What are the 5 most worrying mutations of COVID-19 and what danger they really represent?

All viruses naturally mutate over time and Sars-CoV-2, which is no exception, has already mutated thousands of times. But scientists identified the most resistant and dangerous genetic variants

The new SARS-CoV-2 coronavirus that was first detected in the Chinese city of Wuhan in December 2019 continues to surprise scientists. Declared a pandemic on March 11, 2020, coronavirus has begun to change genetically into new “substitutions”, “variants”, or “mutations”. All synonymous words when defining a new subspecies of threat.

SARS-CoV-2 has been acquiring minor random mutations since it jumped from animals to humans.

Many people view the virus as an entity capable of making decisions to ensure its permanence among us. But the reality is that viruses decide nothing. Simply, when they infect a cell, almost automatically, they begin to multiply, copying its genetic information. During the copying process, it is common for errors to appear, which, although many times they have no effect, sometimes produce changes. As a consequence, the three-dimensional structure of these macromolecules can be altered, and with it the properties of the virus.

Coronaviruses are also one of the few RNA viruses with a genomic correction mechanism, which prevents the accumulation of mutations that could weaken it. Genetic changes can be beneficial for the virus. Changes in nature are random and always seek to prevail over time and survive.

New mutations

Today, in the middle of the race against the virus that causes COVID-19, mutations appear rapidly, and the longer it takes to vaccinate, the more likely, a new variant will emerge that may challenge the current testing setup, treatments and immunizations. The coronavirus is becoming more genetically diverse and health specialists claim that the high rate of new cases is the main reason, because each new infection gives the pathogen the opportunity to mutate while making copies of itself, threatening to destroy with the progress made so far in controlling the pandemic.

The 5 most dangerous variants of coronavirus

The UK Variant

Names: 20I / 501Y.V1; VOC 202012/01; B.1.1.7 Notable mutation: N501Y

After noting an increase in cases of both infections and deaths in the United Kingdom, on December 8, scientists and public health experts concluded that behind this, there is a new variant of COVID-19. Two weeks later, the British Health Minister, Matt Hancock, stated that the new strain of coronavirus detected in England was “out of control” and that is why the Government had to act “quickly and decisively”, referring to the confinement imposed in London and the southeast of the country.

The British government’s scientific adviser, Patrick Vallance, explained that this variant of SARS-CoV-2, in addition to spreading rapidly, is becoming the “dominant” form, which led to “a very strong rise” in hospital admissions in December. The new strain would have appeared in mid-September in London or Kent (southeast), according to him.

According to the preliminary study on this new virus lineage, a distinct phylogenetic group (called the B.1.1.7 lineage) was detected within the COG-UK surveillance data set. Variant B.1.1.7 contains 17 mutations, including several in the peak protein. One of them, N501Y, has been found to help the virus bind more closely to the cellular receptor ACE2. However, it is not clear whether the variant’s increased contagiousness comes from N501Y alone or whether it also involves some combination of other spike protein mutations.

“So far there is no real evidence to show that the variant is more infectious in children than the original,” says Cambridge University microbiologist Sharon Peacock, who is executive director of COVID-19 Genomics UK (COG-UK) Consortium, a group that analyzes the genetic changes of the virus. Both Pfizer and Moderna believe their COVID-19 vaccines will continue to work against B.1.1.7. Recent data from the UK hints that the variant may be more lethal than the original, but the analyzes are preliminary.

Spain Variant

Names: 20A.EU1; B.1.177 Mutation: A222V

The 20A.EU1 variant, identified for the first time in Spain, contains a mutation called A222V in the viral peak protein. The spike is a component of SARS-CoV-2 that binds to a receptor on human cells called ACE2, and this binding helps the virus to enter those cells and infect them. The spike protein is also the part of the pathogen that is the target of human antibodies when fighting infection.

In laboratory tests, human antibodies were slightly less effective in neutralizing viruses with the A222V mutation. Over the course of several months, variant 20A.EU1 has become dominant in Europe. However, epidemiologists never saw any evidence that it was more transmissible than the original. Researchers believe that when Europe began to remove travel restrictions last summer, the dominant variant in Spain spread across the entire continent.

This new mutation of the virus has been identified thanks to an international effort led by the University of Basel and the ETH University of Zurich, with the participation of the SeqCovid-Spain consortium, led by researchers from the Higher Council for Scientific Research (CSIC) and funded by the Carlos III Health Institute

“We have seen a similar pattern with other variants in Spain in the first wave in spring. A variant driven by an initial super-contagious event can quickly become prevalent throughout the country,” said CSIC researcher Iñaki Comasco-author of the study and coordinator of the SeqCovid-Spain consortium. “A variant fueled by an initial super contagion event can quickly become prevalent across the country.”

South Africa Variant

Names: 20H / 501Y.V2; B.1.351 Notable mutations: E484K, N501Y, K417N

In January, South Africa identified a new variant of the coronavirus that is causing a second wave of infections. “A variant of the SARS-COV-2 virus, currently named Variant 501.V2, has been identified by our genomic scientists here in South Africa,” Health Minister Zweli Mkhize wrote on Twitter. 

“The evidence that has been collected clearly suggests that the current second wave we are experiencing is being driven by this new variant,” added Mkhize.

Variant B.1.351 appeared around the same time as B.1.1.7 and quickly spread in South Africa to become the dominant version in the country. Like its European counterpart, B.1.351 contains the N501Y mutation, although the evidence seems to suggest that the two variants arose independently. But scientists are more concerned about another mutation called E484K that appears in the South African version. According to scientists, genetic change can help the virus evade the immune system and vaccines.

The E484K mutation is not a new variant in itself, it is a mutation that occurs in different variants and has already been found in the South African (B.1.351) and Brazilian (B.1.1.28) variants. The mutation is in the spike protein and appears to have an impact on the body’s immune response and possibly the efficacy of the vaccine. On February 1, Public Health England (PHE) announced that the COVID-19 Genomics consortium (COG-UK) had identified this same E484K mutation in 11 samples carrying the UK variant B.1.1.7 (sometimes called the UK variant or Kent variant), after analyzing 214,159 sequences.

Using yeast cells, evolutionary and computational biologist researcher Jesse Bloom and his lab colleagues created a series of spike proteins with nearly all of the more than 3,800 possible changes in protein components that could be driven by genetic mutations. The scientists then tested how well or poorly human antibodies bound to each altered peak and found that E484K, as well as similar mutations at that particular point in the protein, made it up to 10 times more difficult for antibodies to bind to the peak in some persons. Bloom’s lab also found that some antibody cocktails, such as the one currently being tested by pharmaceutical and biotech companies Regeneron and Eli Lilly, may be less effective against mutations present in variant B.1.351.

At the end of this month, South African researchers published a preprint study (research that has not yet been peer-reviewed) showing that a serum containing antibodies from COVID patients was considerably less effective in neutralizing this variant. And in another preliminary preprint published on January 26, the scientists reported that they put B.1.351 in serum drawn from people who had been vaccinated with the Pfizer or Moderna vaccine. They found antibodies in that serum that showed reduced neutralizing activity against the mutant, compared to its activity against the original virus. But vaccines produce so many antibodies that a drop in activity could still leave enough to neutralize the virus. Vaccines also stimulate other protective components of the immune system. Still, Moderna has started working on a specific boost injection for new variants.

Brazil Variant

Names: B.1.1.28; VOC202101 / 02, 20J / 501Y.V3; P.1 Notable mutations: E484K, K417N / T, N501Y

Names: VUI202101 / 01, P.2 Notable mutation: E484K

In January, a group of researchers reported that they had detected two new variants of the coronavirus in Brazil, both descendants of a somewhat older common ancestral variant. Although they share mutations with other newly discovered versions, they appear to have arisen independently of those variants. The P1 variant is mainly found in outbreaks in and around Manaus, the capital of the Brazilian state of Amazonas. It is not yet clear whether the course of the disease is different for this variant. Among other mutations, it has three spike protein changes. These three changes are almost identical to the changes in South African. Mutations can potentially make it more contagious and reduce the effectiveness of pre-existing or vaccine-induced immunity. This is currently being investigated nationally and internationally.

The Rio de Janeiro or P2 variant (derived from lineage B.1.1.28) is found throughout Brazil. One of the three P1 mutations also occurs in this case. This mutation could potentially make it more contagious and lead to reduced immunity after a previous infection with previous variants. At present, it is also being investigated nationally and internationally whether this is really the case. Like P1, it is not yet clear whether P2 leads to changes in the course of the disease.

Of the two virus subtypes, researchers are currently more concerned with P.1 as this variant contains more mutations than P.2 (although they both have E484K), and has already been seen in Japan and other countries. Although P.1 may have accumulated its mutations in an immunosuppressed individual, genetic researcher Emma Hodcroft of the University of Bern in Switzerland says it might be more difficult to pinpoint when and where this variant first emerged because Brazil does not sequence nearly as many viral samples as the UK.

Hodcroft points out that both Brazil and South Africa had large COVID outbreaks in 2020. With so many infected people creating antibodies against the virus, a version that could evade the immune system and reinfect a person who had recovered could have a major advantage and then become more widespread in a population.

Japan Variant

Names: B.1.1.7; P.1 Notable mutations: E484K, K417N / T, N501Y

The health authorities of Japan have detected a new variant of COVID-19, apparently different from those detected in the United Kingdom and South Africa, in several people who returned to the country at the beginning of the month from Brazil.

“To further analyze the variant we must first isolate it. That could take between several weeks and several months and therefore it is difficult to say now when we will be able to give details,” explained a person in charge of the Japanese Ministry of Health.

Japan announced on Sunday that it had detected a new variant of coronavirus, without being able to immediately determine if it was more contagious or dangerous than the already known variants. The variant was discovered in two adults and two children who arrived in Japan on January 2 from Brazil.

The Japanese infectious diseases center came to this conclusion after sequencing the genes of the virus, in which it detected 12 mutations, and noted that at the moment “it is difficult to determine the infectivity, pathogenicity or effects in the methods of tests and vaccines”, and recommended keeping affected patients in isolation.

The variants of SARS-CoV-2 that are currently causing the most concern, due to the speed with which they are spreading, are the British, South African and Brazilian, named after the place where they were first detected. According to the most accepted nomenclature for the classification of virus lines, these variants correspond to B.1.1.7 (British), B.1.351 (South African) and P.1 (Brazilian).

The UN agency’s emergency director, Michael Ryan, used a metaphor to explain what it means that the new mutations have an influence on the virus’s ability to spread.

“It’s like substituting a player in the second half of a soccer game, it doesn’t necessarily change the result, but it gives the virus new energy and more impetus, it increases the challenge, but it doesn’t change the rules of the game, just the strength of the competition,” he concluded.