The sons of Omicron: New COVID variants — what researchers are seeing, and what they worry about
At the Karolinska Institute, Sweden's largest medical research university situated near the banks of the Klara Sjo canal in Stockholm, virologists and epidemiologists pore over row after row of colour-coded letters displayed on computer screens.
The rainbow-like patterns represent complex genetic sequences of new descendants of COVID-19's Omicron variant that have recently emerged in different countries around the world.
In a specialized lab known as a clean room," where personal protective equipment is worn and positive air pressure prevents contamination, the researchers use primers," synthesized fragments of DNA, to mutate the viral spike gene of SARS-Cov-2, the virus that causes COVID, changing the spike gene to match that of circulating variants.
Then, in a biosafety cabinet, essentially a ventilated laboratory workbench behind glass, they use these genes to produce pseudoviruses, virus-like particles that look just like the SARS-Cov-2 virus on the outside but with altered insides that make them suitable for testing in a lab.
The goal of this work is to understand just how much of a threat these new variants might pose if they are able to get around - essentially escape" - the antibodies many of us have acquired either by getting COVID, or by being vaccinated against it.
A month ago, Karolinska virologist Daniel Sheward and his colleagues were testing the sensitivity of these variants using random blood samples taken from Stockholm residents - many of them vaccinated multiple times or previously infected - when the researchers made a disturbing discovery: Omicron variant BA.2.75.2, a descendant of the BA.2.75 lineage common in India, was proving to be adept at avoiding COVID antibodies, raising the possibility it could thrive even among the vaccinated or previously infected.
The last time we saw escape of this magnitude was the first emergence of the original Omicron," said Sheward, who is the lead author of a recent preprint study outlining the findings.
In our hands, this was the most resistant variant we'd ever tested."
More than two and half years into a global pandemic, Karolinska is one of many research institutes around the world on the cutting edge of monitoring the SARS-Cov-2 virus and drawing attention to what it could do next and what threats it could pose to a world that, for all intents and purposes, acts as if the pandemic is over.
The Star spoke to eight different researchers and specialists about what the next step may be for a virus that has already changed our world. They described a future that could bear witness to the emergence of new strains that, while likely to be widespread because of their immune-resistant properties, are also expected to be less deadly than their progenitors.
In a world with such sons of Omicron spreading across continents, the societal fallout is likely to be felt for years to come.
Whether the pandemic truly does come to an end will depend, in part, on this immune-evading capabilities of BA.2.75.2 and similar variants, and to what extent society takes precautions to protect itself.
For while much of life returns to normal, there is a spectre stalking our future: the potential of some new variant that is not only immune- and vaccine-evasive, but also possibly more virulent than those that have come before it.
What we are seeing so far
The early data around BA.2.75.2 as well as variants BQ.1.1 and XBB, all descendants of Omicron, isn't encouraging.
When viruses such as SARS-Cov-2 replicate, they introduce mutations - essentially tiny mistakes - into their genetic codes. These mistakes result in a variant of the original virus. Most of the time, these mutations don't affect the virus at all. But, sometimes a mutation can give a virus the ability to evade our antibodies and outcompete earlier variants.
Through vaccination or infection, our antibodies learn to recognize the spike protein of a virus and attack it before it can make us sick. But if a mutation has altered the spike protein, the part of the virus that allows it to attach to human cells, our antibodies can have a tougher time recognizing a new variant.
Emma Hodcroft, a molecular epidemiologist at the University of Bern in Switzerland, likens the ability of antibodies to recognize the spike proteins of viruses to how we recognize our friends. Even if our friends change their clothes or hair, we can still recognize them, she says.
But if they change a lot of things at once, like changing their outfit, taking off their glasses, cutting their hair, getting a bunch of piercings and putting their arm in a sling, you might not recognize them anymore. That's essentially what's happening here."
The good news is that our antibodies don't lose all their recognition abilities, just as we would be able to recognize a friend again once we got used to their new appearance.
Our immune systems can do that as well. We can update our recognition keep-up, but we have to see the new thing in order to learn the new face' as it were," she said.
Researchers at Peking University in Beijing recently published a pre-print study that found mutations on what are known as receptor binding domains," parts of the spike protein that are very good at helping the virus get around a person's immunity.
The new variants carry mutations on several of these domains, making them more likely to evade immunity, says Yunlong Richard Cao, an immunologist at Peking University and lead author of the pre-print study.
Cao and his team found that Omicron subvariants BQ.1.1 and XBB were especially antibody-evasive strains, far more so than BA.5, the Omicron variant now dominant in Canada and the United States.
Worryingly, XBB - detected in more than a dozen countries, including India, Australia, Denmark and Canada - seems to be able to avoid antibodies arising from three-dose vaccinations, breakthrough infections of earlier variants and existing monoclonal antibody treatments. Likely the most immune-evasive variant discovered yet, XBB has been dubbed by some alarming headlines a nightmare variant."
Given that most mutations on these hot spots are known to be antibody-evasive, these new variants will gain an advantage in spreading," Cao says.
This ability to skirt around existing immunity, he warns, means there will be a high chance of another wave of infections driven not by one variant, but a collection or swarm" of strains both locally and across larger geographic areas.
Singapore, for example, is already witnessing a wave of XBB, which currently makes up about 55 per cent of new infections. Four weeks ago, barely any XBB had been detected there.
For now, BA.2.75 and its descendants, as well as XBB, are not considered variants of concern, according to the World Health Organization, but they are under surveillance.
Cornelius Roemer, a computational biologist at the University of Basel, noted on Twitter early this month that it is becoming quite clear that BQ.1.1 will drive a variant wave in Europe and North America before the end of November. Its relative share has kept more than doubling every week."
In Canada, as of last week BA.2.75.2 has been detected 77 times, BQ1.1 has been detected 36 times and XBB has been found seven times, according to the Public Health Agency of Canada.
An agency spokesperson said it is too early to tell if these sub-lineages are growing in Canada at present.
The increasing concern around these emerging variants has earned them unofficial Twitter hashtags that spare users from constantly typing awkward combinations of letters and numbers. BQ.1.1 is known as #Cerberus; its parent BQ.1 is known as #Typhon; BA.2.75.2 is being called #Chiron; and XBB has earned the moniker #Gryphon.
Whether or not these new immune-evading variants will lead to worse health outcomes than previous variants is the key question.
So far, the news on that front is encouraging.
The good news - and the worst-case scenario
The evidence to date suggests that while we can expect an increase in the number of cases as these variants spread, the severity of illness will not necessarily be worse than what we have already experienced.
Dr. Peter Juni, professor of medicine and clinical trials at the University of Oxford, says two things have changed the game in our battle with COVID and help explain why outcomes are not expected to be as severe: one, the vaccination of the majority of the world's population; and, two, the infection and reinfection of the population by Omicron and its variants.
This combination of vaccine-induced immunity and infection-induced immunity results in a dramatic decrease in the risk of serious outcomes compared to what we've experienced before," says Juni, who left his post as scientific director of Ontario's COVID-19 Science Advisory Table last summer to take up his post at Oxford.
He says if the new variants had arrived before vaccinations, This would have created havoc in every health-care system and every population worldwide. The reason it doesn't cause havoc is because we have so much immunity now through vaccination and infection in the population."
There is a worst-case scenario, of course.
It is possible, Juni notes, that a variant that is both very good at evading the immune system - and also more virulent than existing strains - could one day arise. In effect, a more severe version of COVID that is not slowed by our vaccine- and infection-derived immunity.
That is what is particularly concerning to Marc-Andre Langlois, professor at the Faculty of Medicine at the University of Ottawa and the executive director of the Coronavirus Variants Rapid Response Network, a group of researchers from across the country created to help the Canadian government respond to variants of concern.
There are some variants out there right now ... that have the possibility of increased transmission and causing severe disease if the immune response doesn't recognize these viruses quickly enough once they infect," Langlois says.
As long as the virus is given an opportunity to infect people, we're giving the virus an opportunity to continue evolving. And we don't know into what the virus will eventually evolve in six months."
The bad news
Even if a new variant becomes dominant but does not prove more deadly, experts are still worried about how our society will deal with a new potential viral reality in which existing immunity might provide less protection against infection.
Hodcroft of the University of Bern notes the new variants are arriving at a time of year when people tend to spend more time indoors with windows and doors closed as the weather gets colder. Perhaps unsurprisingly, this will likely lead to an increase in COVID cases. But this seasonal peak of cases, combined with the arrival of one or more new variants, along with growth of other existing respiratory viruses, such as influenza, could spell trouble for the health-care system.
Of course, even a small per cent of a big number, if you have enough cases, could be enough to put a lot of pressure on our health-care systems, even just because of nurses or doctors being out sick," Hodcroft says. On top of that, we could see impacts on the airlines as we saw this summer, so that could even trickle down to trains, schools or delivery if enough people are sick at the same time.
They don't have to be really sick, just too sick to work."
Ontario's health-care system is already facing intense pressures thanks in part to COVID.
Since the beginning of the year, Ontario emergency departments, primarily in rural areas, have closed more than 100 times, according to the Star's count. Ambulance offload times - the time it takes for a patient to be transferred from paramedics to the care of a hospital emergency department - have nearly doubled in the past three years. An increasing number of seniors needing alternate levels of care has prompted the province to bring in a controversial law that would allow hospitals in southern Ontario to send such patients to faraway long-term-care homes.
For Dawn Bowdish, professor of medicine at McMaster University and Canada Research Chair in Aging and Immunity, the risks of increased COVID cases reach to a societal level and have medium- to long-term consequences.
Long COVID is going to take a lot of people out of the workforce for a really long time," Bowdish says. There will also be a whole slew of middle-age to sort of older working-age people who end up retiring early because of health consequences that are post-COVID or maybe they're caregiving for someone. We already know that the number one reason that people leave the workforce early is chronic health conditions of themselves or someone they care for."
A new Statistics Canada study on long-term effects of COVID finds that about 1.4 million Canadian adults experienced symptoms at least three months after infection. The most common symptom reported was fatigue, followed by cough, shortness of breath and brain fog.
At least 17 million Europeans contracted long COVID during the first two years of the pandemic, according to a September study by the WHO. The study, which looked only at people in the 52 member states in the WHO European region, found a 307 per cent increase in new long COVID cases between 2020 and 2021, and that women were twice as likely as men to contract the condition. In cases severe enough to require hospitalization, the risk of long COVID increases with one in three females and one in five males likely to develop the condition, the study found.
An unhealthy population is a poor population," says Bowdish. We're going to see Canadians collectively are going to be less healthy and live shorter lives than we did in the pre-COVID world."
The fact that the SARS-Cov-2 virus keeps evolving and infecting people essentially presents a dilemma. We are desperate for the pandemic to end - and in many cases act like it's over - yet the more we pretend, the more opportunity the virus has to propagate and evolve.
Humanity has been lucky in that the evolution of the immune-evading variants has not resulted in an even deadlier disease and that most people have enough latent protection from vaccination or previous infection to mount some defence.
For now, those watching the horizon for signs of the next threat are hoping what we have will be enough to defend against whatever comes next.
Kenyon Wallace is a Toronto-based investigative reporter for the Star. Follow him on Twitter: @KenyonWallace or reach him via email: kwallace@thestar.ca