He just didn’t know it was going to happen so fast.
For most of 2020, most people – including most experts – were not particularly worried about the virus’s ability to develop. The SARS-CoV-2 was changing, but so far this was nothing to worry about. Then, in late fall, he jumped. Distinctive new versions of the virus have caused alarming waves in Brazil, South Africa and the United Kingdom.
In a few short months, the options have become a global concern. Almost every time public health experts talk about the trajectory of the health crisis, they focus on options, the loose tool that can ruin hard-earned progress.
Their sudden appearance surprised scientists and marked the beginning of the next chapter of the pandemic. The mass vaccination campaign, which could feel like a wave of relief, is instead a sinister, urgent race against the changing virus. The road to herd immunity, the powerful stage when the virus will not be able to cause new outbreaks, seems longer and more complicated. Vaccines may not completely defeat them, but simply chase the ever-changing virus.
As scientists work to deal with the options, the situation gives the public a rare front-row seat and a real-time view of the unpredictability of viral development. The virus is changing and scientists are preparing for a wide range of possible futures.
“We have to come to terms with the fact that I̵
People like Bloom are mapping the genetic escape routes that the virus can take, so when mutations inevitably occur, scientists can quickly interpret whether they are likely to pose a threat.
This does not necessarily mean a world where the pandemic never ends. Prospects improve with the release of vaccines. If vaccines become obsolete, they will be updated.
“There will be new variants and new ways in which the virus can slightly evade our immune response, but that’s the key – it probably won’t be that much,” said Sarah Kobe, who is studying viral evolution at the University of Chicago.
In the labs, scientists are testing whether the current variants remain susceptible to antibodies caused by natural infections and vaccines. Companies are preparing new versions of vaccines and testing additional booster photos, just in case.
The hidden, rapid arrival of variants has put scientists in the familiar position of not being able to predict where the virus is headed.
“If you really push virologists and make them honest, not revisionist, the majority, if not all, of the individuals in the community would say, ‘It’s probably going to work, it’s probably going to work,'” said Paul Duprex, director of the Center for vaccines at the University of Pittsburgh.
The last few months have been a wake-up call: “Don’t think we’re smarter than evolution.”
Even before the options appeared, there were hints that scientists underestimated the ability of the virus to change.
Since last spring, a 45-year-old man with a severe autoimmune disease has been in and out of a Boston hospital for five months with a surprisingly long-lasting chronic coronavirus infection. Through the sequence of the virus at different points in time, 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, where the immune system trains much of its firepower to block infections. After a man is given a drug with antibodies, new mutations appear that may have helped the virus thwart treatment.
Thousands of kilometers from the United Kingdom, the virus has been found in a 70-year-old immune cancer survivor. After the patient received cycles of antibody-rich plasma therapy aimed at overcoming his disease, the researchers saw that different options gain and lose positions in the man. One version of the virus increases when it has been treated with plasma, then recedes as antibodies decrease, and then dominates again when the last course of plasma is given.
The researchers created a laboratory version of this variant. They found that one of its genetic changes reduced the virus’s susceptibility to antibodies, but also carried a potential Achilles’ heel, making it less effective at infecting cells. A second change – a missing part of the genome – appears to compensate, increasing the virus’s ability to infect cells. This change was also found in the rapidly spreading version, which caused a blockade in the UK this winter.
In Pittsburgh, a 70-year-old man who received advanced cancer treatment that knocked out part of his immune system was admitted to hospital with covid-19 pneumonia. He had been ill for more than two months, and during his illness, researchers were able to track the virus that infected him, revealing clues as to why the virus could change so flexibly.
Many scientists have suggested that because the virus has a correction mechanism to correct errors when it multiplies, it will not mutate quickly. But changes in the virus are not typographical errors in the genetic code – there are no lines called deletions. The virus could not read what it did not have.
“We underestimate the virus’s ability to evolve since the beginning of the pandemic,” said Kevin McCarthy, a microbiologist at the University of Pittsburgh’s Vaccine Research Center.
These patients, who all died, provided clues to the evolutionary ability of the virus before the options caught the world’s attention.
Scientists know that viruses copy themselves into human cells – and sometimes make mistakes in the process. When infections resolve quickly and mutations accumulate slowly, this does not give the virus much chance of culturing a huge reservoir of genetic diversity. But in immunocompromised people, the virus is much more likely to change its genetic pattern. When well-meaning doctors apply a little pressure – like a circle of antibody-rich plasma to try to save a patient’s life – there may be a version of the virus that takes precedence and can avoid treatment.
No one knows if any particular variant occurred in an immunocompromised person, but so far the cases have turned out to be an ominous crystal ball, foreshadowing what is happening in the population. With the virus infecting more than 100 million people worldwide, it has been given maximum opportunities to change its disguise.
“It suggests to me that there is an evolutionary leap from some hidden source of viral evolution,” said Jonathan Z. Lee, who is studying HIV drug resistance at Brigham and Women’s Hospital. in Boston. “We have a blind spot in the community where evolution is happening, and we can’t see it until we see it has spread far enough.”
Remarkably tolerant jump
Not every mutation turns a virus into a supervillain. Most have little effect or may actually dig up the virus. And even mutations that seemingly work in favor of the virus can come with compromises.
Genetic tweaking, which allows the protein peak to fly under the radar of the immune system a little more thief, for example, may seem unequivocally beneficial to a virus. But such a change can also backfire, making it less effective at penetrating the body’s cells. The virus, which is invisible to the immune system, sounds scary, but can be clumsy in critical ways.
One of the open questions about the evolutionary capacity of the coronavirus is whether there is a limit to its ability to change. The spike is fixed on the cells, like a key placed in a lock. Many scientists had suggested that if this key changed too much, it would no longer be able to open the door.
“Protein protein seems remarkably tolerant of change. … I don’t think most people would expect that, “said Francis C. Collins, director of the National Institutes of Health.
But there were warnings about the tendency of the spike to change shape before the options.
At Rockefeller University in New York last summer, virologist Paul Bieniash and colleagues put the characteristic coronavirus protein under pressure in a laboratory.
In the tubes, they place a spike through an immune glove, exposing it to successive cycles of antibodies designed to screen out spike versions capable of avoiding neutralization. Such experiments have limits on what they can predict how the virus will behave when it spreads through humans, but what Biennias has seen is a mutation in a site called E484.
A prominent virologist told the team, “I’m not worried about that,” Bienias recalls. Yet months later, changes to E484 appear in real life – on the variants found in South Africa and Brazil.
Bloom of the Fred Hutchinson Cancer Research Center in Seattle experienced a similar shock from the recognition late last year. His lab tested every possible mutation in the protein that binds to the cells to see which poses the greatest threat to immunity, and E484 has become a focal point for their work.
“I think everyone in the community was surprised by how quickly these experiments became relevant,” Bloom said.
What scientists are discussing now is where the virus should go.
It may be in a period of rapid evolution in which the virus adapts to become better at infecting humans. After a while – how much more a matter of debate – this pace may slow down. Or the virus, like the flu, may simply be in constant contact with the immune system.
“Is the malleable infinity?” Is plastic enough to allow something to happen? There is no simple answer, “said John Moore, a professor of microbiology and immunology at Weill Cornell Medicine.
The immediate consequences for ordinary people are not terrible. It remains important to reduce transmission to give the virus less chance of changing – and to vaccinate people. But scientists have a long way to go. Kizzmekia Corbett, scientific director of the coronavirus vaccination program at the NIH Vaccine Center, recently said that the emergence of variants felt like a “second pandemic.” Companies and scientists are already starting tests on updated vaccines so that they are ready if needed.
“I think this virus shows more, say, genetic flexibility than some might have expected,” said Vincent Munster, head of viral ecology at NY’s Rocky Mountain Laboratories. “While we really can’t look to the future, it would be good to at least anticipate that this could be a future scenario, so we’re actually prepared.”