New Coronavirus Variants May Cause More Re-infections, Need Updated Vaccines | Science

By Kai KupferschmidtJan. 15, 2021 at 4:55 p.m.

Science‘s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

When the number of COVID-19 cases started to rise again in Manaus, Brazil in December 2020, Nuno Faria was stunned. The Imperial College London virologist and associate professor at Oxford University had just co-authored an article in Science estimating that three-quarters of the city’s residents had already been infected with SARS-CoV-2, the pandemic coronavirus – more than enough, it seemed, for herd immunity to develop. The virus should be done with Manaus. However, hospitals were filling up again. “It was difficult to reconcile those two things,” says Faria. He started looking for samples he could sequence to find out if changes in the virus could explain the resurgence.

On January 12, Faria and her colleagues published their first findings on virological.org. Thirteen of the 31 samples collected in mid-December in Manaus were found to be part of a new viral line which they called P.1. Much more research is needed, but they say one possibility is that in some people, P.1 escapes the human immune response triggered by the lineage that ravaged the city earlier in 2020.

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Emerging variants of the coronavirus have been in the news since scientists sounded the alarm on B.1.1.7, a variant of SARS-CoV-2 that first caught the attention of scientists in England in December and which is more transmissible than viruses circulating previously. But now they’re also focusing on a potential new threat: variants that could bypass the human immune response. Such ‘immune breakouts’ could mean that more people who have had COVID-19 remain susceptible to re-infection and that proven vaccines may, at some point, need an update.

At a meeting of the World Health Organization (WHO) on January 12, hundreds of researchers debated the most important scientific questions raised by the wave of new mutations. The WHO also convened its COVID-19 emergency committee on January 14 to discuss the impact of the new variants and the travel restrictions many countries are imposing to contain them. The committee called for a global effort to sequence and share more SARS-CoV-2 genomes to help track mutations. He also called on countries to support “global research efforts to better understand critical unknowns regarding specific mutations and variants of SARS-CoV-2”.

The most transmissible variant, B.1.1.7, is already spreading rapidly in the UK, Ireland and Denmark, and probably in many other countries. The U.S. Centers for Disease Control and Prevention on Friday released a modeling study showing that the strain could become the predominant variant in the U.S. in March. But scientists are equally worried about the 501Y.V2, a variant detected in South Africa. Some of the mutations it carries, including those named E484K and K417N, modify its surface protein, its peak, and have been shown in the laboratory to reduce the ability of monoclonal antibodies to fight the virus. In a preprint published earlier this month, Jesse Bloom, evolutionary biologist at the Fred Hutchinson Cancer Research Center, showed that E484K also reduced the potency of some donors’ recovery sera by 10 – although he quickly added that that doesn’t necessarily mean the mutation would drop people’s immunity to the new strain by ten.

P.1 adds to the concerns as it appears to have touched a similar constellation of mutations and emerged in a location with a high level of immunity. “Anytime you see the same mutations happening and starting to spread multiple times, in different strains of the virus around the world, that’s very strong evidence that there is an evolutionary benefit to these mutations,” Bloom says.

Like B.1.1.7, the variant identified at Manaus is already in motion. As Faria finished his analysis of Brazilian genomes, a report was published on a variant detected in travelers arriving in Japan from Brazil – and it turned out to be P.1.

Bad friends

It is still unclear how these new variants affect the course of the pandemic. In Manaus, for example, P.1 might have nothing to do with the new outbreak of infections; People’s immunity could just wane, says Oxford epidemiologist Oliver Pybus. At a press conference today, Mike Ryan of the WHO warned that changes in human behavior are still the main driver of the resurgence. “It’s too easy to blame the variants and say it was the virus that did it,” he said. “Unfortunately, it’s also what we didn’t do that did it.”

While the variant plays a crucial role, it could be the driving force behind the boost because it is spread more easily, like B.1.1.7, not because it can evade the immune response. “Of course, it could also be a combination of these factors,” Pybus says. Likewise, in a recent modeling study, researchers at the London School of Hygiene & Tropical Medicine calculated that South Africa’s 501Y.V2 variant may be 50% more transmissible but not better at evading immunity. , or just as transmissible as the previous variants but able to escape. immunity in one in five previously infected people. “Reality may lie between these extremes,” the authors wrote.

Ester Sabino, molecular biologist at the University of São Paulo, São Paulo, is launching a study to find re-infections in Manaus that could help decide between these hypotheses for P.1. She is also working on sequencing more samples from Manaus starting in January to track the spread of the variant. “We don’t have the data yet, but I guess it will be 100% now,” she says. Laboratory studies on the variants are also underway. The United Kingdom today launched a new consortium, G2P-UK (for “genotype to phenotype-UK”), led by Wendy Barclay of Imperial College London, to study the effects of emerging mutations in SARS-CoV -2. One idea discussed at the January 12 WHO meeting is to create a biobank that would facilitate studies by housing virus samples, as well as plasma from vaccinees and recovered patients.

Interactions between new mutations can make it more difficult to determine their effects. The UK, South Africa, and Manaus variants all share a mutation called N501Y, for example, or Nelly, as some researchers call it. But the mutation, which affects the spike protein, also occurs in some variants that don’t spread faster, suggesting that N501Y doesn’t work on its own, says Kristian Andersen of Scripps Research: “Nelly may be innocent, except maybe when she’s with her bad friends. “

Bloom believes none of the changes will allow the virus to completely evade the immune response. “But I would expect these viruses to have some advantage when a large part of the population is immune” – which could help explain the skyrocketing Manaus.

Vaccine updates

So far, the virus does not appear to have become resistant to COVID-19 vaccines, says vaccinologist Philip Krause, who chairs a WHO working group on COVID-19 vaccines. “The bad news is that the rapid evolution of these variants suggests that while it is possible for the virus to evolve into a vaccine-resistant phenotype, it may happen sooner than we wish,” he adds. . This possibility adds to the urgency of putting in place good surveillance to detect such escape variants early on, explains biostatistician Natalie Dean of the University of Florida. But it also adds to the urgency of vaccinating people, explains Christian Drosten, a virologist at Charité University Hospital in Berlin. “We have to do everything in our power to vaccinate as many people as possible as quickly as possible, even if that means running the risk of selecting certain variants,” he says.

If vaccine resistant strains of SARS-CoV-2 emerge, the vaccines may need to be updated. Several vaccines could be easily modified to reflect the latest changes, but regulators might be reluctant to allow them without seeing updated safety and efficacy data, Krause says. If new variants circulate alongside older strains, multivalent vaccines, effective against multiple lineages, may even be needed. “To be clear: these are downstream considerations,” Krause says. “The public shouldn’t think it’s imminent and that new vaccines will be needed.” But Ravindra Gupta, a researcher at the University of Cambridge, says manufacturers should start producing vaccines designed to generate immunity against the mutated versions of the spike protein, as they keep appearing. “It tells us that we should have these mutations in our vaccines, so that you cut off one of the pathways for the virus to go away.”

Right now, increased transmissibility is the biggest concern, says virologist Angela Rasmussen of Georgetown University. “I wonder why [that] is not part of the conversation, ”she said. The US hospital system, she says, “is at full capacity in many places and further increases in transmission can tip us to where the system is collapsing. Then we’ll start to see potentially huge increases in mortality.