England must complete the Six Nations without Sam Underhill after the Bath flanker was ruled out for three months by ankle surgery.
It is a setback for Eddie Jones who is now missing one of the stars of the 2018 autumn campaign and must yet again enter a competition with one of his two young opensides unavailable.
Tom Curry has recovered from his own ankle injury sustained against South Africa in November – a blow that gave Underhill his chance – so Jones still has a strong option in the position, but the head coach wanted both players duelling for the jersey.
Underhill suffered ankle-ligament damage against Leicester on December 30 and while it was initially thought the 22-year-old had merely rolled the joint, he was subsequently forced to undergo an operation that will keep him out until mid-April.
England launch their Six Nations title challenge against Ireland in Dublin on February 2 before hosting France a week later.
Jones received some good news on Friday, however, after Saracens named Maro Itoje in the second row for their Champions Cup clash with Lyon on Sunday.
Itoje missed five matches, including the European double-header with Cardiff Blues, due to a knee injury picked up while training for the autumn opener against the Springboks.
He was initially able to continue playing but when the pain persisted, an additional examination confirmed he needed extensive rehabilitation.
"I chipped a bit of the bone leading up to my knee and I damaged a little bit of the middle ligament in the patella," Itoje said.
— Saracens Rugby Club (@Saracens) January 11, 2019
"It was a weird one because I could run, I could jump, I could do everything I needed to do – I was able to do all of that with pain.
"I was able to flex my quad, so all the markers you would test for injury, I passed them all. There was still a little bit of discomfort, then it eased, then it came back again.
"On the whole it was feeling relatively good but it just wasn't getting any better so we had to have a deeper look at it and the results came up."