If you're truly taking the time to install the 32-bit version of Office 365 on the machine (you have to take special steps to do so; it is no longer the default), it sounds like you might be running Sage 50 as Administrator and have a security mismatch.  Try the steps in the article Error: "No email program or default profile could be found. For more information or to configure Webmail in Sage 50, select Email Setup from the Maintain Menu." , in particular, options IV and V. 

I was checking with some colleagues and they mentioned that this is a particular issue in Version 2002, Build 20194 of Office. (My screenshot is just an example of where to find the information). If you have that particular build, update Office again to resolve the issue. 

We have the same issue here - user can send just one PO then errors out with the same error.  Only change to the PC is an Outlook update recently. Will be trying John Parr's suggestion to update Outlook again.

This is typically a problem in the Outlook service itself, unfortunately. They have broken it at least three times in the past year (this confirmed build and I know of two others in 2019)

Updating Outlook past version 20194 resolved our issue, thank you!

Excellent, great to hear!