H5N1 is a subtype of influenza A virus that has evolved significantly since its emergence in 1996. Its ability to infect new animal hosts, such as its recent jump to dairy cows, creates potential cause for concern. However, scientific evidence suggests the current threat of a major new human pandemic from H5N1 is low.
At the dawn of 2025, a Louisiana man died after being hospitalized with severe bird flu. His early-January passing touched off a spate of media reports discussing the potential dangers from the H5N1 virus.1
As of March 18, there have been 70 confirmed human infections this year from what is more commonly an animal virus.2 Of the 70, only the Louisiana man’s case has been fatal.
What exactly is the threat posed by the H5N1 virus? How likely is it that we will face another global pandemic so soon after the emergence of COVID-19?
This article examines the history of H5N1, the nature of the virus, and the potential dangers it poses.
H5N1 – also called avian flu or bird flu – is not a new virus. It was first detected in 1996 in China. The next year, it spread rapidly through poultry in Hong Kong. After 18 human infections, none of which were fatal, its spread slowed.
The virus reemerged in 2003, with significant outbreaks in birds throughout Asia and later in Africa and Europe. Sporadic human infections occurred. In 2022, the virus mutated, and a new subtype of H5N1 developed. This version was genetically different from earlier forms of the virus and spread to North America, infecting domesticated poultry and wild mammal species. Over the past year, this new subtype also has been spreading in dairy cows.
This version of the virus is decimating bird populations. UN health officers believe it has caused the deaths of more than 300 million birds worldwide. As of March 2025, more than 166 million birds were infected in the US, and the spread to dairy cows is both new and unexpected.
Since its 1996 emergence, 964 laboratory-confirmed cases of H5N1 in humans have been reported across 24 countries, and 466 – or 48% – proved fatal. A separate variant, H7N9, has infected 1,568 humans since 2013, resulting in 616 fatal cases (39%) reported to the World Health Organization. However, severe cases are much more likely to be reported than mild ones, so the actual infection/fatality rate is thought to be much lower.
The Louisiana man who succumbed to H5N1 in early 2025 was older than 65 and reportedly had underlying medical conditions. He was hospitalized after exposure to a backyard flock of birds and to wild birds.
Human H5N1 infection varies widely in severity. Some patients remain asymptomatic, while others develop a range of conditions, from conjunctivitis and mild upper respiratory tract symptoms to lower respiratory tract diseases such as pneumonia – and death.
Forty-six people in the US contracted H5N1 from March to October 2024. All had mild symptoms lasting a median of just four days, and none was hospitalized or died. Early detection and quick antiviral treatment may have played a role in these positive outcomes.
In addition, no additional human cases were identified among close contacts of those testing positive for the virus, which is consistent with a current lack of evidence for human-to-human transmission of H5N1 viruses in the US.3
A 2016 paper that examined almost two decades of severe infections caused by two subtypes of bird flu – H5N1 and H7N9 – found that people tend to gain the strongest immunity from influenza viruses in childhood, which could provide lifelong protection. That study showed that immunity from a first infection provided 75% protection against severe disease and 80% protection against death with a matching bird-flu virus.4, 5
A 2025 research study, published in Nature Medicine, found that an individual’s birth year was closely linked to the volume of H5N1-fighting antibodies in their blood. Older adults, born before 1968, who were exposed to H1N1 or H2N2 seasonal influenza viruses in childhood appeared to have immune responses that last a lifetime. These cross-reactive antibodies are unlikely to prevent H5N1 infections, but it is believed that they could reduce the severity of disease.
As of early 2025, the current risk for a severe human pandemic developing from the H5N1 virus remains low. Currently, human-to-human transmission appears extremely limited and potentially non-existent. Except for one case of a patient with an undetermined exposure source, all other patients had occupational exposure to infected animals.
That said, ongoing surveillance of this virus is imperative to understand how it is evolving.
While most zoological pathogens do not adapt well in humans, the H5N1 virus has been showing sustained, even increased, activity in infecting wild and domestic animals and mutating to spread to new species. Each time the virus adapts to a new mammalian host, it develops additional properties and is one step closer to potentially infecting humans more effectively. Most modern pandemics have begun through the transmission of “zoonotic” pathogens between animals and humans. For example:
In the unlikely event of a H5N1 pandemic, three current H5N1 virus vaccines are FDA-approved. Canada’s government has purchased a limited supply of 500,000 vaccine doses in case of a widespread human outbreak. The UK government has agreed to a contract for more than five million doses of human H5 influenza vaccine.
Today’s threat level of an H5N1 human pandemic can be labeled “Low.” While there is reason to pay close attention, those in the scientific community generally agree that there currently is no cause for alarm.
RGA is directly involved with collecting high-quality data and monitoring equally high-quality research. RGA is an executive member of the leadership forum of the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota, which provides a window into the latest data and information.
Sharing this information is key to maintaining and improving public health. Staying informed about H5N1’s evolution is crucial for accurate risk assessment and proactive policy adjustments in our interconnected world.
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