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You are asking me to prove a negative, that is impossible. I'll just say that since calibre-debug and calibre run the exact same code, the only difference being that calibre-debug adds some extra print statements, that your antivirus program claims that one modifies the registry and the other doesn't, strains credulity, to put it mildly.
Antivirus programs are giant steaming piles of ...
I have no idea why comodo says what it says. I wouldn't be surprised if the idiotic antivirus program tries to modify the registry itself and gets confused.
In any case, you have three options
1) Get a better antivirus program, or even better, stop using antivirus at all, since the entire category of software is just a giant snake oil bottle.
2) Exclude calibre.exe from your antivirus
3) Keep using calibre-debug.exe and hope and pray that your antivirus does not suddently decide to start quarantining it.
I am not going to spend any more of my time trying to debug problems caused by antivirus software
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