The pathogenesis of a 2022 North American highly pathogenic clade 2.3.4.4b H5N1 avian influenza virus in mallards (Anas platyrhynchos)

) and all exposed ducks, including ducks co-housed with inoculated ducks, were infected. Infection appeared to be subclinical for 58.8% (20/34) of the ducks, one duck was lethargic, about 20% developed neurological signs and were euthanized, and 18% developed corneal opacity. The mallards shed virus by both the oral and cloacal routes within 24-48 h post-infection. Oral shedding substantially decreased by 6-7 days post-infection, but 65% of the ducks continued to shed virus cloacally through 14 days post-exposure (DPE) for the direct inoculates and 13 DPE for contact-exposed ducks. Based on the high transmissibility, high virus shed titres, and mild-to-moderate disease, mallards could serve as efficient reservoirs to amplify and disseminate recent North American clade 2.3.4.4b viruses.