They never said. They did say that Opie was old enough to remember her. I think the only mention of her actual death by Aunt Bea was that angels came down and carried her away to Heaven. She just wasn't comedy material, and so it was ignored, like Barney's reference to being Andy's cousin. In later episodes they were just childhood friends.
But, if I am wrong, I would like to know, too. I thought that Opie should have come back in his 30s and become the sheriff in a new Mayberry show, while the older characters were still available. After all, what else was he doing after Happy Days but directing movies I didn't care for?
Other people asked questions on various topics, and are still waiting for answer. Would be great if you can take a sec and answer them