Loose Ends Surrounding the Spanish Flu: Explaining the Extreme Mortality in Young Adults

Introduction and Objectives
In the century since the 1918 influenza pandemic, insights have been sought to explain the pandemic’s signature pattern of high death rates in young adults and low death rates in the elderly and infants. Our understanding of the origin and evolution of the pandemic has shifted considerably. We review evidence of the characteristic agerelated pattern of death during the 1918 pandemic relative to the “original antigenic sin” hypothesis. We analyze age-stratified mortality data from Copenhagen around 1918 to identify break points associated with unusual death risk.
Methods
We review clinical, epidemiological and phylogenetic evidence of the origin and evolution of the 1918 influenza pandemic. In addition, we looked at the death patterns
of different age cohorts in Copenhagen in 1918 and sought to place these patterns in the context of long time series of outpatient records of influenza-like illness. For this we used detailed, long time series of age-stratified monthly death records along with population census statistics searching for break points in the age profile of cases.
Results
Whereas infants had no meaningful risk elevation, death risk gradually increased, peaking for young adults 20–34 years of age before dropping sharply for adults ages 35–44 years, suggesting break points for birth cohorts around 1908 and 1878. Taken together with data from previous studies, there is strong evidence that those born before 1878 or after 1908 were not at increased risk of dying of 1918 pandemic influenza.
Conclusion
An increasing number of interdisciplinary studies covering fields such as virology, phylogenetics, death, and serology offer exciting insights into patterns and reasons for the unusual extreme 1918 pandemic mortality risk in young adults. Although the peak death risk during the 1918 pandemic coincided with the 1889–1892 pandemic, the 1908 and 1878 break points do not correspond with known pandemics.