Northampton lock Courtney Lawes will miss England's autumn schedule with an ankle injury that will keep him out for about 12 weeks.
The 31-year-old is set to have surgery on the injury he sustained during the Premiership defeat by Sale last month.
Lawes was substituted in the ninth minute after competing for the ball in the air and falling awkwardly.
First-place England end their disrupted Six Nations campaign in Italy on Saturday, 31 October.
Lawes, who has 85 caps, started three of the four matches before the tournament was postponed in March amid the coronavirus pandemic.
England head coach Eddie Jones will also be without Sale centre Manu Tuilagi for the rest of the competition, after he ruptured his Achilles tendon during the same game.
With the experienced Lawes and Tuilagi missing, Jones has named 12 uncapped players in a much-changed training squad.
England face the Barbarians on 25 October, before completing the 2020 Six Nations against Italy and then playing four games in the Autumn Nations Cup.
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