When an environment has Blue Prism Application Server(s) deployed, can Runtime Resources and Interactive Clients...

Yes it is potentially possible but this is not generally recommended. Devices connected directly to the database may be limited in terms of managing or leveraging Credentials.

No, all Runtime and Interactive Clients must be connected to the database via a Blue Prism Application Server

Yes, but Runtime Resources that are connected directly to the database cannot be instructed to start processes by the scheduler