Relatives attend the funeral of a COVID-19 victim in Manaus, Brazil, on January 13.
MICHAEL DANTAS / AFP via Getty Images
By Kai Kupferschmidt
Science‘s COVID-19 reports are supported by the Pulitzer Center and the Heising-Simons Foundation.
When the number of COVID-19 cases started to increase again in Manaus, Brazil, in December 2020, Nuno Faria was amazed. The virologist at Imperial College London and an associate professor at Oxford University had just written an article in Science estimate that three-quarters of the city’s inhabitants had already been infected with SARS-CoV-2, the pandemic coronavirus – more than enough, it seemed, for the development of collective immunity. The virus must be done with Manaus. However, hospitals were filling up again. “It was difficult to reconcile these two things,” says Faria. He started hunting for samples he could sequence to find out if changes in the virus could explain the resurgence.
On January 12, Faria and her colleagues posted their first findings on virological.org. Thirteen of the 31 samples collected in mid-December in Manaus ended up being part of a new viral strain that they called P.1. Much more research is needed, but they say one possibility is that, in some people, P.1 avoids the human immune response triggered by the lineage that devastated the city in early 2020.
Related
Emerging variants of the coronavirus have been in the news since scientists raised the alarm about B.1.1.7, a variant of SARS-CoV-2 that first caught the attention of scientists in England in December and is more transmissible than than previously circulating viruses. But now, they are also focusing on a new potential threat: variants that could wipe out the human immune response. These “immune breakouts” may mean that more people who have had COVID-19 remain susceptible to reinfection 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 discussed the most important scientific questions raised by the wave of new mutations. WHO also convened its Emergency Committee COVID-19 on January 14 to discuss the impact of the new variants and the travel restrictions that 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 asked countries to support “global research efforts to better understand the unknown unknowns about SARS-CoV-2 specific mutations and variants”.
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 released a modeling study on Friday showing that the strain could become the prevalent variant in the United States in March. But scientists are also concerned about 501Y.V2, a variant detected in South Africa. Some of the mutations it carries, including the so-called E484K and K417N, alter its surface protein, peak, and have been shown in the laboratory to reduce how well monoclonal antibodies fight the virus. In a preprint published earlier this month, Jesse Bloom, an evolutionary biologist at Fred Hutchinson Cancer Research Center, showed that E484K also reduced the potency of convalescent serums from some donors by 10 times – although he is quick to add that this does not necessarily mean the mutation would cause people’s immunity to the new strain to drop 10 times.
P.1 raises concerns because it appears to have reached a similar constellation of mutations and appeared in a location with a high level of immunity. “Whenever you see the same mutations coming up and starting to spread over and over again, in different viral strains around the world, it’s really strong evidence that there is some evolutionary advantage to these mutations,” says Bloom.
Like B.1.1.7, the variant identified in Manaus is already in motion. When Faria was finishing his analysis of the Brazilian genomes, a report was published of a variant detected in travelers arriving in Japan from Brazil – and it ended up being P.1.
Bad friends
It is not yet clear how these new variants are affecting the course of the pandemic. In Manaus, for example, P.1 may have nothing to do with the new outbreak of infections; people’s immunity may simply be declining, says Oxford epidemiologist Oliver Pybus. At a press conference today, Mike Ryan of WHO warned that changes in human behavior are still the main driving force for the resurgence. “It is very easy to blame the variants and say it was the virus that did it,” he said. “Unfortunately, we didn’t do that either.”
Even though the variant plays a crucial role, it may be driving the increase because it is more easily transmitted, like B.1.1.7, and not because it can escape the immune response. “Of course, it could also be a combination of these factors,” says Pybus. Likewise, in a recent modeling study, researchers at the London School of Hygiene & Tropical Medicine calculated that South Africa’s 501Y.V2 variant could be 50% more transmissible, but no better at escaping immunity, or as transmissible as the previous variants, but able to escape immunity in one in five previously infected people. “The reality can be between these extremes”, wrote the authors.
Ester Sabino, molecular biologist at the University of São Paulo, São Paulo, is launching a study to find reinfections in Manaus that can help decide between these hypotheses for P.1. She is also working to sequence more samples from Manaus starting in January to accompany the release of the variant. “We don’t have the data yet, but my guess is that it will now be 100%,” she says. Laboratory studies investigating the variants are also underway. The UK today launched a new consortium, G2P-UK (from “genotype to phenotype-UK”), led by Wendy Barclay of Imperial College London, to study the effects of emerging mutations in SARS-CoV-2. An idea discussed at the WHO meeting on January 12 is the creation of a biobank that would help with studies, housing samples of viruses, as well as plasma from vaccine recipients and recovered patients.
The interactions between the new mutations can make it more difficult to detect their effects. The UK, South Africa and Manaus variants 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 the N501Y doesn’t operate alone, says Kristian Andersen of Scripps Research: “Nelly can be innocent, except maybe when she’s dating your bad friends. “
Bloom believes that none of the changes will allow the virus to escape the immune response entirely. “But I would expect these viruses to have some advantage when a large part of the population has immunity” – which may help explain the increase in Manaus.
Vaccine updates
So far, the virus does not appear to have become resistant to the COVID-19 vaccines, says vaccinologist 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 evolve into a vaccine-resistant phenotype, it could happen sooner than we would like,” he adds. That possibility increases the urgency to put good surveillance in place to detect such escape variants from the beginning, says University of Florida biostatistics Natalie Dean. But it also increases the urgency to vaccinate people, says Christian Drosten, a virologist at Charité University Hospital in Berlin. “We have to do everything in our power to vaccinate as many people as quickly as possible, even if it means running the risk of selecting some variants,” he says.
If vaccine-resistant strains of SARS-CoV-2 appear, vaccines may need to be updated. Several vaccines can be easily changed to reflect the most recent changes, but regulators may be hesitant to authorize them without seeing updated safety and efficacy data, says Krause. If new variants circulate with the older strains, multivalent vaccines, effective against several strains, may even be necessary. “To be clear: these are later considerations,” says Krause. “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 should start producing vaccines designed to generate immunity to mutant versions of the spike protein, because they keep coming. “It tells us that we must have these mutations in our vaccines, so that you close one of the pathways for the virus to fall.”
For now, increasing transmissibility is the biggest concern, says virologist Angela Rasmussen of Georgetown University. “I am intrigued why [that] it is not an important part of the conversation, ”she says. The US hospital system, she says, “is crowded in many places and additional increases in transmission can push us to the limit where the system collapses. Then we will begin to see potentially huge increases in mortality. “