Will it end with a new generation, a future-proof vaccine or will the virus keep mutating until it eventually runs out of steam?
Two-and-a-half-years in and Australia is in the grip of a fourth COVID-19 wave.
It's predicted to be shorter and sharper than before, but it will not be the last.
So what will the end look like?
Experts differ on what will finally bring this pandemic to a close.
Future-proofing vaccines
Deborah Burnett is on a team at Garvan Institute of Medical Research working on a transmission-blocking or "universal" vaccine.
Since the first variants were identified in late 2020, COVID-19 has mutated to produce multiple variants and subvariants, putting us in what some call a "COVID soup".
New subvariants appear more likely to evade current vaccines (although the vaccines we have now are still extremely effective at preventing serious illness and death).
A "variant-proof" vaccine would target a part of the virus which cannot easily mutate, making it effective against not just the variants we have had so far, but future ones, too, Dr Burnett says.
"There was this idea of herd immunity and, at first, people thought that, maybe, you could get that from natural infection, and then people thought you could get that from vaccines," she says.
"But, unfortunately, the virus has found a way around that by mutating."
In an article in the Lancet medical journal earlier this year, Annelies Wilder-Smith from the London school of hygiene and tropical medicine wrote that, until we have new vaccines that protect against transmission, "public health and social measures will still need to be tailored towards mitigating community and household transmission in order to keep the pandemic at bay".
The team at the Garvan Institute have developed a tool to test and triage multiple vaccines from labs around Australia, to select the most-effective ones, and have seen "promising results" from pre-clinical trials, Dr Burnett said.
"We’re really hoping that, in the next year or two, there is a vaccine available that effectively ends transmission so it will finally be over."
'Running out of ways to mutate'
Professor Robert Booy thinks we are nearing the end of the pandemic — but says it won't come about because of a transmission-blocking vaccine.
"This new wave is a conglomeration of a whole bunch of subvariants but they’re still Omicron — in 12 months we haven’t had a new variant, we’ve just had mutations," Professor Booy, an infectious disease and vaccine expert, says.
The Omicron variant of the SARS-CoV-2 virus has been the only "variant of concern" since Delta was downgraded in June this year.
And, in the year or so since Omicron was first detected, it's spun off into more than 300 subvariants (which we know of).
"My most likely conclusion is to go 12 months without changing variants suggests that the virus is running out of ways to mutate," Professor Booy says.
"And it’s quite clear also that the new infections and the new waves are resulting in less severe diseases and I think that’s because we’ve got hybrid immunity — a combination of vaccine-induced and wild virus-induced immunity."
Vaccinations — and boosters for people who are eligible — still matter, and will "make a real difference" in riding out the latest wave, Professor Booy says.
The current vaccines have dramatically reduced serious illness, and adults with severely compromised immune systems can now get a fifth dose (and there is a push to widen eligibility as cases rise).
And new vaccines are still coming out, including shot-free vaccines and variant-specific boosters.
There are also currently 175 vaccines in clinical development.
'Time for community mandates has past'
COVID-19 will "fizzle out" and, like the common cold, become a virus we get at a young age, says James Trauer, an associate professor at Monash University's school of public health and preventative medicine.
"Children born today, who start getting their first exposure before they hit school, it’s not going to be an issue for them."
Because of this, he says, community-wide mandates are no longer needed.
"I don’t see any role to reducing community-wise transmission. I think we still need to look at reducing transmission in high-risk settings, [such as] hospital and aged care [but] the sort of controls we would need to put in place to reduce community-wide transmission are just not acceptable to people now and not really necessary either.
"The exception to that could be if we’re suddenly hit by a bad variant — but, with each month that doesn’t happen, we can be a little more comfortable that it’s not just around the corner."
He says the focus should shift ahead to the next pandemic.
"We do need to look at sustainable interventions that can protect us from future pandemics and just improve respiratory health generally and strengthen our public health system, and work on social determinants of health, [such as] air quality and building ventilation."
