It's quite impossible to know the answer. You could come to a ballpark by adding up deaths from known huge smallpox plagues but there are a number of agents suspected in the Black Death and it's even possible that there were a number operating at the same time (anthrax, plague, smallpox, possibly ebola, possibly something else.) then there is the Plague of Athens. What was that? Then there is a South America.

How do you come close to a reasonable number?