England's injury crisis intensified moments before kick-off at the Stadio Olimpico when Tom Curry was forced to withdraw during the warm-up.
The flanker appeared to sustain a leg problem whilst practising driving mauls with his teammates, requiring assistance from two medical staff members to leave the pitch.
Shortly after disappearing down the tunnel, confirmation came that Curry would play no part in proceedings.
Sam Underhill was elevated from the replacements to fill the openside berth, representing a like-for-like swap.
England star Tom Curry suffered an injury during the warm-up
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Chandler Cunningham-South, who had travelled as a reserve, subsequently joined the bench as Steve Borthwick maintained six forwards among his substitutes.
The timing could scarcely be worse for the Curry family, with Tom's twin brother Ben having already confirmed his campaign has reached a premature conclusion.
The Sale Sharks captain took to Instagram to share the disappointing news, stating: "Gutted to say that my season is over. Been a tough few months already; however, I'm feeling really positive about next steps and can't wait to get cracking with the rehab."
The 27-year-old underwent hamstring surgery prior to the autumn internationals and briefly returned for his club in December's Champions Cup before suffering another setback.
Both siblings had been named in Borthwick's Six Nations squad, though Ben never made it to the pre-tournament training camp in Girona.
England arrived in Rome desperate to arrest a worrying slide in form.
It is a nightmare start for Steve Borthwick, who is in dire need of a victory to alleviate pressure at England
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Consecutive losses against Scotland and Ireland have left Borthwick's men languishing in fourth position, with their title aspirations long since extinguished.
The defeat at Murrayfield ended any prospect of claiming the Calcutta Cup or Triple Crown, whilst Ireland subsequently crushed their Six Nations ambitions at Twickenham.
Their current record of four defeats in five away fixtures equals the worst such run throughout the entire Six Nations era.
Borthwick responded to these comprehensive losses with radical selection, implementing an unprecedented twelve alterations to his starting lineup, including three positional switches.
The head coach struck a measured tone ahead of the encounter, declaring: "We're expecting a big test in Rome and it's one the players are really looking forward to.
"We know the challenge Italy will bring at the Stadio Olimpico and we've selected a team we believe will deliver the level of performance we're striving for."
England are desperate for victory despite their Six Nations dream going up in smoke after consecutive defeats
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Italy's Gonzalo Quesada offered a generous assessment of his opponents despite their recent struggles, noting: "They're the ones who win the most free-kicks from the scrum and the ones who run the most yards with the ball, they're the best at dominating tackles."
England have never lost to Italy in 32 previous encounters.