Sick California farmworkers could help uncover the evolution of bird flu

Federal scientists are closely examining the H5N1 gene sequences from California dairy workers, looking for dangerous mutations that could make the virus, called avian influenza or bird flu, more adept at jumping from animals to people and then spreading.

“It can tell us how the virus is evolving,” said Stanford infectious disease expert Dr. Abraar Karan. “It’s a window into what’s going on.”

Samples of the virus were obtained through swabs from two patients with the state's first known human cases of bird flu, the California Department of Public Health confirmed Thursday. Although the patients' whereabouts have not been disclosed, their illnesses are unrelated. They became ill independently after exposure to cows and did not spread from person to person. The risk to the population remains low.

Both cases were mild with little or no respiratory symptoms. The main complaint was a common eye infection called conjunctivitis, caused by workers not wearing adequate eye protection when working with infected cattle. The virus attaches to cells in the membrane that lines the eye.

Samples of the California virus have been sent to the US Centers for Disease Control, which is genetically decoding them. But the work is challenging because samples often contain very low levels of active viral RNA, the molecule on which flu genomes are written.

By comparing samples to each other and to other samples in the U.S., scientists can determine whether the virus is mutating in a way that makes it more likely to infect other people.

If this is the case, the risk of the disease sweeping through the population and potentially triggering a dangerous outbreak increases.

The same sequencing technology is the key tool in identifying and tracking the emergence of new SARS-CoV2 variants, a field of work called “genomic epidemiology.” With widespread use during the COVID-19 pandemic, it has become easier, faster and more ubiquitous, proving to be one of the most important innovations of the 21st century.

H5N1, like our more familiar flu viruses, is constantly changing as it multiplies and diversifies. Viruses are in an evolutionary arms race – as the immune system produces new antibodies, the virus develops new mutations.

Each iteration is intended to offer an advantage, such as the ability to bypass the immune system or create an extreme risk of infection.

Viruses spread in small and sometimes large ways. It is not yet known what genetic changes would allow H5N1 to better infect people or become airborne.

“When this happens, the virus itself undergoes mutations that can change its dangerousness,” Karan said. “We have to be aware of these changes.”

Genetic sequencing will also help ensure that future vaccines and antiviral drugs are a good “fit” and protective.

To stave off an outbreak, the federal government's Center for the Biomedical Advanced Research and Development Authority (BARDA) announced Thursday that it is providing about $72 million to four pharmaceutical companies – CSL Seqirus, Sanofi and GSK – to deal with the next ones Steps to take in the production of H5N1 vaccines. The vaccines now in bulk warehouses are being transferred into ready-to-use vials or pre-filled syringes to immunize people so they are ready for distribution.

“As infections in domesticated animals continue to spread, the risk of infection in humans may increase,” said BARDA Director Gary Disbrow. “Out of an abundance of caution, we are taking steps to increase the amount of vaccines that could be immediately available if needed.”

The virus has already changed significantly since it was first discovered in geese in 1996. In 2020, a new, highly pathogenic form emerged in Europe and quickly spread around the world. In the United States, more than 100 million farmed birds were affected, the worst bird flu outbreak in the country's history.

New mutations have facilitated the spread from birds to several other species, including humans. It has been detected in wild animals such as bears, foxes, seals and skunks, domestic animals such as cats and dogs, and zoo animals such as tigers and leopards. Even marine mammals such as harbor seals, gray seals and bottlenose dolphins can become infected.

The rising case is affecting cows at California dairies — in less than a month, the number of infected herds rose from 3 to 56 — worrying epidemiologists and health experts who monitor farm workers.

Since March, when the H5N1 virus was first detected in dairy cows in the United States, there have been more than a dozen cases of human infections resulting from contact with infected animals.

An early genomic analysis by the CDC found slight differences between human, bovine and avian versions of the virus.

There was a genetic change in humans – a mutation called PB2 E67K – that has a known connection to virus adaptation to mammalian hosts. Scientists emphasized that this is not related to virulence or rapid transmission.

Mutations can explain clinical symptoms – for example, why the virus, like other flu viruses, appears to affect a person's eyes more than the upper respiratory tract.

A case reported in Missouri on September 6 is drawing particular attention. The investigators found no connection with farm animals or unprocessed foods such as raw milk.

Jürgen Richt, a veterinary virologist at Kansas State University in Manhattan, called it “a mysterious case.”

“So you have to cast your net a little wider,” he told Nature magazine. “Maybe they cleaned out a bird feeder in the house. Were they at a state fair? What kind of food did they eat?”

On September 13, the CDC announced that around the same time, two people who had close contact with the infected person also became ill. One of them was not tested for flu; the other tested negative.

In the meantime, researchers are combing through this patient's patchy genomic sequence data from virus samples – and will compare it to the California cases and other samples.

According to John Korslund, a retired U.S. Department of Agriculture veterinary epidemiologist who studies livestock diseases, the two cases in California “are not in themselves a cause for concern about pandemic risk.”

“But each case is still important in its own right,” he said, “because each one of them could signal trends toward viral adaptation for person-to-person spread.”