The Premier League confirmed on Tuesday that 18 players and staff have tested positive for coronavirus, the highest number since weekly testing began.
“Of these, there were 18 new positive tests. Players or club staff who have tested positive will self-isolate for a period of 10 days.”
That figure surpassed the previous highest figure recorded of 16 for 9-15 November.
All remaining seven Premier League games on Tuesday and Wednesday are still set to go ahead.
City had already announced on Christmas Day there had been four positive tests at the club for players Kyle Walker and Gabriel Jesus and two staff members prior to the latest positive cases on Monday.
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.
Southampton revealed that manager Ralph Hassenhuttl will not be in attendance for his side’s match against West Ham on Tuesday as a member of his household has tested positive.
However, the Premier League insisted the protocols put in place are still stringent enough to prevent another shutdown like the three-month stoppage between March and June earlier this year.
“The Premier League continues to have full confidence in its protocols and rules, and the way in which all clubs are implementing them,” the league said in a statement on Monday.
The number of positive tests recorded over a 24-hour period in England and Wales hit new high of 41 385 on Monday, according to UK government figures.
“I think we all sensed this next period might be a tough one with what’s been happening pre-Christmas with Covid in general,” said Chelsea manager Frank Lampard with Sunday’s clash with City now in doubt.