Yesterday, health officials in Louisiana announced that a patient who was hospitalized with severe bird flu in December has died. The individual contracted bird flu after exposure to a backyard flock and wild birds. It is the first death recorded in the United States attributed to H5N1, or avian influenza.

The person was over the age of 65 and reportedly had underlying medical conditions. The Louisiana Health Department has not released any more details about the patient.

A total of 66 people in the US tested positive for bird flu in 2024, according to the Centers for Disease Control and Prevention. In all of the other cases, people developed mild symptoms and made a full recovery. But the Louisiana case is a stark reminder that avian flu can be dangerous. And as the number of human infections rises, health experts worry about more cases of severe illness—and potentially more deaths.

“This is an ongoing game of Russian roulette,” says physician Nahid Bhadelia, founding director of the Center on Emerging Infectious Diseases at Boston University. “The more virus there is in our environment, the more chances there are for it to come into contact with humans.” It was only a matter of time before bird flu turned deadly, she says.

The US is in the middle of an H5N1 outbreak that shows no signs of stopping. The virus has infected more than 130 million birds, including commercial poultry, since January 2022. In April 2024 it spilled into dairy cows for the first time. Though not fatal for cows, the virus has sickened more than 900 dairy herds in 16 states.

Most people who come down with bird flu are farm workers or others who have direct contact with sick animals. Of the 66 confirmed infections in the US last year, 40 had exposure to dairy cows, while 23 had exposure to poultry and culling operations. In the three other cases, the exact source of exposure is unknown.

Since 2003, more than 850 human cases of H5N1 bird flu have been reported outside the United States, and about half of those have resulted in death. In a statement released Monday, the CDC said a death from H5N1 bird flu “is not unexpected because of the known potential for infection with these viruses to cause severe illness and death.” Federal health officials say the risk of getting bird flu remains low for the general public, and there is no evidence that the virus is spreading from person to person anywhere in the country.

One of the puzzling aspects of the current US outbreak is why all the human infections until now have resulted in mild illness. “It could be that they’re young, healthy people,” says Jennifer Nuzzo, director of the Pandemic Center and a professor of epidemiology at Brown University. “It could be that the way they’re being exposed is different from how we’ve historically seen people get infected. There are a number of hypotheses, but at this point they’re all just guesses.”

Nuzzo says it’s very possible that the Louisiana patient’s preexisting health conditions contributed to the severity of their illness, but also points to the case of a teenager in Canada who was hospitalized with bird flu in November.

The 13-year-old girl was initially seen at an emergency department in British Columbia for a fever and conjunctivitis in both eyes. She was discharged home without treatment and later developed a cough, vomiting, and diarrhea. She wound up back in the emergency department in respiratory distress a few days later. She was admitted to the pediatric intensive care unit and went into respiratory failure but eventually recovered after treatment. According to a case report published in the New England Journal of Medicine, the girl had a history of mild asthma and an elevated body-mass index. It’s unknown how she caught the virus.

“What that tells us is that we have no idea who is going to develop mild illness and who is going to develop severe illness, and because of that we have to take these infections very seriously,” Nuzzo says. “We should not assume that all future infections will be mild.”

There’s another clue that could explain the severity of the Louisiana and British Columbia cases. Virus samples from both patients showed some similarities. For one, both were infected with the same subtype of H5N1 called D1.1, which is the same kind of virus found in wild birds and poultry. It’s different from the B3.13 subtype, which is dominant in dairy cows.

“Right now, the question is, is this a more severe strain than the dairy cattle strain?” says Benjamin Anderson, assistant professor of environmental and global health at the University of Florida. So far, scientists don’t have enough data to know for sure. A handful of poultry farm workers in Washington have tested positive for the D1.1 subtype, but those individuals had mild symptoms and did not require hospitalization.

“In the case of the Louisiana infection, we know that person had comorbidities. We know that person was an older individual. These are factors that contribute to more severe outcomes already when it comes to respiratory infections,” Anderson says.

In the Louisiana and British Columbia cases, there’s evidence that the virus may have evolved in both patients to produce more severe illness.

A CDC report from late December found genetic mutations in the virus taken from the Louisiana patient that may have allowed it to enhance its ability to infect the upper airways of humans. The report says the changes observed were likely generated by replication of the virus throughout the patient’s illness rather than transmitted at the time of infection, meaning that the mutations weren’t present in the birds the person was exposed to.

Writing in the New England Journal of Medicine, the team that cared for the Canadian teen also described “worrisome” mutations found in her viral samples. These changes could have allowed the virus to more easily bind to and enter cells in the human respiratory tract.

In the past, bird flu has rarely been transmitted from person to person, but scientists worry about a scenario where the virus would acquire mutations that would make human transmission more likely.

For now, people who work with birds, poultry, or cows, or have recreational exposure to them, are at higher risk of getting bird flu. To prevent illness, health officials recommend avoiding direct contact with wild birds and other animals infected with or suspected to be infected with bird flu viruses.