England flanker Tom Johnson has been ruled out of the RBS 6 Nations championship with a knee ligament injury.
Head coach Stuart Lancaster announced at Wednesday's tournament launch that Johnson is facing three months on the sidelines.
Loosehead prop Alex Corbisiero will miss England's first two fixtures, against Scotland and Ireland, after undergoing a procedure to clean out his troublesome knee. And England will also be without Freddie Burns for at least the Scotland game on February 2, with the Gloucester fly-half expected to be out for two to three weeks with knee ligament damage.
Lancaster added that it was "too early to tell" whether Manu Tuilagi will have recovered from an ankle injury in time for the tournament opener at Twickenham.
In more positive injury news, full-back Alex Goode has overcome a shoulder problem and will play for Saracens against Cardiff Blues in the LV= Cup this weekend.
Lancaster said: "Tom Johnson is probably facing a three-month recovery time. For him it is a tough blow.
"Alex Corbisiero's knee hasn't settled down. It keeps swelling after small amounts of exercise. There is a loose body in there. He has gone in for a scope today to get that loose body taken out and hopefully that will settle down for him.
"We will get him rehabbed and back playing for London Irish. That will take him out of the first two games as a minimum.
"Freddie Burns has had a scan on his MCL. It is a grade two injury so not as bad as first feared but it will keep him out for two or three weeks. We will try to get him back as soon as we can."
Worcester's Matt Kvesic was called into the squad to replace Johnson after the Exeter flanker was injured in the Chiefs' Heineken Cup defeat to Leinster.