Warning! The following contains spoilers for Supergirl's midseason premiere. Read at your own risk!
Things were getting tense for Supergirl's D.E.O. as its agents tried their best to protect Kara's otherworldly identity from the increasingly aggressive Colonel Haley. Their efforts couldn't thwart disaster though, and slowly but surely, Haley started figuring out that Supergirl was none other than Kara Danvers. Things escalated to the point where Alex was left with no choice but to erase some of her Kara-related memories, along with the rest of the D.E.O. And things could get even worse for Alex.
To recap how the midseason premiere "Suspicious Minds" led to this outcome, Alex initially thought she had Haley on the ropes when she learned of the Colonel's aggressive tactics to hurt aliens in the D.E.O.'s custody. Unfortunately, the non-powered Danvers sister underestimated the Colonel's response to perceived threats, and she was thus thrown off when Haley turned the tables and threatened to out Alex as a traitor who'd choose to protect her sister over national security.
Haley had all the cards and, despite being saved by Kara from almost certain death, she still decided to take her big shot. She told Kara her civilian life was over, and that Supergirl was now property of the D.E.O. and under new command.
A stunned Kara could only sit there after that terrible decision was made, but Alex sprang into action and knocked Haley unconscious. The siblings then called up J'onn, and one quick mind wipe later, Haley was back at work and completely unaware of Supergirl's identity.
Though her memory was wiped, Haley's resolve remained fixated on discovering Supergirl's identity and brought in another alien capable of forcing the truth from the D.E.O. agents. J'onn, Alex, and others aware of Kara's identity collectively agreed to have their minds wiped. It was against Kara's wishes, but Alex knew her sister's safety came before all else. It appears now that decision may come back to bite Alex, as the next episode's trailer shows things don't go as planned.
Obviously, erasing Alex's memories of Kara as Supergirl may have been a bit trickier than it was to alter everyone else's. J'onn may have gone far deeper into Alex's memories than intended, erasing any knowledge that could even potentially lead her to believe Kara is Supergirl. Taking out that particular set of memories may have fundamentally changed her, or at least who she became after years of being in Kara's inner circle.
What's worse, Alex seems to know something is wrong, which may make it harder for Kara to handle everything. Alex assured Kara she was comfortable with the decision ahead of time, so perhaps she'll be able to find a way to deal with this new situation that doesn't throw things into further chaos. She will hopefully find a way to deal with Haley that allows J'onn to restore Alex's memories if he can. Along with everyone else's, maybe.
It's just another entry on Kara's list of problems, and let's not forget that Lex Luthor is on the horizon, and Kara's doppelgänger is being trained over in Russia. Alex's situation will likely just pull Kara's attention in one direction, keeping her distracted while other forces work against National City. Kara has seen some tough situations in past seasons, but it's looking like Supergirl is setting the stage for perhaps the sisters' biggest challenge to date.