George Ford and Elliot Daly have been called up to the England squad as a replacement for the injured pair of Owen Farrell and Jonny May, the Rugby Football Union (RFU) confirmed on Monday.
In-form Leicester Tigers flyhalf Ford, 28, has started all 12 of Tigers' Premiership games and is the league's top points scorer so far, but was omitted from Eddie Jones' 36-man squad after falling behind Marcus Smith and Farrell in the pecking order.
The replacements come during a turbulent week for England's Six Nations preparation as the squad were evacuated from the team hotel in Brighton after an electrical fire broke out nearby on Tuesday night.
The team switched hotels, and the fire was thought to have started in a manhole near the Harbour hotel on the Kings Road. Pedestrians took footage of flames coming up from the pavement and the East Sussex Fire and Rescue Service cordoned off the area.
Ford, who has been capped 77 times, was left out of the autumn internationals and last played for England in the 32-18 defeat by Ireland in the final round of last year's Six Nations championship in March.
Farrell has not played since injuring an ankle on England duty in November and was expected to return to club action for Saracens at the weekend but missed their 45-24 victory over London Irish after sustaining an injury in training on Friday.
May withdrew from the England squad ahead of their five-day training camp in Brighton due to a knee injury, and has been replaced by Saracens' Daly, who has played 52 times for England.
RFU added that Courtney Lawes, who is undergoing protocol for return to play following a head injury, will be unavailable to train this week, and that Nick Isiekwe has joined the squad as injury cover for the 32-year-old.
Prop Joe Marler has also withdrawn from the squad for this week's training camp after testing positive for COVID-19.
Marler, who plays for Harlequins in the Premiership and has made 72 appearances for England, went into isolation after returning a positive test on Tuesday.
"A subsequent PCR test taken that morning confirmed the result," England Rugby said in a statement. "All of the other England players and staff have undergone daily lateral flow testing -- all of which returned negative results."
England, who finished fifth in last year's Six Nations, kick off away to Scotland on Feb. 5 before facing Italy in Rome and hosting Wales and Ireland, and complete their campaign away to France on March 19.