Beginning in the fall of 1918 and continuing into early 1919 there was a worldwide influenza pandemic. The spread of the so called Spanish Flu was accelerated by the close living quarters and travel of soldiers involved in World War I. It is estimated that nearly a third of the worlds population was infected, and between 20 and 50 million people died as a direct result of influenza or of secondary infections like pneumonia. The Spanish flu was unique from any other influenza epidemic in that it was most devastating to otherwise healthy individuals between the ages of 15 and 45. All other flu outbreaks have affected children and the elderly in much higher rates than any other age group.

The Spanish flu was characterized by a very aggressive respiratory infection that destroyed lung tissue.  In many cases, victims had their lungs fill with fluid, making them unable to breathe. Unlike some influenza viruses, the Spanish flu variant only infected the respiratory tract, and was unable to move to and damage other organs in the body such as the spleen. In fatal cases of the Spanish flu, individuals often succumbed in just a few days. In many areas public gatherings were forbidden and people only went out if they were wearing surgical masks. There were not enough doctors and nurses to treat the ill and it was reported that the morgues were packed almost to the ceiling with bodies stacked one on top of another.

The have been two other influenza pandemics in the 20th century, each occurring when a different HA subtype developed the ability to infect humans and spread between them. The 1918 influenza was caused by the H1 subtype (H1N1) and subsequent pandemics were caused in 1957 by the H2 subtype (H2N2) and in 1968 by the H3 subtype (H3N2). However, neither the 1957 nor the 1968 pandemics reached the same level of devastation as the 1918 Spanish flu.