Scientists underestimated the coronavirus — and are racing to keep up with

He just didn’t know it would happen quite this fast.

For much of 2020, most people — including most experts — weren’t particularly worried about the virus’s ability to evolve. SARS-CoV-2 was changing, but so far that hadn’t amounted to anything especially concerning. Then, in late fall, it jumped. Distinctive new versions of the virus sparked alarming surges in Brazil, South Africa and the United Kingdom.

In a few short months, variants have become a global preoccupation. Nearly every time public health experts talk about the trajectory of the health crisis, they dwell on the variants, the loose cannon that could wreck hard-won progress.

Their sudden emergence caught scientists off guard and set the stage for the next chapter of the pandemic. The mass vaccination campaign that could have felt like a wave of relief is instead an ominous, urgent race against a changing virus. The path to herd immunity, the powerful milestone when the virus won’t be able to spark new outbreaks, is looking longer and more complex. Vaccines may not totally vanquish but simply chase a continually changing virus.

As scientists work to get a handle on the variants, the situation gives the public a rare front-row seat and real-time view of the unpredictability of viral evolution. The virus is changing, and scientists are preparing for a wide range of possible futures.

“We do have to come to terms with the fact that I’m pretty confident that SARS-CoV-2 is going to be more like influenza, which is with us all the time because the virus is changing, and we have to worry about keeping our vaccines updated,” Bloom said. “On the other hand, I think that a year from now, it’s going to be much less of a problem.”

People like Bloom are building maps of the genetic escape routes the virus could take, so that when mutations inevitably arise, scientists can quickly interpret whether they’re likely to pose a threat.

That doesn’t necessarily mean a world where the pandemic never ends. The outlook is improving as vaccines are rolled out. If vaccines become outdated, they will be updated.

“There will be new variants and new ways in which the virus might be escaping our immune responses a little bit, but that’s the key — it’s probably not going to be that much” of an escape, said Sarah Cobey, who studies viral evolution at the University of Chicago.

In laboratories, scientists are testing whether the current variants remain susceptible to antibodies conjured by natural infection and vaccines. Companies are preparing new versions of vaccines and testing extra booster shots, just in case.

The stealthy, speedy arrival of variants has put scientists in the familiar position of being unable to predict where the virus is headed.

“If you really push virologists, and get them to be honest and not revisionist, the majority, if not all the individuals, in the community were saying, ‘It’ll probably be all right, it’ll probably be fine,’ ” said Paul Duprex, director of the Center for Vaccine Research at the University of Pittsburgh.

The past few months have been a wake-up call: “Don’t think that we are cleverer than evolution.”

Even before the variants emerged, there were hints that scientists had been underestimating the virus’s capacity to change.

Starting last spring, a 45-year-old man with a severe autoimmune disease was in and out of a Boston hospital for five months, with what turned out to be an astonishingly long chronic coronavirus infection. By sequencing the virus over different time points, doctors found that the virus was changing rapidly — highlighting the potential for what his team of doctors called “accelerated viral evolution.”

Instead of just one or two genetic tweaks, the virus accumulated 21 mutations, and they were concentrated in the spike protein — the spot where the immune system trains much of its firepower to block infections. After the man was given an antibody drug, new mutations emerged that may have helped the virus thwart the treatment.

Thousands of miles away in the United Kingdom, the virus took hold in a 70-year old cancer survivor with a compromised immune system. After the patient received rounds of antibody-rich plasma treatment aimed at beating back his disease, the researchers saw different variants gaining and losing ground within the man. One version of the virus increased when he was treated with plasma, then receded as the antibodies diminished, then dominated again when a last course of plasma was given.

Researchers created a lab version of that variant. One of its genetic changes reduced the virus’s susceptibility to antibodies, they found, but also carried a potential Achilles’ heel, making it less efficient at infecting cells. A second change — a missing portion of the genome — seemed to compensate, increasing the virus’s ability to infect cells. That change was also found in the fast-spreading variant that triggered a…