Preprint: Two epidemics, one genotype, different outcomes: Evolutionary changes of Avian Influenza H5N1, genotype EA-2024-DI

B3 Avian Flu Diary (Mike Coston) — zoonotic outbreak commentary · 2026-06-28 · Netherlands · PUUV

Credit Avian influenza overview March–May 2026 #19,224 If anyone has any doubts over the impact of the 2025-2026 avian flu season in Europe, one need only look at the above graphic from this weeks Avian influenza overview March–May 2026 , published by the ECDC. After a fairly robust series of outbreaks between 2020 and 2023, reports declined sharply in 2023-2024. The following year, they picked up speed, and over the past 12 months they have skyrocketed in Europe. The reason behind this revival was the introduction of a new genotype ( EA-2024-DI ) which rapidly supplanted the previously dominant EA‑2021‑AB , which had driven the resurgence of avian flu after a lackluster 2019-2020 season. New genotypes come about due to reassortment, the swapping of gene segments by two or more flu viruses infecting the same host. While birds are the most common host for reassortment, it can occur in any flu susceptible host, including humans. In the first couple of years following H5N1's arrival to north America, more than 100 new genotypes were detected . While most reassortants are unable to compete with the fittest of the group, several overachievers emerged, including B3.13 ( Bovine HPAI ) , D1.1 ( primary driver in birds ), and D1.2 ( detected in pigs ). Last Friday, in Eurosurveillance: Detection of antibodies against avian influenza in European dairy cattle, the Netherlands, January 2026 , we looked at the first confirmed spillover of HPAI H5N1 to European cattle, which cited genotype DI.2.1 ( a sub-branch under the EA‑2024‑DI umbrella ) as the causative agent. All of which brings us to a new preprint, published Friday in bioRxiv , which looks at the impact - and continued evolution - of EA-2024-DI in Europe over the past 2 years. They make particular note EA‑2024‑DI.2.1 which has not only driven huge die offs in wild birds, it has increasingly being found in mammalian wildlife and farm mammals. This is a lengthy, and data-dense, report, so I've only posted the Abstract and some excerpts from the Discussion. Follow the link to read it in its entirety. I'll have a bit more after the break. Two epidemics, one genotype, different outcomes: evolutionary changes of Avian Influenza H5N1, genotype EA-2024-DI Bianca Zecchin, Isabella Monne, Marta Dianati, Alessio Bortolami, View Enrico Savegnago, Erga Shkodra, Sandra Revilla-Fernándezd, Mieke Steensels, Steven Van Borm, Emiliya Ivanova, Ivana Rončević, Vladimir Savić, Alexander Nagy, Charlotte K. Hjulsager, Casper Thorup, Lars E. Larsen, Imbi Nurmoja, Ari Kauppinen, Niina Tammiranta, Francois-Xavier Briand, Beatrice Grasland, Ann Kathrin Ahrens, Anne Pohlmann, Anne Günther, Timm Harder, Peter Malik, Laura Garza Cuartero, Svetlana Cvetkova, Juris Ķibilds, Žanete Šteingolde, Egidijus Pumputis, Simona Pileviciene, Chantal J. Snoeck, Manon Bourg, Oxana Groza, Beatriz Bellido Martin, Ron Fouchier, Sanne Thewessen, Oanh Vuong, Monika Ballmann, Marc Engelsma, Cathrine Arnason Bøe, Anna Pikula, Krzysztof Śmietanka, Margarida Dias Duarte, Margarida Henriques Mourão, Iuliana Onita, Dejan Vidanovic, Zuzana Dirbakova, Martin Tinak, Brigita Slavec, María José Ruano, Maite Barrios, Fereshteh Banihashem, Caroline Bröjer, Stina Hedblom, Siamak Zohari, Claudia Bachofen, Ashley C. Banyard, Holly A. Coombes, Ben Clifton, Benjamin C. Mollett, Joe James, Michael J. McMenamy, Robyn McKenna, Ken Lemon, Calogero Terregino, Alice Fusaro doi: https://doi.org/10.64898/2026.05.25.727580 Preview PDF Abstract Since 2020, high pathogenicity avian influenza H5Nx viruses of clade 2.3.4.4b have become enzootic in Europe, causing recurrent epidemic waves characterized by extensive reassortment events. Here, we describe the emergence of a single high-fitness genotype (EA-2024-DI) that has driven two consecutive waves, evolving into distinct sub-lineages. While its circulation is ongoing, during the 2025-2026 wave it caused an unprecedented number of cases in wild birds . Using phylodynamic analyses of a large dataset of genomic sequences, we compared the spatial diffusion and host transmission pattern of the EA-2024-DI sub-lineages across the three most recent epidemic waves (2023-2024, 2024-2025 and 2025-2026). We show that the genotype has persisted over time and has spread primarily through wild Anseriformes , but with a marked change in the transmission patterns between the different waves and a shift in the epicenter from Eastern to Central Europe , the latter having emerged as an important hub for virus diffusion throughout Europe. Our results reveal a recent increase in the frequency of viruses from wild and domestic mammals carrying mutations enhancing virus replication in mammalian hosts , highlighting the importance of proactive monitoring of this group of hosts to better understand its role in the virus ecology and evolution. (SNIP) Discussion Since the introduction of the HPAI A(H5) of clade 2.3.4.4b in 2020, European epidemic waves have been characterized by the emergence of new genotypes with an ever-increasing ability to infect a broad range of wild birds4 . From 2020 to 2023, a rapid turnover of genotypes was observed, most of which became extinct after one or two epidemic waves , whilst others continued to circulate persistently at low frequencies in well-defined ecological niches (e.g., genotypes EA-2021-I, EA-2024-DT, EA-2022-BB andEA-2024-DA)4,6,16. Since October 2024, for the first time in Europe, a single genotype, EA-2024-DI, has driven two successive epidemic waves , 2024-2025 and 2025-2026, but with a completely different outcome . An unprecedented number of cases in wild birds was recorded during the 2025-2026 epidemic wave, representing a six-fold rise compared to the equivalent period (1 October-31 March) of the 2024-2025 wave (https://eurlaidata.izsvenezie.it/). What drove this exceptionally high level of viral circulation in the wild avian population? This study reveals that, during the 2024-2025 epidemic, two sub-lineages, EA-2024-DI.1 and EA-2024-DI.2 were co-circulating . These variants evolved from the EA-2024-DI genotype that emerged in Europe in late 2023. The current 2025-2026 epidemic, however, has been caused by a newly emerged drift variant of EA-2024-DI.2, namely EA-2024-DI.2.1. (Continue . . . ) As we've seen already in Europe, North America, South America, and Antarctica - when HPAI reaches new territories, it gains access to a more genetically diverse pool of LPAI viruses - and that often helps to fuel its evolution; sometimes in unexpected ways. A little over 2 years ago, HPAI H5 infection of cattle, sheep, and goats was thought highly unlikely. Today, we've seen it on at least 2 continents (and likely a 3rd ), likely driven in large part by its increasing genetic diversity. This past week, HPAI H5N1 reached Australia for the first time, and there it will find access to not only more unique LPAI viruses, it will find a whole new range of warm-blooded hosts. While it is impossible to know what evolutionary advantages HPAI may find down under, past performance suggests we should be wary. But even if HPAI somehow fails to establish a beachhead in Australia, H5 seems to be evolving with very little constraint on the other 6 continents it has already conquered. Arguably Europe's EA-2024-DI.2.1 , and North America's B3.13 and D1.1 genotypes are the biggest HPAI threats we've seen to date, but they could easily all be eclipsed by something ` new and improved' sometime in the near future. Stay tuned.

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