UPDATE as of 8:11 a.m. ET
The Bills have a chance to improve to 5-0, against a Titans team that has been affected by COVID-19. Forget about the "Music City Miracle" replays. The Bills improve to 5-0 heading into a Week 6 TNF showdown with the Chiefs. That's a big line on the road.
Pick: Bills 26, Titans 21
This is a difficult game to write about. The Titans are facing an unprecedented situation in terms of the number of players on their reserve/COVID-19 list and the lack of time in their facility over the last two weeks. In fact, after the latest positive result in Wednesday's round of testing, NFL Network Insider Ian Rapoport reports that the "game being played as scheduled is clearly in doubt." I would take the high-flying Bills, even if everything was normal in this game, and there is nothing normal about this season.
Buffalo Bills 31, Tennessee Titans 20
MDS's take: We're not even sure if this game is going to be played, given the COVID-19 situation with the Titans, but if it is played, I see the Bills winning big.
MDS's pick: Bills 40, Titans 20.
Florio's take: We'll likely be picking this game again, during the week when they play the makeup games. For now, the Bills are too good and the Titans seem to be in disarray.
Florio's pick: Bills 30, Titans 17.
What to watch for: The Titans are without several key players, including Adam Humphries, Jeffery Simmons and Corey Davis, who have been placed on the reserve/COVID-19 list. And the team hasn't practiced or been in its facility to prepare for this game. Keep an eye on how they start the game after having so much time off. If Tennessee gets off to a slow start, this could get ugly quickly. -- Turron Davenport
Bold prediction: The Bills finally get lose in the running game for at least 150 yards. They rank 28th in the league in rushing yards per game, but the Titans rank 29th in rushing yards allowed. It's a true matchup of a stoppable force meeting a movable object. But Buffalo's ranking seems more like an outlier, given its top-10 finish last season and improved backfield. -- Marcel Louis-Jacques
What to know for fantasy: Last week, Buffalo quarterback Josh Allen tied the longest streak in Bills history with his fourth straight game of 280 passing yards and multiple touchdown passes. The only other instance of that for the Bills was Drew Bledsoe in 2002.
Louis-Jacques' pick: Bills 38, Titans 24
Davenport's pick: Bills 35, Titans 21
This is a second straight road game for the Bills, which is always a challenge. The Titans are essentially coming off their bye after the COVID-19 postponement of their game last week. I think the Bills are rolling on offense and the Titans have defensive issues. That plays out as Josh Allen keeps it rolling.
Pick: Bills 30, Titans 27
Will this game be played? That's the big question after the Titans (3-0) had multiple players test positive for the coronavirus this week, forcing the game, originally scheduled for Sunday, to be pushed to Tuesday. That change will force Buffalo's Week 6 game, originally scheduled for Thursday of next week, to be pushed to Sunday, Oct. 18. If Tennessee has even more issues, things could get truly messy.
Whenever this game it played, it should be a good one. The Bills (4-0) have been absolutely dominant on offense, and would have a field day against Tennessee's shoddy defense. The Titans, provided they don't come in with too much rust from a long layoff, could, in turn, be expected to score quite a bit against Buffalo's struggling defense. The Bills should be favored if there is a game, but that is a big if.