https://www.paho.org/en/who-we-are/history-paho/purple-death-great-flu-1918#:~:text=The%20United%20States%20lost%20675%2C000,but%20they%20were%20too%20late.

The United States lost 675,000 people to the Spanish flu in 1918-more casualties than World War I, World War II, the Korean War and the Vietnam War combined. Pharmaceutical companies worked around the clock to come up with a vaccine to fight the Spanish flu, but they were too late.

My guess would be the flu pandemic since "only" a little over 100k Americans died in WW1