Photo courtesy of Dr. Anastasia Vlasova
A veterinary virologist at The Ohio State University College of Veterinary Medicine, Dr. Anastasia Vlasova helped sequence the genome of the canine coronavirus recently found in Malaysia. Next, she'll focus her research on how the virus adapts to human hosts.
When researchers last week reported they'd identified a canine coronavirus in eight people suffering from pneumonia in Malaysia, alarm bells started ringing around the globe.
Could the researchers, news articles mused, have discovered the eighth unique coronavirus known to cause disease in humans?
That question has yet to be answered. The paper, based on research begun several years ago, made no claims about whether the dog coronavirus was the cause of the patient's pneumonia, or whether people can transmit the disease to one another.
Still, in a world transformed by a different coronavirus, the discovery highlights the potential dangers posed by new forms of the pathogen — and the efforts being made by people, including veterinarians, to discover them before it's too late.
Although part of the same large viral family, the canine coronavirus is not closely related to SARS-CoV-2, which causes COVID-19, nor is it related to canine respiratory coronavirus (CCoV), a source of usually mild illness in dogs. It is not known if the newly identified strain can cause illness in dogs. It is considered a canine coronavirus because its genome closely matches other canine coronaviruses.
There are hundreds of known coronaviruses that occupy numerous animal species, including birds, cats, dogs, pigs, ferrets, camels and cows. They don't make their host sick usually, and most do not transmit between species. But occasionally, a virus mutates such that it can jump species, or "spill over."
Of the seven known coronaviruses that infect people, four cause what we call a common cold. The other three, evolved within the past two decades, can make some people severely ill: SARS-CoV, MERS-CoV and, most recently, SARS-CoV-2.
All three are thought to have come from bats, although questions remain about the origins of SARS-CoV-2. Now, scrutiny turns to dogs.
Among eight authors of the paper about the suspicious canine coronavirus found in Malaysia is a veterinarian, Dr. Anastasia Vlasova, who helped identify the nature of the virus by sequencing its genome. Once categorized, the virus was given the name CCoV-HuPn-2018, an abbreviation for canine coronavirus-human pneumonia-isolated in 2018.
Vlasova is a third-generation veterinary virologist from Russia and an assistant professor at The Ohio State University College of Veterinary Medicine. She is part of an informal global collaborative of researchers working to predict and prevent a coronavirus from sparking another pandemic.
Vlasova talked with the VIN News Service about the importance of studying coronaviruses, lessons from the Malaysia case — including why there is no reason to panic — and how science is preparing for the future. This interview has been condensed and edited.
Why is it important to learn all we can about coronaviruses right now?
Before the original SARS coronavirus emerged in 2003, threats associated with coronaviruses for humans were really underestimated. Coronaviruses in people were associated only with minor colds, and everybody thought it was going to remain that way. First, SARS coronavirus, and then MERS coronavirus demonstrated that it's not exactly so. They can cause larger epidemics and more severe disease in humans.
Why coronaviruses are actually a great threat to humans is because these viruses have the largest RNA genome. What it means to all of us: They can very, very easily mutate and adapt to new hosts, to new ecological niches; they can very quickly expand their geographic range.
Right now, of course, the world's population is growing fast … and that density creates very favorable conditions for coronaviruses to spread. The same [applies] with animal populations: More demand for pork, beef and poultry leads to, again, crowding large numbers of animals in the same facilities, which is good for the circulation of coronavirus.
In the developed world, we claim territories that used to be wildlife territories, and we can acquire coronaviruses from those sources and reservoirs. In developing countries, people naturally live in much closer contact with wildlife, domestic animals, stray dogs, you name it. All of that creates very, very, very many opportunities for coronavirus transmission. And global travel is a factor because what previously would stay contained to a small region now has the opportunity to spread all over the world.
How did your work on the canine coronavirus discovered in Malaysia come about?
What happened was, epidemiologists led by Dr. Gregory Gray [an infectious disease epidemiologist at Duke University] were looking into causes of a very high prevalence of pneumonia in children and adults in Sarawak, Malaysia. Those pneumonias would not respond to antibiotic treatment, so they started looking into viral pathogens. They found influenza, parainfluenza, respiratory syncytial virus, adenovirus, rhinovirus and some proportion of coronaviruses. At the time, coronaviruses were not considered to be associated with severe disease in humans. An even bigger surprise: They found that at least half of those coronaviruses were canine coronaviruses.
Because such discoveries are very harshly questioned, they tried to find someone who could actually isolate the virus and characterize its full genome. They found Dr. Linda Saif and myself. [Saif is a virologist and immunologist at The Ohio State in food animal health research and veterinary preventive medicine.]
Dr. Saif asked me to work on it. It was quite challenging because it was COVID lockdown when I started.
Did starting research on one coronavirus in the middle a pandemic caused by another coronavirus make the project seem a lot more urgent?
Yes. There was a big push to finish it faster. We had so many restrictions, but finally managed to assemble the whole genome and confirm it's a novel strain of canine coronavirus.
I always want to mention: It's not a virus related to SARS-CoV-2. It's a different virus. I already saw some news online that it's a new variant of COVID-19. Those people didn't talk to us. This coronavirus is from another genus, alphacoronavirus, while all SARS coronaviruses are betacoronaviruses. I like to be absolutely clear about that.
One interesting thing we found was a unique mutation in the N gene of this coronavirus that we couldn't find in any other canine coronaviruses isolated from dogs. This deletion is interesting because it was previously only reported for SARS coronaviruses. It's possibly a similar mechanism to how SARS coronaviruses adapted to humans when they first transmitted from bats. One study looked into a number of isolates from humans and a number of isolates from bats for SARS coronavirus, and they also identified this mutation only in human isolates.
We've speculated at this point that it may downregulate the innate immune response and help the virus to survive in a human host. That's just a topic for our future studies. It's not confirmed.
What do you know about whether this canine coronarvirus can be transmitted between humans?
To become a truly human pathogen, a virus should be able to infect human cells, which we think this virus can, but also it should be capable of human-to-human transmission. That's something we do not know at the moment. However, the virus [Vlasova sequenced] was isolated from the youngest patient, who was only 5½ months. This baby was not in direct contact with any dogs, as far as they could recollect, and not crawling around yet. So, this could be the first indication that actually that baby got this virus from an older sibling, or parents or something like this, which would mean that human-to-human transmission is possible. But to really establish it, we need to design another study. That's what we're working on right now. And even if we establish that, we need to evaluate the efficiency of this transmission, which probably wouldn't be very high.
The patients in Malaysia were sick in 2018 and there hasn't been a major outbreak in the intervening years. Is that a good sign?
It would be a really good sign. We do not need another pandemic right away. If it's been happening for years and years, and we're just now catching up with it, hopefully, many humans have partial immunity to it, which is great. If many of those transmissions — dog-to-human or cat-to-human — were dead-end transmissions, which means it infected one person and it didn't spread from that person to anyone else, that person still developed some immunity.
Were you worried that publishing this paper was going to panic pet owners?
I'm very worried about it. Not so much here, because I think single pet owners in the United States have absolutely nothing to worry about. If their dog is not exposed to large numbers of other dogs, the dog cannot contract this virus anywhere.
I'm specifically worried about Malaysia, where I understand they have large populations of stray dogs, and also dogs intermingle with the wildlife and humans. I think it may cause panic. We're trying to calm people down, because they're worried about mass culling of dogs, and that would be a very, very unfortunate outcome, because [this canine coronavirus] is not something absolutely new, and, right now, we don't think it's a huge threat. We are trying to communicate very, very carefully — and with all the details possible — that there is no need to panic.
What can veterinarians in the trenches do to help with surveillance? Anything more than what they already do?
I do believe that more surveillance is needed, especially considering that pigs may be potentially susceptible to some of those viruses. I don't know if they're specifically susceptible to this one, but it's definitely worth surveying the porcine species. Bovine? Probably not so much, but cattle have their own coronaviruses. In other words, we need to establish what prevalence of virus is there, and then monitor if there will be any increase or genetic modification.
So really, it's more the food animals that you're talking about rather than cats and dogs?
Well, we definitely need to survey cats and dogs, but I just don't know how willing vet clinics would be to incorporate it. It's a lot to ask. I don't think we need to screen [individual] healthy animals. Where I would screen apparently healthy animals is where large numbers of animals are accumulated in the same place, because it would be a situation where coronaviruses would have a chance to spread.
Are there other recent studies that highlight some of the trends you're seeing?
You probably heard about another coronavirus, porcine delta-coronavirus, that also was recently confirmed to infect humans. [The research led by scientists at the University of Florida was posted in March as a preprint.] Porcine delta-coronavirus — that was thought to be a bird and pig pathogen strictly — recently was isolated from three children in Haiti with fever, abdominal pain and cough. They did an exhaustive search for all other common pathogens associated with enteric diseases, and didn't find anything. All they were able to find is this porcine delta-coronavirus. And for one of the children, they were able to rule out pig contact.
I think the important message here is that animal coronaviruses are much more capable of infecting humans than we previously thought. The question is: What will happen after they infect us? That's what determines if this virus is going to become a major troublemaker.
I've been in this field for over 20 years, and I had previously heard statements like this: "This such-and-such person was working with animal coronaviruses and got sick." But they were always dismissed, like, "That cannot be because it cannot be."
Now we understand it's not that simple. Even within the same host, the same coronavirus, if you isolate all the viral particles, they will all have slightly different genomes here and there. That's why it's so easy for them to adapt. Even if 99% of them will not survive once they're in the new host, there will be one or two that will.
That's like something out of a scary movie.
Yeah. I mean, I'm just glad coronaviruses are not as dangerous as Ebola virus, for example.
What would you like readers to take away from this conversation?
Right now, all our epidemiological research is reactive: Something happens and we're trying to figure out how to respond to that. It's always a race against time. We need to know so much about these coronaviruses, especially the ones on the animal-human interface. We need to know what genetic traits they have. We need to know what genetic traits are associated with the ability of these viruses to become human pathogens. We need to learn how to track them while they're still in animal reservoirs to be able to predict which ones [will] more likely spill over to a human host and cause large-scale outbreaks.
If someone said that 10 years ago, I would say, “Hmmm, is it really possible?” But I did hear from at least one group — I cannot say who that is yet — but they are working on this. They are taking all the coronaviruses out there and trying to identify their genomic traits and see if they can develop a predictive model — a model that can tell which animal coronaviruses have a greater potential to become human pathogens. And they're already testing it on some coronaviruses, and it seems to be working. It would be an excellent tool. Like all who study coronaviruses, they know that COVID-19 is probably not the last outbreak or epidemic of a coronavirus. We need to get prepared so our response is better, faster and more efficient.