# Fatal human H3N8 influenza virus has a moderate pandemic risk

## TL;DR

A 2023 H3N8 avian influenza virus that killed a human in China poses a moderate pandemic risk due to its ability to infect and spread among humans.

## Contribution

The study evaluates the pandemic risk of a zoonotic H3N8 virus using a decision tree and experimental models.

## Key findings

- Most people lack cross-neutralizing antibodies against the H3N8 strain.
- The virus binds to human-like sialic acids and replicates in human bronchial cells.
- It spreads via direct contact in ferrets but not through aerosols, and pre-existing immunity does not prevent severe disease.

## Abstract

In China, low pathogenic avian influenza (LPAI) H3N8 virus is widespread among chickens and has recently caused three zoonotic infections, with the last one in 2023 being fatal. Here we evaluated the relative pandemic risk of this 2023 zoonotic H3N8 influenza virus, utilizing our previously published decision tree. Serological analysis indicated that a large proportion of the human population does not have any cross-neutralizing antibodies against this H3N8 strain. LPAI H3N8 displayed a dual affinity for α2–3 and α2–6 sialic acids and replicated efficiently in human bronchial epithelial cells. Furthermore, we observed H3N8 transmission via direct contact but not aerosols to ferrets with pre-existing H3N2 immunity. Although pre-existing H3N2 immunity resulted in a shortened disease course in ferrets, it did not reduce disease severity or replication in the respiratory tract. This study suggests that this zoonotic H3N8 strain has moderate pandemic potential and emphasizes the continued need for avian influenza surveillance.

Low pathogenic avian influenza (LPAI) viruses circulate widely amongst birds and are a major public health concern for their ability to cross over to other species, including humans. Here we characterize the pandemic potential of an H3N8 LPAI virus that caused a lethal human infection. While this strain was only able to transmit by direct contact, we found that it did exhibit some human adaptations, and pre-existing immunity did not reduce replication or pathogenesis, suggesting that it is a moderate pandemic risk and needs to be monitored given the potential public health threat.