The 2020 Penn State running backs room, which once had an All-America candidate, two talented sophomores and a pair of promising freshmen, is now down two.

Noah Cain, last year’s second-leading rusher as a freshman and the starter in Saturday’s season opener at Indiana, is out for the season, head coach James Franklin said Tuesday.

Cain carried three times for 13 yards on the opening possession of the game before leaving. Franklin did not disclose the nature of Cain’s injury but the player was seen on the sideline with a walking boot on his left foot.

“Love Noah, so much respect for Noah,” Franklin said at his weekly news conference. “He really had an unbelievable offseason and worked really hard for this opportunity.”

Redshirt junior Journey Brown, the team’s top rusher with 890 yards in 2019, already is sidelined with an undisclosed medical condition and could miss the entire season. Franklin declined Tuesday to give an update on Brown’s condition when asked about it.

So that leaves three running backs – sophomore Devyn Ford and true freshmen Keyvone Lee and Caziah Holmes – available for Penn State when third-ranked Ohio State comes into Beaver Stadium on Saturday night.

Ford rushed for 69 yards in 20 carries in Saturday’s overtime loss, including the much-discussed 14-yard run for the touchdown that he wasn’t supposed to score, and gave the Hoosiers 1 minute, 42 seconds to come back and tie the game. Lee and Holmes combined for 11 carries and 51 yards, with Lee catching two passes for six yards.

The Lions now have three running backs in very different roles from less than a week ago. Ford, who averaged just over four carries and 24 yards in 12 games last season, now must get accustomed to being the lead back.

“I just think you’re going to have to change your mentality,” Franklin said. “It’s one thing when Noah was the starting back and Devyn was going to rotate in and be a complimentary piece, to now being the guy. I think he’ll grow into that. There’s no doubt that he has the talent to do that, and there’s no doubt that we believe in him. But there is a difference between being the lead dog and a rotational piece.”

Franklin said that Lee and Holmes, a pair of four-star recruits from Florida, have shown “flashes of really good things” in preseason, but now must prepare for increased responsibilities after beginning the season No. 4 and No. 5 on the depth chart.

“We thought we would have a little bit of time to let them gain some experience, maybe not in big moments early on, and let them grow into that,” he said. “But here’s where we are. They’re both extremely talented. We have a lot of belief and confidence in them. But experience matters and we’ve got to speed up that maturation process a little bit for them.”

With quarterback Sean Clifford rushing for a career-high 119 yards, including a 35-yard touchdown run, the Nittany Lions gained 250 yards on the ground against Indiana.

Franklin admitted that he and new offensive coordinator Kirk Ciarrocca were working on getting comfortable with each other in the season opener but denied that had anything to do with the confusion late in regulation on Ford scoring when he was supposed to gain a few yards and go down.

“Obviously whenever you have a new staff and you have some changes, you’re still working through those things and getting comfortable,” he said. “Will we be better in game two, just getting more comfortable with everybody and how Kirk calls a game and how we operate and all those types of things? Yeah, I think that’s natural.”

Franklin also disclosed that a player whom he did not identify returned a positive result in COVID-19 testing before the game and was unable to play. He said the test later turned out to be a false positive, but the player’s father was upset about it.

“His son was hurting,” he said. “I don’t want to speak for the administrators and presidents but, the way I understood it, we were just putting health and welfare as the priority in a way that still gave us a chance to have a season and try to balance those two topics. Neither one was going to be perfect but we tried to balance it the best we possibly could.”