New virus/no Rx: The most serious epidemic was the 1918 epidemic, which killed 50-130 million people worldwide. Using the lower number in the estimate, that's 3% of the population. This kind of pandemic occurs when there's a big change (antigenic shift) in the flu virus, so that no one has partial immunity. Mortality was also high because we had no anti-flu drugs and no antibiotics to treat complications.
Answered 3/25/2023
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