We are seeing this as well with a client recently updated to Sage 50 2021.  We use the COM interface and the partner Username/Password used for years is being refused.  It may be possible that the Client denied access when asked the permit question

Anyone know how to reset this to allow our interface application access?

If they answered no and clicked remember this option you can try Options→Global→General Tab. In this screen click on the RESET button for the option "Reset all one-time messages" and click OK.   Close and reopen Sage. Then run your program and ask for permission.