Ireland will be without influential centre Garry Ringrose and stalwart lock Devin Toner when they face Scotland in the Guinness Six Nations on Saturday.
Leinster midfielder Ringrose has a hamstring injury, while Toner aggravated an existing ankle problem in Saturday’s 32-20 defeat by England in Dublin.
Wing Keith Earls appears to have proved his fitness after a hip concern by training on Tuesday, but Ireland must now travel to Edinburgh without three key operators, with CJ Stander already missing due to facial fractures.
Ireland confirmed their mounting injury issues on Tuesday, with head coach Joe Schmidt now facing a significant reshuffle of his resources.
Scrum coach Greg Feek said: “Devin’s ruled out for this week with his ankle and Garry Ringrose also. His hamstring isn’t quite right so he won’t be with us either.”
The absence of Leinster lineout specialist Toner will prove the biggest miss to boss Schmidt and Ireland.
The 32-year-old has only missed six Test matches since Schmidt took the helm in November 2013, with the Kiwi coach drawing heavily on his set-piece acumen.
Ireland approached this year’s Six Nations appearing in a position of strength at lock, but were struck by injuries to Iain Henderson and Tadhg Beirne before the tournament started.
Ulsterman Henderson’s finger problem and Munster star Beirne’s knee complaint thinned Ireland’s locking stocks and Toner’s absence will heavily test Schmidt’s squad depth.
Connacht’s Quinn Roux looks set to slot into Ireland’s second row alongside James Ryan, with Ultan Dillane poised to take a seat on the bench.
Munster lock Billy Holland has also been added to Ireland’s squad this week as further cover.
“Quinn did really well at the weekend, he came on and put in a couple of big hits,” said Feek.
“He’s been leading the lineout at Connacht this year, and he’s really progressed there and matured as a player.
“Luckily for us, we have good depth there at the moment.”
Ringrose’s absence could tempt Schmidt into shifting Robbie Henshaw back into the centres, after the Leinster star struggled with his move to full-back in last weekend’s England loss.
Munster’s Chris Farrell and Ulster’s Will Addison are further midfield options for Schmidt, while Rob Kearney could return at full-back.
England hope that Maro Itoje will return in time to reinforce the final stage of their Six Nations title pursuit after being struck down by a knee injury.
Itoje will miss the clashes with France and Wales due to a grade two medial ligament tear sustained in the second half of Saturday’s remarkable victory over Ireland at the Aviva Stadium.
But if his rehabilitation progresses well, the British & Irish Lions lock could be back for the last two rounds against Italy and Scotland.
Offsetting the news of his absence is the return to fitness of flanker Brad Shields, centre Ben Te’o and wing Joe Cokanasiga, who missed the stunning start to the championship in Dublin through injury.
“Maro had the scan and saw a specialist yesterday (Monday). It’s ligament damage to his knee,” forwards coach Steve Borthwick said.
“We anticipate him being able to play at the latter part of the tournament. Hopefully he’ll heal fast and we’ll have him back ASAP.
“Which game that is for depends on how his rehab goes over the next couple of weeks, but we’d expect him to feature later on.”
As cover, Itoje’s Saracens team-mate Nick Isiekwe has been called into England’s 35-man training squad that has assembled to begin preparations for Sunday’s visit of France to Twickenham.
Courtney Lawes, who was a second-half replacement against Ireland, and Joe Launchbury are competing to fill the vacancy in the second row alongside George Kruis.
Itoje will remain at the squad’s Surrey training base to continue his rehabilitation and in the meantime England must decide how to cover for the loss of a player who Eddie Jones believes will soon be recognised as the best lock in the world.
“Maro’s a fantastic player and a great personality around the squad. Clearly it’s significant that he’s out, but we have a lot of brilliant players in his position,” Borthwick said.
“You’ll always miss a player of his calibre, you’ll take some strength out of your team, but we have very good and experienced players to come in.
“It was a tough decision to leave Joe out against Ireland and he was brilliant in the way he supported the team, which is great credit to him.
“We all saw the impact Lawes had off the bench, the hitting power he has and how he can carry.
“We approach team selection by picking the team that we want to get the result for that weekend. We always look at different combinations and we’ll be doing that over the next few days.”
Itoje sustained the injury to his right knee in the second half of England’s remarkable win at the Aviva Stadium when being cleared out of a ruck by Ireland flanker Peter O’Mahony.
He was ruled out for five weeks after suffering a chipped patella to the same knee in the build-up to the autumn series, playing throughout November until the nature of the injury was discovered.
Thomas Young looks set to make his Six Nations debut for Wales in Saturday’s clash against Italy.
The 26-year-old Wasps flanker, whose two previous caps were gained on tour against Tonga and Samoa in 2017, could make Wales’ matchday 23 following last week’s fightback victory over France.
Wales have a 31-man playing group at their Nice training base, and the likes of Young and Leicester back Jonah Holmes – a Test debutant earlier this season – might be involved in Rome.
The 24-19 win against France last Friday – secured after wiping out a 16-point interval deficit – was Wales’ 10th successive victory.
And if they beat Italy for a 13th time on the bounce, it will equal Wales’ all-time unbeaten record of 11 Tests set between 1907 and 1910.
Wales head coach Warren Gatland is due to name his team on Thursday ahead of departure for Rome.
"It's very reminiscent of Llandudno," says Robin McBryde as Wales coaches and players meet the media on the beachfront of Nice. (Allwch chi gymryd y dyn allan o'r Gogledd...) pic.twitter.com/wYNHsU19jO— Welsh Rugby Union 🏉 (@WelshRugbyUnion) 5 February 2019
Young, son of Wasps rugby director and former Wales prop Dai Young, has been among the Premiership’s strongest performers this season.
And the Stadio Olimpico encounter is likely to offer him an opportunity of leaving an impression early in World Cup year.
“He has been a consistent player,” Wales assistant coach and forwards specialist Robin McBryde said.
“He is a consistent performer for Wasps every week. He’s playing in a league where there are big men week-in, week-out, and the intensity is there.
“He’s had several man-of-the-match awards. In defence he makes intelligent decisions of when to compete for the ball, and in attack he links up with the backs. He is doing that here as well.
“Our training is a bit different to club level – the intensity and metres covered is up – but he has dealt with it.
“It is an opportunity for anyone down here to stake a claim and make a name for themselves. If anyone gets the opportunity, they have to take it and make the most.”
Wales again trained in glorious Cote d’Azur sunshine on Tuesday, and McBryde added: “It’s very reminiscent of Llandudno, so I feel at home.
“It has been good to recuperate after a tough match last Friday night. You couldn’t ask for better surroundings.
“But we have to be aware not to slip into holiday mode. We’ve got some hard work to do before Italy.
"To become Wales' most capped hooker is a huge honour. Over the last 20 years the quality that has come through the hooking berth has been exceptional." - @KenOwens1088— Welsh Rugby Union 🏉 (@WelshRugbyUnion) 3 February 2019
Read about Ken's Parisian milestone 📰 - https://t.co/bUPQq2WV3Y pic.twitter.com/47nK8wgZdJ
“Everybody realises the importance for the first two games and the momentum it can create by getting positive results.
“We can’t rest on our laurels. Italy are a tough nut to crack, and we have areas to improve on from last Friday.”
Gatland is keeping selection cards close to his chest, but it would be no surprise to see changes being made in the starting XV and on the replacements’ bench.
“Italy will be buoyed by the last 15 minutes when they came back strongly against Scotland (last Saturday),” McBryde said.
“There wasn’t a lot in the game. They showed how dangerous they can be in attack against Scotland. They are comfortable at lineout time, so it will be a big test for us.”