It's going to be about Space AIDS. How the council refuse to acknowledge it as a threat and in private refer to it as "the Turian disease".
Okay, in reality, it involves Cerberus, the off-the-rails org from the first one becoming much more of a serious threat. Amazon let slip a little more recently, it showed in the news room articles. Also, Shepard is MIA at the opening of the setting, but will likely still be the protagonist. Non-antagonistic Geth are also a possibility, as the retain individual free will (despite hive-related sapience level, no hive mind) and had a burgeoning religion shattered in pieces over Citadel station.