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Case Reports
. 2022 Nov 10;13(1):6817.
doi: 10.1038/s41467-022-34601-1.

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

Pengtao Bao #  1 , Yang Liu #  2 , Xiaoai Zhang #  3 , Hang Fan #  3 , Jie Zhao  4 , Mi Mu  1 , Haiyang Li  5 , Yanhe Wang  3 , Honghan Ge  3 , Shuang Li  3 , Xin Yang  3 , Qianqian Cui  6 , Rui Chen  2 , Liang Gao  2 , Zhihua Sun  2 , Lizhen Gao  2 , Shuang Qiu  2 , Xuchun Liu  2 , Peter W Horby  7 , Xiubin Li  8   9 , Liqun Fang  10 , Wei Liu  11   12
Affiliations
Case Reports

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

Pengtao Bao et al. Nat Commun. .

Abstract

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Timeline of the clinical course of the patient, identification of causative pathogen and dynamic changes of laboratory indicators during hospitalization.
A Timeline of the clinical course of the patient. B Dynamic changes of laboratory indicators during hospitalization. The blue dotted line represents the upper limit of the normal range, and the green dotted line represents the lower limit of the normal range. RBC red blood cell, WBC white blood cell, PLT platelet, NEUT neutrophil count, LYM lymphocyte count, CRP C-reactive protein, ALT alanine transaminase, AST aspartate transaminase, PT prothrombin time, APTT activated partial thromboplastin time, BUN blood urea nitrogen, CREA creatinine.
Fig. 2
Fig. 2. Imaging of the patient’s chest.
Computed tomographic (CT) scan obtained on day 6 of illness (A–C). CT scan showed multiple patchy high-density shadows in both lungs, especially in the lower lobe of the right lung and the left lung. Chest radiographs showed patchy high-density shadows in both lungs on day 7 of illness (D). After treatment 2 days, the pulmonary shadows were absorbed slightly on day 8 of illness (E) and on day 9 of illness (F). The consolidation shadow in the left lung was more absorbed than before on day 16 of illness (G–I) and day 31 of illness (J–L).
Fig. 3
Fig. 3. Phylogenetic trees of genes of the A (H3N8) influenza virus.
Phylogenetic trees for the full-length HA (A) and NA (B) genes of H3 and N8 subtype influenza viruses. A/Henan/ZMD-22-2/2022(H3N8) virus was indicated with red color.
Fig. 4
Fig. 4. Hypothetical reassortment route and segment origins of the A (H3N8) influenza virus.
The colors of the segments indicate their origin.
See this image and copyright information in PMC

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