H5N1 is infecting millions of animals. If it crosses over to humans, it will be worse than COVID

Experts are on pins and needles over an avian virus called H5N1 that has killed 53% of the humans it infected

By Troy Farah

Science & Health Editor

Published March 7, 2023 5:45AM (EST)

A rooster is held in a cage on a farm on January 23, 2023 in Austin, Texas. The poultry industry as well as private flocks are suffering a health crisis as the bird flu continues to spread across the United States. (Brandon Bell/Getty Images)
A rooster is held in a cage on a farm on January 23, 2023 in Austin, Texas. The poultry industry as well as private flocks are suffering a health crisis as the bird flu continues to spread across the United States. (Brandon Bell/Getty Images)

Public health experts are continuing to raise the alarm about a highly contagious avian disease that has quickly spread across the globe. The virus — known as H5N1 or colloquially, bird flu — has been causing significant problems over the past year, spawning a "panzootic," or a pandemic among animals. The evolving disaster is contributing to commercial egg shortages and killing large amounts of wild and factory farmed animals — and a few hundred humans.

There have 873 human H5N1 cases since 2003, but an estimated 53 percent have been fatal.

True to its name, avian flu symptoms are flu-like, which means high fever, cough, sore throat, muscle aches, diarrhea and pneumonia. The virus not only spreads easily, it can trigger severe illness and has a high mortality rate in humans — much higher than COVID-19.

There have 873 human H5N1 cases since 2003, but an estimated 53 percent have been fatal, which is comparable to some Ebola outbreaks. COVID has an estimated one percent fatality rate, while seasonal flu is 0.1 to 0.2 percent. These rates can change with context, so they aren't always a good metric of risk, but they do tell us something about the severity of the disease. 

As more cases are reported in more countries, H5N1 has alarmed public health experts. Some have urged governments to stockpile flu vaccines for all strains and begin clinical trials testing new defenses against the pathogen. Dr. Sylvie Briand, the director of epidemic and pandemic preparedness and prevention at World Health Organization (WHO) described the situation as "worrying" on February 24, especially the increase of infections in mammals. "WHO takes the risk from this virus seriously and urges heightened vigilance from all countries," Briand said.

In Peru, for example, health officials reported the deaths of 585 sea lions in mid-February. As of March 3, that number had risen to nearly 3,500, representing approximately 3.3% of the total sea lion population in the country, according to BNO News. The deaths of 63,000 birds, including pelicans, boobies and guanayes, were also reported.

Nearby countries have also been affected, including Argentina, which detected its first case on an industrial farm on March 1, responding by immediately suspending all poultry exports.

But other countries from Spain to Chile to Estonia to Scotland have all been disclosing their own cases. In the U.S. alone, 47 states have experienced outbreaks of bird flu throughout poultry operations in the past year, resulting in nearly 60 million birds being euthanized to prevent further spread.

The pathogen is not new. According to the Centers for Disease Control and Prevention, reports from northern Italy in 1878 describe a "fowl plague" that could have been H5N1. It wasn't until 1955 that the virus was formally identified as a type A influenza virus. In 1996, the H5N1 sub-type was first identified in farmed geese in Southern China with an outbreak in humans occurring in Hong Kong the following year. Eighteen people were infected and six died. (The name H5N1 refers to the combination of two proteins called hemagglutinin and neuraminidase.)

Genetic analysis of an outbreak on a Spanish mink farm in October revealed that the virus had picked up at least one mutation that favors mammal-to-mammal spread.

Ever since, public health experts have been acutely aware that H5N1 could spell big trouble if it were to spread widely. Despite a handful of cases over the decades, that hasn't been the case. While it is not out of the question that bird flu could start a pandemic in humans, experts say we are still a few steps away in the virus' evolution for that to happen. Nonetheless, each infection is another opportunity for a mutation that might turn the tide.

This is not mere speculation; such a thing happened with SARS-CoV-2, the virus that causes COVID-19. As SARS-CoV-2 has infected more and more people, it has mutated further. Some of those mutations turned out to be beneficial, which made it more adept at infecting humans. That is what makes all these cases of infection in mammals all the more concerning, even more so than the hundreds of thousands of birds that have perished in the last year or so.

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Because H5N1 is a virus specifically evolved to attack birds, it isn't as good at infecting the cells of mammals — yet. But if you can count on one thing for viruses to do, it's mutate. And some versions of H5N1 have been gaining genetic advantages that make it more adept at spreading among mammalian organisms.

For example, genetic analysis of an outbreak on a Spanish mink farm in October revealed that the virus had picked up at least one mutation that favors mammal-to-mammal spread. Nearly 52,000 mink at the facility had to be euthanized, which is another reminder that mink farming is a very misguided practice. Mink also have similar respiratory systems to humans, which does not bode well for us, because a flu virus that thrives in mink will likely do well in humans too.

"This is incredibly concerning," Tom Peacock, a virologist at Imperial College London, told Science in January 2023. "This is a clear mechanism for an H5 pandemic to start."

"As far as we can tell, the virus from the mink farm didn't infect any workers, nor did it spread from the farm, so that particular farm outbreak is probably concluded," Peacock told Salon in an email. "The bigger risk is probably mink farming as a practise during this H5N1 outbreak – a virus only needs to get lucky once, and we think a mink farm is an ideal way for a virus to learn to efficiently spread from human to human."

Bird flu often kills its human hosts too fast for it to spread very far.

In a recent blog on Imperial College London's website, Peacock questioned if a H5N1 pandemic was "inevitable," concluding that many open questions remain and experts disagree whether it's impossible or inescapable.

It really comes down to the level of human infections, which so far have remained low, and whether the virus can mutate to facilitate widespread human-to-human transmission. "One thing is for sure, the more the virus circulates in animals, the more interface there will be with humans, paving the way for that unlucky zoonotic event," Peacock wrote.

Thankfully, so far zoonotic transmissions — that is, when a virus jumps from an animal to a human — remain rare. Though a handful of people catch H5N1 every year, cases tend to spiral out before becoming a major outbreak, let alone a pandemic. That's partially because bird flu often kills its human hosts too fast for it to spread very far and because so far, there are very few examples of human-to-human transmission.

Meanwhile, cases of avian flu have been making headlines, such as an 11-year-old girl from Prey Veng province, in the south of Cambodia, who died on February 22. Her father was also infected, but didn't have symptoms and another 11 people tested were negative for H5N1.

But genetic sequencing of the virus in these two cases revealed it was an older strain of H5N1, called, while the variant causing the most concern is named This may just seem like a random jumble of numbers and letters to most people, but as we've learned with SARS-CoV-2, the virus that causes COVID, even small mutations can make big differences in how these pathogens attack.

In the Cambodian case, it's a bit of a relief that the strain is older than the one sickening birds worldwide, because it doesn't seem to have the mutations necessary to easily spread among humans. However, the WHO has reported a handful of infections with the strain, with one case in China, two in Spain, one in the U.K, one in the U.S. and one in Vietnam. All of these cases have fizzled out and human-to-human transmission remains rare.

"We have a fairly good understanding of the minimum it would take for these viruses to go pandemic and it is quite a few mutations all at once, many of which are very rare in the field," Peacock said, but noted that many human infections are likely missed, particularly those which are mild, asymptomatic, or from parts of the world where testing isn't readily available. "Furthermore, reassortment — co-infection between an avian and human influenza virus — has the ability to allow an avian influenza virus to pick up several of these mutations all at once. In fact, several previous pandemics have probably started due to reassortment between avian and human influenza viruses."

Peacock advised against touching or handling sick or dead birds, particularly poultry, waterfowl and seabirds. He also said to keep pets away from birds, as cats and dogs are susceptible to avian influenza. Report groups of dead birds or wild scavenger animals that are obviously sick or behaving strangely (such as seizures, paralysis, or shaking) to the local health authority.

Despite the relatively low level of risk right now, many countries are prepping flu vaccines and antiviral drugs, such as baloxavir and tamiflu, which are believed to be efficient against H5N1. The U.S. currently stockpiles vaccines for many influenza viruses, including H5N1. According to the New York Times, the CDC is sending flu virus samples to drug companies to help them develop vaccines while also exploring if commercial test manufacturers are interested in developing H5N1 tests not unlike those used to detect COVID.

But a pandemic doesn't have to be extremely deadly to cause widespread destruction. Even a sharp uptick in hospitalizations and sick workers could distribute chaos. Though this panzootic is heating up, it still has a ways to go before unfolding into a human pandemic.

"It's a really dangerous time to be a bird," Andrew Pavia, chief of the division of pediatric infectious diseases at the University of Utah, told Scientific American. "But as of today, the risk to humans remains very low. Our concern is what's going to happen as it circulates more and more."

By Troy Farah

Troy Farah is a science and public health journalist whose reporting has appeared in Scientific American, STAT News, Undark, VICE, and others. He co-hosts the drug policy and science podcast Narcotica. His website is troyfarah.com and can be found on Twitter at @filth_filler

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