Just hours before the match was due to kick off at Goodison Park, City said they had returned a number of positive tests in addition to the four cases on Christmas Day that included striker Gabriel Jesus and defender Kyle Walker.
While Arsenal have not reported any cases arising from their clash with City, the Gunners revealed on Monday that Gabriel, who was already self-isolating after coming into contact with an individual who had tested positive, had come down with Covid and will miss their next two games at least.
The club's training ground has been closed for an "indeterminate period" with further testing on players and staff to take place before it can reopen.
With a risk of the virus spreading, the Premier League's medical advice was to cancel the game, meaning it must now be rescheduled.
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The AstraZeneca serums can be stored in a fridge while the Pfizer formulations have to be stored at -70C in specialised equipment. One vaccine has been developed by AstraZeneca and the UK's Oxford University and the other by Pfizer and BioNTech.
'The Premier League can today confirm that between Monday, 21 December and Sunday, 27 December, 1,479 players and club staff were tested for Covid-19, ' a statement from the league read.
The club said their squad and associated bubble will have testing before a decision is made whether to resume training.
The number of positive tests recorded over a 24-hour period in England and Wales hit new high of 41,385 Monday, according to United Kingdom government figures.
Orient had 17 positive tests back in September when they were scheduled to face Spurs, who have reached their own semi-final against Brentford, after being ushered through to the fourth-round.
"Everyone at the Club wishes all of our colleagues a speedy recovery ahead of their return to work, training and competition".
Recent rumours have suggested that the Premier League authorities might be mulling over a circuit break which would mean there will be no football for two weeks as the government tries to control the spread of the new strain.