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A year ago, much of this country — like much of the world — was abiding by stay-at-home orders in hopes of suppressing the coronavirus enough that the lockdowns could be safely lifted.

That strategy turned out to be way too simplistic.

Now, we are racing to give vaccines, hoping enough people will become immune that the whole community, or “herd,” will be protected, COVID-19 will stop spreading, and we can go back to normal.

That is also starting to look too simplistic.

“In November and December, we had a virus that didn’t seem like it was changing much. And we had vaccines. And it looked like we had a simple solution,” said Larry Corey, a University of Washington virologist and chair of a COVID-19 vaccine clinical trials working group. “The concept of herd immunity is a mathematical concept that does sometimes work. But this is not the flu. The entire global population is susceptible. Now, we’re finding that the coronavirus can escape from immunity — and can re-infect.”

The idea that all will be well if we pump out enough vaccines is a “delusion,” Corey believes.

He is part of a growing scientific consensus. In January, the journal Nature surveyed more than 100 immunologists, virologists, and infectious disease researchers working on the virus that has so far killed 2.5 million people, including more than 500,000 in the U.S. Almost 90% of those experts thought the coronavirus is likely to persist, but will evolve into a milder “endemic” form, taking hold in pockets of the globe and sticking around indefinitely. Half of the experts doubted that the virus can be permanently eradicated even from regions with high vaccine coverage and public health measures such as masking.

The prediction that COVID-19 will become less deadly but indelible fits with the history of infectious diseases that originate in animals and jump to humans. The 1918 flu virus that killed 50 million people worldwide evolved into a seasonal version. Even bubonic plague, a.k.a. the Black Death, a gruesome medieval bacterial disease that periodically culled the human race for more than three centuries, is now endemic in parts of Africa and Peru.

On the other hand, the viruses that cause polio and measles were effectively extinguished in most parts of the world by vaccination campaigns. But it wasn’t easy. Those all-out crusades took decades to achieve and sustain herd immunity.

“We’ve only eradicated one virus from humankind — smallpox. And that’s because humans are its only host,” said physician F. Perry Wilson, director of Yale’s Clinical and Translational Research Accelerator. “But I think we can eventually get to very low levels” of COVID-19.

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An adaptable foe

To be sure, COVID-19 vaccines are marvels, arriving in record time and conferring stronger immunity than natural infection.

Experts estimate herd immunity would kick in when 75% to 85% of people are protected through natural infection or vaccination. But already, the shots appear to be sharply cutting hospitalizations in Israel, where about half the population has had at least one dose of Pfizer’s two-dose vaccine, and in the United Kingdom, where three vaccines have been approved. Data from U.S. nursing homes is also encouraging.

Corey, who is also a professor at the Fred Hutchinson Cancer Research Center, believes preventing severe disease, especially in vulnerable people, is the real value of COVID-19 vaccination.

“I have no idea whether we can eradicate it. But eradication is irrelevant if you take the fear out of it because data show you can get sick, but you’re not going to die, alone and intubated, in a hospital,” he said.

The thing is, we are in an evolutionary war with a foe that has shown the ability to adapt quickly to outwit us. For most of 2020, researchers tracking the coronavirus believed it was accumulating genetic changes, or mutations, at a relatively slow rate of about two per month. Recent genomic sequencing, however, suggests constellations of mutations that make the virus more transmissible and more harmful have been arising repeatedly, spontaneously, rapidly, independently — and largely undetected — around the world. Scientists call this phenomenon “convergent evolution.”

In December, just as vaccines were rolling out, a more transmissible coronavirus variant was identified in the United Kingdom; it is now in at least 60 countries, including the U.S., where the Centers for Disease Control and Prevention said it could become dominant this month. Strains were also discovered in Brazil and South Africa that are not only more contagious, but can evade some of the protective antibodies generated by the new vaccines, rendering the shots less effective. The Brazilian variant has even sickened some people who had recovered from infection with the original pandemic strain. That strain, first reported as cases of “viral pneumonia” in Wuhan in December 2019, originated in animals, probably bats.

Vaccine-makers can develop booster shots — Moderna already is — but that puts the herculean task of vaccinating the world’s 7.8 billion people even further out of reach, like a game of vaccine whack-a-mole.

“Vaccine-resistant variants really gum up the works of this whole process” of curbing the pandemic, said Wilson at Yale. “There will need to be a mechanism to get [booster] vaccines quickly.”

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The measures that have made the pandemic socially and economically devastating may also need to be continued.

“We expect many cities, regions and countries to have to resort to another round of lockdowns and mandatory social distancing, at least until ‘second generation’ vaccines are available, covering the novel … variants,” analysts at investment bank SVB Leerink wrote to clients last month.

In all, about a dozen first-generation vaccines are in use in various countries. But the inoculations are so new that many Americans are hesitant to roll up their sleeves. And crucial questions are still under study: How long does immunity last? Can some vaccinated people — like many unvaccinated people — get asymptomatic infections and transmit the virus without realizing it? How well do the vaccines work in people with weakened immune systems or chronic illnesses?

Even if vaccines enable the developed world to quickly douse the coronavirus, it will burn on in poor countries at the back of the line, potentially reigniting global outbreaks. As of last month, 75% of the world’s available COVID-19 vaccine supply had been administered in just 10 countries, while more than 130 countries hadn’t received a single dose, according to United Nations officials.

“You don’t get to low levels of infection in the U.S. with the virus rampaging through other countries,” Wilson said. “But right now, I don’t think there’s the political will” to make vaccine rollouts more equitable.

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Survival of the fittest

As Darwin taught, evolution is about survival of the fittest. A virus will not survive if it kills off all hosts in a geographic area, ending its ability to keep spreading. That’s why, over the long haul, milder endemic forms of infectious disease tend to displace deadlier ones.

One model of the coronavirus’ transition to an endemic virus, developed by researchers at Emory University and Penn State University, predicts that it will eventually be just a minor childhood infection, no worse than the common cold. Adults would be protected from disease by immunity they acquired as kids.

The model extrapolates from what is known about four endemic coronaviruses that cause common colds, plus the SARS and MERS coronaviruses that caused severe disease but did not spread widely after emerging in 2003 and 2012, respectively.

“Social distancing and an effective vaccine are critical for control during a virgin epidemic and the transition out of it, but once we enter the endemic phase, mass vaccination may no longer be necessary,” the authors, led by Emory postdoctoral fellow Jennie Lavine, wrote in the journal Science.

How long might the coronavirus take to morph from an existential threat to a nuisance? That depends on how contagious the virus becomes, and how long immunity lasts.

“This transition may take anywhere from a few years to a few decades,” the researchers concluded.