Severe Influenza. Genetic polymorphisms associated with pH1N1 susceptibility and disease severity identified to date are limited, and much of the data is derived from small cohorts. An improved understanding of the sequence of immune responses to influenza as well as the application of newer technologies that employ high-throughput expression array or sequencing technologies can be used to guide a more focused approach to identify specific pathways that may be differentially activated by individuals with severe disease. Based on available data, we can identify several immune pathways and their genetic variants that warrant further investigation.