Comparison between human infections caused by highly and low pathogenic H7N9 avian influenza viruses in Wave Five: Clinical and virological findings

The newly emerged highly pathogenic (HP) H7N9 avian influenza virus during Wave Five has caused 28 human infections, while differences in disease severity between low pathogenic (LP)- and HP-H7N9 human infections remain unclear.Clinical data, concentrations of serum cytokines, dynamics of virus shedding and PaO2/FiO2 from patients infected with LP-H7N9 (n = 7, LP group) and HP-H7N9 (n = 5, HP group) viruses during Wave Five were compared. In addition, critical mutations associated with H7N9 virulence in mammal/human were analyzed.Lymphopenia, elevated aspartate aminotransferase, alanine aminotransferase, C-reactive protein and lactate dehydrogenase were common features, with higher incidences of leukopenia and thrombocytopenia in the LP group. The acute phase of both groups was accompanied with elevated cytokines associated with disease severity, including MIF, MCP-1 and IP-10. Diffuse exudation of the lungs and consolidation were observed from all patients. The dynamics of virus shedding and PaO2/FiO2 were similar between both groups. Notably, a higher prevalence of neuraminidase inhibitors (NAIs) resistance in the HP-H7N9 virus was found.Our results indicate that this newly emerged HP-H7N9 virus caused similar disease severity in humans compared with LP-H7N9 virus, while higher case fatality rate and prevalence of NAI-resistance in human HP-H7N9 infections were of great concern.