New England offensive tackle Isaiah Wynn is one of four Patriots to start at different positions on the offensive line this season. Winslow Townson/AP Images for Panini

For the third straight game, the New England Patriots started a different offensive line combination on Sunday, and this one lasted less than 11 minutes.

Hjalte Froholdt started at right guard on Sunday against Denver, making his NFL debut as a lineman. The fourth-round draft pick in 2019 missed his rookie season because of a shoulder injury. Steven Senne/Associated Press

When right tackle Jermaine Eluemunor suffered an ankle injury with 4:26 remaining in the first quarter against the Denver Broncos, more alterations were made to a unit that was already shorthanded.

Hjalte Froholdt, a fourth-round draft pick in 2019 who missed his rookie season because of a shoulder injury, made his offensive lineman debut in the NFL by playing right guard.

Rookie Micheal Onwenu started at right guard but also played right tackle and left guard. Isaiah Wynn, who started at left guard, went back to his normal left tackle spot, and rookie Justin Herron, after starting at left tackle, played became the right tackle.

Meanwhile, Joe Thuney was at center instead of his normal left guard spot because of the absence of David Andrews and James Ferentz.

For a line that was already mixing and matching, there was a lot of shuffling that went on in the loss to the Broncos.

“It was a big challenge,” said Coach Bill Belichick. “Playing without guys, getting guys hurt, moving around, had some guys that haven’t played together much, hadn’t practiced together much.

“We need to get on the field, we need to practice, we need to develop some continuity as a team, but especially there.”

The Patriots went into the season shorthanded when tackle Marcus Cannon opted out because of the COVID-19 pandemic. Andrews, who missed last season because of blood clots in his lungs, suffered a thumb injury in the second game against the Seattle Seahawks and required surgery. After missing three games, he is eligible to return Sunday afternoon against the San Francisco 49ers.

Right guard Shaq Mason missed the loss to the Kansas City Chiefs because of a quad injury, then went on the COVID-19 list the day before the game with the Broncos. Ferentz, brought up from the practice squad to start at center against the Chiefs, also went on the COVID-19 list last week.

So the Patriots finished the Denver game with two rookies picked in the sixth round (Herron and Onwenu), plus Froholdt making his debut – joined by Thuney and Wynn.

The Patriots had never practiced with that combination of linemen working together.

“The more injuries or more issues you have, the more multiples come into play,” said offensive coordinator Josh McDaniels. “I give our guys a lot of credit. We had a lot of guys play multiple positions and prepare to play multiple positions last week. They deserve a lot of credit for being able to go in there and function.

“Some guys played on the same side of the line of scrimmage, like Isaiah (at) left guard, left tackle, and you had Justin who played on the left side, right side, same thing with Mike.

“It’s a challenge, but that’s what we prepare hard for. Our guys prepared hard last week for all the potential possibilities we might encounter on Sunday, and they went out there and played hard and lined up and did their job for the most part and gave us a chance.”

Quarterback Cam Newton rushed for a team-best 76 yards, but three running backs managed only 41 yards on 15 carries. Newton was sacked four times and the Broncos had seven quarterback hurries.

Help should be coming in the near future with Andrews and Mason rejoining the starting lineup at some point, but it has been an unsettled situation.

Wynn, Thuney, Onwenu and Herron have all started at more than one position because of the injuries and illnesses.

“Definitely with the game of football, it’s one of those things that happens,” said Onwenu. “We do preach next man up, so everyone’s able to step in. We’ve got faith in anyone to step in and be able to complete the job.

“It would have been nice to practice and get those reps and get that repetition going on. We have to compete and do our job.”

Thuney had never played center before stepping in for Andrews in the game against the Las Vegas Raiders in Week 3. He went back to left guard against the Chiefs, but when Ferentz tested positive, it was back to center.

“It really comes down to doing your job in the position you’re in,” said Thuney. “That’s just kind of the business we’re in. We’ve just all got to execute better as an offensive line, and it starts with me.’

The Patriots practiced Wednesday afternoon, giving them a chance to get the offensive line situation straightened out.

“I can’t wait,” Onwenu said prior to practice. “These last two weeks didn’t feel normal. I’m a rookie and I haven’t been here, but there’s a lot of uncertainty and everyone’s going along as we get the information.”