Khawaja dealt with back spasms during the series opener in Perth, batting at No.4 in the first innings, then wasn't required in the stunning day two run chase.
Stepping up in Khawaja's absence to open with debutant Jake Weatherald on Saturday, Travis Head pulled off an all-time Ashes knock in his first time batting at the top in a Test in Australia.
After Head's blazing 123, calls immediately came for him to move from No.5 to open regularly.
Josh Inglis has also thrust his name into the equation after cracking an unbeaten 125 off 107 balls as an opener to lead a Cricket Australia XI side to an eight-wicket victory over the England Lions in a four-day match at Lilac Hill.
Khawaja will be assessed further after returning home to Brisbane to work out if he is even able to play in the pink-ball Test at the Gabba.
When asked if the 38-year-old would definitely play, if he was fit, McDonald said on Monday: "I'm not sure where he's (Khawaja) at, medically.
"There was discussions around further investigation to whether it was more serious than what we first anticipated.
"We get to camp in six days time (in Brisbane) so it's a long way out, a lot of information to gather between now and then.
"Hopefully he's fit and available for selection."
Khawaja will turn 39 in December and is averaging 27.44 during the past two years.
Not only did Khawaja make just two runs when he eventually batted on day one, he dropped a regulation catch in slips during England's second innings that would have dismissed dangerous wicketkeeper Jamie Smith for a duck.
The 85-Test veteran left the field shortly after missing that chance and wasn't spotted for the rest of the match.
Cricket Australia chief executive Todd Greenberg was forced to defend Khawaja after he played golf in the three days leading into the series opener.
Khawaja didn't have an injury going into the game, but the left-hander started having back spasms only hours into day one.
"That back spasm took its toll in the first innings and got worse into day two, which is something that's pretty common," McDonald said.
"It's difficult once your back starts going into spasm to get it under control.
"Unfortunate for him, but it opened up the opportunity for Heady to go up there and do what he did, which was amazing."
Head opens in white-ball cricket, and has done the job in Tests in Asia, but Australia have been reluctant to use him there at home.
The classic knock, being hailed as one of the greatest in Ashes history, has given selectors plenty to think about.
Khawaja has gone through six different opening partners since David Warner retired from Test cricket in January 2024.
Star quick Josh Hazlewood appears no chance to play at the Gabba after missing the first Test with a hamstring injury.
Australia haven't provided an update on Hazlewood for more than a week, but McDonald denied the injury would be bad enough to sideline him for the whole series.
But captain Pat Cummins is making a compelling case to return for the second Test, starting on December 4.
Left-arm wizard Mitchell Starc starred with a 10-wicket haul in Perth, Brendan Doggett grabbed five scalps on debut, while Scott Boland starred in the second innings after struggling on day one.
"If you were to rush at something and lose Patty, because you're one-nil down, then makes the series a lot more difficult," McDonald said.
"One-nil up, if it had been one-nil down, then it would have been the same conversation."
Veteran spinner Nathan Lyon was required to bowl just two overs in Perth and could be left out of the pink-ball Test, which have been traditionally dominated by pace bowling.
"If you looked at Australian pink-ball cricket in general terms, the middle sessions have been quite benign, and Nathan's done a lot of work there," McDonald said.
"To jump to the conclusion that you would automatically assume that it's just going to be another bowler-dominated game, we can't make those assumptions."
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