We don't even want to touch this dreadful thought with a six-foot pole. Haven't we seen enough death with George, Lexie, Mark, and Derek? But if Camilla Luddington stays as Jo, it'd be really weird if Jo just casually mentions her husband. Their relationship has been a crucial part of her growth, after all. Death, even a random one, would feel more on brand with the show's notoriety for emotional drama instead of a slow fade. Just as the series has repeated the tumor plotline, it could revive the lethal accident trope (think of Grey's many plane, bus, and car crashes).
There's also the dark possibility that Alex could kill himself. It's happened before on House, when the show wrote off Kal Penn's Dr. Kutner by having the physician end his life out of the blue. While Alex has dealt with hard situations before, we sincerely hope the writers don't go down this route.