What do we know about the new variant emerging from Brazil?

This variant, known as P.1 or VOC202101/02 in the UK, was first detected in travellers from Brazil who arrived in Japan in January 2021. It involves 17 unique amino acid changes, three deletions, four synonymous mutations, and one 4nt insertion. It has several mutations that are known to be biologically important, including E484K and N501Y.

The N501Y mutation, which is also a feature of the English variant, has been linked to increased infectivity and virulence in mouse models. Meanwhile, the E484K mutation is thought to be associated with escape from the neutralising antibodies produced by the body against SARS-CoV-2. This mutation is present in the South African variant as well.

P.1 has not yet been detected in the UK, and travel bans have been put in place to try to prevent it reaching the country. There is, however, another variant from Brazil (known as VUI202101/01 in the UK) which contains a small number of mutations that has been found in the UK. As of 14 January 2021, eight cases of this variant—which appears to be of less concern—have been confirmed. Public Health England (PHE) said the “spread and significance of this variant remains under investigation.”

Susan Hopkins, PHE covid strategic response director, said, “For now, our advice following detection of a Brazilian variant in the UK remains the same, even though this is not the variant detected in Manaus with more mutations: the best way to stop the spread of the virus is to wash your hands, wear a face covering, and keep your distance from others. While in lockdown, it’s important that we stay at home unless it’s absolutely essential to go out.”

What do we know about the South African variant?

The South African variant emerged around the same time as the English one, and has since been detected in at least 20 countries. Genomic data from South Africa suggested that the variant, known as 501Y.V2, quickly displaced other circulating lineages in the country as it appears to have a higher viral load and is therefore more transmissible. This variant shares similarities with the English and Brazilian variants in that it contains both the N501Y and E484K spike protein mutations.

New California L452R variant

Less is known about L452R. That variant was first detected in May 2020, but it’s become increasingly common since the fall. According to the Eureka Times-Standard, the L452R variant was found in about 3.8% of cases that were subject to gene sequencing in November. By late December to early January, the variant was represented in 25.2% of sequenced virus samples. However, relatively few samples have been sequenced, and sequencing isn’t done  evenly across the state. According to the Santa Clara County Public Health Department, the new variant has been found in Santa Clara County, Humboldt, Lake, Los Angeles, Mono, Monterey, Orange, Riverside, San Francisco, San Bernardino, San Diego and San Luis Obispo counties. But it’s too soon to say how many cases overall in California are due to the L452R variant.

Just because a particular virus variant begins to overshadow others does not necessarily mean that the strain is more transmissible. Sometimes a strain just gets lucky, multiplying itself in a few superspreader events that spark even more infections throughout the community. The rise in L452R coincided with a surge in coronavirus case numbers in California, making it possible that the mutation was “carried by the surge rather than causing it,” infectious disease specialist Trevor Bedford said on Twitter.

Researchers worry about L452R, though, because some of its mutations affect the virus’s spike protein, the key the virus uses to enter cells. The spike protein is the target of the Pfizer, Moderna and AstraZeneca coronavirus vaccines, as well as several of the promising vaccines still in trials, including the Novavax vaccine and Johnson & Johnson’s vaccines. Mutations to the spike protein could make those variants of SARS-CoV-2 less susceptible to the vaccine. 

“This variant carries three mutations, including L452R, in the spike protein, which the virus uses to attach to and enter cells, and is the target of the two vaccines that are currently available in the United States,” said Charles Chiu, a virologist at the University of California, San Francisco (UCSF), who has been tracking the variant. “Now that we know this variant is on the rise in our local communities, we are prioritizing it for study. Researchers at UCSF and elsewhere will now be able to perform the critical laboratory experiments to determine whether or not this virus is more infectious or affects vaccine performance.”

Even as some people receive coronavirus vaccines, new variants like L452R highlight why it’s important to keep up social distancing precautions until enough people get vaccinated to slow the virus’s spread, said Erica Pan, acting state health officer for the California Department of Public Health. 

“It’s too soon to know if this variant will spread more rapidly than others, but it certainly reinforces the need for all Californians to wear masks and reduce mixing with people outside their immediate households to help slow the spread of the virus,” Pan said in the statement. “We also urge anyone who has been exposed to the virus to isolate from others to protect themselves and their loved ones.”

Do the current vaccines work against the Brazilian, English, and South African variants?

The three main vaccines—Pfizer BioNTech, Moderna, and Oxford AstraZeneca—all target the spike protein of the virus, where these variants have mutations. Researchers are still fairly confident, however, that the vaccines will work against them—although they are not sure whether protection could be reduced—because the spike protein is so large that many mutations would be needed to completely escape. Studies are now underway to test whether the vaccines are effective against these new variants.

Could the virus still mutate to escape the vaccines?

In an interview with The BMJ, Andrew Pollard, who leads the Oxford vaccine clinical trials, said the crucial period will be when lots of people are vaccinated, as this will put the virus under a lot of pressure. “When that happens some viruses just can’t compete against that immunity. Will it mutate instead? With this coronavirus we don’t know the answer to that question yet, and that’s why surveillance is going to be critical in the year ahead to make sure that we’re not in a position where, at the point of population immunity, the virus escapes. And if it does, we need to know that, so that we can redesign the vaccines,” Pollard said. He added that the Pfizer, Moderna, and Oxford vaccines are “relatively straightforward to redesign for a new variant.”

Is there any link between the Oxford vaccine trials—carried out in Brazil and South Africa—and the new variants?

Pollard doesn’t think so. He told The BMJ, “The number of people in the vaccine trials is so small that it’s unlikely that our efforts would put any pressure on the virus to drive it to select new variants. Most trials only have a few hundred people vaccinated in cities of hundreds of thousands or millions of people. I don’t think vaccination has anything to do with new variants today.”

He explained, however, that the variants may be arising in Brazil and South Africa because of high transmission (as many as 40-50% of people being infected) in populations living in crowded conditions. Pollard said, “In those settings, variants of the virus that emerge that are able to spread despite existing post-infection immunity will be selected. If that’s the case, it doesn’t necessarily mean that we’re going to find ourselves in a position where vaccines don’t work against hospitalisation or severe disease, but it may be more difficult to prevent milder disease and transmission. We need to monitor the situation carefully and work out the process that would be needed to make an adjusted vaccine, should the need arise.”

How is the UK monitoring and studying new variants?

The Covid-19 Genomics UK (COG-UK) consortium is carrying out large scale and rapid whole genome sequencing of virus samples, which enables it to identify new variants. It currently provides 48% of the genomic data supplied to GISAID, a global initiative which carries out real time surveillance of the pandemic.

The G2P-UK National Virology Consortium has been launched to work with COG-UK to study how mutations may affect key outcomes, the transmissibility of variants, the severity of illness they cause, and their response to vaccines and treatments.

The group is headed up by Wendy Barclay, head of infectious disease and chair in influenza virology at Imperial College London. She told a Science Media Centre briefing that there were two variants in Brazil being watched—one that was picked up in some travellers into Japan, and the other which is more prevalent in Brazil at the moment. She added, “The sequences that are in the spike protein there, are in the spike protein receptor domain. Studies from other groups and our own are suggesting that they might impact the way that some people’s antibodies can see the virus. It’s important that we carry out this work now and carry it out carefully and in several different laboratories to really firm up those results, because they have big implications.”

How will the new variants be investigated?

G2P-UK co-lead Michael Malim from King’s College London said, “Once a sequence of interest is identified we’ll be able to synthesise that spike gene and make virus particles in the laboratory. Then we’ll test the sensitivity of that virus to inhibition of infection in laboratory models to a range of sera from vaccines and natural infection, and work out if there is a change. It would take about two to three weeks from knowing which sequence to focus on to having those results. So, pretty quickly, we would know where the variant, for example, could potentially break through vaccination.”

Are countries collaborating as variants arise?

A global surveillance system is something that the World Health Organization is working on, according to Barclay. She said, “A group like ours could play a role. Surveillance and update systems will require the basic biology. They need underpinning biology that will come from the studies that we, and other groups around the world, do. That will feed into the WHO draft plan for how we deal with this virus, which is going to be with us for the foreseeable future.”

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