In the times of GTK 3 or a X.Org session, Orca, the screen reader, could receive keyboard input basically however it liked.
Under GTK 4 and a Wayland session, Orca does not receive any keyboard input from GTK 4 apps, because GTK 4 is no longer using the legacy keyboard notification API, and is not running under X.Org.
As a result of that, no screen reader commands work in this context (user can not stop speech, can not access Orca settings, etc.). Probably the most annoying situation will occur in the terminal emulator, because the user can not use any screen reader commands to review the command input (so no word by word reading, no copying of only a part of the output, no reliable line by line review (scrolling the terminal view does not count as it is unreliable with a screen reader everywhere)).
There's actually a discussion about a XDG desktop portal, which, if implemented, would allow fixing the situation, see https://github.com/flatpak/xdg-desktop-portal/issues/1046.