Will the arrival of the Omicron BA.4 and BA.5 variants re-launch the epidemic in France?

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Forgotten by the media for several weeks, theepidemic From Covid is making the headlines again with variants BA.4 and BA.5 settling in France, after its breakthrough in Portugal in particular. Specialists in the epidemiology and development of infectious diseases within the “Infectious Diseases and Vectors” unit: EcologyAnd the hereditaryEvolution and Control” (Montpellier University, CNRS, IRD), Mircea Sofonia, lecturer professorAnd Samuel Allison, Director of Research, deciphered the situation in France. What can we say about these variables? They will cause a new one mysterious this summer ?

Conversation: The Omicron variant, which has become the majority worldwide, continues to spread and evolve. But his new avatars are now set as BA.1 and BA.2 and then BA.4 and BA… How do you find your way?

Samuel Allison: In fact, there is enough to get lost in this abundance of labels! Greek letters were introduced by the World Health Organization (Who is the) in 2021 using an alpha variant. This is perhaps the worst classification, because it was developed without taking into account evolutionary biology. These are from bangu where Nextclade More convenient. Furthermore, the WHO appears to have discontinued its updates and groups under the generic term Omicron all variants of type BA.

we represent Circulation of different fonts in France in a recent work (See above) The first Omicron wave generated by the BA.1 line appeared at the end of 2021. Soon this was replaced BA.2 . linecausing a second wave of hospitalizations in April 2022. Now, it is the BA.4 and BA.5 lines that take precedence.

Mercia T Sofonia: These strains were identified in May, but may have appeared during December 2021 in South Africa, and are likely from BA.2, Majority Line In France since March 2022.

While the BA.2 variant was different from BA.1 such as alternate delta It was alpha variablethe evolutionary difference between BA.4 and BA.5 is more limited.

However, even if the number of new mutations is limited, some are challenging. Thus, the 452R mutation of protein Spike is known to impart greater affinity to the human ACE2 receptor, which the virus uses to enter our cells. 486V boom, still in Spike ProteinIt gives it a great ability to evade the virus.

However, one should be careful with the logic before partial similarity Applied to isolated mutants. Because the effect of the latter is neither absolute nor cumulative; It depends on all Genotypewith potential synergistic phenomena and opponentsincluding remote sites on genome (We are talking about epistasis).

TC: Are these mutations innovations of these variants, or do BA.4 and BA.5 “indulge” in all the possibilities tested by their predecessors – delta, gamma, beta, alpha?

MTS: Let’s remember thatOmicron It is not a descendant of the previous variants, but a distant cousin, and that viruses do not mutate in a voluntary or directed manner. The mutations discovered in the genome of the new strain appeared by chance.

The 452R mutation was not present in the BA.1 or BA.2 lines, but was found in the delta variant. It is furthermore one of the three mutations required in the screening tests currently being performed on everyone PCR test positive in France.

The 486V surge is not associated with any of the lines scattered within Oceanbut so-called experiences deep mutational scanningwhich consist of the generation of mutagenic proteins, have been determined to be involved in escape intoimmunity.

to her : Regarding the differences between variants, two genetic mechanisms are involved: mutations and Reassemble. The latter allows the shuffling of entire parts of the genome When two viruses of different strains infect the same host.

At the biological level, several hypotheses coexist to explainAppearance of Variables: increased circulation in a population, animal reservoir involvement or chronic infection in immunocompromised individuals. In fact, the latter fails to eliminate the virus, which in turn leads to longer and more deadly infections. Advance publication (so it should be taken with caution, as it has not yet been peer-reviewed) by the New York team, this is how it describes The evolution of the BA.1 virus within the patient with the accumulation of major mutations and, above all, its transmission to at least five other people.

In the case of BA.4 or BA.5, since their differences with BA.2 are very limited, they can only be persistent mutations during viral spread.

TC: Why are BA.4 and BA.5 now common in France?

to her : One can easily estimate the growth advantage of one line over another in a population. According to our team, BA.5 is around 9% in France compared to BA.2.

On the other hand, it is complicated to know where this feature comes from. Does BA.5 spread more, because it is more Contagious ? Or is it because it escapes immunity better? a Pre-release by Japanese team and one Posted by Chinese team Highlighting the role of immune escape in particular Across 486V boom.

Regardless of the origin of this feature, it could contribute to the recovery of the epidemic in France.

MTS: A second mechanism is also at work in France: immunity Anti-SARS-CoV-2 – mainly hybridthat is, at the same time Post vaccination and post infection Decreased over time since the last immune event (whether infection or vaccination).

If the protection conferred by Omicron infection or A 3e Vaccine dose It remains noticeable after five months versus a serious form that, on the other hand, is significantly reduced compared to any infection. Thus, the susceptibility of the population to infection with the virus, that is, the analogue of herd immunity, is reshaped over time, which ultimately opens up the possibility of resuming the epidemic.

In short, BA.4 and BA.5 proliferate as our immunity progresses, and do so faster than BA.2, because they have the double advantage of infection and immune escape. Therefore, BA.4 and BA.5 induce a wave sooner than BA.2 would have done.

TK: The situation in Portugal could have been worrying. But can we learn from trends observed in other countries?

MTS: I have reservations about cross-country comparisons: they are more sensitive, because the current circulation depends, in addition to the sanitary measures in place, on the epidemiological and immunological history, which varies increasingly according to the country.

At the level of France, it is still difficult to make a quantitative comparison between the relaxation measures that contribute to recovery, and the summer context that limits it, with longer and warmer days favoring social interactions in an open environment.

to her : Portugal is one of the European countries where the BA.4 / BA.5 wave is the most advanced and is accompanied by an increase in hospitalizations. It’s hard to see why it showed up there so early, but as with all the beginnings of epidemics, It is likely that the role of ‘superspread’ random events has a lot to do with it.

Globally, in South Africa, the BA.4/BA.5 wave appears to be in decline. In the United States, on the other hand, BA.2 was first superseded by BA.2.12, but appears to have been replaced by BA.5.

TC: Can we anticipate the consequences of these substitutions between variables on epidemic peaks in the future?

to her : In 2021, in France, a new variant replaced the old one, because it was more contagious. Since December 2021, it is ratherimmune escape who leads the way.

This makes design difficult scenarios. Forms our teamstarting with theseReverend Institute orPierre Louis Institute of Epidemiology and Public Health Already taken into account vaccination coverage In the population and the proportion of people who contracted a natural infection.

On the other hand, including the time elapsed since the last vaccination or natural injury is a challenge, because two years after EpidemicTwo vaccination campaigns and a massive BA.1 wave, everyone now has a different immunity!

MTS: We have developed tools to account for the immune heterogeneity of populations. Given our limitations, We are currently focusing on the long termbut in theory, it should be possible to use this framework to explore potential short-term scenarios.

At the moment, it is difficult to determine the exact size of the new epidemic wave that has begun. This wave, in the genetic or viral sense, has already progressed well and BA.5 is likely to become the majority by June 20. If we can count on summer to reduceEffect Compared with thewinterit alone will not prevent a wave of radioactive contamination. As a reminder, one of the peak traffic in France remains in August 2020, and the 4e wave (delta) It peaked in July 2021.

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