The W-Shaped Mortality-Age Distribution of Novel H1N1 Influenza Virus Helps Reconstruct the Second Wave of Pandemic 1918 Spanish Flu

Abstract

Interferon is essential in human defense against influenza virus. The non-structural gene segment (NS) of influenza virus has a critical role in counteracting human interferon-mediated antiviral responses. The second wave of 1918 H1N1 Spanish influenza pandemic was characterized by an enhanced mortality and a W-shaped mortality age distribution. In contrast to the U-shaped mortality-age distribution that targeted the very young and elderly during the first wave, young adult population were also affected during the second wave. The NS of the 1918 H1N1 Spanish influenza virus (1918PV) isolated during the second wave contributes to the virulence of 1918PV. This unique NS of 1918PV is able to inhibit human interferon production at both the pre-transcriptional and post-transcriptional level and induce cytokine dysregulation. The NS of 1918PV has entered the swine population in 1918 and re-emerged in the 2009 novel H1N1 influenza A pandemic virus (2009PV). Both seasonal and pandemic novel H1N1 influenza A viruses produced a W-shaped mortality age distribution. Information from the 2009 novel H1N1 Influenza A pandemic may help to reconstruct the mysterious surge in mortality during the second wave in the 1918 H1N1 Spanish influenza A pandemic. The W-shaped mortality-age distribution of 2009PV indicates the importance of a universal influenza vaccination policy for public protection. The high incidence of cytokine dysregulation and Streptococcus pneumoniae co-infection in hospitalized patients reflects the importance of pneumococcal vaccination and the development of immunomodulating agents that can control influenza-induced cytokine dysregulation.