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Lukaku put Inter ahead in the 49th minute at the San Siro, but the Bundesliga club responded with a penalty from Ramy Bensebaini in the 63rd minute and a goal from Jonas Hofmann with six minutes remaining.
But Lukaku had the last word sending the ball from close range in the last minute.
Previously, in the same Group B, Shakhtar Donetsk was the leader after hitting Real Madrid 3-2 in Spain.
Antonio Conte’s exhausted Inter had been looking to bounce back from a 2-1 derby loss to AC Milan at the weekend, but was struggling with five players lost to coronavirus.
Winger Achraf Hakimi was ruled out hours before the match, joining four other Inter players who were unavailable due to positive tests: Milan Skriniar, Roberto Gagliardini, Andrei Radu and Ashley Young.
Hakimi joined former three-time Champions League champion Inter from Real Madrid in the summer and had impressed in their first matches.
Matteo Darmian took the place of the Moroccan international with Danish Christian Eriksen starting behind Lukaku and Alexis Sánchez, who was the favorite to start over Lautaro Martínez.
Alessandro Bastoni returned to the group after recovering from the coronavirus, and came off the bench in the second half.
Borussia coach Marco Rose opted for Breel Embolo, Hofmann and Marcus Thuram to support Alassane Plea.
Inter had the best of the first half with Lukaku missing an opportunity to break through just before the break, connecting with a Sanchez cross, only to send the ball into goal.
Lautaro replaced Sánchez for the second half with the Argentine forward nodding widely, before Lukaku broke through in the middle of a fight in front of goal.
But Moenchengladbach leveled from the penalty spot in the 63rd minute when Arturo Vidal’s foul on Thuram was confirmed after a VAR review.
Bensebaini stepped forward to leave Samir Handanovic in Inter’s goal with no chances.
Lautaro shook the post, but it was the Bundesliga team that grabbed second when Hofmann hit a cross from Florian Neuhaus.
The former two-time UEFA Cup champions thought they had done enough, but Lukaku managed the tie at the last gasp for his sixth goal in five games this season.
ea / dj