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So, Cole can't go back to his own time, Ramse had a son in the future that won't exist if they stop the virus, and Cassie was sent to 2043 and was stuck there for 8 months, and came back a badass because she's been learning a thing or two from Deacon and the West Seven. All caught up? Good. So now she's come back to kill Jennifer Goines (who is planning on releasing the virus because she's been told to do so by the Army of the 12 Monkeys), and she believes that Cole is emotionally compromised because he's defending everyone Cassie thinks is a bad guy, including Ramse. But, Cole manages to get the virus from Jennifer by being nice to her.
The team then goes off and sets all the remaining vials of virus on fire. And as soon as they do, the timeline changes. (We know this because people get bloody noses when the timeline changes). It even changes in 2044 and Jones (since she's had her special time-travel friendly injections) can actually see the timeline change around her. It's Cole vs. Cassie again when she starts demanding Ramse give her answers about the larger plans of the Army of the 12 Monkeys (since he lived with them for years way back in Season 1), so she takes matters into her own hands and uses the tether meant to bring Cole home – on Ramse. The two of them go rocketing into the future, leaving Cole to deal with Jennifer.
Back to 2044. Turns out that in the timeline change thanks to the virus being destroyed, the plague still happened – but to a lesser degree AND it happened later. Hundreds of thousands of people were saved, but the question remains, "Where were The Messengers going?" (You remember the Messengers? The creepy people that hijacked the facility and took the time machine back to parts unknown last episode?) Everyone thinks Ramse has those answers because of his connection with the Army of the 12 Monkeys, so Deacon waterboards him to try and get him to talk. Ramse instead freaks Deacon out by telling him about the past. Turns out, when Ramse was back in the past he looked up Deacon and called the cops on Deacon's dad when he was a child and saved his life.
Meanwhile, Jennifer Goines suddenly knows a lot more than she used to. She tells Cole that she DID change in the time jump, but not in the way he thinks. Obsessed with prime numbers, Cole gets her to a pay-by-the hour motel. And…they've been recognized. She wants Room 607, but they go to room 210. Jennifer starts going nuts. That's when the hotel manager shows up and takes them to a room that Cole apparently rented permanently in 1944 – room 607. Also, there's a picture of Cole and Cassie from 1944 in the room. WTF!?!? Cole learns that Jennifer was definitely told by someone that her purpose in life was to start the virus. He caringly, and kindly, tells her she just needs to get away from all this and find her real purpose.
Back in 2044, Jones explains the plot thus far to her team of scientists, explaining that they all have been living in an altered timeline she wasn't a part of. Oh, big news: Dr. Lasky is alive in this timeline! Jones learns she has a boyfriend she's never met: Dr. Eckland! Also? Cassie has a surprise for Ramse – his son. So it turns out, the timeline change allowed his son to be born after all (remember, kids, the virus STILL happened). But Cassie won't let Ramse see or talk to him until he gives her some answers about The Messengers. And Ramse still insists he knows nothing.
Also in 2044, Jones is kidnapped by The Daughters, who have an interest in James Cole. They want him back in 2044. They hand her a note of where and when to find James (Room 607 in 2016, to be precise). And then Cassie goes back to get Cole from the Emerson Hotel and hands him the note, which reads "I found my purpose." Well hot damn, 2044's Jennifer Goines, leader of the daughters, did Cole a solid.
Having been convinced that she needs Cole, Jones brings him back to 2044 (also the threats from the daughters helped). After learning that Cassie threatened to hurt Ramse's son and not believing it, Cole is asked by Katerina to continue the work everyone's been doing. Because now there's hope. Katerina asks if he's still with her and he says he is.
Dr. Eckland moves out of his room with Jones. He tells her that even though they don't know each other anymore, he's willing to slowly find his way back to where they were. Which is, wow, really sweet. So now Cole is headed back to 1944 with Cassie to figure out if The Messengers are there (given there's a picture of him and Cassie from 1944, its not a stretch to assume he needs to go there). And also to find out who took a groovy old timey photo of them, which Cole found in his 1944 hotel room. And…he's a little jealous about what's up with Cassie and Deacon being buddies.