The Bears will try to avenge their season-opening loss to the Buffalo Bills when they take on the San Francisco 49ers this coming Sunday night, but it will take quite the upset to accomplish that feat.

The Niners open their new stadium this week and the emotions will be running high. But that’s not all that will be working against the Bears. A cross-country trip to an area where the Bears have traditionally struggled will be a source of concern. And to top it all off, the Bears have some injuries to some key players that they’ll have to contend with.

Veteran wide receiver Santonio Holmes was added to the roster mid-preseason as a third option to the Bears’ dynamic passing game. But Holmes will be called to duty on Sunday, because the best wide receiver tandem in the NFL — Brandon Marshall and Alshon Jeffery — was injured against the Bills and their playing status is in doubt. Marshall (ankle) and Jeffery (hamstring) were both listed as questionable on the injury report, and their absences would severely hamper the Bears’ chances of pulling off an upset.

The offense will have to turn to running back Matt Forte to carry the offensive load. Forte, who finished with 169 total yards against the Bills, rushed the ball only 17 times in Week 1. The Bears are a pass-first offense and it’s difficult to conceive head coach Marc Trestman straying too far from that formula because it had great success for the team last year, but if the Bears are missing one or both of their dynamic wide receivers, I can’t see how they’ll move the ball without utilizing Forte more.

Jay Cutler has not had much luck against San Francisco in his career. He was out with an injury back in 2012, the last time the Bears played on the road against the Niners. But the time before that, he threw five interceptions in a 10-6 loss back in 2009. Things have certainly changed in the culture of the organization since then. Cutler has a lot more weaponry than he did back then, but his presence in prime time, nationally-televised games has always been a concern.

The offense isn’t the only concern for the Bears heading into this game. Niners quarterback Colin Kaepernick made his first career start against the Bears back in 2012 and lit them up like a Christmas tree. He passed for 243 yards and two touchdowns while systematically dissecting the Bears defense. While I still don’t put much stock into Kaepernick as a passing quarterback this far into his career, there’s no stopping him from repeating that performance if the Bears can’t put pressure on him.

Week 1 was a dud for prized offseason pickup, Jared Allen. The new defensive end was credited with just one tackle and hardly pressured Bills quarterback EJ Manuel. For that matter, Lamarr Houston — the other starting defensive end who is also new to the team — was just as invisible. At least former Lions end Willie Young registered a sack and applied some pressure in the backfield. The Bears will need more out of these three, as well as defensive tackles Jeremiah Ratliff — who had a nice first game against the run — and Stephen Paea.

Although I expect Kaepernick to have his fair share of success passing the ball against this Bears defense, I expect the Niners to run all over the Bears until they can prove to stop it. The Bills racked up 193 net rushing yards and there’s no reason to believe the Bears will be any better at defending it this week. Expect heavy doses of running backs Frank Gore and Carlos Hyde.

Teams that start the season 0-2 generally don’t find their way to the playoffs. According to CBS Sports, since 1990 only 23 of the 198 teams that started 0-2 made the playoffs, a 12% success rate. The Bears are staring down that barrel right now and it’s hard to picture them recovering from that kind of setback. I’m one who doesn’t put much stock into statistics, because I feel that stats tell you what has happened … not what will happen. With each win a team amasses, the percentages of making the playoffs change, so it’s not like it would stay at 12% the rest of the season.

Still, this is a disconcerting situation the Bears find themselves in. I don’t see a clear path to victory. Cowboys running back DeMarco Murray rushed for 118 yards last week against this Niners defense, so I can see Forte finding some daylight this week. But the Bears will also be without starting center Roberto Garza and left guard Matt Slauson, both of whom suffered injuries in Week 1.

Cutler needs to have the game of his life. Forte needs to play like the complete back he is. Shea McClellin needs to show up to play. The defensive line needs to pressure Kaepernick. Lance Briggs needs to find the fountain of youth. And the safeties need to prevent the big play.

If all that happens, the Bears can pull off the massive upset. If not, the Bears will be down 0-2 and looking for answers.

Prediction: San Francisco 31, Chicago 17