Could Agents of SHIELD be setting up Melinda May as the new vessel for Izel? The mythological being known as Izel acted as Agents of SHIELD's arch antagonist in season 6 and was responsible for creating the devilish flying beasts known as the Shrike. Izel's true intention was reaching Earth and using the Monoliths to open up a rift into her home dimension, allowing those who dwelt there to invade and experience true sensation for the first time. The Shrike were vital in this plot, as the creatures infested human bodies and turned their hosts into Izel's slaves. Ultimately, Melinda May appeared to take down Izel with a special sword in Agents of SHIELD's season 6 finale, despite suffering a fatal wound of her own.
As Agents of SHIELD season 7 begins, the team have followed Earth's latest potential invaders, the robotic Chronicoms, to 1931 New York. With an LMD Coulson in tow, the group eventually figure out that the androids plan to prevent the creation of HYDRA, thereby stopping the birth of SHIELD and leaving Earth ripe for the taking in the future. While all this is going on, Agent May is still recovering from her battle with Izel, and is expected to make a full recovery, but the premiere's final sting takes a different direction. Enoch, SHIELD's resident friendly Chronicom, walks into the Zephyr to find Agent May has escaped from her chamber, and the camera pans up to see a rabid-looking May clinging to the ceiling.
On one hand, it's possible that May is simply traumatized by her experience in the Fear Dimension and didn't recognize Enoch or her surroundings, clambering up into the rafters instinctively. But May looks far from herself in this scene, and the cold glare she gives to the camera doesn't seem characteristic of the May Agents of SHIELD fans know and love. Izel's most troublesome ability was possession of others - a ploy that wreaked havoc among the SHIELD team and cost the lives of several red-shirts along the way. Since May stabbed Izel from behind, it's assumed the villain didn't have time to use this technique. Additionally, May manages to throw the sword to Mack before collapsing and the Shrike swiftly die, suggesting Izel is gone for good. With May unconscious, however, there's no real way to confirm she's possession-free. Izel's transference power is rapid, and she could've made the switch on the verge of death, taking the closest vessel she could get to. The Shrike could've died simply because Izel was badly wounded.
Not only would this explain May's double-quick healing and strange, icy glare in season 7's premiere episode, but Izel possessing May would also pay off a major Easter egg from Agents of SHIELD's 1930s setting. As the suited-up team exit the Zephyr and empty onto the streets of NYC, there are a pair of prominently placed movie posters - one for Dracula and one for The Phantom of the West. The former could be an allusion to the Shrike - bat-like creatures who drain their hosts in a similar fashion to the iconic vampire. Phantom of the West is about the titular "Phantom" murderer who may be one of 7 different people. This clue could hint towards one of the SHIELD group being a secret villain themselves.
Agents of SHIELD has a track record of bringing back past villains, so Izel's survival certainly isn't out of the question. It's also hard to imagine Agent May getting a happy ending after such a tragic series-long character arc that has seen a string of romantic relationships come to a deadly conclusion. This would suggest an emotional, possibly even sacrificial end to May's Agents of SHIELD story, and even if that doesn't involve possession at the hands of Izel, there's certainly something wrong with The Cavalry in season 7.
Agents of SHIELD season 7 continues with "Know Your Onions" June 3rd on ABC.