Warning: SPOILERS for Midnight Mass.
One of Midnight Mass’ first twists reveals Monsignor Pruitt has turned into a vampire, but who was it that first killed him and caused the transformation? Mike Flanagan’s religious horror series follows his notable Haunting of Hill House and Bly Manor shows on Netflix, this time substituting a haunted house for vampires. Midnight Mass explores the life of a small community on a remote island, revealing the societal hypocrisies, struggles, and religious fanaticism that coincide with the supernatural in Crockett’s town.
The most curious figure in Midnight Mass is Father Paul, the new priest who turns out to not only be the town’s de-aged Monsignor John Pruitt, but a vampire. When on his religious journey, John comes face-to-face with a vampire, which he calls an “angel,” that makes John drink his blood, de-aging him by about 30-40 years. As he works with the vampire on Crockett, it’s revealed John has continued to drink the vampire’s blood and give it to his daily parishioners, allowing the supernatural blood to work miracles on the Midnight Mass characters' bodies. Aside from John’s sudden youth, the blood causes Leeza to regain the ability to walk, Mildred to grow young as well, Annie’s vision is restored, Ed’s body feels more youthful, and Erin sadly loses her baby.
While John had been ingesting the vampire’s blood for some time, he hadn’t actually died to complete his vampiric transformation until halfway through the series. After Joe Collie’s dog Pike had suddenly died from vomiting blood and foaming at the mouth during Midnight Mass' Crock Pot Luck, Pruitt returned home late one night with the same reaction. Bev, Wade, and Sturge are all around to see his convulsions and sudden death, with Wade even confirming that he had no pulse. Moments later, Pruitt miraculously awakes, though he now isn’t a human like before. Flanagan's horror series didn’t explicitly reveal who killed John, though it was implied he was killed by the 1080 poison kept in the church’s pantry, which was what killed the dog. Bev Keane seemed to be in charge of the poison, taking the blame for putting it around town and implying she used it to kill the dog (though she denies this), so Bev seems to be the culprit for killing John and propelling his vampiric resurrection.
Bev held high regard for Monsignor Pruitt as a miracle from God, returning with his youth and bringing blood to give such miracles to the other parishioners. Her intent to poison and kill him wasn't malicious, it was her way of progressing the miracles by God in the town that would have to begin with John. Since he was resurrected, it was clear that drinking vampire blood worked for bringing him back to life, but it also gave him a thirst for human blood. Flanagan adapts Midnight Mass' Bev in a way that she doesn’t really have any compassion for other people in town, no matter how much she professes it through her piety, so killing John in order to see God’s miracle isn’t something that would be put past her. The realization that Bev was the one to originally kill John is also supported by her being the one to put the 1080 poison back into the church’s closet after he dies.
It’s also possible, though less likely, that Monsignor Pruitt poisoned himself. This wouldn’t have been as a purposeful suicide, but just to make sure that the transformation could actually work and give eternal life. He reveals later that the only reason he brought Midnight Mass' vampire back to Crockett was so he could use the blood to keep Sarah and Mildred alive, fearing their deaths. In order to use the blood on them, he would want to test it out on himself first. Since John is quite shaken by the event, even though he accepts his vampiric resurrection, it seems more likely that the Midnight Mass character who poisoned him was Bev.