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Sunday’s match winner picked up an injury after his late strike against the Hammers and the manager says it could also rule him out of the Manchester derby this weekend.
There is a mixture of youth and experience in the squad that travelled to the Ukraine and Silva’s absence could well pave the way for Phil Foden’s second appearance, with Guardiola admitting the youngster is in contention to play.
Quizzed on the strength of the travelling party, the Catalan explained: "Kevin [De Bruyne] was suspended and Silva has a little problem.
“I don’t know whether he will recover for Sunday.
“He felt something uncomfortable after the goal. Hopefully he can play on Sunday."
“Phil Foden is here. He has the same chance to play. We are so proud that he is here with us and, if he plays, hopefully he will do OK."
City head into the game on a 20-match winning run and with top spot in Group F already secured.
And while a trip to Old Trafford follows Wednesday evening’s encounter at the Metalist Stadium, Guardiola insists his side are focused only on what’s in front of them.
"We just play to win the game,” he declared.
“I assure you, sooner or later we will lose, but the next day we will recover.
“I can promise you, we are going to try to win the game."
City’s impressive current form has led many to talk of celebrations in May, but Guardiola again reiterated that the present does not guarantee success at the end of the season.
His side will give their all to reach the final, he says, and that includes against a Shakhtar side who he believes will pose another tough challenge.
"We are playing well but it does not mean we will go on to win the competition. We will try to be there [in Kiev].
“I was impressed [at the Etihad]. We are happy to be in the last 16 already but it is going to be a tough game. They make a perfect defensive structure.
“We travel to Ukraine to win the game. I assure you, we are going to prepare mentally to win."
Your Tuesday media round-up!
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