Manu Tuilagi has suffered a fresh injury blow and withdrawn from England's training squad for their three-day camp in Bristol.
The Leicester centre, who has recovered from a career-threatening groin problem and successive knee surgeries among a series of other injuries, had been hoping to make a first England appearance for two years, and potentially his first start in four years, this autumn.
However, the Rugby Football Union announced on Sunday the 27-year-old would not be involved in training this week.
— England Rugby (@EnglandRugby) September 23, 2018
Tuilagi played in the 44-37 defeat to Worcester in the Gallagher Premiership earlier in the day, alongside Ben Youngs – who has also withdrawn.
A Leicester spokesman said: "Ben and Manu went off in the second half of Sunday's game with niggles which are expected to keep them out of training for the next few days. They will be assessed by the club in the next few days."
Harlequins prop Joe Marler, who has won 59 caps and acts as England's second-choice loosehead behind Mako Vunipola, also misses out.
Marler was due to link up with the 36-man party on Sunday but has pulled out for personal reasons. His place will now be taken by Exeter's Ben Moon.
Worcester's Nick Schonert is another injury withdrawal, while Leicester's Jordan Olowofela – who reached the World Rugby U20 Championship final with England this summer – has been called into the party.
England will name their squad for the November internationals on October 18 before they fly to Portugal ahead of matches against South Africa, New Zealand, Japan and Australia at Twickenham.