Ok, I know, another fan theory, but I have some information to back it up. In a Game informer podcast with Neil Druckmann and Bruce Straley, the Creative Director and Game Director for Uncharted 4, Neil accidentally told important information when being asked about the fact that there is a Character in The Last Of Us named Sam, and there is also Sam Drake in Uncharted 4. They were asked about naming two characters in different games the same name, and they weren't aware that they did that which is understandable as Sam is a pretty common name.

Just look up Game informer special edition podcast and it will come up.

The part that was very interesting w. Then the conversation quickly mas that at about the 7:50-8:20 mark, the interviewer asked about Sam Drake in Uncharted 4 and Sam in The Last Of Us and if it is just a coincidence, they both didn't know they named them the same and Neil Druckmann responded by saying" I guess they both get bitten by...and turn". They then move on as it seems they all know they just released a huge spoiler.

I'm not saying anything in particular, but with the Uncharted series being know to have mystical themes in the games and Uncharted 4 being based on pirate treasure, based on this quote, I think it is possible that there are some kind of un-dead pirates or pirate zombies as the mystical enemy that is usually towards the end of the Uncharteds. This also suggests that Sam Drake may die and somehow "turn" as in become a zombie per-say and Nathan Drake may have to kill him or whatever the outcome.

I know this is a little far fetched, but you have to think something is based on this quote, unless it was completely false and said on purpose.

Let me know what you think about this slip up.

Nah man

@jeffgoldblum: I know I was very doubtful, its just weird that he said it.

I wouldn't read too much into it. Game devs often seem to drop 'spoilers' during interviews. It's good press. Makes for excellent Internet headlines: "Uncharted Dev Drops Huge Spoiler!!"

Uncharted 4 starts in November of 2013 which is a couple months after the(September) spore outbreak in Last of Us is supposed to have happen. So if both games were that seriously connected then the outbreak would have already happened months ago.

Seems thin. ....Also, nobody cares about the Sams in these games.

@neocalypso: I don't think the games are at all connected, it was just that when hearing both names Neil Druckmann made the connection and said what he said.