Aston Villa’s visit to Manchester City probably could not come at a worse time for Dean Smith and his players.
They are going up against a team in ominous form, with eight successive victories, and arrive at the Etihad on the back of a 'significant' Covid-19 outbreak that has ripped through their squad.
Smith insists he will have a team capable of challenging City, but the implications of the outbreak remain unclear.
The Villa manager can at least take encouragement from the way that the home side have dealt with a similar outbreak of coronavirus cases that threatened to derail City's season.
Guardiola's men were forced to call off their game at Everton on December 28 and closed their training ground for three days before it was reopened after a deep clean.
Although all cases have not been confirmed, the number of first-team players to test positive runs into double figures, with Kyle Walker, Gabriel Jesus, Ederson, Ferran Torres and Ilkay Gundogan among those forced to sit out games this season.
Guardiola has been careful with his players, with Walker and Jesus yet to play in consecutive matches since coming out of quarantine.
“Some recover quicker or faster than the other ones,” Guardiola said of his experiences. “I would say not even the doctors know exactly the side effects from having tested positive.”
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Sergio Aguero will miss another game on a Wednesday; he remains in self-isolation after coming into close contact with someone that tested positive.
And Guardiola has had to field questions on recent controversies, including players hugging during goal celebrations and Benjamin Mendy's ill-judged New Year's Eve party.
But there is no doubting the seriousness with which the club takes the illness and the impact it can have.
Despite being high-end, super-fit athletes, coronavirus can have serious implications on players’ fitness even weeks after testing negative.
Data injury analyst Ben Dinnery, of the Premier Injuries website, says that those that have been asymptomatic can quickly get back up to speed but there have been examples where a full recovery has been complicated.
“There are massive grey areas because the research just isn’t there. It’s affecting players in different ways,” Dinnery told Goal.
“Some can come back after 10 days and may have lost that little bit of sharpness and for others it can take a lot longer.
“Most Premier League players will have a home gym and so for those that are asymptomatic, they can be monitored remotely by the club. They can maintain base level fitness patterns and you can almost hit the ground running.
“How it differs is there is no way of replicating what happens on the training pitch. It’s not sports specific or in a highly-charged environment.
“Then, you have those that have been affected and it’s dependent on the severity. What we know is that it’s a respiratory illness, so it affects lung capacity and being able to take any cardio load.
“There’s various levels of that but ultimately what it will come down to is levels of fatigue and whether players are able to train or not."
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City midfielder Gundogan revealed how the illness hit him hard earlier in the season and it was a long way from being a welcome break from a hectic period of games.
Manchester United’s Paul Pogba and Chelsea’s Kai Havertz have also said how the virus affected them for weeks after their initial recoveries as they struggled for full fitness.
“Pogba suggested that even though you’re back on the training pitches, you’re just not back to full capacity,” Dinnery added. “You just don’t have that ability to push on further.
“A lot of it is about taking players back to close-season levels. You almost have to take a mini-preseason. What we know is that fatigue has a huge influence on injury incidents, particularly soft muscle problems.
“That’s another difficulty and that’s what clubs are having to manage. That’s why players may be on the training pitches but not ready.
“The old adage is: training is not a return to play and playing is not a return to performance."
Smith remains upbeat about the quality and fitness of his team and can take confidence from the way that Fulham were able to draw at Tottenham after coming back at short notice.
And Guardiola is certain Villa will be a huge test even if they are missing some key players.
"We don’t know which players will be available," he said on Tuesday. "But the quality they’ve shown this season compared to last season is incredible.
"I don’t know the situation at Villa but we wish them to be healthy. I expect the best, so we have to create them problems."