England flanker Tom Johnson has been ruled out of the Six Nations with a knee injury.
Both Gloucester fly-half Freddie Burns and London Irish prop Alex Corbisiero are doubtful for the opening two matches against Scotland and Ireland because of knee problems.
Leicester centre Manu Tuilagi is also a doubt for the Calcutta Cup match with a leg injury.
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Calum Clark, 23, is already out of the Six Nations with a shoulder injury.
Exeter back-row forward Johnson, 30, and Burns have both damaged medial ligaments in their knee.
Corbisiero is to have his troublesome knee “cleaned out” on Wednesday. He and Burns will miss the second game against Ireland as well as the Scotland opener on Saturday, 2 February.
Johnson was carried off during Exeter’s 29-20 Heineken Cup loss against Leinster on Saturday and England coach Stuart Lancaster initially said he would be absent for the first four to six weeks of the tournament.
But it later emerged that Johnson would miss the entire Six Nations.
Lancaster has brought uncapped Worcester back-row forward Matt Kvesic into the England squad as cover for Johnson.
England senior elite player squad:
Forwards: Props: A Corbisiero (London Irish), D Cole (Leicester Tigers), J Marler (Harlequins), M Vunipola (Saracens), D Wilson (Bath Rugby); Hookers: D Hartley (Northampton Saints), T Youngs (Leicester Tigers); Locks: J Launchbury (London Wasps), C Lawes (Northampton Saints), G Parling (Leicester Tigers), M Botha (Saracens); Back-rows: T Croft (Leicester Tigers), J Haskell (London Wasps), T Johnson (Exeter Chiefs), B Morgan (Gloucester Rugby), C Robshaw (Harlequins), T Waldrom (Leicester Tigers), T Wood (Northampton Saints), M Kvesic (Worcester).
Backs: Back three: C Ashton (Saracens), M Brown (Harlequins), B Foden (Northampton Saints), A Goode (Saracens), D Strettle (Saracens), U Monye (Harlequins); Centres: B Barritt (Saracens), J Joseph (London Irish), M Tuilagi (Leicester Tigers), B Twelvetrees (Gloucester Rugby); Fly-halves: F Burns (Gloucester Rugby), O Farrell (Saracens), T Flood (Leicester Tigers); Scrum-halves: D Care (Harlequins), L Dickson (Northampton Saints), B Youngs (Leicester Tigers).