Human Influenza A Virus H1N1pdm Full-length Genome Sequencing in USA and Taiwan in 2015-16 Flu Season and Disease Correlation

During the 2015-16 winter, the US experienced a relatively mild influenza season compared to Taiwan which had a large number of total and severe cases. While H1N1pdm viruses dominated global surveillance efforts in this season, the global distribution of genetic variants and the contribution of genetic to disease severity has not been investigated. Nasal samples collected from influenza A positive patients by the Johns Hopkins Center of Excellence for Influenza Research and Surveillance (JH-CEIRS) active surveillance in the emergency rooms of major hospitals in Baltimore, Maryland, USA (Baltimore sites) and Taipei, Taiwan (Taipei sites) between November 2015 and April 2016, were processed for multi-segment PCR amplification and deep sequencing of the of influenza A virus gene segments. In the Baltimore sites, the majority of the viruses were the H1N1pdm clade 6B.1 and no H1N1pdm clade 6B.2 viruses were detected. In the Taipei sites, more than half of the H1N1pdm viruses were clade 6B.1 and 38% were clade 6B.2. These were consistent with the global observations that most 6B.2 viruses circulated in Asia and not North America. Of the 103 H1N1pdm nasal samples, 73 yielded sufficient coverage to enable the assembly of sequences for all 8 influenza A virus genome segments. Whole genome analysis identified two genetic subgroups present in each of the 6B.1 and 6B.2 clades. One 6B.1 intraclade reassortant virus containing five 6B.2 segments from the Taipei sites was observed. Clinical data showed 6B.2 patients had higher odds of pneumonia than 6B.1 patients. These data on H1N1pdm viral genetic variants which are linked to patient clinical and demographic data, improve our understanding of the impact of viral mutations to influenza disease severity and reaffirm the importance of active influenza surveillance across different geographic areas in the same influenza season.