COVID-19 has disrupted everyday life worldwide and is the first disease event since the 1918 H1N1 Spanish influenza (flu) pandemic to demand an urgent global healthcare response. There has been much debate on whether the damage of COVID-19 is due predominantly to the pathogen itself or our response to it. We compare SARS-CoV-2 against three other major pandemics (1347 Black Death, 1520's new world smallpox outbreaks, and 1918 Spanish Flu pandemic) over the course of 700 years to unearth similarities and differences in pathogen, social and medical context, human response and behavior, and long-term social and economic impact that should be used to shape COVID-19 decision-making. We conclude that <100 years ago, pandemic disease events were s...