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The Bayer Leverkusen right-back, on-loan from Atletico Madrid, made a sliding recovery challenge on Darwin Machis just eight minutes into the World Cup qualifier and put the ball out for a corner.
However, the opposition winger landed on him awkwardly, causing him to writhe in pain on the pitch.
The 28-year-old's ankle was pointing in completely the wrong direction and Machis, who plays for La Liga side Granada, appeared to be in tears as soon as he saw the damage.
He was initially shown a red card by the referee but VAR later correctly reversed the decision. Arias, meanwhile, spent six minutes on the turf as he was comforted by his teammates and attended to by medical personnel before he was stretchered off and taken to hospital.
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Arias had only recently made the move to Leverkusen for the season after receiving reported interest from Wolves, Everton and Newcastle but now looks for a lengthy spell on the sidelines as he prepares to undergo surgery and subsequent rehab.
He was replaced by Stefan Medina and the hosts were able to recover from the early injury setback to win comfortably.
Duvan Zapata opened the scoring in the 16th minute before his Atalanta teammate Luis Muriel bagged a brace in the first half.
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