England suffered a blow ahead of their Six Nations title defence when experienced prop Joe Marler withdrew from the squad on Monday, saying he wanted to be with his family during the coronavirus pandemic.
Marler's move, just three days after he was named in Eddie Jones' 28-man squad, leaves Ellis Genge as the only capped loosehead prop for England's tournament opener against oldest rivals Scotland at Twickenham on February 6.
Meanwhile, in another setback for Jones' side, Wasps lock Joe Launchbury will be out of contention for at least the first three rounds of the competition because of a broken leg.
Marler and Launchbury have been replaced in the squad by Wasps prop Tom West and Bath second row Charlie Ewels respectively.
"Always grateful for the opportunity so not an easy decision, but want to do right by my family in these crazy times and won't be meeting up with the squad for this tournament," the 72-times capped Marler said on Twitter.
"Look forward to watching the team rip in. Go well Rose x."
Marler, 30, opted against touring Australia in 2016 following a controversial season where he was banned for two matches and fined £20,000 ($27,000) for calling Wales prop Samson Lee "Gypsy boy" during a Six Nations match at Twickenham.
Two years later, Marler announced his international retirement, only to reverse the decision ahead of a 2019 World Cup in Japan where England reached the final before losing to South Africa.
Marler's absence leaves Genge in line to start the Calcutta Cup clash against Scotland, with British and Irish Lions loosehead prop Mako Vunipola omitted from England's original squad for the Six Nations due to an Achilles injury