live in Wuhan, how did Wuhan become the epicenter of the outbreak? Well, the RNA sequence also showed that the virus didn't jump straight from bats to people. Another animal, the Malayan pangolin, appears to have served as a bridge between the two. A pangolin weighs about as much as a cat does, but there's nothing fluffy or cuddly about them. They're covered in an armor of overlapping scales that makes it look like a tiny tank.

Rita Rio:

Pangolins are described as scaly anteaters, and they have a significant importance in Eastern cultures. There is medicinal properties, as well as dietary uses for their skin, scales, and meat. And pangolins, it's interesting because they're also highly trafficked animals, one of the most highly trafficked in the world, especially in parts of Asia, and they are considered endangered.

Rita Rio:

Interestingly, they also harbor a virus that has some genome similarities to the SARS-CoV-2. What we think is that there were two species jumps, so a species jumped from the reservoir host, the bat, into the pangolin, and then from there, subsequently to humans.

Host:

Because of the pangolin's value in Eastern medicine and diet, it's likely that a vendor brought one to a wet market in Wuhan without realizing that it was infected. In many ways, wet markets in China are similar to open air farmers markets in the United States. There, you can buy fresh produce, seafood, and pork. But at some wet markets, you can also buy live animals, including exotic ones like porcupines, otters, and pangolins.

Host:

Live animals for sale at wet markets are housed in close proximity. Different species can be crowded together. It's in that crowding and species diversity and the stress that the animals feel that make it more likely that a virus in one type of animal may infect another type of animal, including a human.

Rita Rio:

I think we just have to be cognizant that humans are just another form of animals. There's nothing special in terms of a microbial transfer that can happen between different species of animals, including humans. But what we do know is that the more closely related we are to other species, there's going to be a greater chance of swapping these microbes, and that's because, you think about it, some of the molecular doors that these pathogens use for access and entry into a new host are very similar because of evolutionary conservation.

Host:

The fact that we're so similar to bats is one reason they are behind so many zoonotic diseases that make humans sick that originated in other animals. SARS in 2003, MERS in 2012, Ebola in 2014, and COVID-19 today, they all emerged from bats. But why bats? What makes them so special?

Rita Rio:

I think most people don't appreciate that bats are very species rich. We know that there's over a thousand different species of bats, and if we take some just back-of-the-envelope calculations, for every four species of mammals, one of those is a bat, so bats are very species rich. And we also know it's a very ancient lineage, too, and so that's given that group ample time for diversification.

Rita Rio:

They've been able to coevolve with various viruses for what we think is a pretty long amount of time, and this coevolution is associated with the attenuation of effects, so it's not so bad to the bats. Additionally, there's also some really cool data that's showing that bats may be very different in terms of immunological properties relative to other mammals, so how they counter pathogens or how other foreign agents or other foreign agents may be a bit different than the prototype mammal.

Rita Rio:

Then, if you also think about bats and their ecology, particularly how they roost, there's a high density in their roosting location. Think of roosting locations, most people think of caves. We know that there are species of bats where over 300 different bat individuals can roost in a square foot.

Rita Rio:

That high density in the bat population also promotes a lot of viral circulation. These can be maintained in the population because young and old bats are mixing, and so the transmission may be circulating quite naturally and quite efficiently given the ecology of these bats.

Rita Rio:

But I think, yeah, that bats definitely deserve a lot more recognition for their role in emerging viruses than the scientific field has dedicated, especially to determine what makes them such a competent reservoir host and why they don't get so sick, and especially for viruses that are of these high human health significance.

Host:

Bats can swole with viruses that cause them no harm, but when one of those viruses makes its way to a person, it can have grave results. Humans don't have the benefit of coevolving with the virus from millennia. Their immune systems can't cope with it. They're what's called immunologically naive. Try saying that as a tongue twister. The immune cells someone produces and what those cells do have to change in crucial ways before their immunity stops being naive and turns into a jaded, cynical immune system that can fight off an infection because it's so over it.

Rita Rio:

We have a really elegant immune system and there's two arms to this. There's innate immunity, and just like it sounds, we're all born with this innate immunity. How innate immunity works, it recognizes these pretty general patterns on disease agents and then it tries to mount an appropriate response. And sometimes, maybe even most of the times, actually, it will mount a response in a way that we don't even know that we're being challenged, because we know this as humans, we're constantly being exposed to microbes in the order of hundreds to thousands a day.

Rita Rio:

Innate immunity might be able to handle it, but then there's this other arm of our immunity that takes over if innate immunity can't handle it, and that's our adaptive immunity. Adaptive immunity has to be gained throughout our lifetime. Adaptive immunity, I think the key players that most people think about are the B-cells, which produce the antibodies, and the T-cells.

Rita Rio:

What happens there is that for adaptive immunity to kick on, we believe there has to be a certain threshold of the disease agent, a certain abundance of the disease agent to be reached. Whereas innate immunity recognizes these very general motifs that are associated with pathogen groups, the adaptive immunity's going to cue in on specific sites called antigens.

Rita Rio:

These antigenic regions, they can be very, very small and they're very, very specific, but what happens is we need time to mount these responses. It takes about seven to 14 days for antibodies to produce by B-cells the first time we ever encounter a specific antigen.

Rita Rio:

But then after a challenge is cleared, we also have memory to these pathogen sites, so it's never going to take a plan of subsequent exposure. It's not going to take that duration of time. It will be much faster. And this is the beauty of how vaccines work.

Rita Rio:

One of my favorite examples of adaptive immunity is a study that was published a couple of years back that looked at the survivors of the 1918 flu. And we know that these individuals, they were very young when they were exposed almost a hundred years ago. But these individuals, when they were studied in their 9th and 10th decade of life, what they had is they still harbored memory, so antibodies in recognition of the 1918 influenza, so if they had ever encountered the 1918 influenza, it would be a very efficient clearance.

Rita Rio:

Immunological memory depends on the pathogen. It may last for the duration of an individual's lifespan or it may be much shorter, and it depends on different pathogen types.

Host:

How long will our immune system's memory of SARS-CoV-2 persist? It's too soon to tell, but if other corona viruses are any guide, our immune system won't remember it for a century.

Rita Rio:

We don't know. It's like a real-time experiment going on right now. But if it's anything like the other corona viruses, we do not mount a very long immunity to other members of the Coronaviridae, meaning that if this happens, we would probably have to constantly get reinfected or get boosters for the vaccine.

Host:

One thing we do know is that just as bats and pangolins can infect people with a novel virus or a bacteria or parasite or some other kind of microbe, people can infect other animals, too. It is a two-way street. In April, a tiger at the Bronx Zoo tested positive for COVID-19. That's the first time an animal tested positive for the virus in the United States. Odds are she contracted it from a zoo employee with an asymptomatic case of COVID-19, but that's rare, though. Most of the time when microbes are transferred between humans and other animals, nothing happens.

Rita Rio:

There's a lot of transfer, and the transfer is going to happen more readily when we're more biogenetically related to the other animals. Tigers are mammals, and so this is not surprising. There's a lot of good data that shows that with dogs, and I love to use the dog example because I have three of them, but we swap a lot of our microbes with our household pets. There's even studies that suggest that we could link owners to their dogs just on microbiota profiles and the similarities that they have with each other.

Rita Rio:

Yeah. There's a lot of transfer back and forth, and most of the time, it's nothing that makes us sick. We think that most of these microbes are commensal, so they neither harm us or do good. Sometimes, they may be even beneficial associations that we gain. And unfortunately there's the bad side and they could be pathogenic at times as well. I just think we have to be cognizant that, again, we're animals and this microbial transfer can swap between different animal species.

Host:

But don't panic. According to the CDC, there's no evidence that animals play a significant role in transmitting SARS-CoV-2. It's human-to-human contact, not human-to-pet contact that is sustaining the spread. Only a small number of pets worldwide are known to have caught the virus anyway and mostly after close contact with people who had COVID-19. So rest assured, Mr. Pricklepants is almost certainly going to be just fine.

Host:

But to be on the safe side, it's a good idea for your pets to do what bats can't, practice social distancing. Don't let people outside of your immediate family hold or pet them. And if you get COVID-19, stay away from them and your family until you're fully recovered. You may not be able to control what happens in a bat colony half a world away, but you can have some control over what happens in your family and your community.

Rita Rio:

I think we're all very, very conscious about our neighbors and respecting our neighbors and keeping them safe. And I think with this, with COVID-19, we all have to have really high individual responsibility and collectively, that's going to make a really nice, big impact, but we all have to be in. On the flip side, too, we also hope that our neighbors have respect for our well-being and so they also have high responsibility as well.

Host:

This won't be the last time a disease jumps from a bat to a person or from some other animal. As humans keep encroaching on wildlife habitats by cutting down the trees that bats roost in, for instance, more and more illnesses may spill over from their world to ours, because when those habitats collide, you create more chances for microbes to pass between them.

Rita Rio:

I think we live in a very hyper globalized world right now. All you have to do is look at our daily air traffic patterns on just a normal day. An example, I can go from one part of the world to another part of the world in a matter of hours, and I can also bring the microbes that I have been exposed to. This is basically how COVID-19 has spread to a pandemic level within just a few short months.

Rita Rio:

I think as a community, I think we need to start thinking more as a global community because of these connections and we need to be much more vigilant, and we need efficient and reliable coordination in terms of surveillance at many different levels, scaling from local to international, and particularly in communicating what may be these emerging trends and also towards our efforts to impede spread.

Rita Rio:

We lost a lot of time where we could have done something when the COVID-19 clusters were smaller, and when these are smaller, they're much more manageable. Unfortunately, this did not happen and COVID-19 exploded all over the world. I really do hope in the future that we have better surveillance and coordination of response on an international level and that we learn valuable lessons from this because there is going to be, inevitably, another spillover in our future.

Host:

If you're interested in learning more about West Virginia University's response to the COVID-19 pandemic, visit coronavirus.wvu.edu. Follow us on social at WVU Health on Facebook, Twitter, and Instagram. Make sure you subscribe to this podcast on your favorite podcast app to get the latest episodes as they're released.