In a Race Against an Ever-Changing Virus, Are We Losing Ground?

Laird Harrison

July 21, 2021

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

A year ago, scientists looking at the future of the COVID-19 pandemic felt optimistic. Vaccine development was zooming toward unprecedented achievement. And unlike the viruses that cause influenza or AIDS, they thought, this virus — SARS-CoV-2 — couldn't mutate to evade the fully primed human immune system.

"Thankfully, SARS-CoV-2 does not seem to have evolved any such tricks yet — suggesting that we still have an opportunity to stem its spread and the pandemic by pursuing a relatively straightforward vaccine approach," wrote two Yale University immunologists in a July 31, 2020, essay for The New York Times.

Those were the days.

Since then, the United Kingdom, South Africa, India, and Brazil have all discovered "variants of concern" — mutant strains that spread more easily and may cause more severe illness.

The new kid on the block, the Delta variant first detected in India, appears to be far more contagious than the original virus. It is quickly becoming the dominant source of new COVID-19 cases everywhere, causing an uptick in new cases even where large percentages of the population have been vaccinated.

At the same time, the effort to vaccinate the whole world is hitting such significant barriers that the hope of extinguishing the virus this way has quickly faded.

"I think there is broad consensus that the virus will not go away," Amalio Telenti, MD, PhD, chief data scientist of the San Francisco, California-based Vir Biotechnology company, told Medscape Medical News.

Vaccines a High Hurdle to Virus

That doesn't mean that COVID-19 death tolls will continue to climb indefinitely, or even reach the heights of last winter. The virus has not yet developed the ability to completely escape the immune response stimulated by the best of the current vaccines.

"What we've seen with the data is that — at least with the mRNA vaccines — they provide great efficacy against the Delta variant," Ravina Kullar, PharmD, MPH, an infectious disease specialist and epidemiologist at the University of California Los Angeles, told Medscape Medical News. But it does mean that humanity is facing a fight that could extend into the foreseeable future.

From the start, epidemiologists talked about "herd immunity," the condition where such a high proportion of a population is immune to a disease that it can't find enough new hosts to continue replicating. That can happen naturally if enough people become infected.

In the beginning of the pandemic, a handful of scientists argued that allowing widespread infection provided the quickest option for containing the virus through natural immunity. That approach quickly fell into disrepute as epidemiologists calculated the millions of deaths that would result.

And there is no guarantee that natural immunity can knock a virus out. Often a virus evolves to evade the immune response, reinfecting more people until they develop new immunity. This results in waves of contagion that ebb and flow over time, as occurs with influenza.

Vaccination offers a slower but much safer approach to crushing a virus. That happened with smallpox, eradicated worldwide in 1980 after decades of global vaccination efforts. In addition, vaccination may be more effective than natural immunity. That appears to be the case with SARS-CoV-2.

It Comes Down to Math

But so far humanity has not been able to eradicate any other viruses besides smallpox through vaccination. The success of such an effort depends on multiple factors, including the efficacy of the vaccine and other health measures such as — in the case of SARS-CoV-2 — social distancing and masking.

The race between the evolution of the virus and the vaccination of human beings boils down to a math problem. On average, everyone infected with the original SARS-CoV-2 that emerged in Wuhan, China, infected 2.5 other people. Epidemiologists calculated that by immunizing 70% of the population, vaccines could decrease that average to less than 1 new person infected, causing the virus to dwindle away.

People infected with the Delta variant, by contrast, appear to infect more people — estimates range from 3.5 to 7 new infections. That raises the bar for herd immunity as high as 85% of the population.

Vaccination efforts at the moment don't appear likely to achieve that level. In many countries where the vaccines are widely available, the rate of new vaccinations has fallen, putting them behind schedule to reach even the original target of 70%.

At its current rate, the US won't hit that proportion until December. But 11% to 14% of Americans say they don't want to be vaccinated if they have a choice. Add that to 10% who want to "wait and see," and herd immunity in the US looks out of reach.

In some low-income countries, the prospect of herd immunity looks even more remote: only about 1% of their populations have been vaccinated so far.

So why did scientists think herd immunity was ever possible? The first pictures of SARS-CoV-2 suggested a virus that would only evolve slowly.

Coronaviruses have the ability to proofread their genetic material when they replicate. This makes mutations less likely than with many other viruses. And the virus was under little evolutionary pressure because it had plenty of fresh victims with no immunity.

But as the virus spreads, encountering more and more people and more and more immune responses, mutations become more likely. "If you put it in hundreds of millions of people, more variations are going to arrive," John P. Moore, MA, PhD, a professor of microbiology and immunology at Weill Cornell Medicine in New York City, told Medscape Medical News.

Some scientists think the virus can never change enough to totally escape immunity generated by the vaccine. These vaccines stimulate antibodies that attack parts of the spike the virus uses to latch onto its host's cells. In the most contagious variants, including Delta, the virus has changed parts of its spike, making it less susceptible to the antibodies.

The vaccines still stimulate antibodies that attack other parts of the spike, so their effectiveness is only partially diminished. In addition, the vaccines stimulate cellular immunity, a process by which immune cells destroy the infected cells before they can release viruses.

"We have growing evidence now that the cell-mediated immunity that is also elicited after a natural infection and after vaccination is preserved against the variants," said Pauline Vetter, MD, an infectious disease specialist at Geneva University Hospitals in Geneva, Switzerland.

Additional doses of vaccine, booster shots with improved formulas, and even completely new types of vaccine are all under research.

Is a Finish Line in Sight?

Could the virus run into an evolutionary cul-de-sac? "You can't mutate the spike proteins indefinitely without them losing some function," Moore said. "They're not infinitely plastic. And yet, you could imagine there are some variants that could be worse."

The complex interaction of these factors and others — such as the durability of the immune response — makes forecasting the future of the pandemic difficult.

But most experts think it won't go away. In a survey of 119 immunologists by Nature, 89% said they expect the virus to become endemic, "one that continues to circulate in pockets of the global population."

In that way it could resemble the flu, perhaps waxing and waning with seasons, worse one year, better another year as both virus and the defenses against it evolve.

Parts of the world could approach herd immunity through vaccination. In the US, that could mean whole states, or perhaps cities. "We're not going to have a national herd immunity, but we are probably close to herd immunity in significant regions of the country," Moore said. "I live in Manhattan. Life is pretty normal."

In Los Angeles, meanwhile, Kullar warns that the death rate is rising once again, and local health officials are requiring even vaccinated people to wear their masks in public places.

"I think we just need to keep in mind that the pandemic is not over yet," she said.

Moore, Vetter, and Kullar have disclosed no relevant financial relationships. Telenti is an employee of Vir Biotechnology.

Laird Harrison writes about science, health, and culture. His work has appeared in national magazines, in newspapers, on public radio, and on websites. He is at work on a novel about alternate realities in physics. Harrison teaches writing at the Writers Grotto. Visit him at or follow him on Twitter: @LairdH.

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