"Given this variant, which is clearly more infectious, the risks of us catching an infection was going to go up," Giles said on a video call.
"It's a reminder of what this can do a team, and a sports team in particular, right now when we are sort of living at a different rate to society. We are almost misaligned, or at odds, with how society is operating. And that is particularly difficult when you know one case can shut you down, let alone seven."
England's revised, hastily assembled ODI squad includes nine new caps and will be captained for the first time by Ben Stokes and coached by Chris Silverwood, who had been due to take some time off during the white-ball series but has been pressed back into action.
After 10 days of isolation, the initial squad will be back in time to play the T20 series, which starts on July 16.
"We're in unprecedented territory in terms of replacing an entire squad and management team," Giles said, who has drafted in players from all over the country, "and I'm proud of how everyone has come together in order to get it done."
Most of those who tested positive are without symptoms, Giles said, but some have minor, flu-like symptoms.
All players in the initial squad received at least one vaccine jab, but not everyone was fully vaccinated.
England has played matches in Bristol, London, Durham, Cardiff and Southampton in the past 12 days alone. There was a two-match test series against New Zealand in June, while a five-match test series against India starts in August.
"We have extremely busy schedules, and we have been doing this for the last 14-15 months," Giles said. "To expect them to adhere to the sense that they go to the ground, they stay away from each other, they go back to the hotel, put their masks on and go straight back to their room, eat on their own, is almost impossible without losing people.
"It's a knife edge we are working around all the time — looking after our people and keeping them sane as much as anything, and protecting the revenues of the whole game. It's a difficult balance to strike."
British Prime Minister Boris Johnson on Monday set out government plans to lift the remaining coronavirus restrictions in England, saying they should end on July 19.
Giles said cricket authorities would be seeking help from the government to see how this affects sport. For example, would close contacts of a positive test be allowed to continue playing in a fully open society?
"We are hopeful, post-July 19, that some things may change — that we may have more freedoms in the event of a positive case to treat things different," he said. "It's what sport needs going forward."
The new 18-man squad and staff drafted in will need to submit negative tests and complete "bridging protocols" before joining the squad in Cardiff.
That match will take place in front of a 50% capacity crowd, with the second game at Lord's on Saturday representing cricket's first 100% crowd since the pandemic began. The series then concludes at Edgbaston.
Stokes has been pulled out of Durham's English County Championship match against Warwickshire. He had been left out originally by England in a bid to manage his comeback from a finger operation.
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Revised England squad: Ben Stokes (captain), Jake Ball, Danny Briggs, Brydon Carse, Zak Crawley, Ben Duckett, Lewis Gregory, Tom Helm, Will Jacks, Dan Lawrence, Saqib Mahmood, Dawid Malan, Craig Overton, Matt Parkinson, David Payne, Phil Salt, John Simpson, James Vince.
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