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Influenza vaccines have been in use for more than 60 years. One of the earliest clinical trials of influenza vaccine efficacy was conducted in United States Army personnel in 1943. Approximately 11,000 unvaccinated young men received a flu shot that had one strain of both influenza type A and type B. The study's endpoint – the development of a febrile illness – showed that 7.1% of unvaccianted recruits developed a fever vs. only 2.2% of the vaccinated became sick. This early study assumed the fever was caused by influenza viruses and if they didn't get sick, the success could be attributed to a flu shot.
The problem with this 'end point' is that many different viruses and bacteria can cause febrile illness, often referred to as influenza-like illness (ILI). For example, there are at least 52 immunologically distinct adenoviruses (different types) that can cause human illness. According to the Centers for Disease (CDC), there are about 30 strains of coronaviruses. Seven strains are known to infect humans and most commonly cause upper respiratory tract illness (a cold) or flu-like illness....