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London - England captain Dylan Hartley said "injuries were the nature of the beast" as his side prepared to begin the defence of their Six Nations title with 15 players missing.
In the latest setback, Harlequins prop Kyle Sinckler withdrew on Tuesday from England's training camp in Portugal with a hamstring strain.
England will be bidding for an unprecedented third successive outright Championship title when they launch their tournament campaign against Italy - a team they have yet to lose a Test match against - in Rome on February 4.
But they have been badly hit at prop by a number of injuries, with looseheads Matt Mullan, Ellis Genge and Beno Obano all set to miss at least part of the tournament.
As things stand, they are missing 15 players with back Henry Slade (shoulder) joining an injury list that already included wing Elliot Daly and back-row forwards Nathan Hughes and Billy Vunipola.
Flanker James Haskell and prop Joe Marler are also suspended.
England coach Eddie Jones has repeatedly made clear that his ultimate aim with the side is to win the 2019 World Cup in Japan.
But Hartley, speaking at the Six Nations launch in London on Wednesday, said: "As a team we've got a long-term goal but the focus is on the here and now - Italy will be a difficult challenge.
"We want to start the Six Nations with a bang.
"The tournament is long and if you take your eye off the ball you become unstuck," he added.
As for England's fitness problems, Northampton hooker Hartley said there was no getting away from the brutal nature of professional rugby union.
"I think it's the nature of the beast, club or international rugby, people get injuries but we are in a good position.
"We've got players coming in, good depth. And the young guys bring the energy."
Italy lost all five of their fixtures in last season's Six Nations but captain Sergio Parisse, speaking alongside Hartley, was confident the Azzurri were making progress under Irish coach Conor O'Shea.
"We are still building the team, of course," said Parisse. "Every single round is tough for us.
"But I'm really confident about the way we are working. Our aim is to perform in every single game.
"We want to win we don't just want to be competitive but of course we are realistic."
Six Nations chairman Pat Whelan said this year's edition would feature several firsts with France playing a home Championship in Marseille, rather than Paris, when they face Italy on February 23.
And in a sign of the Six Nations' growing global popularity, US television network NBC is now an official broadcast partner.
"2017 set record numbers across TV and digital platforms, and we are looking to build on them," said Whelan.
