School leaders say bubble closures are having a "devastating" impact on pupils as thousands more are being forced home to isolate.
At least 165 schools in Greater Manchester alone have sent pupils home for remote learning after positive Covid tests.
Currently children have to self-isolate for 10 days if another pupil in their bubble tests positive for coronavirus.
The latest official figures showing 239,000 children in England are out of classrooms - as the numbers trebled in the space of a week.
The number of schools affected continues to rise, with education bosses saying the situation has become "relentless".
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While some youngsters have managed to avoid any periods of isolation, many other pupils have had to go back and forth for numerous rounds of remote learning since schools reopened.
Children in Year 5 at Bridgewater Primary School in Little Hulton are on their second lot of isolation since May half term, according to the Manchester Evening News.
They only returned to school last Tuesday after one lot of isolation and have now been told to stay off again.
And many high schools are now having to send entire year groups home because of rising cases - including Droylsden Academy, which has sent Years 7 and 10 to learn remotely, Reddish Vale High, where the whole of Year 10 has been sent home, and Newhouse Academy in Rochdale, where all Year 8s are now home.
At St Anne's RC High in Stockport, some Year 10 pupils were due to return from isolation on Monday, but after further cases at the school, they've been told to stay off for another week so that the whole year group is all learning remotely.
At Little Lever School in Bolton, Years 7 and 8 are both learning remotely because of the number of staff having to isolate.
In a video message to parents, Glyn Potts, head of Newman RC College in Oldham, shared his frustration over the current situation.
He said: "Regrettably we know that we've got over 400 young people isolating at home out of the 1,200 who should be in school, which is just absolutely devastating - and regrettably we've just had another positive case so we're sending home some more students.
"This is just relentless and I accept fully that it's of huge frustration to parents. It is incredibly complex and difficult for us and we have very little say in how we can manage this."
Many parents and school leaders have been calling for "ridiculous" isolation rules to end - saying it's not only having a detrimental impact on children's education and mental well-being, but stopping parents from being able to work.
In Oldham, where at least 3,500 pupils are currently isolating from 94 bubble closures, Gerard Jones, the authority's managing director of children and young people, said "school attendance remains a major challenge".
"We are still pushing for a revision to isolation arrangements and for a decision on vaccinating young people over the age of 12 from the government," he said.
"On Friday overall school attendance nationally was about 83%, whilst in Greater Manchester it was about 76% with a declining trend nationally and locally. These figures are based upon about 65% return from schools, so the real picture is probably worse.
"We would normally expect to see school attendance at about 95% so that’s quite a gap. This will disadvantage pupils from Greater Manchester and the North West if exams return as planned next year."
The rise in confirmed cases is partly due to extra testing being done in some secondary schools again in a bid to detect asymptomatic cases.
Schools were given funding to help set up supervised testing this term as part of a package of support from the government following the rapid spread of the Delta variant in this area.
The bubble isolation system should end as soon as possible, the Children's Commissioner for England has said as some reports say the under-fire system could be scrapped by July 19.
Dame Rachel de Souza said there was an urgent need for children to get back to normal as lockdown restrictions had been a "real trauma" for many young people.
An announcement may be made in the coming days to allow schools time to prepare, with the requirement to quarantine expected to be replaced with a new testing regime, the Guardian reports.
