Maro Itoje has conceded defeat in his battle to be fit for the climax to England's Guinness Six Nations against Scotland on Saturday.
Itoje last week suffered a setback in his recovery from the knee injury sustained against Ireland on the opening weekend of the tournament and has now been omitted from a 31-man training squad named for the final-round fixture at Twickenham.
"Maro's a class player, but his health comes first and that's the most important thing," said defence coach John Mitchell, who was unable to provide a date for his return.
Head coach Eddie Jones was non-committal when asked about Itoje's condition in the wake of Saturday's rout of Italy, declaring "we'll just wait and see", but the second row's Championship is now definitively over with only 53 minutes played.
It was hoped he would return to face the Azzurri only to re-injure the same knee that was damaged in Dublin when taking part in a forwards drill at the squad's Surrey base.
Bizarrely, Jones raised the prospect of the British and Irish Lion being propelled back into the matchday 23 against Italy soon after he had been left out, stating that he could make a rapid recovery.
While the loss of Itoje is a blow, England can at least take heart from the performance of George Kruis at Twickenham on Saturday.
Jones singled out Kruis as his man of the match on the grounds of his work-rate and the 29-year-old is set to continue his second row partnership with Joe Launchbury against the Scots.
Twenty-year-old Harlequins fly-half Marcus Smith has been called into England's training squad for the first time in this Six Nations in a snub to Danny Cipriani, who does not appear to be in Jones' World Cup plans.
Mitchell confirmed that Jack Nowell is available for selection after recovering from the shoulder stinger injury sustained against Wales on February 23, confronting Jones with a selection dilemma on the right wing.
Fijian-born 21-year-old Joe Cokanasiga was outstanding in Nowell's absence as he celebrated his fourth cap with a man of the match display that Sir Clive Woodward said evoked memories of New Zealand superstar Jonah Lomu.
Jones has dismissed the comparison as "ridiculous" and Mitchell sounds an equally cautious note.
"We've got to be very careful comparing people. Joe is Joe and he will cut his own path," Mitchell said.
"He's very young in terms of his international experience so it's important that we focus on improving him and making sure we can keep his feet on the ground.
"Joe is getting better with each outing. He'll continue to improve and we'll focus on his basics."
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