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

Bianca Zecchin; Isabella Monne; Marta Dianati; Alessio Bortolami; Enrico Savegnago; Erga Shkodra; Sandra Revilla‐Fernández; 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; François‐Xavier Briand; Béatrice Grasland; Ann Kathrin Ahrens; Anne Pohlmann; Anne Günther; Timm Harder; Péter Malik; Laura Garza Cuartero; Svetlana Cvetkova; Juris Ķibilds; Žanete Šteingolde

doi:10.64898/2026.05.25.727580

Evolutionary BiologybioRxivMay 26, 2026

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

Bianca Zecchin iD, Isabella Monne iD, Marta Dianati iD, Alessio Bortolami iD, Enrico Savegnago iD, Erga Shkodra, Sandra Revilla‐Fernández iD, Mieke Steensels iD, Steven Van Borm iD, Emiliya Ivanova iD, Ivana Rončević iD, Vladimir Savić iD, Alexander Nagy iD, Charlotte K. Hjulsager, Casper Thorup iD, Lars E. Larsen, Imbi Nurmoja, Ari Kauppinen iD, Niina Tammiranta iD, François‐Xavier Briand iD, Béatrice Grasland iD, Ann Kathrin Ahrens iD, Anne Pohlmann iD, Anne Günther iD, Timm Harder iD, , Alice Fusaro iD

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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.