Human infection with a reassortment avian influenza A H3N8 virus: an epidemiological investigation study

A four-year-old boy developed recurrent fever and severe pneumonia in April, 2022. High-throughput sequencing revealed a reassortant avian influenza A-H3N8 virus (A/Henan/ZMD-22-2/2022(H3N8) with avian-origin HA and NA genes. The six internal genes were acquired from Eurasian lineage H9N2 viruses. Molecular substitutions analysis revealed the haemagglutin retained avian-like receptor binding specificity but that PB2 genes possessed sequence changes (E627K) associated with increased virulence and transmissibility in mammalian animal models. The patient developed respiratory failure, liver, renal, coagulation dysfunction and sepsis. Endotracheal intubation and extracorporeal membrane oxygenation were administered. H3N8 RNA was detected from nasopharyngeal swab of a dog, anal swab of a cat, and environmental samples collected in the patient's house. The full-length HA sequences from the dog and cat were identical to the sequence from the patient. No influenza-like illness was developed and no H3N8 RNA was identified in family members. Serological testing revealed neutralizing antibody response against ZMD-22-2 virus in the patient and three family members. Our results suggest that a triple reassortant H3N8 caused severe human disease. There is some evidence of mammalian adaptation, possible via an intermediary mammalian species, but no evidence of person-to-person transmission. The potential threat from avian influenza viruses warrants continuous evaluation and mitigation. The H3N8 influenza virus is known to circulate in wild birds but cross-species transmission to mammalian hosts was also reported. In this case study, the authors report human infection with a reassortment avian influenza A H3N8 virus in a four-year old boy that developed severe symptoms.

Automated summary

This is a study on a four-year-old boy infected with a reassortant avian influenza A H3N8 virus. The virus was found to have increased virulence and transmissibility, and was detected in pets and environmental samples from the patient's house.