Covid-19. What we know about BA.4.6, this new sub-variant of Omicron

The BA.4.6 subvariant has tripled in one month in the United Kingdom, where it now accounts for 11% of new contaminations. In the United States, it is identified in no less than 61% of new cases, according to health authorities (CDC).

And it is already present in France, in 2% of the sequences analyzed, as in many other countries around the world.

BA.5 remains dominant, but…

As a reminder, in France, the dominant sub-variant remains BA.5, which represents more than 90% of contaminations since mid-July and the end of the seventh epidemic wave.

The emergence of new sub-lineages is a normal and expected evolutionary phenomenon. In the absence of an epidemiological or clinical signal, this does not constitute a worrying signal in terms of public health.

Public Health France

Like all other viruses, Covid-19 has already mutated hundreds of thousands of times. Only the versions most “advantaged” by their new characteristics manage to supplant the others – generally because they are much more transmissible. On the other hand, it is impossible to predict their dangerousness: they can just as well be less deadly than more virulent. The Delta variant, in 2021, replaced a much less dangerous version of the virus, before being supplanted by the inherently less deadly but much more contagious Omicron.

Finally, each of the avatars of the virus is more or less resistant to vaccines and antibodies linked to a previous infection: since the arrival of Omicron, vaccines have been shown to be much less effective in countering the infection, and reinfections are frequent. The launch of vaccines “adapted” to Omicron should improve protection.

A recombinant variant

The BA.4 subvariant was first detected last January in South Africa. The massive distribution of BA.5 did not make it disappear, however. And for now, how BA.4.6 appeared remains quite mysterious. Its first detection dates back to April 25, 2022.

However, according to Manal Mohamed, a microbiologist at the University of Westminster in The Conversation, it would be a so-called “recombinant” variant. Recombination occurs when a new version of the virus emerges when a single person is infected with two variants at the same time.

It was spotted in France for the first time in June:

Within BA.4, the BA.4.6 sublineage was first detected during the week of June 13 and its detection during surveys appears to be stabilizing around 2%

Public Health France

High immune escape

Quite recent, it has not yet revealed all its secrets. It remains a “descendant” of Omicron, therefore a highly contagious and less lethal version than the Delta variant, for example. Only real-life observations, first, can tell us about its ability to thrive and the possible damage it can cause. Another unknown remains, that of the immune escape:

BA.4.6 will be similar to BA.4 in many ways, but carries a spike protein mutation […]. This R346T mutation has been observed in other variants and is associated with immune evasion

Manal Mohammad, microbiologist at the University of Westminster

“Which means that it helps the virus to escape the antibodies acquired during vaccination and a previous infection”, continues the researcher.

According to a study published in September by researchers at the University of Oxford, the production of antibodies would be even lower with BA.4.6 than with the other subvariants of Omicron in circulation.

A situation that could be resolved by the forthcoming availability in Europe of vaccines specifically adapted against Omicron. According to Moderna, which is preparing to market a bivalent vaccine – as a reminder – against the original strain and the BA.1 sub-variant, this version “is effective against all Omicron strains”.

Another worrying hypothesis: on BA.4.6, as on a few other subvariants that are still in the minority, several treatments (Evusheld, Paxlovid, etc.) would simply become ineffective, according to a study by Columbia University.

Vaccination remains the key

Even with the “old” vaccines – the new ones are not yet available, and will only be available as a booster at first – protection remains high against severe forms of Covid-19.

A complete vaccination schedule (two doses plus a booster) also confers protection against infection, even if it is much less than against the original virus.

US President Joe Biden bluntly announced the end of the pandemic this Sunday – even as an eighth wave threatens and more than 500 people die of Covid every day in the United States.

No one can know if BA.4.6 will be able to impose itself in Europe and/or in France. A small successor, BA.4.6.1, much more contagious, could directly beat him the pawn.

France has been experiencing the start of an eighth epidemic wave for two weeks, with a 50 to 70% increase in contamination each week.

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