Watt fell to the ground while engaged in a block on the Chiefs' opening drive. The veteran defensive end was helped to the sideline by the Texans training staff and was looked at in the sideline tent before being taken off on a cart. He was eventually taken to a hospital in an ambulance.
O'Brien also confirmed that outside linebacker Whitney Mercilus will be out for the remainder of the season with a torn pectoral muscle.
"The deal in this league is that the train doesn't stop moving," O'Brien said. "These guys are there, and they're going to have to step in.
"It's going to be multiple guys. You don't replace J.J. Watt or Whitney Mercilus with one guy. That's ridiculous. So it's going to a lot of different guys that are going to chip in to help."
On Monday morning, Watt tweeted to apologize to his teammates and the city of Houston.
I can't sugarcoat it, I am devastated.
All I want to do is be out there on that field for my teammates and this city.
— JJ Watt (@JJWatt) October 9, 2017
Watt, 28, missed the last 13 games of the 2016 regular season because of a back injury. He played in his first regular-season game since his September 2016 back surgery in this season's opener against the Jacksonville Jaguars. In four games, Watt had 13 tackles, but he did not have a sack.