Avian flu ‘would dwarf the COVID pandemic in terms of impact,’ researcher says

Even for the most pandemic-weary among us, avian influenza has become impossible to ignore, especially as Canada starts vaccinating those at highest risk of infection. Recent headlines have dredged up questions that we are loathe to revisit: Where did this new virus come from? How dangerous is it? And how worried should we be? The Globe spoke with Dr. Richard Webby at the St. Jude Children’s Research Hospital in Memphis, where he’s been studying avian influenza viruses since they first started popping up in people nearly three decades ago.

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This interview has been edited and condensed for clarity and length.

The H5N1 story we’re talking about today can really be traced back to as early as 1997. That was the first time this avian influenza sparked human pandemic fears, correct?

Correct. In 1997, in the markets of Hong Kong, over the course of a few months, there were at least 18 people infected, six of those were fatal. In wild aquatic birds, there’s all different shapes and flavours of flu; H5 is just one of them. This was the first time we’d seen H5 in humans but most importantly, it was the first time we’d seen direct bird to human transmission.

People have some familiarity with the term avian influenza but when we start talking Hs and Ns, it can get a bit dizzying for people. Can you explain what these letters refer to?

Influenza viruses only make in the range of 10 to 12 proteins; two of the most important are the H, or hemagglutinin, and N, neuraminidase.

That H protein is what takes the virus and attaches it to the host cell to get it inside. Once the virus particles have been made, [the N protein] helps the new ones get off that cell and head out to infect another one.

So really important proteins. All of our vaccines work against targeting that H protein.

Fourteen years ago, you gave an interview with Nature where you said “if there’s anything that keeps us up at night, it’s the H5 virus.” Can you expand on that? What is so worrisome about H5?

Influenza viruses have to actually be activated by host enzymes before they can infect a cell and replicate. Typically most flu viruses are activated by enzymes that live in our respiratory tract.

But mutations that occur within the H5 and H7 hemagglutinin types allow them to be activated by a much wider range of host enzymes, and some of these enzymes are present outside of the respiratory tract.

It means that this virus can now replicate outside of the confines of the respiratory tract, get into other organs and cause more systemic infections. So it has the capacity to cause much, much more severe disease than all of the other H subtypes, and the H5 just seems to be able to do that even a little bit better than the H7.

So if there is a virus we don’t want in humans, it’s one of these highly pathogenic H5s. And that is the virus that is circulating in birds and cows around the world now, one of those forms of the virus.

What’s been the biggest “uh-oh” moment for you in this current chapter of the H5N1 story?

The biggest uh-oh is really the introduction of this virus into cows. You pick up a textbook of virology and look at hosts that influenza A viruses can infect – cow’s not on that list. Similarly, dolphins or porpoises – not considered to be a host of influenza. And H5 has come along and infected them all.

While H5 is just circulating in birds, there’s not a lot of pressure on that virus to change to be more human infectious. The concern has always been, well, that’s going to change when this virus finds its way into a mammalian host and starts to transmit. It’s going to pick up some of these mammal-adapting changes and that’s going to make it more infectious to humans. Luckily, we’re now a year and a bit into the cow story, and that hasn’t happened. These viruses continue to behave more like avian flu viruses and haven’t adapted to be more infectious for humans.

Can you give us a sense of the scale of damage this virus has already caused in the animal world?

It’s been catastrophic. There have been many, many, many hundreds of millions of birds [domestic poultry] that have been mostly depopulated or infected by this virus across the globe in the last 12 months.

But also this virus came into the Americas into a population of [wild] birds that hadn’t really had much exposure to this version of the flu, right. So they didn’t have much immunity to it, and it roared through.

You think about some of the sea mammal die-offs in South America; tens of thousands of mammals have succumbed to the virus.

It’s a worry for humans, but this virus could wipe out some bird species if it got into the wrong places.

Post-COVID, many people can’t bring themselves to consider the possibility of another pandemic. It would help to hear from an expert like yourself, who’s been watching H5N1 for decades now. How concerned are you today about the possibility of an H5N1 pandemic?

That’s tough. Given everything we know about the virus today, this is a low-risk virus for the general human population. In its current form, this virus is poorly infectious for humans. You’ve got to be exposed to a lot of virus to be infected.

Of course, this could change tomorrow. There’s a scientific paper that came out from colleagues at the Scripps Institute that suggested that even a single change, a single mutation, in the right place could make the H5 virus switch from binding to birds cells to binding better to human cells. I would’ve probably put my money that it would’ve taken two to three changes to do that.

So yes; low risk now. But the confidence that it’s going to be low risk in a week’s time is very, very low to me.

People now know what it was like to live through a COVID-19 pandemic. If there were an H5N1 pandemic, can we say anything about how it might be different?

Again, we don’t know. But if the H5 virus managed to cause a pandemic, and maintained the ability to cause disease that it has now, I think the H5 would dwarf the COVID pandemic in terms of impact. There would be many, many, many, many more severe infections and deaths.

The capacity for this virus to cause disease is really scary. Our group at St. Jude has been essentially following these viruses since 1997 and the current batch of H5s are the nastiest that we have seen.

But there’s always the other side of it, and there is some thought that these mutations – that would switch the virus from being a bird virus to being a human virus – might also lessen the ability of the virus to cause severe disease. There could be a trade-off. But we can’t put money on that.

Let’s talk vaccines. Where are we at with H5N1, do we have a vaccine that’s well-matched to this current version of the virus, and how quickly can we get it into people’s arms?

If you’re looking for any sort of silver lining: In terms of all of these potentially pandemic viruses, we know more about vaccinating against H5 than we do for almost anything else. Because we’ve been worried about it since 1997. So we know what dose to give people, we know how to formulate it, there’s been many, many human clinical trials with this.

Existing stockpiled vaccine was made against a slightly earlier version of the H5 virus but we’re pretty confident from studies that have been done that it’ll cross-react well to the viruses that are out there now.

So bottom line: we can vaccinate, we know how to make the vaccine, there’s some available now. But more vaccines would have to be made and that does take time.