David Wallace is out of Ireland's World Cup squad after sustaining a knee injury in the match against England.
The Munster flanker went down in agony with a badly twisted knee after being tackled by centre Manu Tuilagi and was carried off for treatment.
Leinster flanker Shane Jennings has been called up as a replacement.
The IRFU also announced prop Cian Healy is a major doubt for the World Cup opener against the United States after picking up an eye injury.
But Ireland coach Declan Kidney is confident Jamie Heaslip (concussion) and Jerry Flannery (shin) will both be fit for the tournament.
The World Cup was expected to be the international swansong for 35-year-old Wallace.
"I've never seen a man as physically fit as he is," said Kidney. "It's heartbreaking for him and extremely disappointing for us.
"David took the news like the man he is. You have to deal with these things.
"It is extremely disappointing for us and will be good news for someone else. That is the cut-throat nature of sport."
An IRFU statement on Healy said: "Cian Healy had taken a knock to his eye during the game and following further investigation has shown an injury to his eye socket.
"Medical advice has dictated that Healy's departure date for the tournament has been put back by four days, when he will then fly out to join up with the rest of the squad in New Zealand."
Kidney admitted it was disappointing to lose all four matches ahead of the World Cup.
"We wanted to pit ourselves against the best teams and that is what we have done," he said.
"We needed these games and we will learn from them.
"You can always find positives, but we are not going to cloud over the fact that we did not manage to win the game."