Sourcing the 1918 Spanish Influenza Pandemic With a Walk Down Viral Memory Lane

Despite the name Spanish influenza, many believe that the origin of the 1918 pandemic came from a United States military base. Spreading like wildfire in the spring of 1918, it is estimated that the pandemic infected 500 million people or one-third of the United States population. The US Centers for Disease Control and Prevention (CDC) estimates that 50 million people died worldwide, including 675,000 in the United States alone. The 1918/1919 pandemic has been referred to as a more recent metric to highlight the power of pandemics and the likelihood that we are overdue for the next one.

For many, though, the origin of this pandemic and how it impacted its victims has been questionable. Investigators recently wrote in the Journal of Human Vaccines and Immunotherapeutics of possible European origin, noting that clinicians back then didn’t have the tools to really understand both the origin or how the virus claimed its victims. This was no easy task, and ultimately required a partnership between a virologist and a military historian.

The duo points to modern tools not available back then that allow us to look not only at the history, but also the virology—the field of gain-of-function and phylogenetics, which seeks to establish the evolutionary relationships and history between organisms, and, in this case, bacteria and viruses.

“We point to individual pathologists in the United States and in France, who strove to construct the first universal vaccines against influenza,” the pair writes. “Their efforts were not misdirected, because the ultimate cause of death in nearly all cases flowed from superinfections with respiratory bacteria.”

Influenza had been largely overlooked in the face of vaccines and disinfectants, but between 1915 and 1916, more than 30,000 US troops were admitted to hospitals suffering from the disease. Following this, investigators indicate that early papers in The Lancet in 1917 detailed a disease that caused a rapid progression from minor symptoms to death, which was likely due to a superinfection. Pointing to other articles, they note that, in the face of these high mortality rates, doctors were perplexed that there was little or no spread between individuals.

“When they looked back, in 1919, after clinically examining tens of thousands of cases, the Aldershot team emphasizes that ‘in essentials the influenza pneumococcal purulent bronchitis that we and others described in 1916 and 1917 is fundamentally the same condition as the influenza pneumonia of this present pandemic,’” the investigators wrote.

Imagine if we could look back, though, with the tools we have now and assess viral mutation and how these cases led to superinfections. Gain-of-function research has shown that it only takes 4 or 5 mutations in the HA gene to allow an influenza virus to spread between people. This provides insight into the possibility that the 1916 virus mutated to have a higher rate of infectivity over mortality.

What about influenza vaccine development during this time? Pathologists have been repeatedly found to have been investigating or emphasizing a need for a vaccine in the face of this “purulent bronchitis.” Efforts were underway though, whether it be from New York bacteriologist William Park or the Royal Army Medical Corps in London, the time of this great pandemic was not without desire to solve the crisis. With these findings, the investigators do highlight, though, the efforts put forth by pathologists and medical providers to help remedy the situation. Unfortunately, the research did not provide a large impact on reducing the spread of the virus, but it did indeed reduce mortality. The future likely holds more pandemics, but also tools to combat disease, and the truth is that we must use all the resources we possess to help prevent and better prepare for the next pandemic.