A repeat of the Spanish flu would be one thing, and honestly I don't know how likely it is. Unlikely but hugely destructive would be one way to say it -- I also

A repeat of the Spanish flu would be one thing, and honestly I don't know how likely it is. Unlikely but hugely destructive would be one way to say it -- I also doubt there would be another potential candidate, because the only way for new super destructive diseases that don't burn themselves out before they spread would be to create the kind of European medieval city that for centuries killed more people than were born there and which was full of filth.