The incident occurred shortly after Sunderland had taken the lead through a deflected Nordi Mukiele strike. In a desperate attempt to recover a loose ball, Romero appeared to be nudged by Black Cats forward Brian Brobbey, causing the Argentine international to lose his footing and collide with his own goalkeeper, Antonin Kinsky.
The impact was immediately identified as serious by those on the pitch. Sunderland midfielder Noah Sadiki was seen frantically gesturing for medical personnel to rush onto the field as both Tottenham players remained down. The Stadium of Light fell silent as trainers attended to the pair for several minutes, with backup goalkeeper Brandon Austin initially readied to replace the struggling Kinsky.
While Kinsky was eventually able to continue after having a protective bandage wrapped around his head, the situation was more distressing for Romero. The Argentine World Cup winner was visibly shaken and eventually helped to his feet, but wasn't able to continue, and could not hide his despair as he made his way toward the touchline.
The sight of the usually uncompromising defender in floods of tears resonated with the travelling support. It marks the second major injury scare for Romero in recent weeks, following a concussion-related substitution during a high-stakes Champions League clash against Atletico Madrid last month.
To make matters worse for the visitors, the debut of De Zerbi was further marred by a frustrating intervention from VAR.
Before the injury drama, Tottenham thought they had a lifeline when referee Rob Jones pointed to the spot after Randal Kolo Muani appeared to be brought down by Omar Alderete and Luke O’Nien.
However, after a recommendation to review the footage at the pitchside monitor, Jones opted to reverse his original decision, much to the anger of the Spurs bench.
Mukiele’s 61st-minute goal, which took a massive deflection to wrong-foot Kinsky, ultimately proved to be the winner. The result leaves Tottenham languishing in 18th place and in very real danger of relegation, especially if they now lose Romero for any significant period.
Tottenham will need to win their next game when they host De Zerbi's former club Brighton next Saturday, having slipped two points adrift of safety.