ScienceCOVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation
Family members are attending a funeral of a COVID-19 in Manaus, Brazil, on January 13.
PHOTO: MICHAEL DANTAS / AFP / GETTY BEELDE
When the number of COVID-19 cases started to increase again in December 2020 in Manaus, Brazil, Nuno Faria was stunned. The virologist at Imperial College London has just co-authored an article in Science it is estimated that three-quarters of the city’s residents were already infected with SARS-CoV-2, the pandemic coronavirus – more than enough it seemed that the herd immunity would develop. The virus must be done with Manaus. Yet hospitals were full again. “It was hard to reconcile these two things,” Faria says. He began hunting for samples he could follow to determine if changes in the virus could explain the revival.
On January 12, Faria and his colleagues post their initial conclusions on the website virological.org. Thirteen of 31 samples collected in Manaus in mid-December appear to be part of a new viral offspring they called P.1. Much more research is needed, but according to them, the possibility is that P.1 in some people evades the human immune response caused by the gender line that devastated the city earlier in 2020.
Emerging coronavirus variants have been in the news since scientists sounded the alarm about B.1.1.7, a SARS-CoV-2 variant that first attracted scientists to England in December and is more transmissible than viruses previously. distributed (Science, January 8, p. 108). But now they are also focusing on a potential new threat: variants that could put an end to the human immune response. Such “immune escape” may mean that more people who have had COVID-19 are susceptible to reinfection, and that proven vaccines need an update at some point.
At a meeting of the World Health Organization (WHO) on 12 January, hundreds of researchers discussed the most important scientific questions raised by the wave of new mutations. WHO also convened its COVID-19 Emergency Committee on 14 January to discuss the impact of the new variant and the travel restrictions that many countries have in place to limit it. The committee called for a global effort to sequence more SARS-CoV-2 genomes to detect mutations.
The more transmissible variant, B.1.1.7, is already spreading rapidly in the United Kingdom, Ireland and Denmark, and probably in many other countries. But scientists are just as concerned about 501Y.V2, a variant found in South Africa. Some of the mutations it carries, including those named E484K and K417N, alter the surface protein, peak and have been shown in the laboratory to reduce how well monoclonal antibodies fight the virus. In a preview published earlier this month, Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Research Center, showed that E484K also reduced the potential for restorative sera from some donors 10-fold – although he quickly added, it would not necessarily cause the mutation to drop people’s immunity to the new strain tenfold.
P.1 contributes to the concerns because it appears to have struck a similar constellation of mutations and originated in a place with high immunity. “Every time you see the same mutations occur and that start spreading several times in different viral strains around the world, it is strong evidence that the mutations have an evolutionary advantage,” says Bloom.
As in B.1.1.7, the Brazilian variant is already on the move. Just as Faria was analyzing the Brazilian genome, a report was published of a variant detected in travelers arriving in Japan from Brazil – and it turned out to be P.1. (As Science U.S. researchers also reported several new variants, but their importance was unclear.)
HOW THIS NEW variants that affect the course of the pandemic are unclear. In Manaus, for example, P.1 has nothing to do with the new rise in infections; people’s immunity can simply decline, says Oxford University epidemiologist Oliver Pybus. Or it can boost because it is more easily transmitted, such as B.1.1.7, not because it can evade the immune response. “Of course, it could also be a combination of these factors,” says Pybus.
In a recent modeling study, researchers from the London School of Hygiene & Tropical Medicine also calculated that the 501Y.V2 variant of South Africa may be 50% more transmissible, but not better at evading immunity, or just as transmissible. as previous variants, but which it can evade. immunity in one in five people previously infected. “The reality may lie between these extremes,” the authors wrote.
Ester Sabino, a molecular biologist at the University of São Paulo, São Paulo, has launched a study to find reinfections in Manaus that could help decide between these hypotheses for P.1. Lab studies investigating the variants are also underway. On 15 January, the United Kingdom launched a new consortium, G2P-UK (for “genotype to phenotype-UK”), led by Wendy Barclay of Imperial College London, to address the consequences of emerging mutations in SARS-CoV 2 to study. One idea discussed at the WTO meeting on 12 January is to set up a biobank that can help studies by housing virus samples, as well as plasma from recipients of vaccines and recovering patients.
Interactions between the new mutations may make it more difficult to tease their effects. The variants from the United Kingdom, South Africa and Manaus all share a mutation called N501Y, for example, or Nelly, as some researchers call it. But the mutation, which affects the ear protein, also occurs in some variants that do not spread faster, suggesting that N501Y does not work alone, says Kristian Andersen of Scripps Research: ‘Nelly may be innocent, except maybe if she’s with her bad friends hang out. ”
Bloom believes that none of the changes are likely to cause the virus to completely escape the immune response. “But I would expect the viruses to have some benefit if many have immunity” – which may help explain the increase in Manaus.
SO FAR THE VIRUS does not appear to be resistant to COVID-19 vaccines, says vaccinator Philip Krause, who chairs a WHO working group on COVID-19 vaccines. “The not-so-good news is that the rapid evolution of these variants suggests that if it is possible for the virus to develop into a vaccine-resistant phenotype, it could happen faster than we would like,” he adds. The possibility contributes to the urgency of putting good oversight in place to detect such escape variants early on, says University of Florida biostatistician Natalie Dean.
People queue to receive COVID-19 vaccine in Birmingham, UK
PHOTO: JACOB KING / PA WIRE / BLOOMBERG / GETTY BEELDE
Some scientists are concerned that proposed changes in vaccine doses may accelerate the evolution of such strains. The UK was desperate to tame a massive increase in cases, deciding on 30 December to allow between 12 and two weeks between the first and second dose of two authorized vaccines, rather than the three or four weeks used in clinical trials of the vaccines have been used, so more people can get their first dose quickly and have at least some immunity. And the Trump administration has decided to send all available doses immediately, rather than withholding 50% to guarantee people receive their second doses on time. The policy, which according to the Biden government will follow, could accidentally extend the dosing interval if future deliveries of vaccines do not arrive or are not administered on time.
Major delays with the second dose can create a pool of millions of people with enough antibodies to slow down the virus and get sick, but not enough to eradicate it. This could very well be the perfect recipe for forming vaccine-resistant strains, says virologist Florian Krammer of the Icahn School of Medicine on Mount Sinai: ‘If we end up with only one dose without doses available for a timely boost, to me opinion be a problem. ‘
Others say, however, that the spread of the virus carries unnoticed greater risks. “It’s a massacre out there,” said evolutionary microbiologist Andrew Read of Pennsylvania State University, University Park. “Half of them should be twice as many people with partial immunity as full immunity.” Historically, few viruses have succeeded in developing vaccine resistance, with the notable exception of seasonal flu, which develops so rapidly on its own – without vaccination of the vaccine – that it requires a newly designed vaccine annually.
If vaccine-resistant SARS-CoV-2 strains emerge, vaccines need to be updated. Several vaccines can be easily modified to reflect the latest changes, but regulators may authorize them without seeing updated safety and efficacy data, Krause said. As new variants circulate along older strains, even multivalent vaccines are needed, which are effective against different sexes. “To be clear: these are downstream considerations,” Krause says. “The public should not think that this is imminent, and that new vaccines will be needed.” But Ravindra Gupta, a researcher at the University of Cambridge, says manufacturers need to start producing vaccines designed to generate immunity to mutated versions of the vein protein, because they are still popping up. “It tells us that we need to have these mutations in our vaccines so that you can turn off one of the possibilities for the virus.”
For now, increased portability is the biggest concern, says virologist Angela Rasmussen of Georgetown University. ‘I’m surprised why [that] is not a bigger part of the conversation, ”she says. The U.S. hospital system, she says, “is capable in many places and further increases in transmission could cause us to tip over the edge where the system collapses. Then we will see a huge increase in mortality.”