I was not going to suggest assembly. For control of the serial port it can be a DOS program like QBASIC. The commercial version of QBASIC would handle com port events in real time. I used it to parse a X.25 feed feed from a communications Satellite many years ago. The current version of VB should have the equivalent thing.
I am guessing here, but I think he wants a program to respond in real time. So it has to be event-driven, not just any sort of program to read data from the port. Of course, you can use port-polling, but that means the CPU will suffer a big performance hit. It may not mufti task well with port polling. Instead, it should be interrupt driven.
Maybe the OP will clarify.