Wales boss Wayne Pivac must make at least four changes to his starting line-up for Saturday's Guinness Six Nations clash against Scotland.
Wing Hallam Amos, centre Johnny Williams, scrumhalf Tomos Williams and flanker Dan Lydiate have all been ruled out of the trip to Murrayfield.
The quartet suffered injuries during Wales’ 21-16 victory over Ireland in Cardiff on Sunday, with Lydiate possibly missing the rest of this season due to knee ligament damage after his first Wales appearance in more than two years lasted just 11 minutes.
Amos and Johnny Williams are both sidelined because of head injuries, while Tomos Williams has a hamstring problem.
Elsewhere, centre Jonathan Davies is set to miss a second successive Six Nations game as he continues recovering from ankle trouble, and wing Josh Adams remains suspended following a breach of Covid-19 protocols.
And to compound Pivac's midfield concerns, George North scratched an eye against Ireland, while Nick Tompkins is thought to have a shoulder injury.
On the plus side for Pivac, though, British and Irish Lions back Liam Williams is available again after completing a three-match ban. He was sent off during the Scarlets' Pro 14 defeat against Cardiff Blues last month.
Josh Navidi is Lydiate's likely replacement, with Liam Williams looking set to replace Amos, Tompkins or Owen Watkin lining up in midfield and Gareth Davies taking the number nine shirt.
Wales say that any squad call-ups will be made and announced in due course following Covid-19 testing and results.
“We watched Dan a lot over the Christmas period, and he has been the in-form six in Wales,” Wales assistant coach and defence specialist Gethin Jenkins said.
“I am really gutted for him. It’s a tough pill to swallow for him and for us as a squad.”
Seasoned campaigners like 34-year-old centre Jamie Roberts, who won the last of his 94 Wales caps more than three years ago, and scrumhalf Rhys Webb have been tipped in some quarters to be summoned by Pivac as reinforcements.
But Jenkins added: “I don’t really want to talk about those options and who might come in next because we’ve got to wait for some of the injury stuff to come back, plus the Covid protocol to deal with, which affects how people outside of the squad are tested.”
And on North and Tompkins, he said: “We are only 48 hours after the [Ireland] game, so we are still assessing and looking at where they are in terms of the weekend.”
Wales have beaten Scotland 16 times from the countries’ last 19 meetings, yet they will meet opponents in pristine shape after a memorable Calcutta Cup win against England – their first at Twickenham for 38 years.
Jenkins added: “It’s the same for them as it is for us. When you win, you have got to back it up. You can’t think you are top of the world, you’ve got to knuckle down and work on the stuff that got you that win.”
Wales made more than 200 tackles in edging past 14-man Ireland, but Jenkins said: “I don’t see making 200 tackles as a positive. It is more a negative.
“If we are making 200 tackles, it means stuff isn’t going right in other areas. If we have to make that many tackles, we are probably not as accurate somewhere else.
“It is good that we’ve got work-rate, intent and all that, but ideally it would be a lot less than that. That is what we are driving this week.”
Jenkins won 129 caps for Wales – a figured bettered only by current captain Alun Wyn Jones – so it is little surprise that much of his defensive philosophy is generated from working with former long-time Wales defence guru Shaun Edwards.
“I would have to say, without going too far away from it, because I’ve lived it with Shaun and been involved in the system so much that I have obviously learnt so much from that,” he added.
“The majority is from that, but you go round as a coach and see different environments, and I’ve been lucky enough to do that a few times.”
