I think I resolved the issue for now. I was using the HDMI cable on both monitors, switched to DP on both and now I can't replicate the issue, so I guess that is the good news for now. 
I have a work laptop (Latitude 5520) that connects with WD22TB4. I got 2 external monitors connected, S2721DGF and S2721QS and Laptop display is the primary display. When all monitors are ON, everything works great. If I turn off S2721QS, then S2721DGF starts flickering and colors are washed out. Only solution that works is reboot the laptop. So, this is an issue #1. Issue #2 is, If I have both monitors OFF and use laptop display only with dock still connected, S2721DGF is still used as an extended display by the dock. I have to change the display settings to "Extend this display" to be able to use the laptop display only.  Any help/recommendation in resolving these 2 issues. Thanks. 
Latitude 5520 with WD22TB4