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

• Published in: Nature communications 2022-11, Vol.13 (1), p.6817-8, Article 6817
• Main Authors: Bao, Pengtao, Liu, Yang, Zhang, Xiaoai, Fan, Hang, Zhao, Jie, Mu, Mi, Li, Haiyang, Wang, Yanhe, Ge, Honghan, Li, Shuang, Yang, Xin, Cui, Qianqian, Chen, Rui, Gao, Liang, Sun, Zhihua, Gao, Lizhen, Qiu, Shuang, Liu, Xuchun, Horby, Peter W., Li, Xiubin, Fang, Liqun, Liu, Wei
• Format: Article
• Language: English
• Subjects: 13/21; 45/23; 45/88; 49/91; 631/326/596/2562; 692/699/255/1578; 692/699/255/2514; Animal models; Animals; Antibodies; Antibody response; Avian flu; Birds - genetics; Cat Diseases; Cats; Child, Preschool; Coagulation; Disease transmission; Dog Diseases; Dogs; Epidemiology; Fever; Genes; Humanities and Social Sciences; Humans; Infections; Influenza; Influenza A; Influenza A Virus, H3N8 Subtype - genetics; Influenza A Virus, H9N2 Subtype - genetics; Influenza in Birds; Influenza, Human - epidemiology; Intubation; Liver diseases; Male; Mammals; Mammals - genetics; multidisciplinary; Next-generation sequencing; Orthomyxoviridae Infections; Oxygenation; Phylogeny; Reassortant Viruses - genetics; Renal failure; Renal function; Respiratory failure; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Sepsis; Signs and symptoms; Virulence; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34601-1

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.