NASHVILLE, Tenn. (AP) — The Tennessee Titans just put together their most gratifying victory of coach Mike Vrabel's short tenure.

They spent the past two weeks dealing with the NFL's first COVID-19 outbreak with each morning bringing news of yet another positive test. A game postponed and rescheduled with a second pushed back. Only one practice with two walk-throughs and unrelenting criticism.

The Titans remain depleted. They're also still undefeated.

Ryan Tannehill threw for three touchdowns and ran for another as the Titans routed the Buffalo Bills 42-16 on a rare Tuesday night in a showdown between two of the NFL's five remaining undefeated teams pushed back two days after a couple more positive tests for Tennessee last week.

“What this organization has been through over the past couple weeks to really fight through all of that, shake it all off, really limited practice, limited reps and go out and put this kind of win together, I think makes a statement and I’m happy we were able to do that today,” Tannehill said.

The Titans (4-0) continued their best start since winning their first 10 games in 2008 despite not playing playing their last game Sept. 27 in Minnesota. Coach Mike Vrabel said everyone in the organization would get a game ball after this performance.

“I learned a long time ago is the definition of a pro is they make the hard look easy, so whatever situation we’re presented with we got to all come together and make the best decisions for the team each and every time,” Vrabel said.

Malcolm Butler intercepted two passes, the second he returned 68 yards, and both set up short touchdowns for Tennessee. Kareem Orr’s recovery of a fumbled kickoff set up Tannehill’s fourth TD for 21 points off Buffalo's three turnovers. Kalif Raymond's 40-yard punt return also set up a 1-yard TD run by Derrick Henry.

“We expected to win,” Butler said.

The Bills (4-1) had not won five straight games since 2004, and they came in looking for the franchise's best start since 1991 when Buffalo reached the Super Bowl. They also played without starting cornerbacks with Tre’Davious White inactive because of a back injury and Levi Wallace on injured reserve.

Starting wide receiver John Brown also was out for Buffalo, which had scored at least 30 points in the past three games.

“They were ready to go and at the same time we beat ourselves,” Bills coach Sean McDermott said.

Buffalo center Mitch Morse called this a gut-punch.

"It’s tough, they came out and beat us like a drum," Morse said.

Josh Allen came in second in the NFL in yards passing. He threw for 263 yards and two TDs. Stephon Diggs had 10 catches for 106 yards.

The Titans needed the turnovers with seven key players on the reserve/COVID-19 list led by wide receivers Corey Davis and Adam Humphries and defensive lineman Jeffery Simmons. They also were missing a couple assistant coaches and two players activated off that reserve list earlier Tuesday were scratched.

The Titans got a big boost on the Bills' opening drive.

Allen's pass went off Andre Roberts' hands right to Butler, and he returned the interception 29 yards to the Bills 16. Two plays later, Tannehill hit A.J. Brown, who missed the last two games with an injured knee, for a 16-yard TD for the quick lead.

The Bills tied it up with a methodical 15-play drive converting four third downs, taking advantage of a Titans’ defense playing a pair of rookies in end Larrell Murchison and cornerback Chris Jackson. Allen tossed the ball to Isaiah McKenzie for a 3-yard TD tying it up, the ninth different Bill to catch a TD pass from Allen.

The Titans scored 21 of the next 24 points.

Tennessee led 21-10 at halftime after Tannehill ran in from 10 yards seconds before the half. Butler refused to go down after picking off an Allen throw to Gabriel Davis late in the third, and Tannehill found Jonnu Smith for a 4-yard TD and a 28-10 lead three plays later.

RARE TUESDAY NIGHT

This was the 21st time the NFL has played on a Tuesday and the league's first on a Tuesday night since Dec. 28, 2010, when the Eagles hosted Minnesota on a Tuesday because of a snowstorm. That game was the first since the Boston Yanks played at the New York Giants on Oct. 1, 1946.

HEY YOU

The Titans had roughly 8,600 fans on hand for this game. Tennessee originally was going to have fans Oct. 4 for the first time this season, but the outbreak pushed that game with Pittsburgh to Oct. 25. Zip ties were used to keep fans from switching seats, and neck gaiters were given out.

INJURIES

Titans left tackle Taylor Lewan had been questionable with a shoulder injury, and he went to the sideline late in the second quarter after Bills tackle Harrison Phillips landed on him. Lewan went immediately to the sideline and was replaced by Ty Sambrailo, but he returned in the third. ... Rookie RB Darrynton Evans aggravated a hamstring in the second quarter. He did not return.

Bills tight end Dawson Knox hurt a calf.

UP NEXT

Bills will host Kansas City on Monday night. Safety Micah Hyde denied the Bills got caught looking ahead to the defending Super Bowl champs.

“No, no, no, no. We were 100% focused on the Titans," Hyde said. We knew this game was going to be played one way or another. It was not looking forward to the Chiefs or anything.”

Titans host Texans on Sunday.

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Follow Teresa M. Walker at https://twitter.com/TeresaMWalker

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