Southampton's miserable season hit a new low with an embarrassing 0-1 exit from the FA Cup against Burnley on Saturday, while Everton were defeated 2-0 by Iraola's Bournemouth.
Pep Guardiola's troubled side were rocked when Jamie Donley's long-range effort came back off the bar and rebounded in off City goalkeeper Stefan Ortega to give Orient an early lead at Brisbane Road. City finally drew level after 56 minutes when Uzbekistan defender Abdukodir Khusanov deflected in Rico Lewis's shot for his first Manchester City goal since signing from Lens in the January transfer window.
Guardiola had to turn to his bench more than he would have liked just four days before a mammoth Champions League play-off round first leg against Real Madrid. But the introduction of De Bruyne made the difference as the Belgian midfielder scored the winning goal 11 minutes from time. Victory came at a cost for City, though, as new midfielder Nico Gonzalez hobbled off just 22 minutes into his debut after a £50 million ($62 million) move from Porto.
Bottom of the Premier League and seemingly destined for relegation, Southampton got no respite in the FA Cup as second-tier Burnley won 1-0 at St Mary's. Scott Parker's team went in front after 77 minutes when Marcus Edwards scored from close-range on his debut after signing on loan from Sporting Lisbon. Edwards, 26, was once compared to Lionel Messi before being released by Tottenham and rebuilding his career in Lisbon. It is almost 600 minutes since Championship promotion chasers Burnley last conceded a goal, with 10 clean sheets in their last 11 games.