Dylan Hartley is in danger of missing the majority of England's quest to reclaim the Guinness Six Nations title from Ireland due to a knee injury.
Hartley has not played since December 21 after succumbing to what Northampton boss Chris Boyd described as a "grumbly" joint and will miss the pre-tournament training camp in Portugal which begins on Wednesday.
Eddie Jones has tentatively pencilled his co-captain in to return in the third round against Wales on February 23, but England's head coach admits that date might be optimistic.
Dan Cole and Mike Brown – formerly senior players under Jones until falling out of favour last year – have the opportunity to press their claims in Portugal after being selected in the 35-man squad.
Bath duo Anthony Watson and Jonathan Joseph are missing because of their respective Achilles and ankle injuries.
"Ireland are the best side in the world. They are a very well coached and drilled side and have particular things they do well in the game," Jones said.
"To beat Ireland, we need to compete brutally in all the contest areas of the game.
"Obviously it's a World Cup year so that is always at the back of your mind, but clearly our focus is on beating Ireland.
"They are a good team and deserve all the praise they've been getting. They have a number of exceptional players and a very methodical game plan that maximises the strength of their team."
