Now host Cameroon must keep its focus in the unusual circumstances, while tournament debutants Comoros surely need a footballing miracle.
That is Tuesday's (AEDT) second knockout game, and it comes after a tussle between Guinea and Gambia in Bafoussam.
Guinea v Gambia 25/01 3am AEDT on beIN 1
Guinea will be without Liverpool midfielder Naby Keita for this one, after he picked up a second yellow card of the tournament late on in the defeat to Zimbabwe last time out.
The clash at Kouekong Stadium is one between teams that finished second in their respective groups, and Gambia will hope their good fortune holds after arguably riding their luck to reach this point.
Tom Saintfiet's Gambia side have outperformed their expected goals (xG) total, scoring three times from an xG of 2.0, while conceding just once despite an expected goals against (xGA) tally of 4.7. The 3.7 gap between xGA and actual goals conceded was the highest of all teams in the group stage.
Gambia faced the most shots of all teams (58) in the group stage, but remarkably they still kept two clean sheets, including when they pulled off a shock 1-0 win over Tunisia.
Guinea underperformed in its shooting, scoring only twice from an xG of 4.0 across its three group fixtures.
Gambia coach Saintfiet said ahead of the game: "We are not afraid as we have been together with the players for over three years, meaning we have cohesion and great team spirit."
One to watch: Amadou Diawara (Guinea)
Guinea are looking to win their first knock-out match at the Africa Cup of Nations at the sixth attempt, having lost all five of its previous such attempts. Roma midfielder Diawara should be a key figure in their efforts to come through this one, bringing his plentiful Serie A experience to bear.
Cameroon v Comoros 25/01 6am AEDT on beIN 1
Considering Cameroon were the top scorers in the group stage with seven goals, Comoros would have liked its first-choice goalkeeper fit for this one. Second choice would have been fine, third choice a salvageable situation. But instead they are all out of keepers, with Salim Ben Boina injured and both Moyadh Ousseini and Ali Ahamada testing positive for COVID-19.
The minnow will hope its chosen emergency goalkeeper proves a revelation at Stade d'Olembe, but the prospects for Comoros appear bleak, despite it reaching the knockout stages with a shock 3-2 win over Ghana.
This will be the first Africa Cup of Nations encounter between Cameroon and Comoros, which on Sunday reported a total of 12 COVID cases in its camp.
Cameroon has reached at least the quarter-finals in eight of its last 10 Africa Cup of Nations appearances, although it has failed to do so in two of the previous three editions (group stage in 2015 and last-16 in 2019).
No doubt licking his lips at the prospect of facing Comoros will be Cameroon captain Vincent Aboubakar, top scorer in the tournament with five goals in the group stage. The last players to score more than five goals in a single edition of the Africa Cup of Nations were Egypt's Hossam Hassan and South Africa's Benni McCarthy (both 7) in 1998.
One to watch: The rookie goalkeeper
Whoever gets the gloves faces a daunting challenge. Cameroon attempted 35 shots in the group stage, more than any other side, and also tried 63 crosses (only Senegal and Egypt had more). Comoros shipped five goals in three games when it had a recognised goalkeeper, losing two of their three Group B games. It should be ripe for being picked off by the home team in Yaounde.