Differential disease severity and whole-genome sequence analysis for human influenza A/H1N1pdm virus in 2015–2016 influenza season

During the 2015–16 winter, the US experienced a relatively mild influenza season compared to Taiwan, which had a higher number of total and severe cases. While H1N1pdm viruses dominated global surveillance efforts that season, the global distribution of genetic variants and their contributions to disease severity have not been investigated. Samples collected from influenza A-positive patients by the Johns Hopkins Center of Excellence for Influenza Research and Surveillance active surveillance in the emergency rooms in Baltimore, Maryland, USA, and northern Taiwan between November 2015 and April 2016, were processed for influenza A virus whole-genome sequencing. In Baltimore, the majority of the viruses were the H1N1pdm clade 6B.1 and no H1N1pdm clade 6B.2 viruses were detected. In northern Taiwan, more than half of the H1N1pdm viruses were clade 6B.1 and 38% were clade 6B.2, consistent with the global observation that most 6B.2 viruses circulated in Asia and not North America. Whole virus genome sequence analysis identified two genetic subgroups present in each of the 6B.1 and 6B.2 clades and one 6B.1 interclade reassortant virus. Clinical data showed 6B.2 patients had more disease symptoms including higher crude and inverse probability weighted odds of pneumonia than 6B.1 patients, suggesting 6B.2 circulation may be one of the reasons for the severe flu season in Taiwan. Local surveillance efforts linking H1N1pdm virus sequences to patient clinical and demographic data improve our understanding of influenza circulation and disease potential.