Howe thanked Newcastle's travelling fans for "supporting the team" during the game, but the away end then expressed their anger towards Isak after the full time whistle when they chanted "one greedy b\*\*\*\*\*d".
Isak wasn't involved as Newcastle kicked off their Premier League season with a 0-0 draw against rivals Aston Villa.
Afterwards, Howe said "nothing has changed" with the striker, who has been training alone since expressing his desire to join Liverpool.
Howe remains hopeful Isak can be reintegrated in the future, and said: "The door is well and truly open. He has to decide what he wants to do.
"Alex is in control of what he does, I'm not in control of him."
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But Isak's conduct this summer has clearly and understandably angered supporters.
Howe said: "I'm not going to have a big opinion on that.
"The supporters acted really well today because they supported the team.
"That's always my big ask. They've done that unbelievably well during some difficult moments over the years.
"Not everything is plain sailing. We've had some tricky moments, as you know, but they've always been with the team.
"Afterwards, if they want to say something, they're very free to do that."
Howe added: "We never doubted the supporters would be right behind us. They always have been, they've never left our side in any difficult moment.
"I was really proud of that connection between them and us. At the end of the game, that's always a beautiful moment when we thank them for coming and they thank us for our efforts."
Howe was then asked whether the full-time chant brings home the need for a resolution to the Isak situation.
"We would like a resolution," he said.
"When I say we, I'm talking about myself, I'm sure the ownership, everyone, the players, because we need that clarity this season. "Any season will be hard enough without any kind of distraction to swerve your thoughts or unbalance what we're doing.
"I'm not in control of that. There's only one person who can control that."
It's understood Isak's absence at Aston Villa will lead to a club fine.
Howe said: "Other people are dealing with that issue. I'm concentrating on the team and our next game."