Leicester City's Premier League game against Tottenham Hotspur on Thursday and Manchester United's home clash with Brighton & Hove Albion on Saturday have been postponed as rising COVID-19 cases threaten to play havoc with the season.
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Thursday's announcements from the Premier League mean that five matches have been lost in the past week, although the league says it plans to continue with the current fixture schedule.
"While recognising a number of clubs are experiencing COVID-19 outbreaks, it is the League's intention to continue its current fixture schedule where safely possible," it said in a statement.
"The health and wellbeing of all concerned remains our priority."
Earlier in the day, Brentford manager Thomas Frank called for all Premier League games in the coming week to be postponed to allow clubs to recover their depleted squads.
Tottenham, who reported 13 positive tests among players and staff, have had two Premier League games postponed after last week's trip to Brighton was also called off.
United have now had two games postponed following their trip to Brentford on Tuesday being called off after United's training ground was closed due to an outbreak of COVID-19.
United said on Thursday that they would "suspend football training operations at the Carrington Training Complex for a short period to help reduce risk of further transmission".
On Wednesday Burnley's home match with Watford was called off shortly before kickoff after Watford had reported positive tests.
Brighton, Norwich City and Aston Villa have also reported cases as the Omicron variant spreads rapidly across the country.
Leicester manager Brendan Rodgers on Wednesday criticised the Premier League after an initial request to have Thursday's game against Tottenham postponed was turned down.
The Premier League said the decision to grant a postponement came after Leicester reported more cases.
Brentford boss Frank says he is dealing with 13 cases at the London club.
Australian Associated Press