The current strain of bird flu circulating among mammals in the United States may have evolved to infect humans through respiratory infection, meaning it is a step closer to developing human-to-human spread capabilities.

The highly pathogenic avian influenza, or bird flu, H5N1 has infected more than 100 cattle herds in 12 states across the U.S. since March, resulting in four cases of cow-to-human infections. 

Researchers from the University of Wisconsin-Madison, Texas A&M Veterinary Medical Diagnostic Laboratory, and two Japanese universities studied how H5N1 has evolved since the March outbreak by infecting humanized mice and ferrets in experiments funded by the National Institutes of Health.

Ferrets develop similar respiratory tract infections to humans and develop similar clinical symptoms, making them good models for understanding flu transmission patterns.

When infected by directly inserting virus particles into their noses, both mice and ferrets developed respiratory symptoms. 

At this point, however, the virus does not transmit efficiently through respiratory droplets or airborne particles. This makes it much more difficult for the virus to spread from animals to humans and means that it cannot yet spread from human to human.

During a press conference related to the COVID-19 pandemic, former Centers for Disease Control and Prevention Director Robert Redfield said that he is very concerned that the next pandemic will be bird flu, adding that the virus could mutate toward human-to-human transmission.

“It can go animal-to-human and then that’s it. But eventually these viruses can learn,” Redfield said. “Right now, the bird flu is in 27 different mammals in the United States, learning how to infect different mammals. We just want it to stay out of humans.”

All of the infected mice who received a high dose of the virus died, but some of the mice that received lower doses survived. Infected ferrets, however, had less severe symptoms.

Prior to the U.S. outbreak, the World Health Organization had reported roughly 800 human cases of H5N1 in the 21st century, mostly in Southeast Asia and Northern Africa, with a fatality rate of nearly 50%.

So far, only one of the four cow-to-human infections since March presented with respiratory symptoms. All patients have recovered, according to prior reporting from federal public health agencies.

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Earlier this month, the Department of Health and Human Services awarded Moderna $176 million for the furtherance of its mRNA bird flu vaccine, which is expected to enter late-stage clinical trials in 2025.

HHS officials told reporters that the vaccine is not currently necessary for humans and the agreement is part of the department’s “ongoing preparedness action.”