The new year is traditionally seen as a time of fresh beginnings, renewed vigour, and bright-eyed optimism.
Instead, many of us have entered 2022 with heavy hearts and dragging feet. The COVID-19 pandemic has now rounded the corner into its third year, and has brought along its usual bag of tricks - surging case numbers, over-burdened healthcare systems and widespread anxiety.
Does COVID in 2022 just hold more of the same, or could this be the year that things finally turn around? Cosmos talked to Monash University Malaysia molecular virologist Dr Vinod Balasubramaniam about the COVID landscape we're likely to face in year ahead.
"The virus will not be eradicated," Balasubramaniam says, crushing that hope right off the bat.
"Only one disease, smallpox, has ever been eliminated."
Instead, we've shifted the goalposts. Realising the impossibility of elimination, Australia and many other nations are taking the first steps along the road to endemicity - stripping COVID of its virulence a step at a time, until we can consider it little more of a threat than a seasonal cold.
This is an end-point that Balasubramaniam believes is within our grasp.
"2022 will be the year we finally have all the means, measures and tools to control the pandemic to a non-lethal state.
"Eventually, COVID-19 will become endemic - transmission will remain at a steady rate, following seasonal patterns, with fewer spikes in infection. The harm caused may end up somewhere between that of influenza, which kills an estimated 300,000 to 650,000 people annually, and of other coronaviruses, such as the common cold."
Central to the race towards endemism is our collective immunity. Australia's national double-vaccination rate is now above 90 per cent, which ranks among the top 20 most vaccinated nations globally. And yet, with the emergence of Omicron, our case numbers continue to skyrocket. Breakthrough infections are becoming commonplace. Should we be concerned?
"Immunity to any pathogen, including SARS-CoV-2, isn't binary like a light switch, where you either switch on or off," explains Balasubramaniam.
"Instead, it's more like a dimmer switch: The human immune system can confer varying degrees of partial protection from a pathogen, which can stave off severe illness without necessarily preventing infection or transmission."
It's this partial protection that paves the way to endemicity. The partial-protection effect is one of the reasons that existing endemic coronaviruses, such as the one that causes the common cold, produce such mild symptoms. Exposure to these viruses during early childhood lays the foundation for the body's future immune response, and provides enough of a head-start in fighting off new variants that they rarely progress beyond a sniffle.
"Past studies make clear that partial immunity can keep people from getting seriously ill, even as coronaviruses successfully enter their systems," Balasubramaniam says. "Long-term, the same is likely to be true for the new coronavirus, including the current Omicron strain."
This means that our biggest concern is reducing severity, rather than stopping infections. Although evidence suggests that we will need at least one booster shot to achieve acceptable protection from Omicron, we can be confident that our collective vaccination efforts are making headway in the long-term trajectory of the virus. While this new and highly virulent strain has shown itself capable of evading our neutralising antibodies, which are our primary line of defence, Balasubramaniam explains that these are not the only munitions that our immune systems can muster.
"Immune responses are layered and redundant," he says. "Where one layer falters, another can swoop in to help.
"Findings suggest that T cells trained by vaccines or previous infections will respond aggressively to Omicron, rather than standing by. In addition to that, all the vaccines generate memory B cells, which produce high levels of neutralising antibodies if they see the virus or its variants again. Memory B cells, once generated, are long-lasting and this is observed in all vaccinated individuals despite the threat from Omicron."
Balasubramaniam believes that Omicron could prove instrumental in enabling endemicity, acting as a "live attenuated vaccine" that could protect us from deadlier strains such as Delta.
"People infected with the heavily mutated Omicron variant of COVID-19 may have increased immune protection against Delta according to a recent study from South Africa," he says. "If Omicron displaces Delta and proves more mild than past variants, the incidence of COVID-19 severe disease would be reduced and the infection may shift to become less disruptive to individuals and society."
There are some important caveats in this discussion of increasing immunity. While Australia's vaccination rate is pleasingly high, the pandemic won't be over until we can achieve similar results across the globe.
"Endemicity is still a long way off for most countries," says Balasubramaniam. "By 2023, COVID-19 will be on the way to becoming just another manageable disease in wealthy countries, but will still be deadly to billions in the poor world. Of the more than 7 billion doses administered so far, less than 3 per cent have been in countries on the African continent."
The developed world's failure to provide equitable access to vaccines is not only unethical - it's epidemiologically unwise and has the potential to significantly prolong the pandemic.
"We are giving the SARS-CoV-2 virus the room it needs to thrive through uneven and inconsistent national policies to reduce transmission, some of which are undermined by division and politicisation," says Balasubramaniam.
"Every time the virus reproduces inside someone there's a chance of it mutating and a new variant emerging. This is a numbers game. It's a random process, a bit like rolling dice. The more you roll, the greater the chance of new variants appearing. It's basically a ticking timebomb."
Building global immunity will be crucial in breaking the vicious cycle of viral replication and mutation, and the continued spread of the disease.
"The virus will continue to affect our lives and livelihoods unless the global community collectively addresses inequitable access to vaccines, therapeutic agents and diagnostics," says Balasubramaniam.
Until we can coordinate a concerted effort at improving global immunity, the spectre of emerging variants will continue to haunt us.
"Newer variants are inevitable when it involves RNA virus," says Balasubramaniam.
"The virus replication machinery is error prone and each time the virus jumps from person to person, the possibility of creating new variants is always high."
Could things take a turn for the worse? Could we see a variant with the severity of Delta, and the virulence of Omicron?
It's possible, but not probable. Although the potential for mutations remains high while global immunity languishes, evolutionary pressures on viruses generally favour transmissibility over lethality. On this front, COVID may already have approached its limits.
"Viruses generally don't like too many mutations, as it affects their fitness over time," says Balasubramaniam.
Having already amplified its transmissibility in the Omicron variant, there may be little room for further mutations on this front. This is good news: even if deadlier variants arise, it's unlikely that they will be able to compete with Omicron or other highly transmissible variants.
This suggests we should start to move away from looking strictly at case numbers, argues Balasubramaniam, because accepting viral circulation is a key part of endemicity - what we really want to know is how well we're coping with it.
"We will continue to see increases in the number of cases since newer variants will likely still be able to infect vaccinated individuals.
"What we should be looking is the number of severe cases, hospitalisation rate, and mortality."
This recentres our focus on addressing the symptoms of COVID infections, rather than micromanaging the spread.
While we wait for our collective immunity levels to strengthen over time with boosters and repeated exposures to new variants, we need to ensure we don't become complacent about the virus.
Even if, as Balasubramaniam hopes, we are on track to developing sufficient immunity to enter an endemic phase, the threat to human health that COVID poses remains pressing.
"Although COVID-19 is seen as a disease that primarily affects the lungs, it can also damage many other organs, including the heart, kidneys and the brain," says Balasubramaniam. "Organ damage may lead to health complications that linger after COVID-19 illness."
It remains vitally important, if we are going to accept the circulation of COVID in our population, that we continue to develop innovative new treatments to reduce disease severity.
"The clinical management of COVID-19 has come a long way since the early days of the pandemic," says Balasubramaniam. "The availability of effective monoclonal antibodies, dexamethasone, and other treatments have meaningfully increased the chances of survival for those with access to high-quality healthcare."
As well as improving our existing treatments, exciting new therapies are beginning to appear, he says.
"Recent results from Merck-Ridgeback Biotherapeutics and Pfizer on their oral antiviral drugs Molnupiravir and PAXLOVID, respectively, represent a material advancement and increase the chance that the impact of the Omicron variant can be controlled. In its final study, Pfizer reported that PAXLOVID reduced risk of hospitalisation or death by about 89 per cent for high-risk patients and about 70 per cent for standard-risk patients."
Results such as these hold the promise of significantly reducing the risk of progression to severe disease, potentially enabling many more cases to be treated as outpatients, thus easing the pressure on our beleaguered hospitals and their staff.
Importantly, manufacturing small molecules for oral therapeutics is much faster than the process for making monoclonal antibodies, which allows them to be made in large quantities. They are also simpler to administer in lower-resources regions than injected or infused treatments, making them potentially game-changing for the most disadvantaged global populations.
The pandemic has been a crushing weight on our shoulders for the past two years, but we mustn't let weariness weaken our resolve.
"All pandemics end," says Balasubramaniam. "The COVID-19 pandemic will end, but it is not over yet. Already, we have endured two years of missed opportunities, missed education, missed connections with family and loved ones. Without action, 2022 could be the same. But it doesn't have to be.
"We're certainly on the yellow brick road to endemicity by 2023, but vigilance is key if we are to continue on this trajectory. There are still hurdles to overcome and some that are being left behind as we race to build immunity."
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