Isak, who joined Newcastle in August for a reported fee of £59 million, has not played since scoring his second goal for them in a 1-1 draw with Bournemouth last month as he sustained the injury on international duty.
But the Swede has since returned to training after missing Newcastle's victories over Fulham and Brentford, which have lifted the club to sixth in the standings with 14 points from nine matches.
"Isak is making progress but he's not available for this game. We've not picked up any new injuries," Howe told a news conference.
Howe said midfielder Jonjo Shelvey is closing in on a return from a hamstring problem while winger Matt Ritchie is nursing a calf issue and will miss the trip to Old Trafford.
Howe heaped praise on Brazilian midfielder Bruno Guimaraes, who has impressed following his arrival from Lyon and scored two goals in their 5-1 hammering of Brentford.
Guimaraes has been linked by the media with a switch to Real Madrid but Howe said Newcastle "desperately want" him to be happy at the club.
"We want to build a team. We're in the very early stages of that so we don't want to disrupt the group we have, we want to add quality - that's the aim," Howe said.
"... He's fitted in so well and epitomised the team spirit and the drive we need to be successful. The supporters have seen that and taken to him from day one. Off the pitch he's been brilliant. On the pitch he speaks for himself."
