England scrum-half Ben Youngs has been ruled out of the remainder of the NatWest 6 Nations by a ruptured knee ligament.
Youngs sustained the damage to his medial collateral ligament nine minutes into Sunday's 46-15 victory over Italy in Rome and, as he is expected to be out of action for four months, he is also a major doubt for the summer tour to South Africa.
Danny Care is set to start Saturday's showdown with Wales in his absence, with Richard Wigglesworth - called up by Eddie Jones earlier on Monday - poised to deputise.
It is also an important week for Nathan Hughes, who is to be assessed by medics to see whether he will play any role in this Six Nations.
His participation is threatened by a knee injury sustained in December, although the Fijian-born number eight was expected to be back for the latter rounds.
The absence of Billy Vunipola, who will sit out the entire Championship with his own knee problem, will mean Hughes' availability would be a substantial boost, even if Sam Simmonds demonstrated in Rome that he is an exciting alternative.
Care hopes Youngs' misfortune will enable him to become England's most capped scrum-half as a starter.
Care stepped off the bench to equal Matt Dawson's record of 77 Red Rose appearances in the number nine jersey and with Youngs stricken when his knee buckled awkwardly beneath him during a tackle, a place in the starting XV now awaits.
"You never want to see a bad injury like that and I was gutted to see Ben in so much pain," Care said.
"First thing's first, he's a good mate as well as a competitor for the shirt. He's in pain and all our thoughts are with him.
"Hopefully the scan will bring good news and all the boys are thinking of him.
"He was in the changing room after the game and was still in good spirits, we're just hoping it will be good news.