Clough has already seen seven players drop out of the carefully-constructed summer regime and admits they could now struggle to be in his thoughts for the opener at home to Bristol Rovers on 7th August.
“Pre-season is very important. For those who do a full pre-season they've got that foundation straight away and it will hopefully last for that long nine months,” he said.
“We've had six or seven players already who have had to isolate for 10 days and they are going to be behind.
“That 10 days they've missed I don't think they will catch up.
“We're looking ahead to the first game three weeks on Saturday and it puts them in doubt as they will be behind fitness-wise.
“It can affect you throughout the season.
“They are going to have to to try to catch up as quickly as possible, but it's very difficult for them to fit into normal training and do the amount of work that the others have done in that 10 days.”
Clough said the Covid setbacks were inevitable with the current rising rate of infections.
“As soon as you get everyone back in together it's a problem,” he said.
“I think it first started with the partner of one of the players.
“He had to self-isolate then there were a couple of pings and we have just taken all the precautions.
“The lads have been outside most of the time. But, when you include the Academy, we've got something like 75 people coming back to work in the first week of July, so it is inevitable.
“Our physio Tom takes all the precautions that he possibly can. But with this new variant it's very difficult to protect everybody.
“I think we have had one or two positive tests but no real symptoms so I think we're okay from that point of view.”
He added: “Some won't be back until after the weekend, so we will have to assess what condition they are in when they come back.
“That's the next stage on Monday and see if they can play any part against Grimsby on Tuesday.”
Clough is otherwise happy with how players are shaping up, adding: “It's all about hard work, rest, and getting as many minutes on the pitch as they can.
“They need to build a bit of foundation work, but they have been doing that in the summer anyway which is why we've started the games programme a little bit earlier.
“It's about game time now and a little bit of work off the pitch.”