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‘It’s not clear yet how it’s going to play out’

Editor’s note: This is the first in a series of three articles on the unknowns we still face around COVID-19. Part 2: A call for better data. Part 3: COVID-19 and animal populations.

 

With the fourth wave of the COVID-19 pandemic well underway, many of the fundamental questions about the future of the pandemic have changed.

What once was “When will we reach herd immunity?” has instead transformed into “What might it look like to live in a world with an endemic SARS-CoV-2 virus?” and “What will it take to get there?”

While a pandemic refers to the global spread of a virus, a virus is considered endemic when it maintains a constant, predictable and manageable presence within a geographic area or population.

With the emergence of more transmissible variants, most experts agree that it is unlikely that we will reach herd immunity, which can only occur when the number of people susceptible to COVID-19 is low enough that transmission cannot be sustained. Herd immunity can be reached either through natural infection or by immunity through vaccination. But there are a number of reasons why the emergence of more transmissible variants like Delta have pushed the likelihood of achieving herd immunity further out of reach.

“It is not going away, so the question really is how long before (SARS-CoV-2) becomes endemic and do we go through subsequent waves on infection before that happens,” says Ashleigh Tuite, mathematical modeller and infectious disease epidemiologist at the University of Toronto’s Dalla Lana School of Public Health. “If you’d asked me this a year ago about how we reach endemicity, I would have been a lot more optimistic.”

We live with a number of endemic viruses that cause respiratory infections in Canada – whooping cough or the seasonal flu, for example. There are a number of factors that must be accounted for in determining endemicity, not only in modelling projections but also in the longer run. In the immediate, we know that the fourth wave is going to be characterized primarily by infections among the unvaccinated, including the more than 4 million children under the age of 12 in Canada who are not yet eligible for vaccination.

How severe these individual infections will be and what longer-term effects COVID-19 infections may present in children is still largely unknown. But we do know that with its increased transmissibility, Delta has the potential to infect a larger number of people than the original virus.

Due in part to Canada’s high vaccination rate, Ontario COVID-19 Science Advisory Table member and infectious disease economics researcher Beate Sander suspects that hospitalization rates in Ontario won’t likely climb to higher levels until the late fall and early winter despite the recent increase in the number of infections.

“School starts in September, of course, so there will be increased contacts because of that,” says Sander. “Then we also have universities opening again in person, which was not happening in September last year. The other critical piece to that is that we have … a really good vaccine coverage rate in adults. But there is a core group of people that just do not want to get vaccinated.”

As of mid-August, 73 per cent of Canadians 12 and over had been vaccinated; including children under 12 who are not eligible for vaccination yet drops the percentage down to 63.9 per cent. “Given the high transmissibility of the Delta variant … if one-third of our population is not going to be vaccinated and as long as we cannot vaccinate the under 12, there’s just no way to do it with vaccines only and have no public health restrictions.”

Tuite says the unpredictability of new variants and of human behaviour has driven a wide range of projected outcomes for the fall, something that is mirrored in the Center for Disease Control and Prevention’s (CDC) amalgamation of projections for the U.S.

“The thing that is notable about the CDC projections … is that they basically covered the entire realm of possibility showing really optimistic looking projections, with minimal transmission in the fall, and then scenarios where it looks like you would have a wave of infection that would be worse than what we’ve already seen,” Tuite says. “I think what that captures is the fact that at this point, what we will see is much more about human behaviour and that’s so hard to predict.”

Tuite notes that human behaviour, which is guided in part by policy decisions, will shape the characteristics of the virus itself by allowing it to spread and continue to mutate, adding to the numbers of unknowns.

Exactly how severe the impact SARS-CoV-2 will be in the long run remains largely a matter of speculation. Although we don’t have exact comparisons, we may be able to find some clues from past pandemics. The 2003 SARS-CoV-1, or SARS,  outbreak was brought to an end as the result of strict public health measures and containment. But SARS-CoV-2 is much more transmissible and the high number of difficult-to-track asymptomatic infections means that an approach based solely on isolating symptomatic individuals won’t be enough to end this pandemic.

Other historic pandemics have eventually reached endemicity. The 1918 H1N1 flu virus spread over 1918-19 in two to three major waves, killing between 50 and 100 million people. The pandemic only winded down as a degree of natural immunity was afforded to those who recovered. But the 1918 H1N1 strain of influenza became endemic and emerged in smaller seasonal outbreaks over the next 40 years. Genetic descendants of the original H1N1 virus can still be found in modern influenza viruses. This includes the new H1N1 virus – responsible for 2009 “swine flu” outbreaks.

The newness of SARS-CoV-2 and the slippery nature of new variant mutations means there’s still a lot that we don’t know about how this pandemic plays out in the longer run.

For those seeking answers to how and when the SARS-CoV-2 virus will mutate and what that might mean for its human hosts, there are several things we know to look for but for which we don’t yet have definitive answers.

We know that some viruses do eventually evolve to become less pathogenic to their hosts in favour of widespread transmissibility. But there are viruses – such as Ebola – that continue to be extremely lethal to their human hosts. For University of British Columbia’s COVID-19 Research Lead Jeffrey Joy, it’s still too soon to say whether Sars-CoV-2 will evolve to become more dangerous.

“When and how we’re going to reach endemicity depends on how the virus evolves, the type of immunity that people acquire and the interplay between those key factors,” Joy says.

Viral mutations and the punch that they pack depends in part on structural changes to the viral molecule itself. Delta is currently the dominant variant of concern in North America due in large part to several mutations in its spike protein that have allowed for greater transmissibility. The protein is the part of the virus that allows it to bind to human cells and release its genetic material. So far, researchers have recorded 10 mutations in the Delta spike protein allowing for increased transmissibility. The most recently documented, the P681R mutation, largely may be to blame for the efficiency and speed with which Delta has been able to cleave and fuse to host cell membranes.

The unpredictability doesn’t end at the viral mutations that occur as a result of random changes in the virus’s genomic sequencing. Our relationship to the virus in the long run will also depend on how our immune systems adapt and the long-term effectiveness of our vaccines.

“I think we would need more data on the duration and persistence of immunity looking around the world. There seems to be a variation in how well that’s working out,” Joy explains. “If you look at Israel, it doesn’t seem to be going so well in terms of how long immunity is lasting. Whereas in the U.K., the initial immunity definitely does seem to be lasting a little bit better, so we need to understand what’s going on between those two places.”

So far, scientists don’t know whether the decreased severity of the U.K.’s illness burden is due to a stronger degree of natural immunity or an intervention approach like the longer delay between the first and second vaccine doses. It is also unclear whether it’s simply a matter of whether the worst is still to come or if it’s related to some other entirely unknown factor.

The many unknowns posed by the behaviour of individuals and policymakers, and the subsequent emergence of new variants, leave us at one of the more uncertain points of the pandemic.

“How to manage it long term is of great interest to me, and it’s not clear yet how that’s going to play out,” says David Earn, a professor and researcher of mathematical epidemiology at McMaster University as well as a member of Health Canada’s Expert Group on Modelling Approaches. “I don’t think there’s any obvious way that you can think of that would get rid of the SARS coronavirus at the moment. There don’t seem to be prospects for that. But we live with lots of viruses. We successfully control a bunch of childhood infections like measles, mumps, rubella whooping cough … and chickenpox through vaccination. One could hope that we could do that going forward with COVID-19.”

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Maddi Dellplain

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Maddi Dellplain is a B.C.-based journalist and Master of Journalism student at the University of British Columbia.

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