Newcastle will hold their first official training session of 2022 on Thursday with a host of the club's most high-profile players unavailable after recently contracting the coronavirus.

All positive cases are isolating at home, while their remaining teammates will be required to undertake rapid antigen tests before each training day.

While the Knights have not disclosed how many players have been infected, Gardner confirmed it was "a substantial number".

There have been unconfirmed reports that number is in double figures.

Gardner said if, as appears likely, the recent Omicron surge continues during the season proper, extraordinary measures will be needed simply to field a team each week.

"This year, it's looking like a top 36 won't be enough," Gardner said.

"It could be more like a top 60. So we're going to have to condition them to be ready.

"All your reserve graders are going to need to be ready to play first grade.

"If a club has a bad run, they could be down to using under-21s to fill in.

"I think the rules we've seen in previous years won't be the rules we're playing by this year.

"It'll be very much a case of next man up."

Adding to the complexity of the situation, it might not be logistically feasible for players in NSW Cup and under-21s to abide by the same stringent biosecurity restrictions as their NRL counterparts, who are full-time professionals.

With regards to the NRL squad, Knights coach Adam O'Brien and his new physical-performance manager Hayden Knowles face a huge challenge to get the players in shape for trial matches in late February.

Newcastle's first pre-season hit-out is against Canterbury on February 21, and they face Sydney Roosters in the season opener on March 12.

Players were given an extended 10-week break at the end of last season and then the Knights were forced to start their Christmas-New Year holiday ahead of schedule, on December 16, after a young player and club employee tested positive. Understandably given all the time off, there is concern that some players may not be as fit as they usually are at this point in the pre-season.

"We need to get the miles into their legs and get them in condition so they can play," Gardner said.

"Our first trial game is on February 21. So the boys are going to have to be ready.

"March is going to come around pretty quickly."