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Christian Wade and Marland Yarde will be sorely missed on the wings for England. The pair were only taking their first strides internationally this past year, but they didn't look out of place and would have given Lancaster a solid choice of wide assets, both starting and from the bench.
Anthony Watson and Jonny May will be grateful that the pair's injuries have provided their opening in the squad, but the young wing pair were just starting to hit their grooves in international colours.
Tuilagi, of course, stands as the biggest miss, however. His no-nonsense combination of fierce attacking strength and rabid defence is on a par, which Twelvetrees and Barritt aren't entirely capable of in their own capacities.
Up front, Alex Corbisiero's void is fortunate enough to be filled by a player of Joe Marler's standard, but having the prop pair fit and available would obviously have been a major boost.
The side has had a chance to get used to life without Tom Croft, and the galloping flanker could very arguably have been the component who displaced Robshaw if fit.
At the back, Ben Foden is a more acceptable loss, given that Alex Goode is a reliable option in the No. 15 jersey, but the Northampton Saint's talents wouldn't have gone astray.
All in all, there's a sample of key figures missing in crunch areas of the pitch, and a couple of unfortunate injury blows could see gaps popping up where not needed.