It may not be long before Manuel comes back, but 2-3 doesn't feel nearly as good as 3-2, and while the Bills aren't out of the playoff hunt at this early stage in the season, they can't afford to lose momentum on the season as quickly as they did on Thursday night.
The Bills and Browns were tied at 17 when Manuel was injured at the tail end of a drive. The Bills offense was beginning to find its stride, and running back Fred Jackson punched it in for the go-ahead touchdown, 24-17, shortly thereafter. But the Bills didn't score another point from there in a 37-24 loss.
There is obviously no comparison between Manuel and his backup, Jeff Tuel.
The big-bodied, big-armed, mobile No. 16 overall pick has a bit more upside than the unassuming, dink-and-dunk undrafted free agent out of Washington State. Each threw 20 passes, but only one put together four scoring drives. The other led his team to four consecutive punts and only a single drive that lasted more than five plays.
The latter of those two also threw the game-clinching interception, a pick-six to safety T.J. Ward.
Clearly, if the Bills are without Manuel for an extended period of time, they'd like to make life as easy on Tuel as possible. The Bills ran the ball for 142 yards with Manuel at quarterback, but just 13 yards with Tuel under center.
Running backs Fred Jackson, C.J. Spiller and Tashard Choice picked up 141 yards rushing and averaged 4.7 YPA. The running game should be the focal point of the offense, whether it's Tuel or Manuel passing the ball.
As for who that will be, the future is murky in that respect, as it appears Manual will be out four weeks at minimum.
The offense came into focus because of the injury and the game-ending pick-six, but the Bills defense yielded more than expected to embattled quarterback Brandon Weeden. Cleveland starting quarterback Brian Hoyer left the game with a knee injury of his own in the second quarter, opening the door for Weeden's return. At first, it looked like that would play into the Bills' hands.
It took the Browns some time to get things going, but Weeden took advantage of cornerback Aaron Williams on a trio of long throws that gave the Browns all they needed to take the lead and keep it.
Manuel is not the only injury the Bills could be dealing with. C.J. Spiller was a game-time decision, safety Jairus Byrd and cornerback Stephon Gilmore have both missed every game this season, and they also lost wide receivers Stevie Johnson and T.J. Graham during the game.
Now, the Bills—who were riding high off a huge win over the defending Super Bowl champion Baltimore Ravens and looked poised for another win over the Browns—could quickly lose ground on the season.
The Bills' next four opponents have a combined record of 13-3, and two of those teams are undefeated.
All is not lost for the Bills, however. Manuel was trotting on the sideline after the injury, as if he was warming up on dropbacks. He was also spotted riding a stationary bike for much of the remainder of the game.
There is hope that Manuel could return as soon as a month, but the Bills' hope for the season fades more the longer he's out.
Erik Frenz is also a Patriots/AFC East writer for Boston.com. Unless otherwise noted, all quotes obtained firsthand or via team news releases.