COVID-21: A Primer

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The coronavirus is changing. So is the disease it causes.

This story was originally published by The Atlantic. Subscribe to the magazine’s newsletters.

Trying to remember March 2020 feels like sticking your head into a parallel universe. This time last year, Americans were just going into lockdown—presumably for two weeks—to protect themselves from a mysterious but deadly virus. We disinfected mail but didn’t wear masks. Few of us knew that COVID-19 symptoms could last for months, that you might lose your sense of smell, or that your toes might break out in purple lesions. The possibility that millions would die was real but incomprehensible.

The pandemic today is almost unrecognizably different. In the United States, an acute, terrifying catastrophe has given way to the monotony of lowered expectations. There are no makeshift morgues in the streets. Businesses are opening despite a thousand American deaths a day. This week, Mayor Bill de Blasio ordered New York City employees back to work, regardless of their vaccination status, while case counts in the city are on a high plateau. The pervasive sense is that we can’t wait forever for the pandemic to end.

When, exactly, will we reach a point that could be considered a finish line? It’s the natural question, but I think it’s a counterproductive one. Not only because, as Anthony Fauci told me recently, the most honest answer is “We just don’t know.” The inability to give a definitive answer is contributing to misperception of risk, conflating better with good enough. It’s also true that much of what defined the COVID-19 crisis at its worst is no longer an issue. Many health-care workers are vaccinated, and the need to “flatten the curve” is in the past. Tests are widely available, and there are better treatments for the disease. Death rates are falling quickly.

The SARS-CoV-2 pandemic may drag on for years, but the nightmare of last year—of an entirely new viral illness, emerging in a specific sociopolitical context—is behind us. Instead we’re facing a new set of challenges, and they are not easily comparable to what has come before. It’s worth considering a new way of thinking about the period of the pandemic now ahead of us—one that leads us neither to complacency nor to paralyzing despair. In many ways COVID-19 is already over. What lies ahead is COVID-21.

Diseases are not static things. Pathogens change, hosts change, and environments change. In the case of COVID, all three are now different than they were in 2020. What began as one coronavirus has infected well over 100 million people and evolved into new forms that appear to transmit more readily and infect us in subtly different ways. Our immune systems have changed as well, as a result of fending off infections. And, of course, our lifestyles have changed, as have social standardsmedical systems, and public-health programs.

COVID-21 is the product of all these changes in aggregate. It’s the disease as it will be experienced in the months and years to come: with new variants of the virus, new public policies and health behaviors, various degrees of immune memory, and—most important—a cavalcade of new vaccines.

One-quarter of all Americans have now received at least one shot, and that number is racing up. This month, New Yorkers lined up outside Yankee Stadium throughout the night at a makeshift 24/7 vaccination site, until the supply ran out. “If we open 3,000 appointments, they will immediately fill,” says Ramon Tallaj, a physician who oversees clinical care in underserved communities across New York City. Demand seems to be growing. If there were sufficient supply, Tallaj told me, his team could be giving out 40,000 doses every day. And this should happen soon; the White House says that shortages will end in the coming weeks.

The vaccination effort is sure to change the nature of COVID in unexpected ways. The habitat for the virus is changing: It may still stick in the nasal passages of an immunized person, but it shouldn’t continue on its way into the lungs, much less the toes. The key question is just how long this protection will last, especially against a rapidly mutating virus. Clinical trials have shown the vaccines to be fantastic at preventing serious illness so far, but haven’t yet been able to observe how protection might dissipate over long periods.

Because SARS-CoV-2 hasn’t been infecting humans for much longer than a year, it’s impossible to say exactly how immune responses will play out. The common-cold coronaviruses can reinfect the same person after a year or two. Early research on COVID vaccination shows that people develop high levels of antibodies, but that these begin to decline about a month after the first dose. The CDC’s official position on how long immunity lasts after vaccination is “We don’t know.”

Antibodies are not the whole story, though. Monica Gandhi, an infectious-disease specialist at UC San Francisco, believes that we’ll be well protected by other immune mechanisms, even after antibody levels drop. Her research focuses on how HIV evades and weakens the body’s immune system, particularly the T cells. She reminded me that T cells, and also B cells, store a memory of prior infections, and are generally more important than antibodies for maintaining long-term protection against viruses.

Reassuring evidence has already emerged indicating that these cells can form durable memories of SARS-CoV-2. Recently, a group of researchers biopsied the lymph nodes of vaccinated individuals and found “remarkably” strong B-cell development. In a February Science paper, another team found that the T cells generated in people who have had COVID-19 seem to have similar half-lives to the T cells you get from being vaccinated against yellow fever—and yellow-fever protection usually lasts a lifetime.

Another promising sign comes from those who contracted the original SARS coronavirus in 2003. The T cells of people who were infected at the time reliably recognized the spike protein from the virus in lab experiments 17 years later. Gandhi believes that this memory, while not always as protective as having high levels of neutralizing antibodies in your blood, will likely be sufficient to prevent severe disease. “Do I think that we’ll have lifelong immunity from severe infection?” she said. “I am very heartened that we will.”

If that’s the case, then COVID-21 will eventually be a milder, less deadly version of the illness that we started with last year. “The worst-case scenario is we render it a cold,” Gandhi said. “The best-case is we reach herd immunity and the virus goes almost entirely away.”

But others expect a much worse worst-case scenario, in which immunity to severe disease is only temporary. The biologist and former Harvard professor William Haseltine warns against the rosy view: “It seems to me clear that the T-cell theory isn’t going to hold up,” he told me. Although our memory cells could continue to recognize the virus, that won’t necessarily be enough to give us meaningful protection. The disease might end up being milder the second time around, or after vaccination, but he worries that, as the virus mutates, it also could get worse. As for herd immunity, Haseltine called that a “fantasy.” “The best we’ll get is seasonal herd immunity. We have 60 years of experience with coronaviruses, and they come back every year.”

Even the bad version of COVID-21 would be far different from the depths of COVID-19, though. Millions of cases of severe disease would be prevented with vaccines, but boosters would have to be given out at regular intervals. “The Moderna and Pfizer vaccines are shockingly good mimics of natural infection,” Haseltine told me. “But it’s really important to stress the fact that these vaccines are likely to be temporary protection. A year or maybe two.” That means we’d need a more enduring system of vaccine production and distribution. It will be an enormous challenge to keep the public up-to-date with annual or semiannual injections—and if uptake flags and the virus remains pervasive, even immunized people won’t be 100 percent free from risk.

In the end, Haseltine said, we might hope for a universal vaccine that protects against all strains of SARS-CoV-2, as well as future coronaviruses that might emerge. Early research has shown some promise using nanoparticle immunization technology, which combines fragments of different viruses. Fauci and others have been pursuing a universal influenza vaccine for years, and they are now, at last, seeing some indications of success. A universal coronavirus vaccine should theoretically present fewer obstacles, because the viral structure is more straightforward, and it changes less readily. As the race to develop the current generation of COVID-19 vaccines finishes, the race for a universal vaccine begins.

Between Gandhi’s vision and Haseltine’s is another, quite disturbing, one. Imagine that the vaccines work well, but not indefinitely. The virus continues to spread and mutate. COVID can still have severe, even life-threatening, effects. Vaccination brings rates of serious disease and death down substantially, but not close to zero. And we come to think of this as pretty much okay.

In other words, imagine a world in which the disease persists, and is accepted, as something that is far less deadly than it was last year—more like a bad flu than a common cold. As with influenza, the world might lose hundreds of thousands of people to this illness each year. And yet we would come to see its toll as being within the bounds of acceptable loss. As with diseases like malaria, HIV, influenza, and so many others, enormous effort and resources would go into preventing infections and treating sick people. But the singular global war against the SARS-CoV-2 virus that began in 2020 would fade in intensity. Instead of working toward a post-COVID future, we’d come to see the disease as yet another unfortunate but inevitable feature of the modern world.

This version of COVID-21 would be most dangerous, not because the virus has developed some new, sinister mutation, and not because our vaccines turn out to be inadequate. The risk instead would come from the way that it’s normalized. As the bioethicist Jackie Scully wrote in 2004, diseases morph “partly as a result of increasing expectations of health [and] partly due to changes in diagnostic ability, but mostly for a mixture of social and economic reasons.” They change with how we perceive them, and react to them.

We are at an inflection point that will change the reality of this disease. The most insidious future is one in which we fail to change our moral benchmarks, and end up measuring the danger of COVID-21 by the standards of 2020. If wealthy countries with early access to vaccines abandon continued, global coronavirus-vaccination efforts as their cases fall or when the disease becomes milder for them, a still-severe disease could haunt the world indefinitely—and lead to rebounds everywhere.

Avoiding this myopia is the central challenge of COVID-21. It extends to the systemic problems highlighted by this pandemic. Much of the damage the virus has wrought has come indirectly, by exacerbating food and housing insecurity, for example, or restricting access to medical care. The Biden administration has elevated science and begun to focus on comprehensive approaches to prevention. No longer is federal leadership hawking hydroxychloroquine, suggesting injections with “disinfectant,” or stoking xenophobic sentiment. But this sudden sense of order is a beginning, not an end.

Last year’s sense of terror and panic belongs behind us. This is the phase of the pandemic when we can move from haphazard emergency plans to concerted measures to eradicate a life-threatening illness. Despite lingering unknowns about exactly how long immunity will last and how many cases we’ll continue to see, we now have the knowledge and resources to become much more certain very quickly. If we beat COVID-21, the numbering could end there.

The Atlantic's COVID-19 coverage is supported by a grant from the Chan Zuckerberg Initiative.

James Hamblin is a staff writer at The Atlantic

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