Is it possible that application can lose I/O connection to a file?

I have a C application. Which creates a connection to file at startup and it continuously runs for many days.

I am only connecting one time . and not reconnecting it in code. Only checking if

if(NULL == file)

Is there can be case that my application lose I/O connection of that file handler ?

if yes. Is there a way , How can I create test case for it ?