Nelly and Erik, the disturbing mutations of the coronavirus that threaten to worsen the pandemic

Scientists monitoring the evolution of the new coronavirus are restless. After the appearance at the end of the year of two apparently more contagious variants, detected in the United Kingdom and South Africa, a group of researchers published on 12 January the description of a third suspicious variant in Brazil, relatively similar to the previous two. The authors suggest a troubling possibility: convergent evolution, the same phenomenon that caused bats and birds to independently develop wings millions of years ago. The coronavirus could also be mutating in different parts of the world towards the same direction: more transmissible versions and even capable of reinfecting some people who have already had the covid, according to the team that has warned of the Brazilian variant, led by the epidemiologist Nuno Faria, from Imperial College London.

The new variant, detected in the Amazon city of Manaus, presents a unique combination of mutations, but two of them are old acquaintances. Some geneticists call them Nelly and Erik, by similarity with their technical names: N501Y and E484K. Nelly and Erik are two mutations that affect the spike of the coronavirus, the key with which the virus enters human cells. The Nelly mutation is present in all three disturbing variants and Erik joins it in the South African and the Brazilian.

Virologist Rafael Delgado expresses his “concern” about this possible convergent evolution, with combinations of mutations that may be repeated because they represent an advantage for the virus. A preliminary study of the American biochemist Jesse bloom suggested a couple of weeks ago that the E484K mutation multiplies the ability of the coronavirus to escape the antibodies from the blood plasma of some donors who have already overcome the covid. And other research published this tuesday maintains that “most” of the people who have already had a natural infection by the new coronavirus could be reinfected with the South African variant. The work, still a draft pending review, is signed by the virologist Penny moore, from the National Institute of Communicable Diseases of South Africa.

The British variant – with Nelly but without Erik – apparently emerged in the UK in September and has already registered in 40 countries. British authorities estimate that it is between 30% and 50% more transmissible. In Spain, it was identified for the first time in the middle of Christmas, at the Hospital 12 de Octubre in Madrid. “We are detecting right now between 2% and 3% [de variantes británicas respecto al total]. The percentage is small, at the moment, but it has clearly been increasing ”, explains Rafael Delgado, head of the Microbiology Service of October 12. In Denmark, the British variant represented 2.4% of the samples analyzed two weeks ago and it already reaches 7%.

The British variant does not produce a more serious disease, but it is more contagious by all indications, so the end result would be a higher death toll in any case. “Hospitals fill you up before. And, therefore, it is a danger, especially in the situation we are in now, which is already bad. It is worrying ”, says the biologist Iñaki Comas, co-director of consortium sequencing genomes of the coronavirus in Spain. Comas calculates that the British variant only reaches a frequency of between 1% and 5% in the entire Spanish territory, for the moment.

“The British variant fills the hospitals before you. And, therefore, it is a danger ”, warns biologist Iñaki Comas

The South African variant has already been registered in 13 countries, including France and Germany. The Brazilian has only been identified in Brazil, Japan and South Korea. Neither of these two versions of the virus has yet been detected in Spain. “The current wave in Spain is not due to any of these variants, but to those we already had,” Comas emphasizes. It may be a matter of time. The Centers for Disease Control and Prevention (CDC) calculate that the British variant will be the dominant in the US in March.

Some specialists, such as the American Trevor bedford, believe that these new variants have arisen in people with a chronic infection, a process in which defenses fight against the coronavirus for months, until a mutant appears that better invades human cells and manages to escape. Bedford of the Fred Hutchinson Research Center relies on the case of a 45-year-old man who, due to a problem in his immune system, was admitted with covid for five months at Brigham and Women’s Hospital, in Boston (USA). The doctors who treated him reported “an accelerated evolution of the virus” until the patient ended up dying. Among the mutations detected were Nelly and Erik.

It is very rare for a single mutation to change the course of a virus, but there are precedents. A single change in the chikungunya virus made the pathogen capable of infecting a new species of mosquito and thus increasing its epidemic potential, according to A study from the University of Texas. What worries scientists most, however, is the synergistic effect of several relevant mutations. Rafael Delgado is especially concerned about the coincidence of Nelly and Erik in the South African and Brazilian variants.

A preliminary study with 20 volunteers, published on Tuesday, also suggests that the antibodies of those vaccinated – with doses of Pfizer or Moderna – are slightly less effective against the new variants with the Nelly and Erik mutations. “Vaccines may need to be periodically updated to avoid potential loss of clinical efficacy,” conclude the authors, led by the immunologist Michel Nussenzweig, from Rockefeller University (USA). The researchers stress that the observed effect is “modest.”

It is not contemplated that the vaccines will stop working suddenly, but they can progressively lose effectiveness and must be updated

The geneticist Fernando Gonzalez Candelas, co-director of the Spanish consortium, recalls the excessive alarm generated in the last year with other mutations, such as D614G, identified as possibly more contagious since the summer and now absolutely dominant throughout the world. González Candelas, a professor at the University of Valencia, is very skeptical of the hypothesis that the coronavirus is evolving in the same direction. “With viruses you have to be very careful. Even if the same mutation appears several times, it does not mean that there is a convergent evolution. The probability that the same mutation will appear independently is very high ”, he argues. “There is too much anticipated alarm about it.”

González Candelas does believe that the conditions could be creating for the emergence of advantageous strains of the virus. “As the number of people vaccinated or with immunity generated by a previous infection increases, infection by those viruses that can evade these immune defenses is favored,” he reasons. The emergency committee of the World Health Organization stated on January 15 that the risk is “very high” and called for countries to devote more resources to monitoring coronavirus mutations. Almost no one considers the possibility that vaccines suddenly stop working, but their current 95% effectiveness could be progressively reduced to the point of having to update them, as happens every year with the flu vaccine.

“The problem is that much of what we know about the effects of mutations comes from experiments with individual mutations: you put a mutation [en una réplica del virus en el laboratorio] and see what happens. But we lack a lot of experimental information on how all these mutations interact with each other: what is the impact of putting Nelly and Erik together ”, explains Iñaki Comas, from the Institute of Biomedicine of Valencia (CSIC).

Commas, however, is optimistic. “Probably, both the South African and the Brazilian variants have some effect on immunity, due to that E484K mutation, but we do not expect that either of these variants, not even the British one, will affect the current vaccines. The immunity that we get with vaccines is much greater than natural immunity after an infection ”, he reassures. Jesse Bloom himself, one of the scientists who has studied the E484K mutation the most, has declared which is confident that “current vaccines will be useful for quite some time.”

“The most important thing now with regard to vaccines is not to worry about the variants, but to worry about vaccination: that it reaches all populations in all parts of the world,” says Comas. As for the new variants, the Spanish researcher recalls the basic strategy to stop them: “A variant that is capable of skipping a mask has not yet been invented.”

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