The opening montage showing everyone celebrating the end of coronavirus features a Zoom building getting destroyed by rioters.
Jimmy has become a famous comedian known for performing "non offensive comedy", which is shown to be uninspired jokes, only the punchline is now replaced with sappy compliments.
Just the fact that in the future, the doorbells sing.
Stan runs into a fat guy with brown hair. We're led to believe that this is adult Cartman, but it's actualy Clyde, the guy who was named as the second fattest kid in their class and implied (by Abraham Lincoln in "The List") to be the type that would coast by on his looks before crashing as soon as he hit 40.
Clyde still doesn't trust the vaccine because he has a shellfish allergy and is paranoid that one of the scientists who developed the vaccine might have eaten some before distributing it. Everyone points out that he's being shellfish. Later on, he shows his hypocrisy by agreeing to snort cocaine with Wendy, only to draw the line (pun intended) when he suspects that she was trying to give him powdered vaccine because he doesn't want to put chemicals into his body.
Cartman converting to Judaism... and playing up his enthusiasm to insane degrees. He can't even have sex without reminding everyone that he's Jewish.
Cartman's kids grow to hate Kyle because he can't keep his resentment of Cartman from blowing in their direction.
Cartman's wife is called Yentl. Remember, Matt and Trey absolutely loathe Barbara Streisand.
For all of the Character Shilling Kenny got as an adult, he's never given a chance to speak outside of two lines that are muffled by a respirator mask.
Despite becoming a renowned scientist and multi-millionaire, Kenny never really left his upbringing behind. A few old posters from his childhood home can be seen taped up around his lab, including a woman in a bikini, and he walks around in public dressed as if he was homeless.
In addition to keeping him The Unintelligible, he's also The Faceless thanks to his large hat, sunglasses and giant blond beard with gray patches. It's almost like Kenny has a pathological need to keep his face hidden!
Stan's downward spiral may be depressing, but it's still pretty funny when he uses a variation of his dad's famous "It's called [X] and it's classy" line without even realizing it.
Stan: It's not "pounding beer and wine." I drop wine shots into the beer. It's called a "smorgasvein" and it's very cultural!
South Park is forced into quarantine thanks to Clyde being an anti-vaxx moron, which means everyone who isn't a resident has to stay in a makeshift shelter until further notice. And where did the government choose set up this shelter? Why, in the elementary school, of course.
Pictured above, during "Share Time", Mr. Garrison has something he'd like to say:
Mr. Garrison: I'd like to share my dick in your mouth.
Randy's brilliant plan to break out of Shady Acres was just restraining one of the doctors so that Stan could kick him in the nuts.
Several people wear a big wool hat/hood as part of their occupation's dress code, no matter if they're a musical performer, physician, or restaurant waiter. Just like the live action footage of the geisha, it is never explained why they have to wear them.
The mere fact that if the viewer owns an Alexa device, Stan can and will set it off while talking to his. For example, Stan asks Alexa for the nearest liquor store, your Alexa may tell you the nearest one to you. Trey Parker and Matt Stone more than likely knew what they were doing.
When news gets out that there's a single unvaccinated person in South Park, the town flies off the handle in an imitation of 2020's big societal meltdown, complete with a stampede of idiots rushing to buy tissue paper for no real reason.
The military refuses to tell who the person is. Why? Because it's "The Future" and society can't single out people for their personal beliefs, even when it's a life or death matter. They can shoot a person to death if they get near the barricades, but can't reveal who the anti-vaxxer is because it will hurt their feelings.
