Transmission 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, biologist a The Los Alamos National Laboratory detected the first significant mutation in the Covid-19 virus last spring, some scientists were skeptical. They didn’t believe it would make the virus more contagious and said its rapid rise could only be a coincidence.
Now, 11 months later, the D614G mutation he helped discover is ubiquitous around the world, appears in the genome of fast-spreading variants of the United Kingdom, South Africa, and Brazil. Meanwhile, new mutations are emerging in increasingly complicated patterns, prompting major biologists to design new ways to track a fire hose of incoming genomic data.
The goal: to quickly detect variants that may decrease the effectiveness of vaccines for a pathogen that is unlikely to be eradicated soon. The SARS-CoV-2 virus could settle down and become a simple nuisance like the common cold. Or, like the flu, it may retain its ability to cause serious illness in some segments of the population, a scenario that could require regular booster shots.
Source: Los Alamos National Lab
“If we look closely, we can stay ahead of the virus and that’s what everyone is stirring do it right now, ”said Korber, who is working to create new mathematical tools to detect medically significant variants.
The avalanche of new genome data is so large that the Los Alamos lab had to upgrade its servers to deal with incoming data. Meanwhile, Korber makes four Zoom calls a week with experts from around the world to design criteria for deciding when mutations are worrisome enough to merit detailed laboratory monitoring of how vaccines may affect.
A key mystery experienced by early scientists has been the type of virus the coronavirus will prove. So far, it looks more like the flu, which changes shape all the time and requires annual revaccination, than measles, a virus so intolerant to mutation that a vaccine regimen lasts a lifetime.
“Does that mean we have to get a new vaccine every year?” dit Paul Duprex, who directs the University of Pittsburgh Vaccine Research Center. “We do not know”.
On the one hand, mRNA vaccines for Covid-19 have efficacy rates above 90%, much higher than 60% of influenza vaccines in a good year. But vaccine manufacturers Moderna Inc. i Pfizer Inc., along with its partner BioNTech SE, do not risk. Just in case, trials of reinforcing shots targeting B.1.351, the antibody-preventing strain first detected in South Africa, are already underway.
When viruses replicate and copy their genome, errors can explode the long chain of “letters” of RNA or DNA that determine how viral proteins develop. Many of the errors have no effect or can even make the virus less fit. But a small percentage of these changes can give the virus an advantage, making it more infectious or giving it a chance to evade the immune system.
The HIV virus is famous for its rapid mutation rate. In comparison, SARS-CoV-2 mutates at a much slower rate, in part due to a test-reading enzyme that limits changes. But with more than 125 million infections worldwide, some bugs are likely to escape.
At the same time, the virus has found false ways that can bypass its test-reading mechanism, researchers at the University of Pittsburgh have found. Instead of making changes to individual RNA letters, it removes groups of several letters at once, seemingly diminishing the ability of the virus’s natural spelling correction systems to see the change.
74-day battle
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 this time, multiple deletions escaping immunity developed, according to Duprex of the University of Pittsburgh, which reported oncology patient deletions in November.
“If the damn thing is gone, you won’t be able to fix it,” Duprex said.
What makes it so difficult to predict the future of SARS-CoV-2 is that viral evolution is like a three-dimensional game of chess. Not only do individual mutations matter, but also the order and combinations in which they occur. A single mutation can subtly alter the virus in ways that change the impact of other people along the line, according to Mark Zeller, a scientist at Scripps Research Institute of San Diego.
Shared mutations
Both the B.1.351 strain common in South Africa and the P.1 strain that is beating Brazil share several mutations in the peak protein that the virus uses to access cells. This includes the D614G mutation discovered by Korber, which makes the spike more stable, and the E484K mutation, which is believed to reduce the ability of some antibodies to bind to the spike.
However, so far, for reasons that are not fully understood, it appears that B.1.351 appears to have more impact on Pfizer and Moderna vaccines, at least in laboratory tests.
In general, the history of virus elimination has been poor, with smallpox being the main example. There are even bags of polio in some countries, despite efforts to eliminate it. Okay, that doesn’t bode well for the current virus Jesse Bloom, researcher at the Fred Hutchinson Cancer Research Center studying viral evolution.
“Vaccination will eliminate this pandemic in a very substantial way,” Bloom said. “But I don’t think we’re going to eradicate SARS-CoV-2.”
Bloom predicts that it will be “several years” until the virus acquires enough mutations to completely escape existing vaccines. Of the approximately 100,000 possible single-letter mutations for the virus, less than 1% are likely to help the virus bypass 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 antibodies that run current vaccines. In this scenario, there may be a practical limit to how far the virus can mutate and remain fit to invade our cells.
According to Shane Crotty, a researcher at the La Jolla Institute of Immunology, spike protein must retain a shape that allows it to bind efficiently to the human receptor.
“There are an infinite number of possibilities,” he said. “It’s like putting your foot in a shoe. It still has to be basically the right shape and size and it has to be recognizable as a shoe ”.
However, tests on other common cold coronaviruses indicate that they may mutate 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. 17% of the RNA letters of a key part of the spike protein that binds the virus to cells had been altered due to mutations.
To test what this meant for human immunity, they obtained blood samples from patients in the 1980s that could neutralize the 1984 viral strain. Probably, these people had been exposed to the 1984 virus and developed protective antibodies.
Faded protections
When researchers tested samples against 229E virus strains that appeared in the 1990s or later, protection had faded: only 2 of eight blood samples were able to neutralize the 2016 strain and those two they showed very low activity compared to more recent ones. virus.
This provides some tips on how much you could change in the future, in good time. “It’s pretty clear that human coronaviruses are undergoing substantial antigenic evolution,” Bloom said in an interview.
However, it is unknown whether the virus can retain its ability to cause serious disease, as it mutates and more people gain immunity through infections or vaccines.
In a study published in January in the journal Science, disease models in Emory University found that a key factor will be whether protection against serious illness lasts significantly longer than protection against mild or asymptomatic reinfections, typical of coronaviruses that cause common colds.
Although the study was done before the current variants appeared, the basic findings remain, 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 everything decreases quickly.”