For Flu, First Time’s The Charm!
The influenza pandemic of 1918–1919 killed somewhere between 20 and 40 million people — which is more than World War I (WWI). It has been cited as the most devastating epidemic in history. More people died of influenza in a single year than in four years of the Black Death bubonic plague, and this flu pandemic killed more people in 24 weeks than HIV/AIDS has killed in 24 years. Indeed, this is the exact same virus that some people consider “just a cold.”
Why it killed so many young people remains a mystery. Almost half of the casualties were adults aged 20 to 40. Why was this particular strain of flu so deadly to this particular group? Previous research concluded that the virus killed through a cytokine storm (overreaction of the body’s immune system). The uncontrolled and exaggerated immune response caused severe and extensive damage to the body, while the weaker immune systems of children and older adults resulted in fewer deaths. More recent research concluded that people born after 1889 never encountered a strain similar to the 1918 flu, leaving them vulnerable.
A newer study published in Science looked into two types of recent avian flu, H5N1 and H7N9. The research team analyzed the number of people who got sick or died because of H5N1 and H7N9 in 6 countries with outbreaks between 1997 to 2015. H5N1 and H7N9 have already caused hundreds of cases of severe illness or death in humans. Both strains are of global concern because at some point they may gain mutations that will allow them to not only jump from birds into humans, but also spread rapidly between humans. The study showed that people born before 1968 were exposed to flu viruses — H1 or H2 — as children. In later life they rarely fell ill from another flu virus — H5N1 bird flu, but they still died from a different one — H7N9. Those born in and after 1968 were disproportionately affected by H5N1.
So what happened in 1968? Influenza is unique because it comes in many different types and strains — Influenza A, B, C and more recently D; A can be HxNx and for B there is the Yamagata lineage, which is different from the Victoria lineage. In 1968, the dominant type of flu switched from H1N1 to H3N2. Those born before 1968 were likely first exposed to a flu virus that belonged to a group of viruses (called “group 1”), while those born after 1968 were most probably first exposed to a second group of flu viruses (“group 2”). These findings support the previous study that the unusually high mortality in young adults during the 1918 H1N1 (group 1) pandemic may have happened because of a mismatched H3 (group 2) in those born between ~1880 and 1900. The same cohort was strongly affected during the (group 1) 1957 pandemic, but they were not strongly affected when they were even older during the (group 2) 1968 pandemic.
These patterns around bird flu as well as the Spanish flu highlight the importance of understanding not only the biology of the virus, but also the group of people it affects and the interaction between viruses and humans. Although the influenza we know now is not as scary as the 1918 flu, we should not become complacent.
Influenza viruses can be deadly when they meet the “right host”. The bottom line is that exposure to a certain human flu virus as a child could protect you from an only somewhat related flu virus or predict how susceptible people are to future strains, which could inform vaccination strategies and pandemic prevention and preparedness.
