According to the Compatibility matrix, K2 Five (5.3) was created and tested with .NET Core 2.1.7. K2 will support any later patch version than the tested patch version per release so anything that is .NET Core 2.1.x is supported.

Compatibility Matrix: 

https://help.nintex.com/en-US/platform/K2Support/ProductCompatibilityMatrix.htm#.NET_Core

Please do not remove .NET Core 2.1.x or replace it with .NET Core 6.0 on the server. 

We have no plans for removing .NET Core 2.1.X.

On our developerpcs we have K2 Five 5.3 installed and .NET Core 2.1.X, .NET Core 3.1.9, .NET Core 5 and .NET Core 6. Everything works as usual - i.e. no problems.

According to Microsoft alle these .NET Core versions should co-exist without any problems (as they don't "see" eachother)

Yes, as long as .net core 2.1.x is installed on the system then K2 should continue to function normally.