TORONTO -- SARS was eradicated. MERS has rarely spread from human to human.

Every other coronavirus we've discovered, though, remains in wide circulation.

That raises an obvious question: Which way will SARS-CoV-2 go?

Have we missed our window to rid ourselves of it? Now that it's mutating into more infectious forms, is it destined to remain with us for the rest of our lives?

Or is there still a chance that we can take it out for good, that effective vaccinations will eliminate its ability to survive by spreading from person to person?

The World Health Organization (WHO) thinks it's too late for that kind of optimism. Its leaders were openly discussing COVID-19's future as endemic -- that is, permanently circulating -- as early as last May, arguing that even at that time there had been too much transmission of the novel coronavirus for it to ever be fully eliminated.

Back then, the comparison point for WHO emergencies chief Dr. Michael Ryan was HIV. While HIV remains an active virus, it is closely monitored and there are effective treatments. Ryan suggested the virus that causes COVID-19 could end up in the same position.

That's one possibility. Another is that the virus starts attacking its hosts differently or targeting different hosts, becoming even more dangerous.

Ryan referenced this scenario much more recently. Asked Jan. 25 about the possibility of SARS-CoV-2 becoming endemic, he noted the long history of diseases that are now thought of as "diseases of childhood," but started out by attacking all age groups.

"Very often the disease – and this is a sad fact – in historical terms, very often killed many, many people and then as the disease moved into younger people, as older people became immune, the only new susceptibles were in younger kids as they were born," he said.

Another possibility, in-between those two extremes, is that the emergence of COVID-19 variants is hinting at the path forward.

The B.1.1.7 variant was first identified in the United Kingdom, and has been detected in nearly 400 COVID-19 patients in Canada, according to CTV News data. One of its hallmarks is that it appears to be more infectious, spreading more easily from person to person.

That's normal behaviour for a virus, according to Dr. Sumon Chakrabarti, an infectious diseases specialist at Trillium Health Partners in Mississauga, Ont. He told CTVNews.ca that just as humans try to keep viruses at bay, viruses adapt to better evade our defences and to stop themselves from killing too many of us.

"Naturally, with pandemics, you'll see that viruses may start to become more transmissible – but then they become less severe," he said Feb. 3 via telephone.

"They don't want to kill the host. That's not advantageous to it from an evolutionary standpoint."

WILL WE NEED BOOSTER SHOTS?

There are four coronaviruses that freely circulate among human populations, with minimal attempts to control them. They're responsible for various common respiratory infections, including about 10 per cent of cases of the common cold.

Some scientists speculate that these viruses may have been more lethal when they first emerged in the distant past, then mutated over time to better survive without killing their hosts.

Evidence for or against this is limited, because the four coronaviruses jumped from animals to people long before we understood what they were. If it is true, though, it could help explain why the three most recent coronaviruses to emerge – SARS, MERS, and SARS-CoV-2 – are so much deadlier. Perhaps, if they were allowed to run unchecked in the population, they would eventually become less lethal as well.

But nobody knows for sure if that will happen or how long it would take, only that waiting for it would mean a lot more death than the world has seen from COVID-19 thus far.

Vaccines, therefore, are a simpler solution. Most of the major SARS-CoV-2 vaccines seem to work well against the most prominent variants, although there are concerns about the AstraZeneca vaccine's efficacy against the B.1.135 strain of the virus, which is currently dominant in South Africa.

This has raised questions about the possibility of "booster shots" to fight SARS-CoV-2, vaccinations required to be repeated every few years for maximum efficiency, as is the case with the tetanus vaccine.

Colin Furness, an infection control epidemiologist at the University of Toronto, told CTV's Your Morning on Feb. 4 that the simple fact a virus is mutating is not enough on its own to determine whether booster shots will be necessary. The influenza and measles viruses both mutate, he said, but influenza vaccines are reformulated every year whereas the same measles vaccine has worked for decades.

What matters, he said, is whether the part of the virus targeted by the vaccine is also the part that is mutating, and how severe that mutation is.

The established vaccines target the spike protein that helps the virus attach itself to human receptor cells. Researchers have found that the virus is deleting bits of its genetic code to alter the shape of the spikes in order to evade our body's immune response, but to this point, most of the mutations do not seem to be stopping most of the vaccines.

Furness described the novel coronavirus as "a slow mutater," which he said would reduce the need for booster shots over the long term.

"We're going to play whack-a-mole a bit, but I'm hopeful that we will get ahead of it and after a few years of vaccinations, we'll be able to be done – or close to done," he said.

Researchers at Penn State University and Emory University in the U.S. have built a model to simulate SARS-CoV-2 shifting from epidemic to endemic. Their findings, which were recently published in the journal Science, estimate that while the virus "could join the ranks of mild, cold-causing endemic [coronaviruses] in the long run," that could be accompanied by a shift to attacking younger age groups – just as the WHO's Ryan warned.

Once that endemic state is reached, though, the resulting coronavirus could be even less deadly to its human hosts than influenza, the researchers said.

WHY THERE'S NO 'FREE PASS'

Reinfection is another open question when it comes to the novel coronavirus, and an even more important one if the virus becomes endemic.

Although documented cases of someone recovering from COVID-19 and then contracting it again are rare, and generally involve a milder form of the disease the second time around, some experts are now saying that previous infection should not be considered a "free pass."

CTV News Channel Health and Medical Expert Dr. Marla Shapiro said Tuesday that even if a patient's symptoms aren't as severe during a reinfection, their ability to transmit the virus to others remains concerning.

"If you get reinfected, typically it will be more mild, but then there's the societal risk of your ability to pass it on to somebody else who's completely susceptible," she told CTV News Channel.

She said that she can envision a future in which SARS-CoV-2 "stays in the background as a low-grade infection" and requires annual vaccinations.

"The same way that we see flu that is pretty much here to stay and every year we get a new flu vaccine predicting how the strains will drift, it might be that way with COVID as well," she said.

Ryan, the WHO emergencies chief, said in January that the only way he could see SARS-CoV-2 being eradicated is with much stricter public health controls than most of the world has been willing to deploy, along with widespread vaccinations.

"Will this disease continue to transmit? Most likely for a long time … if vaccine coverage lags behind," he said.

"Remember, we've only ever eradicated one disease on this planet, smallpox, and we're struggling against polio and we're struggling to eliminate measles."

With so much of COVID-19's future still an open question, the experts agree, the best approach is to focus on tamping down overall virus activity, reducing its ability to spread and mutate.

"If we don't have COVID-19 under control … more variants will only lead to more virulent variants," Dr. Hassan Masri, an intensive care physician and associate professor of medicine at the University of Saskatchewan, said Thursday on CTV News Channel.

"That's why good control of the disease, in any jurisdiction, has led to not only a decrease in hospitalizations but the lack of emergence of new variants."