Anomalies of the 1919 influenza pandemic remain unexplained after 100 years

The modern world's most lethal single event, the 1918-1921 influenza pandemic, remains an anomaly which is still unexplained. The pandemic's unprecedented mortality was very unevenly distributed with young adults and isolated populations worst affected. Australia was the last continent involved with about 12 000 influenza deaths in 1919. Most cases were clinically unremarkable and recovered quickly, but a small minority developed severe tracheobronchitis compromising oxygenation and immune defences usually dying in the second week of illness. Histopathology showed massive destruction of the respiratory epithelium with evidence of secondary bacterial invasion. No simple explanation (e.g. hypervirulent virus) is consistent with these observations.