Courtney Lawes, Jamie George, Elliot Daly, and George McGuigan are doubts for England's Six Nations opener against Scotland after withdrawing from the training camp through injury.
Lawes limped off in the 29th minute of Northampton's 31-13 defeat to La Rochelle in the Heineken Champions Cup with a calf injury, while McGuigan is out with a knee injury.
Lawes has been beset with injuries of late and if he is ruled out of the tournament all together it will be a serious blow to England's chances of a successful campaign.
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Following Lawes' injury, England head coach Borthwick said: "Right now we are getting it investigated to understand the full extent.
"It didn't look good but he is getting scans and seeing the specialist to understand exactly what the situation is.
"Until we have that information, it is hard to forecast anything. We know he can't train these few days this next week so that is why we made the change."
George has also been withdrawn from the squad with a concussion following a high tackle on Luke Crosbie which resulted in a head-on-head collision, Daly is ruled out with a hamstring injury.
George was cleared by the Saracens medical team to return to the fray after his 10 minutes in the sin bin but was subsequently stood down by the independent match doctor. George faces a minimum seven-day stand-down period, with England starting their Six Nations campaign against Scotland at Twickenham on Saturday February 4.
Tom Dunn and David Ribbans have been called up to the squad by head coach Steve Borthwick as the side joined up on Monday at the Honda England Rugby Performance Centre at Pennyhill Park, Bagshot for a five-day camp, with Jamie Blamire and Ollie Lawrence joining up on Tuesday to replace George and Daly.