New study advances theory on why most U.S. bird flu cases have so far been mild

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Researchers believe immunity to an earlier virus may play a role, but not everyone agrees

A new study used ferrets, the closest animal model for what happens when humans are infected with influenza, to investigate why many human cases of H5N1 bird flu have been mild.Adobe

By Helen Branswell

July 23, 2025

Helen Branswell, STAT’s senior writer on infectious disease, has been reporting on H5N1 bird flu for 20 years.

The H5N1 bird flu virus has historically extracted a heavy toll when it infects humans, with nearly half of confirmed cases ending in death over the past three decades. But of the 70 cases reported in the United States over the past 18 months, only a single death occurred, leaving experts puzzled at how to explain the phenomenon.

A new study published Wednesday adds weight to an argument that the immunity people have developed to the virus that caused the most recent flu pandemic, an H1N1 virus that emerged in 2009, has induced some cross-protection that may be making it harder for H5N1 to infect people, and mitigating the severity of the ensuing disease when such infections occur.

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The paper, published in the journal Science Translational Medicine, reports on a number of studies done in ferrets, the closest animal model for what happens when humans are infected with influenza. It showed that while H5N1 is lethal to ferrets with no immunity to influenza, animals that have previously been infected with influenza A — either H3N2 or H1N1 — appear to have some protection when they are later exposed to the bird flu virus. The protection is particularly strong with H1N1.

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