Emergence of a novel reassorted high pathogenicity avian influenza A(H5N2) virus associated with severe pneumonia in a young adult.

Infection of backyard and poultry with low pathogenicity avian influenza LPAI A(H5N2) viruses has occurred in Mexico since 1994, and the first human infection caused by this influenza virus was detected in 2024. Since its emergence in the Americas, frequent reassortments between high pathogenicity avian influenza HPAI A(H5N1) and LPAI viruses has occurred. In September 2025, the Instituto Nacional de Enfermedades Respiratorias of Mexico City identified an unsubtypeable influenza A virus infection in a young adult patient later determined to be a reassortant HPAI (H5N2) virus with a clade 2.3.4.4b HA. We analyzed clinical and epidemiologic data from this patient. Respiratory samples were tested for influenza RT-qPCR assays. Genomic sequence and phylogenetics analyses were performed to provisionally assign a new genotype to the novel HPAI A(H5N2) reassortant virus. The patient presented with fever and tachypnea, later developed hemoptysis and thoracic pain, with oxygen saturation decreasing to 70%. CT scan showed bilateral ground-glass opacities consistent with diffuse alveolar hemorrhage and zones consistent with consolidation. Clinical improvement was observed and the patient was discharged. Through viral complete genome analysis, we identified an HPAI A(H5N2) virus with genes from both clade 2.3.4.4b A(H5N1) viruses similar to those detected in North America during 2022-2023 and genes from the LPAI A(H5N2) viruses detected in Mexico during 2024. This is the first ever laboratory-confirmed human infection caused by an HPAI A(H5N2) virus infection, suggesting a new genotype provisionally classified as B3.14. The relationship of the virus with the severity of illness remains unknown.