Since 2021, clade 2.3.4.4b H5N1 highly pathogenic avian influenza viruses(AIVs) have become the dominant strain responsible for the ongoing panzootics in birds worldwide, causing unprecedented deaths of poultry and wild birds(https://wahis.
woah.org). Moreover, the H5N1 viruses have caused increasing infections in domestic and wild mammals. Their sustained mammal-to-mammal transmission has been documented in minks in the 2022–2023 H5N1 outbreaks on European fur farms, in marine mammals (sea lion-to-sea lion/seal) in the 2023 outbreak in South America, and in the 2024 US dairy cattle outbreak (cattle to-cattle/farm worker). The concern of H5N1 zoonotic risk was further raised by its increasing spillover in humans. As of January 20, 2025, 964 human infections with H5N1(including 466 deaths) have been reported by the World Health Organisation(https://www.who.int/teams/global-influenza-programme/avianinfluenza/avian-a-h5n1-virus). Notably, the current clade 2.3.4.4b H5N1 viruses have caused at least 70 human cases in the US. Most patients showed mild respiratory symptoms and conjunctivitis, but the first severe case in the US was confirmed and died in
December 2024 (https://www.cdc.gov/media/releases/2024/m1218-h5n1-flu.html).