Will influenza A(H3N8) cause a major public health threat?

•On April 27, 2022, China reported the first-ever human influenza A(H3N8) infection.•Previous studies indicated a possible circulation of the H3N8 in humans in the 1890s.•Urgent studies are needed to understand H3N8 pathogenesis in humans.•Cross-reactivity studies of different H3N8 lineages are also needed. The diversity of zoonotic influenza viruses and their ability to cross the species barrier has always been alarming and requires continuous surveillance in both human and animal populations. Avian A(H3N8) influenza viruses are frequently detected in animals and represent one of the most common subtypes in wild birds. Cross-species transmission of avian A(H3N8) influenza viruses has been reported for multiple mammalian hosts, including the outbreaks in horses and dogs by the equine and canine lineages of A(H3N8), respectively. In humans, there was no evidence of influenza A(H3N8) infection until 25 April 2022, when the Chinese health authority reported the first-ever human H3N8 case in a 4-year-old boy from Henan province. Although there is no information that this virus can sustain human transmission, additional epidemiological and virological studies are needed to better assess the replication potency of the virus in human cells as well as the risk posed to public health. In this study, we briefly discuss the influenza A(H3N8) interspecies transmission of the virus, with emphasis on human transmission.