Are you sure you don't have an audio loop somewhere which is then heard due to something getting unmuted when you close S1? I know my answer is a bit vague but, before I had the Studio 192, I had the 1818 and during the period whilst I was getting to know it and S1, I had the following. My V-Drums audio out phonos were wired in to 1818 inputs 5 & 6. I also had an output of the 1818 going back to the inputs of the V-Drums. This was so I could monitor S1 whilst sat at the drums with headphones. The issue was as soon as I activated record sometimes (which also activated the track's monitor), I would get a deafening burst of noise and it took me a while to work out and realise why. I have done away with the audio return to V-Drums now and just stretch my headphones over from the 192 headphone socket. So I am wondering if you have a wire routed somewhere, which you only hear the results of when you close S1, and therefore things get unmuted or enabled / disabled or re-initialised as S1 closes.
I would start by unplugging all inputs / outputs and add them back one at a time, testing it at every step.