Owen Farrell’s 2022 Six Nations is over before it had a chance to get under way after the England captain was ruled out of the entire tournament with an injury to his ankle.
The injury, suffered in training with club Saracens just days before an expected return from a four-month lay-off after surgery on his left ankle, leaves head coach Eddie Jones with several questions to address on the eve of this year's championship.
Here, we look at what Farrell's absence could mean for England's team and who the candidates are to serve as captain in his absence.
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What did Farrell bring to the team?
Injuries aside, Farrell has been a mainstay of the England team after making his debut under former head coach Stuart Lancaster in the 2012 Six Nations.
He has been of one Jones' most trusted lieutenants since the Australian took charge seven years ago too, being named vice-captain for the 2016 Six Nations and taking over the top job from Dylan Hartley on a full-time basis three years later.
Indeed, no player from all competing nations in the Six Nations has made more appearances in the championship than Farrell since 2016 - the 30-year-old playing all 30 games from a possible 30.
Along with his leadership qualities, the son of rugby league great and now Ireland head coach Andy Farrell has a versatility which has seen him operate effectively at both fly-half and inside-centre during his Test career.
And there is his prodigious goal-kicking ability, underlined by Farrell being fifth on the list of all-time leading point-scorers in Test rugby and trailing only Jonny Wilkinson on the list of England's leading point-scorers.
"It's a massive blow for him personally and for the team it's a blow," Jones said at Wednesday's Six Nations launch, reflecting on the news of Farrell's enforced absence.
"But it's obviously an opportunity for other guys to step up into leadership roles and for other players to play for that No. 12 jumper. We see it more as an opportunity.
"In today's rugby, having your best team on the field is a rare occurrence. We're pretty used to it. There's an opportunity there to build a bit more leadership depth."
What will England's 10-12 combination be?
Given how Jones was quoted as talking about opportunities opening up at inside-centre in Farrell's absence, it would be fair to assume Harlequins' Marcus Smith is set to continue at fly-half following his impressive Autumn Nations Series, backed up by the recalled George Ford and newcomer Orlando Bailey.
No doubt Jones had been hoping to see more of Smith and Farrell working in tandem as England's 10-12 axis, something he has so far only been able to do once - that being in the 32-15 victory over Australia in November in which Farrell injured his left ankle.
Manu Tuilagi, who played there in the autumn wins over Tonga and South Africa, is also sidelined at present with a hamstring injury. Meanwhile, Ollie Lawrence and Dan Kelly are out of the picture entirely after starting at 12 in last summer's wins over the USA and Canada respectively.
Of those in Jones' 36-man squad, the most likely options would seem to be Elliot Daly - recalled following Jonny May's tournament-ending injury - or Henry Slade. The latter has mainly been used at outside-centre by Jones though, while the former has not started in either of the midfield positions for England since 2016.
The one man in the squad who would perhaps be regarded as an out-and-out 12 is Mark Atkinson, but the Gloucester man has just one cap to his name from appearing as a replacement in the 69-3 win over Tonga.
Joe Marchant is generally deployed at 13, although Jones may opt to turn to his uncapped Harlequins clubmate Luke Northmore, with the 24-year-old emerging as a rising star. Either of those would also bring that club connection and understanding with Smith to the position.
There are options, albeit not many, but it's hard to know at this point which direction Jones will turn to at 12.
Who will captain England?
When Farrell missed November's Tests vs Tonga (a Covid-19 false positive) and South Africa (ankle injury), Northampton flanker-cum-second-row Courtney Lawes stepped up as England captain.
However, in the aftermath of Farrell's squad withdrawal this week, England provided a further update outlining that wing May had pulled out due to a knee injury and, significantly, that Lawes has been unable to train due to concussion, with Saracens' Nick Isiekwe called up as cover.
"Courtney Lawes is unavailable to train this week as he is undergoing head injury return to play protocols," part of the RFU statement read.
"England's first game is against Scotland in Edinburgh on Saturday 5 February. Following Owen Farrell's withdrawal from the squad, Jones will now name a new team captain ahead of the Calcutta Cup fixture."
Lawes could of course return to training next week and resume the captaincy, but he may also now not be available.
There has long been a clamour to see Saracens' Maro Itoje in a captaincy position, but he is not viewed as a skipper by Jones, while at Wednesday's Six Nations launch, Sale Sharks flanker Tom Curry attended with Jones in his position of vice-captain.
At just 23, it would be a big ask for Curry to captain England for the first time at Murrayfield. Although, in saying that, many do see him as the long-term answer in terms of England's leadership.
Alongside Lawes and Curry, Leicester loosehead Ellis Genge was also named as an England vice-captain in November, and with Joe Marler having tested positive for Covid on Tuesday, Genge is more likely to start vs Scotland too.
The 26-year-old prop is something of a hothead on the pitch, however, and Jones may be reticent to go there for what is sure to be a white hot atmosphere in Edinburgh.
All things considered, much will rest on the recovery or not of Lawes. The 32-year-old will almost certainly be named captain if he is fit. If not, Curry seems the likely next man up.