Indeed it could be that %windir%\explorer.exe is set to Isolated application.
This could happen when the user launch a new unknown application( described as 'could not be recognized' in security considerations) and get a "Run an executable" alert with explorer.exe on the left (parent application).
In many cases it is actually explorer.exe that lauch apps (parent application) so setting Treat as "Isolated application" will actually block many applications.
In case "Remember my answer" was not checked the changes will not remain after a reboot (alerts not marked to be remembered will be enforced until the corresponding application is terminated, thus for explorer.exe the alert is enforced during the entire session) and the %windir%\explorer.exe policy will not be changed.

If "Remember my answer" was checked then %windir%\explorer.exe policy will be changed accordingly and will be enforced even after a reboot.
COMODO - Proactive Security configuration will trigger likely trigger such alerts because explorer is either set to "Trusted Application" or Custom Policy but changing %windir%\explorer.exe to "Windows System Application" (default configuration for COMODO - Firewall Security, COMODO - Antivirus Security and COMODO - Internet Security) will allow explorer to execute any application (safelisted or not) without alerts
This change will not affect applications other than explorer and thus when some other app try to launch something unknown there will be an alert (thus it will be possible to catch if some other application attempt to launch something suspicious).