Three of Ireland's Six Nations rivals have suffered key withdrawals with less than a fortnight until the start of this year's competition.
France centre Virimi Vakatawa will miss their entire campaign.
The Racing 92 man had an MRI on a sprained knee and will be out for six weeks, ruling him out for the duration of the Six Nations.
The 28-year old came a cropper during Racing's narrow 33-32 defeat to Bordeaux-Begles this past weekend in the Top 14.
Vakatawa started in four of France's games in the 2020 edition, scoring their fourth try in October's 35-27 victory over Ireland at the Stade de France.
La Rochelle back row Gregory Alldritt has already been ruled out of Les Bleus' opening game away to France on February 6.
Meanwhile, England will be without both Joe Marler and Joe Launchbury.
Wasps lock Launchbury sustained a stress fracture in his leg.
While Harlequins prop Marler has ruled himself out due to personal reasons.
Always grateful for the opportunity so not an easy decision, but want to do right by my family in these crazy times and won’t be meeting up with the squad for this tournament. Look forward to watching the team rip in. Go well 🌹 x
— Joe Marler (@JoeMarler) January 25, 2021
Wasps prop Tom West will join Eddie Jones' squad as Marler's replacement, in what will be his first involvement in international rugby.
Launchbury's place goes to Bath lock Charlie Ewels.
Marler explained his decision on Twitter, saying, "Always grateful for the opportunity so not an easy decision, but want to do right by my family in these crazy times and won’t be meeting up with the squad for this tournament."
Italy have suffered a major blow, with Matteo Minozzi withdrawing from the Azzurri squad.
The Wasps man blamed physical and mental tiredness as his reason for pulling out of Franco Smith's panel.
Minozzi started four games for Italy in the last campaign, split between full-back and the left wing. He also managed to cross the whitewash in their defeat to France.
The 24-year old wrote on social media to say he was not in a position to endure living in a bubble for the next two months.