Non-league Chorley knocked coronavirus-ravaged Derby out of the FA Cup with a surprise 2-0 win on Saturday, while West Brom 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.
There are growing concerns over whether the English season should be halted as the new Covid-19 variant wreaks havoc.
Liverpool beat virus-plagued Aston Villa 4-1 in the FA Cup third round on Friday, with their opponents missing the entire first-team squad and boss Dean Smith due to a Covid outbreak.
Southampton's third-round tie against Shrewsbury on Sunday has been postponed after several positive tests at the League One team.
A record-high 40 positive tests were detected among top-flight players and staff in the week between December 28 and January 3 and four Premier League games have already been postponed this term.
Newcastle boss Steve Bruce and Leeds manager Marcelo Bielsa claim there is a moral argument to suspend all matches with the UK death toll from the virus reaching a new high this week with 1,325 deaths reported on Friday alone.
- West Brom woe -
For now, the FA Cup action goes on and 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.
After 21 winless games, Sheffield United finally earned a victory as Jayden Bogle's strike clinched a 3-2 success against third-tier Bristol Rovers.
Chris Wilder's 100th win as Blades boss was the first for the Premier League's bottom club since defeating Chelsea in July.
Leicester rested Jamie Vardy and James Maddison at second-tier Stoke but still won 4-0 as James Justin, Marc Albrighton, Ayoze Perez and Harvey Barnes all netted.
Everton needed extra time to see off second-tier Rotherham 2-1 at Goodison Park.
Cenk Tosun scored his first Everton goal since November 2019 in the first half and Abdoulaye Doucoure won it in the 93rd minute.
Top-flight strugglers Fulham prevailed 2-0 after extra-time in their west London derby at QPR.
Burnley edged past third-tier Milton Keynes Dons 4-3 on penalties after Matej Vydra's stoppage-time equaliser for the Clarets rescued a 1-1 draw.
Among Saturday's other third-round ties, Manchester United host Championship club Watford and holders Arsenal face Newcastle at the Emirates Stadium.
The highlight of Sunday's fixtures sees eighth-tier Marine at home to Jose Mourinho's Tottenham, while Manchester City play Birmingham and Chelsea entertain Morecambe.