England are set to be without centre Ollie Lawrence and hooker Luke Cowan-Dickie for their Six Nations opener against Italy.
Both picked up injuries in last weekend’s Investec Champions Cup and have withdrawn from the training camp in Girona.
England have called up Newcastle’s Jamie Blamire and the Bath pair of centre Max Ojomoh and wing Will Muir.
Ojomoh, 23, is the son of former Bath, Gloucester and England back row Steve.
Harlequins centre Oscar Beard is going through return-to-play protocols after concussion but has travelled to northern Spain.
England have not specified the nature or severity of Cowan-Dickie or Lawrence’s injury but it’s understood both are doubts for the game in Rome on 3 February.
Lawrence’s absence especially would be a major blow to head coach Steve Borthwick, with the Bath man earmarked to start in the midfield against the Azzurri.
It leaves England light for options at inside centre. Henry Slade is better suited to wearing number 13, as is Tommy Freeman, while Borthwick no longer has the option to deploy Owen Farrell at number 12, as has so often been the case over the past decade.
Fraser Dingwall, Northampton’s in-form but uncapped centre, is now a strong contender to make his England debut in the Stadio Olimpico, should Lawrence not be fit.
Saints have been in outstanding nick this season both domestically and in the Champions Cup, with scrum-half Alex Mitchell, fly-half Fin Smith and full-back George Furbank also in the England squad along with Dingwall and Freeman.
All five started in the backline as 14-man Northampton pulled off a sensational win at Munster on Saturday to top their pool, and Borthwick says he will be looking to harness Saints’ momentum as he prepares his England team over the next 10 days.
Meanwhile, Cowan-Dickie had won a recall to the squad after missing last year’s World Cup with a shoulder injury.
“You look at the way Fin, and Mitch [Alex Mitchell] and Tommy Freeman and Fraser Dingwall, the way they have taken Northampton on,” said Borthwick.
“I think they have changed the way they have played slightly, and I think it is a great change.
“Away in Thomond Park in those conditions, the way they stayed in that fight, the way they were relentless in doing the right thing at the right time and the way they took scoring opportunities, I think that shows a team that has the right mindset, the mindset we want to make sure we have with this England team.”
England’s Six Nations squad
Forwards: Ollie Chessum, Dan Cole, Alex Coles, Jamie Blamire, Chandler Cunningham-South, Ben Curry, Theo Dan, Alex Dombrandt, Ben Earl, Ellis Genge, Jamie George (capt), Joe Heyes, Nick Isiekwe, Maro Itoje, Joe Marler, Beno Obano, Tom Pearson, Ethan Roots, Will Stuart, Sam Underhill.
Backs: Max Ojomoh, Danny Care, Elliot Daly, Fraser Dingwall, Immanuel Feyi-Waboso, George Ford, Tommy Freeman, George Furbank, Will Muir, Alex Mitchell, Tom Roebuck, Henry Slade, Fin Smith, Marcus Smith, Ben Spencer, Freddie Steward.