When will COVID-19 be endemic? The four factors that will shape the virus’s future

People enjoy drinks at a bar in Toronto on March 30, two weeks after the Ontario government lifted capacity limits in all indoor public spaces. Provinces have cut back all or most of their measures to combat the spread of COVID-19, but a sixth wave of the virus is a growing possibility.Nathan Denette/The Canadian Press

On the surface, the spring of 2022 could hardly look more different than this time in Canada two years ago. Back then the country was shutting down as COVID-19 hammered an unprotected population for the first time. Now, with most public-health restrictions lifted, Canadians are trying to get on with life and – to the extent possible – leave the pandemic behind.

But in one respect, the situation remains uncannily similar to that first COVID spring: Once again the future is unusually obscured by unknowns. This time, it’s not because COVID-19 is a brand new threat. On the contrary, we have come to know it quite well. What has changed is that we’re attempting to live with it in a more permanent way.

Not since the start of the pandemic has the future seemed so difficult to read.

“We’re in a place of incredible uncertainty,” said Christopher McCabe, who leads the Edmonton-based Institute for Health Economics. “But even in the face of that uncertainty we do need to plan, and we need to plan in a systematic way.”

The world Dr. McCabe and his colleagues are planning for is the one in which COVID-19 is considered endemic. Scientifically, the word simply means the disease is consistently present and infecting some fraction of the population.

However, an endemic virus also implies a level of predictability that has not yet been demonstrated with COVID-19, mainly because of the continuing emergence of new variants. That includes the more transmissible version of the Omicron variant, known as BA.2, which a World Health Organization report last week said has now become the dominant variant of COVID-19 globally.

In Canada, genomic surveillance suggests that BA.2 makes up a growing share of total cases and is spreading at a rate that is roughly 1½ times faster than its predecessor.

But the data are limited because widespread testing was phased out when the first Omicron wave arrived at the start of the year and saturated testing capacity. In urban areas, routine sampling of wastewater of COVID genes has helped to fill in the picture of how much BA.2 is present in the population, but compared with individual case reports it’s a more challenging signal to interpret.

Meanwhile, as mandatory masks and proof of vaccination requirements disappear, individuals are increasingly being left to make their own calculations about what precautions to take.

This, in turn, makes it harder for epidemiologists to determine how individual behaviour will influence the further spread of the virus. Diverse levels of immunity owing to vaccination and previous infection also complicate the picture. While the takeover of BA.2 is fairly certain, its impact on the health system is not.

Looking beyond the BA.2 horizon, the situation gets murkier.

Epidemiologists point out that there are many possible futures that meet the definition of an endemic disease and some are less appealing than others.

EPIDEMIC, PANDEMIC, ENDEMIC:

WHAT'S THE DIFFERENCE?

The WHO defines these terms not by the severity of a disease, but the degree to which it has spread

EPIDEMIC

Epidemic refers to an increase, often sudden, in the number of cases of a disease above what is normally expected in that population in that area. Yellow fever, smallpox, measles, and polio are prime examples of epidemics.

PANDEMIC

Pandemic refers to an epidemic that has spread over several countries or continents, affecting a large number of people. This wide geographical reach leads to large-scale social disruption, economic loss and general hardship.

ENDEMIC

Endemic refers to the constant presence of a disease or infectious agent in a population within a geographic area. This makes the disease spread and rates predictable. Malaria, for example, is endemic in certain countries and regions.

MURAT YÜKSELIR / THE GLOBE AND MAIL, SOURCE:

COLUMBIA UNIVERSITY MAILMAN SCHOOL

OF PUBLIC HEALTH

EPIDEMIC, PANDEMIC, ENDEMIC:

WHAT'S THE DIFFERENCE?

The WHO defines these terms not by the severity of a disease, but the degree to which it has spread

EPIDEMIC

PANDEMIC

ENDEMIC

MURAT YÜKSELIR / THE GLOBE AND MAIL, SOURCE:

COLUMBIA UNIVERSITY MAILMAN SCHOOL OF PUBLIC HEALTH

EPIDEMIC, PANDEMIC, ENDEMIC: WHAT'S THE DIFFERENCE?

The WHO defines these terms not by the severity of a disease, but the degree to which it has spread

EPIDEMIC

PANDEMIC

ENDEMIC

MURAT YÜKSELIR / THE GLOBE AND MAIL, SOURCE: COLUMBIA UNIVERSITY MAILMAN SCHOOL OF PUBLIC HEALTH

For example, if everyone in Canada gets COVID-19 on average about once a year – a scenario that is easy to picture given waning immunity and the limited ability of vaccines to prevent the transmission of Omicron – then the fraction of the population that is infected at any given time would be about 1.4 per cent (based on an estimated five days to clear the virus). At that level COVID-19 would be less prevalent than the common cold, but it would still place an additional burden on population health and productivity – an impact that would grow if the disease circulates at even higher levels.

Caroline Colijn, a mathematician and disease modeller at Simon Fraser University in Burnaby, B.C., compared the effect with what might happen if rates of smoking were to suddenly increase. While that may not necessarily strain hospital capacity, it would produce a negative effect with consequences for people and the health care system. More to the point, she said, those consequences would likely be felt disproportionately across different population groups. “What are the inequalities in how this risk lands?” she said. “Whose lifespan is shortened the most?”

The question illustrates why many experts say the best path forward is not one in which people simply resign themselves to a life with more sickness and its associated costs, but rather one in which they remain alert to the changing risk of COVID-19, and act accordingly.

Based on what is currently known, here are four factors that are most likely to influence our interaction with COVID-19 through the rest of this year.

Virus evolution

Since the start of the pandemic, natural selection has favoured the emergence of variants that are better able to spread through the human population. In Canada, Alpha, Delta and Omicron each drove their own wave of the pandemic and each became dominant by being the most transmissible version of the virus around. That pattern is unlikely to stop. The question is to what extent future waves will have the same impact in a highly vaccinated population such as Canada’s.

SARS-CoV-2, the virus that causes COVID-19.NIAID/NIH via AP

The next few weeks could provide an answer. Based on its properties, the BA.2 subvariant is set to provide another surge in infections just as public-heath measures are falling away. However, the evidence so far does not suggest BA.2 causes more severe illness than other forms of Omicron. And while vaccines have been less effective at preventing infection by Omicron, including BA.2, they continue to be effective at preventing severe disease. This should lessen the chances that BA.2 will force another lockdown even as cases go up.

A different concern is the prospect that a new variant will emerge that evades current vaccines completely. Such a change would be favoured by natural selection and it could arise through a process called recombination, in which viruses from different lineages swap genes to help gain an edge. A current example of recombination is Deltacron, the nickname for a group of Delta variants that sport the Omicron spike protein, which the virus uses to attach to human cells.

Marc-André Langlois, a virologist at the University of Ottawa who leads Canada’s Coronavirus Variants Rapid Response Network, said that Deltacron is unlikely to present a vaccine evasion threat since both of its parent lineages are susceptible to vaccines. But signs of recombination may prove to be the harbinger of something more serious.

“What we’re more worried about is what happens when a variant jumps into an animal host that is co-infected with other coronaviruses,” Dr. Langlois said.

In the worst-case scenario, if a variant can gain a new function that outmanoeuvres existing vaccines, such as an entirely different spike protein, it could reset the pandemic by once again placing the entire population at risk. The response would be to develop and distribute a reformulated vaccine, but this would take time. This explains why monitoring the variants that are circulating in animal populations, such as Canadian white-tailed deer, will remain a high priority in the months ahead, Dr. Langlois said.

A man gets a Pfizer booster shot in Montreal.Graham Hughes/The Canadian Press

Vaccines and antivirals

The tool kit for fighting COVID-19 has been growing in the past six months and will continue to do so as over-the-counter antiviral medications become more accessible.

While reducing illness, these may also help to cut down on disease transmission by allowing those who get infected to clear the virus more efficiently. In the meantime, vaccines can be deployed strategically to blunt approaching waves even when they are not as well tailored to the new variants.

“What you’re essentially doing is transiently pumping up the number of antibodies,” said Matthew Miller, an immunologist at McMaster University. “Even though they’re not ideally matched to the current variants, if you get enough of them they can protect us from getting infected.”

While new vaccines will eventually come on line to take over from those available now, he said, it is unlikely they will play a major role this year.

Among the most promising avenues are inhaled vaccines that stimulate an immune response in the respiratory tract – the point where the virus enters the body. McMaster is one location where such vaccines are currently in early stage clinical trials.

Further down the road, vaccines that target multiple virus proteins apart from the spike could prove more effective at thwarting new variants. The catch is that such vaccines require a longer testing period, Dr. Langlois said, since each additional protein that a vaccine targets creates the potential for unintended side effects that must be ruled out before the vaccine is approved by regulators.

Montrealers line up outside a COVID-19 testing site.Graham Hughes/The Canadian Press

Data gathering

Experts have argued that one of the most important tools for managing the next phase of COVID-19 will be the smart use of data to track the virus at a time when COVID testing is becoming less extensive.

Writing in the journal Nature, Natalie Dean, a biostatistician at the University of Florida, last month advocated for a co-ordinated program of random testing in the United States to better understand where and how the virus is circulating.

Dr. McCabe said that such an effort should be considered in Canada, possibly on a monthly basis.

“We do need that just to be able to capture the underlying prevalence,” he said. The sample might be designed to include a higher proportion of individuals who are most at risk of exposure, such as health and hospitality workers who would serve as an early warning group. The objective would be to help public-health officials stay ahead of future waves of COVID-19 with the added benefit of providing status checks on other respiratory illnesses including seasonal flu.

On the response side, Dr. McCabe said that more data sharing is needed to better illuminate how well various measures worked at preventing disease spread in the first two years of the pandemic and to inform a more targeted response in future in order to avoid further lockdowns.

“Ideally we would want to be in the position to be able to say here’s our evidence-based playbook,” he said.

A woman wears a mask and face shield at sunset on West Vancouver's Ambleside Beach.Darryl Dyck/The Canadian Press

Human behaviour

Perhaps the biggest unknown in the coming months is how people will respond to the strategies and measures that are recommended by the evidence. After two years of multiple waves plus the rise of new variants that are increasingly harder to contain, some of the limits of public compliance have become apparent.

An additional shift in public perception has been the recognition that vaccines have changed the equation by cutting down on the risk of severe disease even as infections continue to spread.

Waning immunity coupled with variants that are better at evading vaccines has meant that proof of vaccination has become a less meaningful indicator of whether someone can transmit COVID-19.

All of these factors have served to normalize COVID-19, removing some of the urgency that was present in earlier waves and, in turn, increasing the odds that individuals will risk infection through the choices they make.

None of this is a surprise, but it will be a problem if people disregard public-health advice when a more virulent form of the virus emerges.

“We need to be nimble,” said Sarah Otto, an evolutionary biologist at the University of British Columbia. “That means getting back to normal – but cautiously – and then digging in when we need to.”

How that plays out over the coming months will be a revealing indicator of what life with an endemic coronavirus will look like, possibly for years to come.

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