The default wait_timeout on the mySQL is 300 seconds. 
Any idle connection is closed automatically after the wait_timeout is reached. 
The ES had been idle for more than 300 seconds. 

A webservice was then invoked and encountered an error.  

The console.log displayed the following errors on the XA:

220914 10152296 68733 ESDEMO64 CASXO0023S Severe error detected in odbc XA interface, RM interface disabled 10:15:22
220914 10152296 68733 ESDEMO64 CASXO0010S Resource Manager for resource odbc Commit failed: reason -00003 XID: MF_CAS MCASESDEMO64 0000000170006168900001000000012 00001 10:15:22

The ES region needed to be re-started to be able to connect again to MySQL.

Full article: https://portal.microfocus.com/s/article/KM000011982