We have sexually transmitted diseases so why can't we have sexually transmitted immunity? What if there's a disease that is systematically working its way through the population, only a handful of people are immune or develop immunity after surviving the infection, and one of the ways to spread the immunity is through sexual contact? Which cultures/societies would be OK with this and which would die out due to social/moral taboos?
Lots of stories are about surviving the apocalypse because the MC (main character) is "special" - immune, magical, tougher than everyone else, etc. What if you survived because you were home bound for some reason - broken leg, anxiety, severe allergies, that kind of thing? What would it be like to be a survivor not because you know how to deal with hardship or have some cool magic but because you had panic attacks the prevented you from leaving the house, thus keeping you from being infected? How long would you last once you had to leave the house due to lack of food and water?
Is it even possible to avoid infection? What is the latency? How long can the virus (or whatever) live in the air or on surfaces? If you were home bound doing online grocery would it be possible to get the plague from the boxes/bags the groceries come in?
Most of what goes wrong in post-apocalyptic fiction is due to the break-down in society - no electricity, no gas, no communications, no food production, no shipping, etc. What if the population dropped dramatically but the majority was at the extremes? People younger than X and older than Y. Would we have the same breakdown? If you lose 50% of the current population but the 50% that survive are between say 25 and 50 years old and spread evenly socioeconomically what kind of world would we be looking at? Does it matter where the survivors are (Industrialized countries vs third world)?
What kind of governments would emerge after the plague is over? Theocracy? Autocracy? Dictatorships? Would we still have a democracy in the US?
Say the virus, plague, whatever, isn't gone - it could mutate and another wave could come at any time. What kind of restrictions would governments put on their people around movement, travel, gatherings? Would it be real safety or security theater? What about in less populated, more lawless areas? How long would we as a society have to go without another outbreak before the restrictions would be relaxed? Removed?