I would enjoy a disease mechanic in the game. I remember that was speculated with the Rise and Fall announcement, but we didn't end up getting it.
It could be tied in to a game event/decision system, where you get a number of sequential events in consecutive turns. Also, buildings like Sewers could increase resistance to diseases, until eventually you reach a point where something like covid is considered a major threat to public health rather than unnoticeable in between the plague, smallpox, cholera and you name it. And at that point you could have tradeoffs not between population dying and closing up, but rather mass unhappiness or closing up.