H5N5 crossed the Atlantic at least nine times before its first known human infection

A new bioRxiv preprint reconstructing the global evolution of H5N5 avian influenza suggests that the virus crossed the Atlantic at least nine times through high-latitude seabirds and shorebirds before causing the first known human infection in Washington State in 2025. The study reveals an ecology and migration pattern markedly different from dominant H5N1 viruses and suggests that H5N5 circulated in North America for approximately a year before the human spillover event.

H5N5 remained a relatively obscure avian influenza subtype until November 2025, when it was identified in a Washington State resident who developed severe respiratory disease and subsequently died. The infection represented the first documented human case of influenza A(H5N5) worldwide. Until then, H5N5 viruses had primarily been detected in seabirds and shorebirds associated with Atlantic coastal and high-latitude environments.

Researchers have now analysed 354 H5N5 viral genomes collected globally to reconstruct how these viruses moved between Europe and North America and eventually reached the Pacific coast of the United States.

At least nine transatlantic introductions

Phylogenetic reconstruction identified at least nine separate movements of H5N5 viruses across the Atlantic. Rather than representing a single successful introduction followed by local spread, the results suggest repeated exchange of viruses between continents. These introductions were more frequent during autumn and spring, consistent with periods of major migratory movement.

The study points particularly to high-latitude seabirds and shorebirds as important hosts transporting H5N5 between continents. A plausible transmission route involves birds moving through Arctic and sub-Arctic regions, where populations originating from different continents can overlap during breeding, staging or migration.

Such ecological connections may provide opportunities for influenza viruses to move between European and North American bird populations through pathways different from those commonly associated with H5N1.

A different ecology from H5N1

One of the most important conclusions is that H5N5 appears to have a distinct host and geographic ecology compared with dominant H5N1 lineages. H5N1 clade 2.3.4.4b has spread extensively through waterfowl and other wild birds and has repeatedly entered poultry and mammalian populations. H5N5, by contrast, appears particularly associated with high-latitude marine birds and shorebirds.

This difference matters epidemiologically because host ecology can strongly influence how influenza viruses move between continents, which species they encounter and where opportunities for reassortment or spillover may occur. The subtype alone therefore does not fully describe the behaviour of an avian influenza virus.

Around one year of circulation before the human case

The researchers also reconstructed a probable pathway leading to the Washington human infection. Their analysis suggests that H5N5 reached North America through transatlantic bird movements and subsequently circulated for approximately one year before the human case was identified.

The genotype responsible for the Washington infection had not previously been documented in the US Pacific Flyway. Genomic reconstruction therefore provides evidence that the lineage had been present for considerably longer than the known detection history suggested.

The first human H5N5 case

The epidemiological investigation of the 2025 Washington case provides an important connection between wild birds, backyard poultry and human exposure. The patient was an older adult with underlying health conditions who maintained a free-ranging backyard flock of approximately 25 ducks and 30 chickens on a rural property frequently visited by wild birds.

The patient developed symptoms in late October 2025 and was later hospitalised with severe respiratory illness. Influenza A(H5N5), genotype A6, was ultimately identified by whole-genome sequencing.

The patient died on November 21, 2025. Investigators subsequently detected H5 virus in apparently healthy ducks on the property and recovered H5N5 from sediment collected from a watering basin. Six of the eight viral gene segments recovered from the environmental sample were highly genetically similar to the virus isolated from the patient. The findings supported exposure associated with the backyard flock environment, probably following introduction by wild birds.

Approximately 135 potentially exposed people were identified during the public-health investigation, but no additional H5N5 infections were detected. There was therefore no evidence of human-to-human transmission.

Seabirds emerge as important hosts in H5N5 spread

The new analysis shifts attention towards high-latitude marine bird populations as important drivers of H5N5 dispersal. Seabirds can migrate over very long distances and connect geographically distant ecosystems.

Species breeding in Arctic and sub-Arctic regions may also bring together viral populations circulating on different continents, creating opportunities for both intercontinental transmission and reassortment.

The repeated H5N5 movements reconstructed in the study suggest that these ecological connections have played a larger role in the evolution of the subtype than previously recognised. This could be particularly relevant for future assessments of avian influenza risk in regions connected by northern migration routes.

Genomic epidemiology reconstructs an unseen transmission history

The study also illustrates the value of genomic epidemiology in understanding how influenza viruses spread over long periods and across large geographical areas.

Individual detections provide only snapshots of where a virus is found at a particular moment. By comparing hundreds of genomes and reconstructing their evolutionary relationships, researchers can infer how lineages moved between host populations and continents even when intermediate infections were never sampled.

In H5N5, this approach revealed repeated Atlantic crossings and helped reconstruct the lineage that ultimately reached Washington State. The results do not suggest that H5N5 currently poses the same epidemiological threat as the globally dominant H5N1 lineage. Only one human H5N5 infection has been documented, and there is no evidence of sustained transmission in people.

However, the combination of repeated intercontinental movement, circulation in multiple wild-bird populations and demonstrated zoonotic potential makes the subtype relevant to avian influenza preparedness.

The study shows that less common influenza subtypes can follow distinct ecological pathways and acquire epidemiological importance before they become prominent in human or veterinary disease reports.