Quins' trip to Worcester on Friday was first to fall after the Twickenham club revealed they would be unable to pick a front row because of one positive test and its domino effect on other players needing to self-isolate as part of contact tracing protocols.
And for a second successive weekend, Irish will be inactive after they returned a number of positives from the latest round of testing which, combined with their contact tracing procedures, means they cannot field a team against Northampton on Sunday.
The news comes on the day that Premiership Rugby (PRL) reported its highest number of positive cases since testing began in July.
A total of 951 players and management from the 12 top flight clubs were tested with 33 people from 10 clubs returning positives, 24 of them players and nine members of staff.
The PA news agency understands that PRL has no plans at this stage to implement a 'circuit-breaker', but all measures will be considered by the body responsible for running the league.
In total, four of this season's 30 Premiership games have now been cancelled because of coronavirus.
Quins returned one positive test for COVD-19 after their Boxing day defeat by Bristol but the knock-on effect has been to whittle down their options at prop and hooker to the point they are unable to play.
All seven players affected enter a 10-day isolation period and in addition, the club have stood down the entire squad from training for a week in order to "minimise the use and possible contamination of the training facility".
Irish have shut down their training ground in response to the continued spread of COVID-19 through their ranks a week after they were forced to cancel their match against Bath at the Recreation Ground.
However, director of rugby Declan Kidney insists it is the intervention of Public Health England and not a shortage of players that prevents them from running out at Brentford Community Stadium.
"It's obviously a huge disappointment for everyone connected to the club that we're unable to go ahead with the fixture," Kidney said.
"We're disappointed because we feel we still had a strong group of players to select from, but due to Public Health England guidelines, we've been told we're not allowed to play the game.
"It's clear that the entire country, especially here in London which is the epicentre of the virus, is at a critical juncture with this current phase of the pandemic.
"Of course it is frustrating, but the health and safety of the players, staff, supporters and public at large is our priority at this time as the country continues to navigate its way through the pandemic."
Under PRL regulations Worcester and Northampton are set to receive four points and, as the clubs responsible for the cancellations, Harlequins and London Irish two.