Electron microscope image of SARS-CoV-2, the virus that causes Covid-19.
Source: BSIP / Universal Images Group / Getty Images
Source: BSIP / Universal Images Group / Getty Images
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When Bette Korber, a biologist at The Los Alamos National Laboratory noticed the first significant mutation in the Covid-19 virus last spring, some scientists were skeptical. They did not think it would make the virus more contagious and said its rapid growth could only be a coincidence.
Now, 11 months later, the D614G mutation he helped discover is ubiquitous around the world, presented in the genome of fast-growing variants in the United Kingdom, South Africa and Brazil. Meanwhile, new mutations are appearing in increasingly complicated models, spurring an impulse from top biologists to devise new ways to track a fire hose with received genomic data.
Purpose: rapid detection of variants that may decrease the effectiveness of vaccines for a pathogen that is unlikely to be eradicated soon. The SARS-CoV-2 virus could calm down and become a simple nuisance like the common cold. Or, like the flu, it may retain its ability to cause severe disease in certain segments of the population, a scenario that may require regular booster photos.
Source: Los Alamos National Lab
“Looking at it carefully, we can stay in front of the virus and that’s what everyone is crushing to be done right now, ”said Korber, who is working to create new mathematical tools to identify medically significant variants.
The flood of new genome data is so great that the Los Alamos lab has had to upgrade its servers to cope with the data received. Meanwhile, Korber participates in four Zoom calls a week with experts from around the world to develop criteria for deciding when mutations are important enough to merit detailed laboratory monitoring of how they can impact vaccines.
A key mystery first discovered by top scientists was what type of virus the coronavirus would turn out to be. So far, it looks more like the flu, which is constantly changing all the time and requires annual revaccination, than measles, a virus so intolerant to mutations that a vaccine regimen lasts a lifetime.
“Does that mean we have to get a new vaccine every year?” SAPS Paul Duprex, who leads University of Pittsburgh Vaccine Research Center. “We do not know.”
First, Covid-19 mRNA vaccines have over 90% efficacy rates, much higher than the 60% rate for influenza vaccines in a good year. But vaccine manufacturers Moderna Inc. and Pfizer Inc., together with its partner BioNTech SE, don’t risk it. In any case, tests of booster shots aimed at B.1.351, the antibody-avoiding strain first identified in South Africa, are already underway.
When viruses replicate and copy their genome, errors can break down the long string of RNA or DNA “letters” that determine how viral proteins develop. Many of the errors have no effect or may even make the virus less suitable. But a small percentage of these changes can give the virus an advantage, making it more infectious or giving it the ability to evade the immune system.
The HIV virus is famous for its rapid mutation rate. In comparison, SARS-CoV-2 moves at a much slower rate, in part due to a sample reading enzyme that limits changes. But with more than 125 million infections worldwide, some errors are bound to creep in.
At the same time, the virus has found false ways that can bypass its evidence-reading mechanism, researchers at the University of Pittsburgh have discovered. Instead of making changes to individual RNA letters, it deletes groups of several letters at a time, apparently decreasing the ability of natural virus spell checking systems to see the change.
74-day bout
Some of the first deletions were seen in an immunocompromised cancer patient treated at the University of Pittsburgh Medical Center who died after a 74-day battle with Covid-19. During that time, several deletions developed that escape immunity, according to Duprex of the University of Pittsburgh, which reported on the deletions of the cancer patient in November.
“If the bastard is gone, you won’t be able to fix it,” Duprex said.
What makes the future of SARS-CoV-2 so difficult to predict is that viral evolution is like a three-dimensional game of chess. It is not only the individual mutations that matter, but also the order and combinations in which they occur. A single mutation can modify the virus in subtle ways that change the impact of others, according to Mark Zeller, a scientist at Scripps Research Institute, San Diego.
Common mutations
Both the B.1.351 strain common in South Africa and the P.1 strain that beats Brazil share several mutations in the spike protein that the virus uses to enter cells. This includes the D614G mutation discovered by Korber, which makes the tip more stable, and the E484K mutation, which is thought to reduce the ability of antibodies to bind to the tip.
However, so far, for reasons that are not fully understood, B.1.351 appears to have a greater impact on Pfizer and Moderna vaccines, at least in laboratory tests.
In general, the history of virus elimination was weak, with smallpox being the main example. Even polio pockets are still in some countries, despite elimination efforts. This does not bode well for the current virus, accordingly Jesse Bloom, researcher at Fred Hutchinson Cancer Research Center, which studies viral evolution.
“Vaccination will eliminate this pandemic in a very substantial way,” Bloom said. “But I don’t think we will eradicate SARS-CoV-2.”
Bloom predicts it will take “several years” for the virus to acquire enough mutations to completely get rid of existing vaccines. Of the approximately 100,000 possible single-letter mutations for the virus, less than 1 percent are likely to help the virus evade antibodies, he said.
A hopeful scenario
While the virus continues to evolve in the short term, one of the most promising scenarios is that it may run out of the big moves it can make to evade the antibodies that make current vaccines work. In this scenario, there may be a practical limit to how far the virus can move and remain able to invade our cells.
The spike protein must retain a shape that allows it to attach effectively to its human receptor, according to Shane Crotty, a researcher at the La Jolla Institute of Immunology.
“There are an infinite number of possibilities,” he said. “It’s like putting your foot in a shoe. It must still have, in principle, the right shape and size and still need to be recognized as a shoe. ”
However, evidence of other common cold coronaviruses indicates that they may move to evade the immune system over time.
In a recent study, Bloom and colleagues compared the 1984 version of a common cold coronavirus called 229E with a version of the same strain that circulated in 2016, three decades later. In total, 17% of the RNA letters in a key part of the protein that binds the virus to cells were changed due to mutations.
To test what this meant for human immunity, they obtained blood samples for patients from the 1980s, which could neutralize the 1984 viral strain. These people were likely exposed to the 1984 virus and developed protective antibodies against it. .
Discolored protections
When the researchers tested the samples against 229E virus strains that appeared in the 1990s or later, the protection disappeared: only 2 out of 8 blood samples managed to neutralize the strain in 2016, and the two showed very low activity compared to those latest virus.
This gives some clues as to how much might change in the future with enough time. “It’s pretty clear that human coronaviruses are undergoing substantial antigenic evolution,” Bloom said in an interview.
However, it remains unknown whether the virus can retain its ability to cause severe disease, as it moves even more people to gain immunity through infections or vaccines.
In research published in January in the journal Science, disease modelers from Emory University has found that a key factor will be whether protection against severe disease lasts much longer than protection against mild or asymptomatic reinfections, something that is typical of coronaviruses that cause common colds.
While the study was done before the current variants appeared, its basic conclusions are maintained, according to Jennie S. Lavine, a postdoctoral researcher at Emory University.
“What we see with Covid-19 at the molecular and cellular level is not incompatible with what we see with endemic coronaviruses,” said Lavine, who was the lead author of the paper. “Immunity decreases, but not all decline rapidly.”