Garry Ringrose will miss Ireland's Guinness Six Nations trip to Italy, having failed to beat his hamstring complaint.
Ireland must do without the much-vaunted Leinster centre for Sunday's Stadio Olimpico trip, though that loss is eased by Chris Farrell being passed fit after a knee-injury scare.
Farrell impressed in Ireland's 22-13 victory in Scotland on Saturday, February 9, but limped out of Munster's Pro14 clash against Southern Kings on Friday night.
Iain Henderson and Tadhg Beirne have returned to Ireland's squad to bolster boss Joe Schmidt's options at lock, though Rhys Ruddock misses out through hamstring trouble and Will Addison is sidelined with a minor back complaint.
"Garry Ringrose and Rhys Ruddock will continue their respective hamstring rehab at Leinster this week," the Irish Rugby Football Union (IRFU) confirmed in a statement.
"Chris Farrell has been reviewed by the Ireland medical team and is fit to train today.
"Will Addison has some lower back stiffness that is being managed at Ulster this week.
"Iain Henderson and Tadhg Beirne, who were named in the initial Six Nations squad, have joined the group at Carton House this week."
Classy Leinster centre Ringrose missed Ireland's Edinburgh victory with a hamstring issue that Ireland had expected would not need much further recovery.
Head coach Schmidt's decision to send Ringrose back to Leinster this week could therefore perhaps be risk-averse, with Ireland yet to face France and Wales in the tournament.
The return of Ulster's Henderson from finger trouble and Munster's Beirne from a knee issue is a genuine boost to Ireland's campaign.
The sole caveat around Henderson remains a Pro14 disciplinary hearing on Tuesday night, where a suspension would rule him out of Sunday's Italy trip.
Uncapped Connacht trio Caolin Blade, Jack Carty and Tom Farrell have also joined up with Ireland in a 34-strong squad to prepare to face the Azzurri.
