Initially this looked like a dupe of Installed New Version - Now Duplicati Won't Run, but it isn’t.
Running on Windows 10, I have Duplicati running as a service. I used the automatic process to update from 220.127.116.11 to 18.104.22.168. After “Activating” the update, the web page could no longer connect to the server, and the tray icon had vanished.
Following the info in the thread linked above I found the newer version of the tray icon in C:\ProgramData\Duplicati\updates\22.214.171.124. I added that version to Windows startup, and noted that wheras the old version looked for the server on port 8200, this one uses 8300. That explains why the server couldn’t be found before.
So now the server can be found, but it’s a clean slate, as though it’s the first run. All my existing config, database, etc., has vanished.
I’ve seen this problem before after Windows updates, so I checked C:\windows\system32\config\systemprofile\AppData\Local\Duplicati, but everything is still there - so that isn’t the cause.
 This is REALLY confusing. I’ve been using Duplicati betas for a while, and the version in Program Files is from back in 2017. It surely isn’t considered sustainable to keep putting an ever-growing collection of new versions in ProgramData and leaving the Program Files version alone?