Well for starters Kizer is 6'5" and weighs over 210 pounds. He's got a cannon and was a top 15 recruit who was offered by tons of teams, including from what I can tell Bama, LSU, Michigan State. Is he human? Yes. But this isn't like a few years ago when we played a converted linebacker playing QB for Maryland. Kizer is a very good player and if we let them get into 3rd and short situations, he will convert those with his legs and keep drives going.
The guy he's throwing to is also a 100% stud and a straight burner. It will be tough for our secondary to prevent him from getting wide open downfield and I would assume Kizer will constantly test us by going long to Fuller. He will get over 100 yards against us and he will score at least one, likely more, touchdowns. Our secondary has to step up or he will single handedly beat us.
It won't take much to get someone going behind Notre Dame's line. Prosise would be an absolute stud at AB. He's shown he can handle a moderate workload and bust big runs where needed. DL is going to have a tough job at the LOS to keep him from making plays.
In short - any huge advantage gained by ND losing its starters is offset by both their replacements and the guys around them.