It’s not so much that digests should or shouldn’t have a reply key (they shouldn’t, and don’t appear to) but rather the fact that Digests should be sending the right email headers to avoid triggering auto replies for out of office messages.
See Detecting Outlook autoreply/out-of-office emails - Stack Overflow et. al Google searches for things like “suppress auto response with mail headers”.
As an aside, it’s true, the digests DO seem to come from the notification email address which is the same as our incoming email POP3 account. That IS the right behavior, because users want to see the mail from the same address they’re familiar with and that they use to send email in to Discourse.
This same problem happened again yesterday due to people being away for the US Thanksgiving holiday (with a different domain and different Exchange server). Not cool; people are getting things like personal phone numbers and email addresses posted as topics.