I believe this poem is in fact about his marriage to his wife Virgina, and her untimely death of tuberculosis. Poe is used to people always leaving. His mother died and his father left them, his friends mother died (who was his first crush), his steady girlfriend whom he planned on marrying left him to marry an older rich man, and he never truly felt accepted or loved. It has been said that Poe and Virginia never had intercourse because Poe didn't actually love her in that way but wanted to be with two family members whom he felt could love him as a family. Had he not married her, she would have been sent to live with other family. He did not want to be lonely anymore, and may have married partially for those purposes. The setting is romantic, but the theme is that often in life a person comes across another whom he cannot forget when they die. This poem is about Virginia, but also about all of the others who have left him in his life, and he had finally come to a breaking point.