England's injury problems continued to escalate after prop Alex Corbisiero and second row Geoff Parling were ruled out of the autumn series.
Corbisiero will be sidelined until early next year having undergone surgery to repair torn shoulder ligaments while Parling is expected to return from concussion in December.
The loss of Corbisiero is a significant setback to England, who are now missing four front rows for the QBE series against New Zealand, South Africa, Samoa and Australia.
The British and Irish Lions loosehead joins Tom Youngs, Dan Cole and Mako Vunipola among the wounded after being hurt in Northampton's 31-24 Aviva Premiership victory over Bath on Saturday.
Corbisiero was poised to play a full role at Twickenham in November having battled back from the succession of serious knee injuries that have hampered his career.
"The specialist's advice is that the tear needed surgical repair so that Corbisiero can play to an optimum level in the future," a Northampton statement read.
"The Saints and England medical teams are liasing on Corbisiero's treatment and recovery."
Just two hours after Northampton's update on Corbisiero had been issued, Leicester director of rugby Richard Cockerill confirmed Parling was facing two months of recovery.
Parling has been concussed five times in 11 months, most recently in the 45-0 Premiership defeat at Bath 10 days ago - the second incident of its kind in three games.
The Lions lock also sustained head trauma in a pre-season friendly against Edinburgh and was unavailable for three weeks.
While Parling is facing a two-month spell out, Cockerill dispelled concerns over his playing career.
"Geoff saw the relevant specialist this week and will have time out of the game now," Cockerill said.
"He'll probably have three or four weeks of complete down time and then he'll be reintegrated into training.
"You'd like to think that by December he'll be playing again. And there's no doubt about that, he will play again. There are no issues over that.
"It's more that he's had successive concussions in a short period of time. You have to take that very seriously, as we do.
"I need him out on the playing field from a rugby point of view, but it's not a bump, bruise or strain that you can play through.
"It's a serious matter and the club take it very seriously and we manage it as such.
"Ultimately there are more important things than playing rugby and you have to look at the bigger picture.
"We've all got injuries from playing rugby, whether it's a worn out back or knackered something. You can deal with that, but you can't deal with head injuries and all that stuff.
"If you take a bang on your head and you don't feel quite right, you know in yourself you have to deal with something because it's serious."
Cockerill revealed that centre Manu Tuilagi's return from a groin injury has been delayed for a further week, ruling him out of Saturday's trip to Gloucester.
"We want to get it dead right, there's no point getting him back on the cusp of right or wrong and irritating that groin again," Cockerill said.
"We know exactly what's wrong with it, it's just that historically we find that most of the Pacific Island boys heal quite slowly.
"Manu's brothers were exactly the same. Genetics mean some people are quick healers and some people are slow healers.
"The Tuilagi gene is big, quick and nasty, but they're slow healers."
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