After missing last week's Premier League defeat to Aston Villa with an ankle injury, Bruno was back on the bench for the midweek Champions League tie against PSG, although he wasn't used. And he was absent from the squad for Saturday night's defeat at Anfield.
It's understood Bruno hadn't suffered any sort of setback in his recovery from the injury but clearly wasn't fit enough to be considered to play any sort of part in the game.
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Bruno will now be closely assessed in the coming days before a decision is made ahead of the trip to the Etihad, where Newcastle are looking to overturn a two-goal deficit.
Sven Botman and Lewis Miley will also have to be closely monitored between now and Wednesday, with the pair not fit enough to start at Anfield on Saturday night.
Botman dropped to the bench after feeling tightness in his thigh, while Miley has a knee issue.
Joelinton remains absent with a groin problem, and Tino Livramento and Emil Krafth are also sidelined.
Updating on injuries, Howe said: "Sven had a tight thigh and we were under the advice not to use him.
"The reason they were here on the bench is because we were giving them every opportunity to declare themselves fit. And in the warm-up they might have felt different.
"The recovery time is so small you don't always get the information and speed you need. With Lewie, he couldn't bend his knee to sufficient angles to declare himself fit."
Asked whether any of those players will be in contention to return at Manchester City, Howe said: "The best chance we have is Sven and Lewie, who were on the bench today. Bruno I'm not 100% sure, there's a chance. The others no."