A Closer Look at the Avian Influenza Virus H7N9: A Calm before the Storm?

ABSTRACT The avian influenza A (H7N9) virus, which circulates in wild birds and poultry, has been a major concern for public health since it was first discovered in China in 2013 due to its demonstrated ability to infect humans, causing severe respiratory illness with high mortality rates. According to the World Health Organization (WHO), a total of 1568 human infections with 616 fatal cases caused by novel H7N9 viruses have been reported in China from early 2013 to January 2024. This manuscript provides a comprehensive review of the virology, evolutionary patterns, and pandemic potential of H7N9. The H7N9 virus exhibits a complex reassortment history, receiving genes from H9N2 and other avian influenza viruses. The presence of certain molecular markers, such as mutations in the hemagglutinin and polymerase basic protein 2, enhances the virus's adaptability to human hosts. The virus activates innate immune responses through pattern recognition receptors, leading to cytokine production and inflammation. Clinical manifestations range from mild to severe, with complications including pneumonia, acute respiratory distress syndrome, and multiorgan failure. Diagnosis relies on molecular assays such as reverse transcription‐polymerase chain reaction. The increasing frequency of human infections, along with the virus's ability to bind to human receptors and cause severe disease, highlights its pandemic potential. Continued surveillance, vaccine development, and public health measures are crucial to limit the risk posed by H7N9. Understanding the virus's ecology, transmission dynamics, and pathogenesis is essential for developing effective prevention and control strategies.