Non-league Chorley knocked coronavirus-ravaged Derby out of the FA Cup with a surprise 2-0 win on Saturday, while West Bromwich Albion suffered an embarrassing exit against Blackpool as the spiking pandemic took its toll on the third round.
Derby were forced to play with only Under-23 and Under-18 players after their first-team squad and interim manager Wayne Rooney were ruled out following a virus outbreak at the Championship club.
Chorley, from the sixth-tier National League North, took advantage of Derby's weakened line-up, all making their debuts and with an average of 19, to reach the fourth round for the first time.
It was Chorley's third league scalp in the FA Cup this season after previous wins against Wigan and Peterborough.
In freezing conditions, with snow cleared off the pitch before kick-off, Chorley went ahead after 10 minutes when Derby failed to clear a long throw and Connor Hall nodded over the line.
Chorley's modest Victory Park ground is so homely that one fan was able to watch from over their back garden fence, while two others used a cherry picker crane to get a glimpse of the action.
Those enterprising fans saw Chorley's Mike Calveley seal their side's memorable success when he poked home from close range in the 84th minute.
The cup upset was a welcome boost for Chorley manager Jamie Vermiglio, whose job as a primary school headteacher has been thrown into chaos by the current national lockdown in Britain.
"It's a very proud moment for us. Credit to our boys, they've been on a journey and we said it before the game, the journey can continue today and it has done," Vermiglio said.
West Brom were victims of an upset at Bloomfield Road as third-tier Blackpool won 3-2 on penalties after a 2-2 draw.
Sam Allardyce's side, second-bottom of the Premier League, featured seven changes and they needed goals from Semi Ajayi and Matheus Pereira to send the tie to penalties.
In the shoot-out, Kyle Edwards, Darnell Furlong and Pereira all missed to hand the 1953 FA Cup winners a memorable victory.
There was relief for Premier League bottom club Sheffield United when they won their first game in nearly six months after beating League One (third-tier) Bristol Rovers.
An early own-goal from Joe Day had put the Blades in front only for Alfie Kilgour to level the scores. The top-flight side re-took the lead thanks to Oliver Burke just before the hour mark only for Rovers to hit back three minutes later through Max Ehmer. But just 60 second later, Jayden Bugle scored what turned out to be the final goal of the game to seal a 3-2 win for Chris Wilder's side.
Premier League high-fliers Leciester ran out comfortable 4-0 winners at Championship (second-tier) side Stoke City, courtesy of goals from James Justin, Marc Albrighton, Ayoze Perez and Harvey Barnes.
Norwich City strolled to a 2-0 win over fellow Championship side Coventry City after midfielder Kenny McLean and forward Jordan Hugill scored inside seven minutes.
Millwall's Danish striker Kenneth Zohore and defender Shaun Hutchinson led the Championship side to a 2-0 win over fifth-tier third-round debutants Boreham Wood, while Nottingham Forest beat Cardiff City 1-0 with an early goal by striker Lyle Taylor.
Luton Town beat Reading 1-0 in another all-Championship clash to reach the fourth round for the first time since the 2012-13 season thanks to midfielder George Moncur.
Headers from Wayne Routledge and Viktor Gyokeres ensured Championship outfit Swansea comfortably made through with a 2-0 victory at League Two Stevenage.
Josh King netted his first two goals of the season as Bournemouth of the Championship swatted aside League Two Oldham with a 4-1 victory at the Vitality Stadium.
King also set-up Rodrigo Riquelme, after David Brooks and Dylan Bahamboula, from the penalty spot, exchanged first-half goals.
Another Championship side overcame League Two opponents when Sheffield Wednesday defeated Exeter 2-0 at St James Park. A goal in each half from Adam Reach and Callum Paterson did the damage.