The situation of The Sentinels. All of them have been stuck in the City of the Sun God for millennia, making sure that Akhenaten does not wake and leave the Black Pyramid. Their father, the one that did this to them is their only link to the outside world and he cannot undo what he has done.
It is particularly sad for Moutemouia, who had children of her own before she was sacrificed to become a Sentinel. Over the centuries her youngest sibling Houy became the only thing that was keeping her from just...letting go.
The worst thing of all is according to the Buzzing all this sacrifice was in vain and eventually Akhenaten would break free.
The revelations in issue 5, pretty much all the survivors on Solomon Island are infected by the Filth and will eventually succumb to it. The saddest thing is, there is nothing that can be done to stop it.
What happened to Sarah between the tutorial and Issue 9. Forced to relive the same day over and over and having thousands of strangers psychically shoved into her head. Once again, nothing can be done to stop it: Sarah has to stay down in the subways and allow new players to replay her memories, because its the only way they'll be prepared to face the Filth. Watching her trying to keep a grip on her sanity is honestly painful to watch, especially as it becomes clear that the process of being forced to replay her memories of the Tokyo incident is actually destroying her mind: the mission "Pieces of Sarah" reveals that her memories of her time before Tokyo are being eaten away and she's been forced to commit them to paper before she forgets them. And it's not working: several notes feature her losing a memory even as she tries to write about it, at one point reverting back to her mantra of "My name is Sarah and I'm still on this planet"... only to realize that she doesn't know where she is or who she is anymore.
Much of her dialogue during her second mission is angry - either at the Filth or at the players - but she just sounds so sad and defeated when she says the following:
Sarah: Wish you could have met me the way that I was...