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Disclosures: Gray reports no relevant financial disclosures.
February 21, 2021
6 min read
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Q&A: After COVID-19, what is ‘the next threat’?

Disclosures: Gray reports no relevant financial disclosures.
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Prior to COVID-19, experts frequently warned that it was not a matter of if, but when the world would experience its next pandemic.

As COVID-19 cases continue to decline in the United States and the vaccine rollout ramps up, a newly published paper asks what new respiratory virus threats may have been missed during this pandemic.

Gray pullquote

“There is a growing demand for innovative and cost-effective approaches to surveil for the next novel respiratory virus threat,” Greg Gray, MD, MPH, FIDSA, and Anfal Abdelgadir, MSc, from the Duke Global Health Institute, wrote in Open Forum Infectious Diseases.

“We need to mitigate novel respiratory virus threats before they fully adapt to humans and become highly transmissible,” they continued. “The most strategic approach would be directing periodic, novel respiratory virus surveillance at the human-animal interface, studying both animal workers and their animals.”

In their paper, Gray and Abdelgadir outlined potential future pandemic threats, including influenza A, coronaviruses, metapneumoviruses, human respirovirus, rhinovirus C, respiratory syncytial virus and many human adenovirus species.

Healio spoke with Gray about potential emerging viral threats and what can be done to prevent pandemics.

Healio: What message do you have for people who might say, “Let’s worry about this pandemic first before we start talking about the next one?”

Gray: We are doing a tremendous amount in response to the COVID-19 pandemic now. In my mind, we need to be thinking about the next threat. There are tremendous opportunities for either another coronavirus or other respiratory virus to cross over to man and even cause more morbidity and mortality than SARS-CoV-2 has. Now that we've had so much negative impact from this virus, what if the next virus is even worse, and how can we stop it? How can we mitigate it? How can we do things better?

Healio: What are the chances that something worse will emerge, and what would that pathogen look like?

Gray: We've seen in the last 20 years quite a few novel virus pathogens that have either emerged or re-emerged to cause problems. I think that the respiratory viruses are the greatest threat. If you have, for instance, an arbovirus, you can usually help reduce its transmission by mitigating the vector — killing the mosquitoes, controlling mosquitoes and controlling ticks. But with a human respiratory virus, it's really difficult to stop in a similar fashion. If you have an enteric pathogen that's transmitted through contaminated water or feces, like cholera, usually you can do something to stop that.

But these respiratory viruses, they're hugely problematic. We've had, as we document in our paper, increased numbers of epidemics of respiratory viruses, and about five different major viral family groups. Any one of these could be the next problem. If you ask me which ones I think would be the highest probability I would go with the influenza viruses, particularly influenza A, and second would be another coronavirus. But certainly there are other viruses. The enteroviruses EV71 and B68 have caused hand foot and mouth-like disease in the United States and in Asia. We've had a bunch of infections with a DNA virus, the adenoviruses. There was an adenovirus 14 outbreak, and it was coined the killer cold virus that raised a lot of alarms in recent years.

Those are viruses that I think are the greatest threat. In addition to those, we have a paramyxovirus group, which includes the human metapneumovirus. We could have problems with a rhinovirus, too. There was also an unusual group of viruses we didn't even know about. We were missing rhinovirus group Cs, respiratory syncytial viruses and parainfluenza viruses.

There are quite a few viruses that have a track record of infecting humans and causing an epidemic. Which one will cause a worldwide epidemic or pandemic? That's the question. What we need to do is conduct effective surveillance for novel viruses to emerge in those viral family groups.

Healio: What has been the effect of limiting and pulling of funding for programs dedicated pandemic preparedness?

Gray: Funding is critically important for infrastructure, as we've seen, including our ability to respond with contact tracing, to administer vaccines and to administer tests. You have to have a continual support chain for public health funding for personnel and for adjusting to whatever the threat may be. Currently, it's all reactive. It's like attempting to mitigate the problem as if you're playing an arcade game like whack a mole. That's what we're doing — we wait for something to emerge and come to our attention, and we try to knock it down. But one day, the virus may not be controllable, and there may not be a way we can respond rapidly. For instance, if the virus has a really high mortality rate, which fortunately SARS-CoV-2 does not, then the whack a mole approach may be too late.

We're concerned that we need to be more aggressive in looking for novel viruses, particularly at the human-animal interface. If you assume that 70% of the emerging human pathogens come from animals, then it makes sense to look at places where humans are in continuous contact with large populations of animals. I think that we should do that where the populations of animals are large enough to sustain novel virus transmission. If you have, for instance, a population of unusual wild animals where the population is very small, a virus would go into those wild animals, burn through the susceptible and wouldn't necessarily be sustained.

In contrast, we have huge farms today for meat production including swine farms, poultry farms and egg farms. Once the virus circumvents the biosecurity and gets in there, there's a continual introduction of immunologically naive animals that can sustain virus transmission. As that virus churns through the new immunologically negative animals, it can mutate just like SARS-CoV-2 is mutating and then develop by chance an affinity to infect humans.

Rather than looking at all these small populations of wildlife animals, we advocate for looking at the human-animal nexus where people come in contact with large groups of domestic animals. That's the basis of a lot of our work — Where do people come in contact with large populations of pigs, chickens or cattle? We've also looked at horses and camels. We think those populations can sustain a virus, and the virus can then mutate and adapt to humans.

Healio: What can be done to properly prepare for another pandemic?

Gray: We need to partner with people in developing countries, particularly the countries that have dense populations of humans living in close proximity to dense populations of animals. It is there where we we've noted in the past hotspots with a high probability for emerging infectious diseases. We have to find ways to partner with them in such a fashion that is encouraging to them. The best way I know to do that is to give them support by looking for respiratory viruses in their people and animals. Many people in developing countries don't have good viral diagnostics, so we go in and we partner with them. We train them, we equip them with supplies and we help them adapt the diagnostics to the present equipment. Then together we work and study the viruses that are being that are causing disease in their humans animals. They, in turn, often share specimens with us so that we can do the more difficult discernments of novel virus emergence or more sophisticated techniques when they can't do them.

This sort of partnership, where we help people in the developing world and hotspots for emerging infectious diseases, develop or adapt diagnostics to detect pathogens in their humans or the animals and then we further examine those same specimens for novel viruses, is much more efficient than some of the other proposals that are being considered. There's one group that wants to assess all the viruses — an estimated 6 or 7 million animals worldwide. They estimate 1.6 or 1.7 million viruses would be found. That project has been criticized. You will find a lot of information that may or may not be pertinent to humans with that project. That has been one strategy to surveil for the next prepandemic virus.

Another strategy is to focus on humans — What are humans coming into hospitals with? What diseases? By the time you see a novel virus coming into a tertiary care center or a big referral hospital and you figure out what it is, it's probably too late. It's already taken hold.

We have argued for something in between these two polar positions — the position of looking at all viruses and animals and the position of waiting until viruses infect humans — to do something in between that we think is more sustainable and cost-effective. We should be looking at the human-animal interface.

Healio: What major lessons should be drawn from COVID-19 for future pandemic preparedness efforts?

Gray: A major lesson is that these emerging viruses are something that are tremendously important. They're a national security threat. Look at what this virus has done to our way of life. In many ways, we've been more concerned about the bad actors, if you will, rogue nations or groups that want to use weapons of mass destruction. But COVID-19 really has us on our knees, and it was a naturally occurring event. We need to think about moving some of the focus on bioterrorism to focus on emerging infectious diseases.

The good news is that we've seen remarkable responses that are praiseworthy in diagnostic development and interventions, such as vaccines, and therapeutic trials for effective treatment. It has been unprecedented, in the last year, that we've seen these successes, and I think that's tremendously commendable for all the organizations and people involved. It gives us hope that we can better sustain these events.

But there's reality that these events — with the nature of the world today — could come at us again as human populations and animal populations are increasing in size and the contact of animal populations with humans increases.