Covid-19: when is a mutated virus considered a new variant?

From the Wuhan strain to Omicron: In two years, SARS-CoV-2 has evolved into different variants, possessing various mutations. But if some are known to the general public, there are actually “thousands and millions”.

Alpha, Beta, Delta and now Omicron… These terms were, until recent months, attached to the Greek alphabet. For the world population today, they refer to variants of Covid-19. The appearance of a new variant now leads to a host of questions and concerns regarding its dangerousness, its contagiousness or its resistance to the immunity developed.

But if there are, for the general public, a few variants which have succeeded each other since the start of the pandemic, on the virological level, there are many more, because any virus presenting a mutation different from the original strain.

“A virus is never stable”

To understand what a variant is, we must first explain how a virus mutates. “In fact, a virus is never stable,” explains virologist Eric Leroy, director of research and member of the National Academy of Medicine, to BFMTV.com. When it integrates an organism, “it develops, multiplies permanently and each time it multiplies, the genetic code by reproducing itself commits errors”, which are called mutations.

“As with all RNA viruses, the replication of SARS-CoV-2 is not very faithful and many mutations appear quickly”, also points out Vidal medical dictionary.

This same source explains that a “mutation is the substitution of one RNA base (in the case of RNA viruses) by another during a replication error”, which leads to the modification of an amino acid. The SARS-CoV-2 genome is made up of nearly 10,000.

These mutations can take different forms, Vidal explains:

  • a substitution – one amino acid replaces another
  • a deletion – an amino acid disappears
  • an insertion – a new amino acid is introduced into the protein
  • or a duplication – an amino acid is abnormally repeated.

“Basically a mutation is just a point change (only one) in the RNA of the virus which leads to a point change in the protein” concerned, summarizes virologist Morgane Bomsel, director of research at the CNRS.

These different mutations can bring a new capacity to the virus, such as increased transmissibility, immune escape (the immunity acquired by the infected individual does not prevent him from being recontaminated), but they can also harm him. “Some may be unfavorable for the virus and prevent it from reproducing”, explains for example to BFMTV.com Vincent Maréchal, professor of virology at the Sorbonne University (Paris). Others are “silent” and do not affect its operation.

“Thousands and millions” of variants

From there, two definitions of the term variant coexist. “A variant, in the virological sense of the term, is defined by the existence, if only of a single mutation, compared to its parent”, explains Eric Leroy. In this sense, there are “thousands and millions of them during an epidemic, a pandemic. And obviously the more the epidemic extends in time, the more there are”.

In the genetic sense, we speak of a variant “when the virus is no longer identical to the basic strain”, also explains Vincent Maréchal. “We see variants all the time, but very few are known.”

The general public therefore only knows, in reality, a very small part of the variants of SARS-CoV-2. If these few variants are more highlighted, “it is because the mutations they contain lead to a change in behavior, a particular variation”, explains Vincent Maréchal. The Omicron variant, for example, is much more contagious than the previous ones.

“The variant as it is understood in the public domain is a viral strain of SARS-Cov-2 which has a property which is noticeable, is particularly important for public health”, declares Eric Leroy.

“There are many variants, but they are not interesting because the differences in properties do not concern us, have no effect or they are marginal effects vis-à-vis our conception of public health. “.

Virus “lineages”

On the other hand, viruses which sometimes do not present exactly the same mutations are grouped together under the term variant. This is how the World Health Organization works, which classifies variants according to their danger to public health. VOCs (“variants of concern”) are the variants that – because they are highly contagious, highly virulent, or allow immune escape from the virus – are considered most at risk. VOIs (“variants of interest”) are considered less dangerous but also affect the population with these same characteristics.

“In some cases, a group of variants with similar genetic changes (…) may be designated by public health organizations as a Variant of Concern (VOC) or a Variant of Interest (VOI) due to shared attributes and characteristics that may require public health action”, thus explains the American CDC, the center for disease control and prevention.

The Omicron variant thus designates different sub-lineages. If its BA.1 and BA.2 sub-lines “carry the K417N mutation”, BA.2 does not have, for its part, “the 69-70 deletion in the Spike protein”, written Public Health France in the December 15 risk analysis on emerging variants of SARS-CoV-2. When we talk about the Omicron variant, we are therefore actually talking about viruses that differ slightly.

The term variant can also, in common usage, be confused with the term “lineage”. Thus, when talking about the Alpha variant, the term “B.1.1.7” is sometimes used. The latter actually designates the line from which the Alpha variant originated.

SARS-CoV-2 phylogeny
Phylogénie du SARS-CoV-2 © GISAID

A lineage is “a group of closely related viruses with a common ancestor,” writes the CDC. When we follow the evolution of mutations over time, “we obtain ‘lineages’ of viruses that can be visualized as branches in the family tree of SARS-CoV-2”, also underlines Vidal.

Towards a new virus?

Given that a virus is constantly changing, acquiring new mutations, one can then wonder to what extent the mutated virus produced can still be associated with the basic virus, SARS-CoV-2. Can a variant eventually mutate so much that it creates a whole new virus?

For the moment, “we remain in the same group, the viruses currently circulating remain closer to each other than SARS-CoV-2 is close to other coronaviruses”, explains Vincent Maréchal, but they continue to evolve. . “The variants make children, and obviously they look more like their parents than their grandparents”, or their common ancestor to all, the historic virus detected in Wuhan.

It is possible that in the very long term – well over two years of the pandemic – viruses will break away from the Covid-19 family tree to create their own phylogenetic tree. SARS-Cov-2, for example, itself descends from another basic virus: “there are 5 coronaviruses in humans, and they have a common ancestor with the current SARS-CoV-2, but they diverged ” over time, explains Eric Leroy.

“So indeed, as and as evolution takes place, viruses will adapt, will evolve little by little”, continues the virologist, “and then possibly one day if conditions allow it, there will be the advent of a virus which is so far removed from its original virus that we end up either with a new species or a new viral genus”.

Salome Vincendon

Salome Vincendon BFMTV reporter

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