Coronavirus has already put paid to one of the FA Cup third round ties this weekend, but several others seem set to go ahead with clubs selecting shadow squads due to players being forced into self-isolation.
The clash between Southampton and Shrewsbury at St Mary's has already been called off as the Shrews reported a "quite astronomical" number of positive cases in their squad earlier this week.
Chief executive Brian Caldwell said that the new variant of the virus had "wiped through" the club and meant that it would be unsafe for them to travel to Southampton and fulfil the fixture.
With some of the players who haven't tested positive deemed to be close contacts of the positive cases, it has meant that the League One Shrews are unable to cobble together a team to take on Ralph Hasenhuttl's men.
The FA have told clubs that, in practice, they must fulfil their tie if they have a minimum of 14 players fit and available, i.e. not suffering from the virus and not self-isolating due to be being a close contact.
No club will be forced to forfeit their tie immediately, with the FA aware of the increasingly fraught individual circumstances of different clubs.
However the FA do want any postponed ties to take place before the fourth round starts on January 23. This presents a problem for Shrewsbury as Southampton face Leeds in the Premier League on January 20.
The FA’s Professional Game Board will meet next week to discuss the postponed fixtures, but it seems likely that Shrewsbury may have to forfeit the tie as they simply don't have enough players to play in it.
Derby County have already confirmed that interim manager Wayne Rooney and his entire first-team squad won't make the trip to Chorley for Saturday lunchtime's third round tie, but that match is still on.
A team made up of Derby's under-23s and under-18s players will take on the National League North side, with under-23s coach Pat Lyons and Gary Bowyer taking charge.
An additional problem for Derby is that six of their more promising under-23s players have been training as part of the first-team 'bubble' in recent weeks, meaning they may still not have enough players for the fixture.
Aston Villa could also be forced to field a young side for Friday night's all Premier League tie at home to Liverpool after they confirmed a "significant" outbreak at the club on Thursday.
With Villa facing a Premier League match against Tottenham next midweek and then both clubs playing midweek matches the week after, it seems unlikely that the game could be rescheduled if it has to be postponed.
That raises the possibility of Villa forfeiting the match should they not be able to raise a side, although their vast youth resources means they should be able to.
Ironically, Liverpool fielded their under-23 side against Villa in the Carabao Cup quarter-finals last season as the first-team were away at the Club World Cup, and it seems as though the roles could be reversed as a young Villa side takes to the pitch this time around.
Sheffield Wednesday are another club to confirm 'significant' Covid cases among the first-team squad, including caretaker boss Neil Thompson, ahead of their tie at Exeter.
Middlesbrough, who faced Wednesday in the Championship last week, are also struggling with what the club call 'a number of positive tests' ahead of their tie at Brentford.
Burnley boss Sean Dyche has also confirmed that the Clarets have a small number of cases ahead of their third round clash with the MK Dons.
"We have got a couple of cases that will affect us," he said.
"We have some at the moment and we are having to be wise and re-pod the players.
"The worry for us across the sport is the knock-on effect. We have a couple of cases, which could affect us over the next few days.
"It's a tough challenge for all, so we're having to be wise and push the rules as hard as we can, to stop any future cases."
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