England have been hit by the loss of vice-captain Jamie George for their Six Nations opener against Ireland on February 1, with Alex Mitchell also a doubt for the Dublin showdown.
Hooker George suffered a hamstring injury in Saracens' Champions Cup defeat by Castres on Sunday and will miss the start of the tournament, the Rugby Football Union (RFU) has confirmed.
Northampton scrum-half Mitchell sustained a knee problem against Munster on Saturday but could yet feature against Ireland after being taken to the squad's pre-Championship training camp in Girona to continue his rehabilitation.
An attritional weekend of European action has also seen Northampton lock Alex Coles, Leicester scrum-half Jack van Poortvliet and Harlequins number eight Alex Dombrandt all ruled out of contention for the Aviva Stadium clash.
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