Aston Villa lost Emiliano Buendia a few days before Mings' injury due to a significant knee injury expected to sideline him for eight months.
The loss of crucial defender Tyrone Mings to an injury in the first half was even more disappointing for Aston Villa boss Unai Emery than his team's 5-1 defeat against Newcastle United.
"It doesn't look good. He is injured. This week has been very tough. We lost Emi Buendia, and today we lost Tyrone Mings, two important players in the squad," Emery told the BBC.
"Everything this week is not working well, but we are going to react. I want to be positive with the players we have, and we can change the situation."
Newcastle scored four goals in the second half to overtake Villa and take the top spot in the standings, as Villa's defence collapsed after Mings departed the pitch.
"We're very pleased. It was a tough game, Aston Villa are a very good team. We knew we had to be at our best. We scored five; we could have scored more, but they were also in the game," Howe told the BBC.
"It was a tight game decided by our ruthlessness in front of goal. Everything clicked for us today ... Now we have to go to Manchester City, which is the hardest place to go. We've got to embrace the challenge and then of course, Liverpool, but we will focus on Man City first," he added.