A 13-year-old girl in British Columbia who was hospitalized with bird flu for several weeks late last year harbored a mutated version of the virus, according to a report published this week in the New England Journal of Medicine.
The case was Canada’s first recorded human infection of avian influenza, which has infected at least 66 people in the United States since last March, according to the Centers for Disease Control and Prevention. This includes the nation’s first severe case, in Louisiana in December.
So far, nearly all of the cases of bird flu in North America have been mild, with symptoms including conjunctivitis, or pink eye, and runny nose, chills, cough and sore throat.
“I think it’s concerning but not totally surprising that we would see some sporadic cases where there is severe illness. Even seasonal influenza can occasionally cause very severe illness,” said Dr. Chanu Rhee, an infectious disease and critical care physician at Brigham and Women’s Hospital and an associate professor of population medicine at Harvard Medical School.
For now, the Canadian teen and the patient in Louisiana are outliers, but the infections illustrate the virus’s ability to cause severe illness — and demonstrates how, during long illnesses, the virus has the chance to mutate to better infect humans.
In both of those cases, virus samples showed that once it was in the body, it mutated in ways that would allow it to stick to cells in the mucous membrane lining the upper respiratory tract.
“The average bird flu virus is not very good at all at sticking to the cells in our mucous membrane, which is what it needs to cause a human infection,” said Dr. William Schaffner, a professor of infectious diseases at the Vanderbilt University School of Medicine.
Still, the presence of these mutations doesn’t mean the virus can definitely spread from person to person.
“Just because there are mutations that could allow it to transmit between people doesn’t mean it will,” said Angie Rasmussen, a virologist at the University of Saskatchewan’s Vaccine and Infectious Disease Organization.
In both cases, no one else was infected, which means the mutations don’t appear to enable the virus to pass between humans, Rasmussen said.
Rhee, Rasmussen and Schaffner were not involved with either patient’s case.
Viral roulette
The mutations in the bird flu, or H5N1, viruses that caused severe infections in British Columbia and Louisiana both occurred in a protein on the surface of the virus that allows it to attach to cells — the influenza equivalent of the coronavirus’s spike protein. Typically proteins on the surface of the H5N1 virus are designed to attach to receptors in birds, which is why the virus is so good at infecting fowl. But the mutations seen in both severe cases allowed these versions of the virus to attach to receptors in the human mucous membrane.
Viruses replicate in any body they infect, but have more chances to do so in people who are immunocompromised or have underlying health conditions that make it more difficult for their immune system to fight off a virus. As the virus lingers, it replicates again and again, occasionally creating mutations that can make the virus more adept at spreading.
“RNA viruses like influenza have these enzymes that basically can’t spell-check themselves, so they make a lot of mistakes and mutations inevitably emerge,” Rasmussen said.
In addition to a mutation on the surface of the virus that allowed it to better infect humans, the virus sample from the British Columbia teen contained a mutation that allowed it to quickly replicate once it infected the cells, something the Louisiana patient’s virus sample did not have.
More concerning than these mutations, however, is the virus infecting humans at the same time the seasonal flu is ramping up, Rasmussen said.
“If you get infected with H5N1 and at the same time get infected with seasonal flu, it’s like shuffling two decks of cards together when they replicate, that can be extremely dangerous,” she said.
This phenomenon is called reassortment. The 2009 swine flu outbreak is thought to have been the result of reassortment between avian, swine and human influenza viruses.
“We already know that reassortment sometimes is really beneficial for the virus and it allows it to make a big evolutionary leap forward much more quickly than random mutations. That’s why the mutations don’t bother me as much as the increasing number of human cases,” Rasmussen said.
She likened the possibility of a virus being able to create a pandemic to playing the lottery.
“A lot of times worrying about whether a pandemic will emerge from this is like buying a lottery ticket. Your odds are low, but if you buy enough tickets, you’ll eventually have a winner,” she said.
As the virus infects more humans, especially if those cases are not closely surveilled, it creates more opportunities for the virus to mutate and mix with other viruses that are already good at infecting people.
“We are basically giving the virus a lot of lottery tickets,” Rasmussen said.
Severe illness
It’s still not clear where or how the Canadian girl was infected, but the version of the virus she had was “most closely related to viruses detected in wild birds in British Columbia around the same time,” according to the new report.
The patient in Louisiana is also thought to have been infected by exposure to birds, in that case, a backyard flock. Other cases in the U.S. have been from exposure to dairy cows or poultry.
“We are around wild animals a lot more than we think we are,” Rasmussen said. “We’re around their feathers, their poop. My suspicion was that it was likely contact with birds that the person didn’t realize, but it may never be known how that person was infected.”
The girl, who had mild asthma and obesity, first went to the emergency room on Nov. 4 for conjunctivitis and a fever, but she was sent home without treatment, according to the report.
She continued to get sick, however, and soon came down with a cough, vomiting and diarrhea.
Three days later, she was back in the emergency room: She had difficulty breathing and her body was unable to get enough blood to her organs. The following day, Nov. 8, she was transferred to the pediatric intensive care unit for respiratory failure, pneumonia, kidney injury and low platelet and white blood cell counts. On Nov. 9, doctors put her on a ventilator to help her breathe and on extracorporeal membrane oxygenation, or ECMO, a lifesaving machine that circulates and oxygenates the blood when the lungs and heart aren’t functioning properly.
“That’s certainly a marker of very severe illness,” Rhee said.
The rest of the month was a blur of daily treatments with antivirals and keeping the girl intubated until finally, on Nov. 28, the breathing tube was removed when doctors determined she could breathe on her own. Tests revealed the virus, even with its mutations, was not resistant to available antivirals.
“This virus, like all the other bird flu viruses, thankfully continues to be susceptible to the antivirals we have available,” Schaffner said.
Whether humans have immunity to avian flu is complicated and depends on a number of factors including what strain of influenza a person was infected with for the first time in their lives, Rasmussen said.
“Viral immunologists think there may be some crossover protection that we have had from previous experiences with influenza viruses, but if so, it is not going to be very much,” Schaffner said.
