While the Dunedin City Royals remain in a handy position, Mosgiel and Green Island have been ravaged by the virus.
Both admit to being underdone heading into the South Island league, which begins this weekend.
They will join seven Mainland region teams to play a full 18-match league, the top two teams advancing to a national league later in the year.
Mosgiel coach Malcolm Fleming said his team was four weeks away from being ready.
It had not had a full squad training — at one point it had had 13 players with Covid-19 and a further nine in isolation.
Between that and opponents falling in similar circumstances, the team had not played a preseason friendly.
With a strong Royals team in wait this weekend, Fleming said adapting would be key.
"It’s a matter of knuckling down," he said.
"This will be the test for the players — how tough are they?"
Mosgiel qualified for the league due to Otago University not meeting an off-field requirement to gain a licence.
Fleming was aiming for a mid-table finish.
"When we decided to go into this last year, we had a meeting with all the players.
"We said, ‘Are you guys interested?’, and 38 of the 39 said, ‘We’re keen as mustard’.
"It’ll be interesting to see how much of that comes true with our backs against the wall."
Shane Carvell’s Green Island squad had also been hard hit, as it prepares to travel to play Nelson Suburbs this weekend.
The team had managed one preseason match although it had been similarly hampered in its buildup.
Carvell said there was a sense of dread about getting messages of newly confirmed cases within the squad, and felt the team was "a week or two" behind where it needed to be.
It battled towards the bottom of last year’s league — a seven-game competition in a transition year — and came up with a 3-2 win over Coastal Spirit in its final game.
That taste from last year would be key going into this year’s full-blown league.
"I think we certainly are aware of what we face, a lot more than what we were last year," Carvell said.
"Playing local football is a good standard, but going into a South Island league, the standard goes up a notch or two even further.
"That’s what we experienced last year. I think the lessons that we learnt and took on board have prepared us for what we face this year."
The Dunedin City Royals have fared the best of the southern teams.
Coach Richard Murray said the squad had managed the virus well, and the side’s increased depth had helped offset the outbreak’s impact.
It had picked up a strong cohort of players from University, as well as several others new to Dunedin, while carrying virtually its entire roster from last year.
After just being pipped by Selwyn for the second national league spot last year, it had high hopes this time around.
"We’re not in it just to be in it," Murray said.
"We’ve picked up some depth and quality in different spots. We want to kick on this year.
"We were a bit disappointed we missed out on that national series last year.
"This year, obviously, we want to go that one step further, even two steps further, and win the league."