I find that strange...
Antivirus programs and Trojans can cause really strange things to happen on Windows. The PixInsightUpdater.exe program runs with
elevated privileges. This can be detected by an antivirus or firewall application, and may trigger unusual background procedures on the folders where the updater has just changed data, which in turn can lead to file access problems when the core application is re-launched.
The whole virus-antivirus thing is a vicious circle without solution on Windows. Concentric layers of "protection" for an intrinsically insecure system. Compare it to the simplicity and efficiency of
setuid on UNIX/Linux.
Could it be that updates triggered from a second or third instance somehow mess up the configuration for other instances?
That cannot happen by design. If there are more than one running instances of the core application, the update process cannot run. Just launch two instances and select Resources > Updates > Check for Updates from any of them. On the other hand, configuration settings are completely isolated among instances; they cannot be merged, also by design.