The Knoxville Cough, also known as the Two Day Flu, the Sickness, the Asian Cough, and the Death Flu, among other names, is a virulent H5N1 strain of the avian influenza which emerged in 2021. It received its namesake from Knoxville, Tennessee where the disease was suspected to originate. In addition, as the flu spread across the United States, the federal Centers for Disease Control and Prevention (CDC) issued a no-travel warning for Minnesota and Ohio as cases of the influenza were identified in St. Paul and Akron, with travel already restricted due to martial law already imposed in most of the Eastern United States. The Knoxville Cough caused more than 100,000 deaths worldwide by July 2021 and was officially labeled a pandemic by the World Health Organization.
Around this time, a governmental emergency broadcast stated that this national flu epidemic was in progress in all fifty states of America, and announced that although the U.S. government was attempting to develop a vaccine, the safest precaution for Americans was to stay indoors and avoid public meeting areas, and that hospitals were overloaded with flu cases, thus unable to accept more patients; the broadcast also mentioned dusk to dawn curfews for Albany, Elizabeth, Jersey City, Newark, New York, and White Plains.
By August 2022, the Knoxville Cough had ravaged various countries, with the United States particularly hard-hit (as its crumbling infrastructure and the high price of petroleum made the distribution of aid materials difficult and in some cases impossible), and by this point had killed six million Americans and in total at least eighteen million people around the world, though likely more, and was one of the factors sealing America's decline. At this point, though peak H5N1 activity had likely passed for most of the world, the virus still circulated in some regions into 2023. Furthermore, Mexico closed its borders to the U.S. to prevent the Knoxville Cough from coming into its country, although with promises to continue to provide material assistance. The President of the United States in his farewell address in 2025, shortly after the detonation of the GKR EMP blast across America, describes the Cough as "the most vicious pandemic in human history".
According to Homefront: The Voice of Freedom, it is briefly mentioned that there were rumors it was caused by an "engineered virus from an unfriendly nation", but such rumors were never actually proven.