Animal H10N5 infections and emerging zoonotic H10N5 coinfection with H3N2 seasonal influenza A virus

On January 27, 2024, the World Health Organization (WHO) confirmed the first case of human infection with H10N5 avian influenza A virus in the Xuancheng Prefecture, Anhui Province, China.1 This is the first reported infection of humans by the H10N5 avian influenza A virus in the world, which has received extensive attention worldwide. Moreover, the patient was coinfected with H3N2 seasonal influenza A virus and had a history of exposure to live poultry. The mixed infection case indicates that there may be multiple avian influenza strains in the local area, and that the epidemic situation of avian influenza is complex, suggesting the potential emergence of new influenza A virus strains, as well as significant threat to human health and the development of poultry industry. The H10N5 avian influenza A viruses have been reported to cause disease in poultry flock and pig.2, 3 The H10N5 strains listed in the Global Initiative on Sharing All Influenza Data (GISAID) were first identified in Hong Kong in 1976. In the decades that followed, more strains emerged in the United States, South Korea, Bangladesh, Canada, Belgium, Japan, and other countries. A total of 113 strains were isolated in the United States, 16 in China, 12 in Korea, 8 in Australia, 8 in Bangladesh, 7 in Canada, 4 in Belgium, 3 in Japan, 3 in Sweden, and 2 in Singapore. In addition, one strain each appeared in Mongolia, Iceland, and the Russian Federation; The most number of strains were isolated from Arenaria interpres (30%), followed by the environment (25%), Anas platyrhynchos (12%), and duck (7%) (Figure 1). The newly reported case confirmed that H10N5 avian influenza A virus can infect humans.4-6 Since H10N5 was first isolated from Hong Kong in 1976, a total of 16 strains of H10N5 were isolated from China (Table 1). 50% of the strains were isolated from ducks, and 19% from wild birds. One H10N5 strain was isolated from pig in 2008. In addition, H10N5 strains have been isolated from curlew sandpiper and chicken. Regarding regional distribution, five strains were isolated from Hubei Province, and four each from Hong Kong and Jiangxi Province. A case of human infection with H10N5 was first reported in Anhui Province in 2024 (Table 1). It is worth noting that Anhui Province is geographically adjacent to Hubei and Jiangxi Province, and there is a possibility of cross-provincial transmission. Retrospective investigations identified H10N5 gene fragments in environments connected to the transmission chain, including live duck wholesale facilities, mobile vendors, and homes. Sequence analysis of the H10N5 virus revealed that the HA segment belongs to the American lineage A/Anser albifrons/South Korea/22JN-163-1/2022(H10N7) (GenBank:OQ296824.1), while the NA segment originates from the Eurasian lineage A/Spot-billed duck (Anas poecilohyncha)/Korea/KNU17/2022 (H6N5) (GenBank: OR674089.1),7 suggesting that risk of human infection with avian influenza correlates with wild bird and animal migrations, which increase the risk of viral complex reassortment events. To avoid the occurrence of similar incidents, various factors should be given due attention: (a) different strains of the avian influenza A virus are prone to recombination, and wild bird migration increases the likelihood that different strains will mix and recombine. Long-term surveillance mechanisms should thus be established to guard against the emergence of new strains. (b) Strengthening the use of animal vaccines to prevent human infection has yielded good results in human H7N9 prevention and control.8 Therefore, creating a stockpile of H10N5 and H3N2 vaccines and immunizing susceptible animals as necessary can be considered a promising approach. (c) Because many influenza genotypes exist, and vaccines offer poor cross-protection, it is difficult to carry out specific vaccine prevention and control for each genotype. Some researchers have attempted to develop universal influenza vaccines.9 While the impact of this research remains unclear, this is a worthwhile direction, and universal vaccine development research should be strengthened by combining artificial intelligence, mRNA, and other advanced technologies. (d) It has been proved that the pathogenicity of low pathogenic H10N5 in chickens can be enhanced after passage in mammals,10 so people should avoid contact with live poultry. The live poultry market remains a high-risk area for avian influenza A virus infection, the government should strengthen the supervision of the live poultry market and create awareness among the public to avoid exposure to this market to reduce the risk of infection. Pei Gao and Jianlei Ding conceptualized and wrote the manuscript draft; Xinshan Li and Bosen Peng retrieved literature; Leyan Wang and Jiayi Feng collected the data; Fei Liu collated and analyzed the data; Shiyuan Zhang drew a picture; Chengfei Li provided critical comments; Bin Xiang and Jinyou Ma revised the manuscript. All the authors agreed to submit the manuscript in its current form. The authors declare no conflicts of interest. This study was supported by the National Natural Science Foundation of China (No. 32002285), the First-Class Postdoctoral Research Grant in Henan Province (No. 202001039), and the Key Science and Technology Program of Henan Province (No. 242102110004). The data that support the findings of this study are available in the Global Initiative on Sharing All Influenza Data at https://platform.epicov.org/epi3/frontend#6133cd.