Covid-19: ever more pronounced concern about variants
Mural depicting the coronavirus in New Delhi, India (Photo illustration).
© SAJJAD HUSSAIN - AFP
Text by: Simon Rozé Follow
8 min
As the British variant continues to spread across Europe and around the world, health officials across the country say they have discovered that it carries a new problematic mutation.
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First of all, there is the N501Y mutation, which
a priori
makes
the variants that carry it more contagious.
This is the case of the British, South African and Brazilian.
Then there is the E484K mutation which makes them, again
a priori
, more resistant.
Here again, the South African and Brazilian variants are concerned.
So far the British one seemed to be exempt.
Until the British health authorities announced very discreetly
via
an update of
a report
that this mutation
"was detected in 11 sequences"
of the local variant.
Darwin Live
"
The emergence of this mutation was observed without any importation of the South African variant
"
which also carries it, explains Bruno Canard, CNRS researcher at the Architecture and Function of Biological Macromolecules Laboratory.
"
We see that this British variant developed this E484K mutation in addition to the N501Y that it already possessed
."
This association is thus the same as that observed in South Africa and Brazil, and it therefore seems to appear naturally.
►Also read
: What do we know about the different variants of Covid-19?
This is a phenomenon of
“
evolutionary convergence
”
, explains Bruno Canard.
"
It is because the coronavirus has an advantage in bringing about this combination
".
Of course, he doesn't do it on purpose.
This phenomenon,
"
it's Darwin
",
natural selection before our eyes.
“
The coronavirus mutates all the time, and the mutations most suited to the environment survive.
He has no intelligence!
"
.
In fact, for more than a year now, according to infections, collective immunity to the coronavirus has been building up, and its "basic" strain has had more and more difficulty in spreading.
But at the same time, like all viruses, Sars-CoV-2 mutates.
Changes that occur at random, during its multiplication in the cells of sick people.
Unfortunately, sometimes these changes give it an advantage: greater contagiousness for N501Y, greater resistance for E484K… By natural selection, these mutations and the variants which carry them take the place left free by the original strain.
This phenomenon also explains why the appearance of these variants is occurring now and not earlier: the selection pressure was not as strong.
Catch up with the virus
The most effective variants therefore replace the old one,
"
and we are running behind,
"
smiles Bruno Canard.
“
The virus has the ball, and we follow, we try to sting it.
How to regain the initiative?
There is only one solution: to try to anticipate in the laboratory what will be the mutations that will give the virus an even greater advantage.
You have to look for all these combinations, and prepare for them right away.
Hopefully Moderna and Pfizer, those working on RNA vaccines, have already started working on such projects to speed up the vaccine production phase on these
upcoming
'super viruses'
to be near as soon as we get there. will see them.
"
This is indeed one of the great advantages of this vaccine technology.
To produce them, all you need is the genetic code of the coronavirus.
By anticipating what changes may occur in the future, this design work can therefore be carried out upstream.
This work is already starting to be done in some laboratories:
"
We have to determine the size of the possible variation space of the virus, does it still have a lot of combinations to play?"
Very interesting work has looked into this question.
The authors looked at this mutational space and saw that the virus still had a lot of headroom.
We are legitimately worried about the E484K mutation, but the virus still has possibilities of combination to have a much better evolution.
We will have to be able to detect them the day these mutations occur,
”
concludes the researcher.
Immune memory
Fortunately, and even if E484K seems to thwart part of our immune response and limit the effectiveness of our antibodies, our immune system has tools to deal with it, as does the emergence of new, more problematic variants.
First and foremost is what is called immune memory.
"It is the rather fantastic capacity of the immune system to remember the pathogens that it has encountered beforehand,
" explains Matthieu Mahévas, Inserm researcher at the Mondor Institute for Biomedical Research.
“Its mechanisms allow you to better defend yourself when you are exposed to an infection a second time.
“
Regarding Sars-CoV-2 and Covid-19, several studies have shown that such an immune memory exists.
►Also read: Covid-19: “immune memory”, the main weapon against the virus?
The challenge now remains to determine its duration and its effectiveness.
Bruno Mahévas coordinated a study which has just appeared in the
prestigious journal
Cell
.
This work confirms in particular that this protection lasts at least 6 months, and probably more.
Another good news: the great flexibility of this immune response:
“
the characteristic of memory cells is their adaptation.
Our immune system has an extremely large repertoire of antibodies developed to recognize RBD
(the region of the virus that it uses to enter our cells).
This diversity is very good news: potentially, in the repertoire of our immune system, we have the necessary tools to neutralize the variants.
"
Thus, to use the image in the catalog, in the event of an attempt at reinfection with a variant of Sars-CoV-2, it is likely that our immune system already has the weapons available to deal with it.
Even if it is one in 100 cells, the immune system will select it in the event of reinfection.
"
A downside, however, the indices supporting this hypothesis have so far only been obtained in the laboratory,
in vitro
:
"
What has been shown by
Michel Nussenzweig's team
in New York is that cloning memory cells, and testing their reactivity towards variants, they observe that they are capable of neutralizing them all
”.
The counterexample of Manaus
However, this efficiency of immune memory seems to be undermined by what is currently being observed in Manaus in Brazil.
The city is facing a terrible epidemic wave even though it was believed that the population's immunity had been reached there.
► To read also: "Manaus has become the world capital of Covid-19"
"
It is obviously disturbing
"
, agrees Matthieu Mahévas.
However, he believes that there can be several interpretations:
"
We do not yet have robust data to know whether we had indeed achieved collective immunity and whether it is indeed reinfection.
What we do know is that there is a spread of the virus in the population.
Perhaps this means that developing immune memory does not prevent the virus from carrying the virus.
In other words, the immune system prevents the infection from getting serious.
It will protect us from it, but that does not mean that it completely prevents the virus from being carried.
"
Immune memory and vaccination
Finally, this immune memory is at the center of many discussions on vaccination.
People already infected, and
a priori
immune, are currently excluded from vaccination campaigns.
It is in fact estimated that their natural immunity is sufficient, at least for a few months.
We could then use this memory to give them only one dose of vaccine.
"
The antibody levels obtained in patients who have had Covid-19, and who have received a single injection of the vaccine, are equivalent to those who have received two
"
, explains Elisabeth Bouvet, who chairs the technical committee on vaccinations at the Haute Autorité de santé.
“
This is called an anamnestic response;
they had kept an immune memory and therefore have a response that is equivalent to that of two doses.
"
Thus, in this context, infection and the immune response which act as first dose, the second then just extend coverage over time.
This protocol is only at the discussion stage, however.
The Haute Autorité de santé must give its formal opinion on the subject in the coming days.
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