Wentz will undergo surgery and there is a wide timetable for a potential return.
"The 5-12 week spectrum is real," Reich told reporters Monday. "We don't know."
Joel A. Erickson of the Indianapolis Star reported Jacob Eason has worked as QB1 with Wentz unavailable.
Given Wentz's injury history dating back to his college days at North Dakota State, drafting the quarterback at all in fantasy likely was a risky move.
Another issue is Wentz hasn't looked very good when healthy recently. His tenure with the Philadelphia Eagles unofficially ended in Week 13 last season when he was benched in favor of Jalen Hurts.
Wentz tied Denver Broncos quarterback Drew Lock for most interceptions (15) in 2020. He also ranked 34th out of 35 qualified quarterbacks in completion percentage (57.4) and was 20th in fantasy points per game among quarterbacks (17.78) in standard-scoring leagues.
The Colts reunited Wentz with Frank Reich, who was his offensive coordinator in Philadelphia from 2016-17, when they acquired him in a trade with Philadelphia during the offseason.
Wentz is in a much better position to succeed with Indianapolis than he was over the previous three seasons in Philadelphia. The Colts have a much better offensive line and better skill-position players to ease the burden on his shoulders.
The switch from Wentz to Eason is certainly going to impact Indianapolis' ability to move the ball. A fourth-round draft pick in 2020, Eason didn't play a snap in a regular-season game as a rookie. The jury is clearly still out on what he can do in the NFL.
Colts wide receivers T.Y. Hilton and Michael Pittman Jr. are going to be severely impacted by the change at quarterback. Hilton's performance has slowed down over the past two seasons due to a combination of age and injuries.
Since putting up 1,270 receiving yards and six touchdowns in 2018, Hilton has 1,263 yards and 10 scores over the past two seasons combined. He's also missed seven games during that span.
Pittman flashed potential as a rookie in 2020, but week-to-week consistency was an issue. The USC alum had a career-high seven receptions and 101 yards in a Week 10 win over the Tennessee Titans but failed to have more than three catches or 66 yards in the final seven regular-season games.
Until Eason establishes himself as a viable quarterback, the best bet for fantasy success from the Colts roster is at running back. Jonathan Taylor ran for 1,169 yards and had 299 receiving yards with 12 total touchdowns in 2020.
Nyheim Hines scored seven total touchdowns on just 152 touches last season.
Expect Reich and offensive coordinator Marcus Brady to feed both running backs a lot until Wentz is able to return. Taylor is a borderline RB1 in fantasy no matter who is at quarterback, while Hines has high upside value as a flex player.