An even deadlier pandemic could soon be here

As the world is just beginning to recover from the devastation of COVID-19, it is facing the possibility of a pandemic of a far more deadly pathogen.

Bird flu — known more formally as avian influenza — has long hovered on the horizons of scientists’ fears. This pathogen, especially the H5N1 strain, has not often infected humans, but when it has, 56 percent of those known to have contracted it have died. Its inability to spread easily, if at all, from one person to another has kept it from causing a pandemic.

But things are changing. The virus, which has long caused outbreaks among poultry, is infecting more and more migratory birds, allowing it to spread more widely, even to various mammals, raising the risk that a new variant could spread to and among people.

Alarmingly, it was recently reported that a mutant H5N1 strain was not only infecting minks at a fur farm in Spain but also most likely spreading among them, unprecedented among mammals. Even worse, minks’ upper respiratory tract is exceptionally well suited to act as a conduit to humans, said Thomas Peacock, a virus expert who has studied bird flu.

The world needs to act now, before H5N1 has any chance of becoming a devastating pandemic. We have many of the tools that are needed, including vaccines. What is missing is a sense of urgency and immediate action.

The world needs to act now, before H5N1 has any chance of becoming a devastating pandemic.

We have many of the tools that are needed, including vaccines. What is missing is a sense of urgency and immediate action.

Beating initial outbreaksThe best defense against a new deadly pathogen is aggressively suppressing early outbreaks, which first requires detecting them quickly. The US, the World Health Organization, and global health officials already have influenza surveillance networks, but many bird flu experts said they do not think the networks are functioning well enough given the threat level. Such surveillance would need to prioritize people in the poultry industry but also expand beyond that.

Thijs Kuiken, an expert in bird flu at Erasmus University Medical Center in Rotterdam, Netherlands, said farms for pigs — another influenza-susceptible species — should also be surveilled for bird flu. People interacting with wild birds and animals, as well as susceptible species of pets like ferrets, are also at higher risk. It is not enough to detect, though; suppression would require a major effort and global coordination.

Unfortunately, mink farms must be shut down — even if it means killing the minks. They are typically killed anyway for their fur at about six months of age. It is hard to imagine a better way to incubate and spread a deadly virus than letting it evolve among tens of thousands of animals with an upper respiratory tract similar to ours crowded together. When the coronavirus infected Danish mink farms in 2020 and the minks generated new variants that then infected humans, the efforts to save the industry were futile because the outbreaks were uncontrollable.

Urgent testing measuresIf different strains of flu have infected the same person simultaneously, the strains can swap gene segments and give rise to new, more transmissible ones. If a mink farmworker with the flu also gets infected by H5N1, that may be all it takes to ignite a pandemic.

Relying on chickens to produce vaccines against a virus that has a 90 percent to 100 percent fatality rate among poultry has the makings of the most unfunny which-came-first, the-chicken-or-the-egg riddle.

To avoid this, quick testing should be widely available and easy to obtain globally, especially for poultry workers and people handling wild birds or wildlife. And current testing capabilities should be quickly expanded. There are 91 public health labs in the US that can test for H5 influenza. Positive results are sent to the Centers for Disease Control and Prevention, where further analyses can detect H5N1 within about 48 hours. But plans should be in place to increase the amount of tests and testing facilities in case demand ramps up.

What about vaccines?Perhaps the best news is that we have several H5N1 vaccines already approved by the US Food and Drug Administration whose safety and immune response has been studied.

The US government has a small H5N1 vaccine stockpile, but it would be nowhere near enough if a serious outbreak occurred. The current plan is to mass-produce them if and when such an outbreak occurs, based on the particular variant involved.

There are several problems, though, with this approach even under the best-case scenarios. Producing hundreds of millions of doses of a new vaccine could take six months or more.

Worryingly, all but one of the approved vaccines are produced by incubating each dose in an egg. The US government keeps hundreds of thousands of chickens in secret farms with bodyguards (it is true!). But the bodyguards are presumably there to fend off terror attacks, not a virus. Relying on chickens to produce vaccines against a virus that has a 90 percent to 100 percent fatality rate among poultry has the makings of the most unfunny which-came-first, the-chicken-or-the-egg riddle.

The only company with an FDA-approved non-egg-based H5N1 vaccine expects to be able to produce 150 million doses within six months of the declaration of a pandemic. But there are 7 billion people in the world.

The mRNA-based platforms used to make two of the COVID vaccines also do not depend on eggs. Scott Hensley, an influenza expert at the University of Pennsylvania, said that those vaccines can be mass-produced faster, in as little as three months. There are currently no approved mRNA vaccines for influenza, but efforts to make one should be expedited.

Scientists are working toward a universal flu vaccine, potentially covering all variants as well as future pandemic ones — a moonshot, perhaps, but worth the investment.

If the WHO is to take the lead in expanding global vaccine manufacturing, it needs the support of wealthy countries and the cooperation of large pharmaceutical companies that have the patents and know-how.

A big challenge to stockpiling flu vaccines is that they can lose potency over time and need updating as new variants arise. The US government is skeptical about creating a large stockpile, fearing that stored vaccines may not be effective against whatever strain became pandemic, and worries that stockpiles will expire anyway. Officials also have faith that they can get new flu vaccines mass-produced rapidly.

Preventative vaccinationWe could also allow voluntary vaccination, especially for high-risk groups like poultry workers and health care workers, who would be treating patients should outbreaks occur. Voluntary vaccination could also produce larger-scale data on the safety and dosing specifics of vaccines. Vaccinating poultry workers has the additional big benefit of helping suppress outbreaks in the first place.

Several influenza experts I spoke to bemoaned the lack of more widespread vaccination for chickens and turkeys. Had all poultry been vaccinated earlier, perhaps H5N1 would have never spread so widely to wild birds. It is late, but mass vaccination of poultry and pigs should begin quickly.

Even getting more people vaccinated — especially poultry and pig farmworkers — against the regular flu can help. With less regular flu in the world, there would be fewer hosts for an H5N1 virus to co-infect, a process that can lead to strains of H5N1 that can spread more easily.

We already have antivirals for influenza, which work regardless of strain, but they need to be administered early, which requires widespread early testing, easy access, and sufficient and equitable stockpiles globally.

Scientists are working toward a universal flu vaccine, potentially covering all variants as well as future pandemic ones — a moonshot, perhaps, but worth the investment.

Warning signsThe pace of developments has been disquieting. Until 2020, when the new H5N1 strain began to spread extensively among wild birds, most big outbreaks occurred among poultry. But now, with wild birds acting as conduits, it is not just the biggest outbreak ever among poultry, causing the death of at least 150 million animals so far, but is also steadily expanding its reach, including to new mammal species like dolphins and bears.

In 2006, when scientists discovered that H5N1 had not spread easily among humans because it settles deep in their lungs, Kuiken, at Erasmus University Medical Center, warned that if the virus evolved to bind to receptors in the upper respiratory tract — from which it could become more easily airborne — the risk of a pandemic among humans would rise substantially. The mink outbreak in Spain is a signal that we might be moving along exactly that path.

It is hard to imagine clearer and more alarming warning signs of a potentially horrific pandemic.

This time, we have not just the warning, but also many of the tools we need to fend it off. We should not wait until it is too late.


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