Covid-19: "We must absolutely avoid the English variant becoming the majority variant".

The B.1.1.7 variant of the SARS-CoV-2 coronavirus, previously known as VUI202012/01 (for Variant Under Investigation), is under close surveillance. When did it emerge, what do we know about its specific features, and what impact could it have on the epidemic, particularly in our country? Answers from Mircea Sofonea, Senior Lecturer in Epidemiology and Evolution of Infectious Diseases at the University of Montpellier.

Mircea T. Sofonea, University of Montpellier

The Conversation: How long has this variant been circulating, and what do we know about the conditions under which it emerged?

Mircea Sofonea: This variant was detected in November, mainly in London, in the south and east of England. It's worth noting that the UK has a very proactive variant detection policy: with a sequencing effort almost 50 times greater than that of France, it is the European country that supplies the largest number of SARS-CoV-2 coronavirus variant sequence data to the GISAID database.

A striking feature of this variant's sequence is the large number of mutations it contains compared to other circulating variants: some twenty in all, compared to an average of around ten. Many of these mutations affect the Spike protein, through which the virus enters human cells to infect them.

By conducting phylogenetic studies, which enable us to track the evolution of the coronavirus over time, we can trace the emergence of this variant back to September, in south-east England. Five months later, not only is it present in high proportions throughout the UK and Ireland, but it has been officially detected in over 50 countries worldwide.

TC: Do we know the reasons for this success?

MS: There are three ways in which a variant can emerge and become established in the genetic landscape of a viral disease:

• The first is chance. Sometimes, when an epidemic is stationary or growing slightly, new neutral variants (i.e. epidemiologically equivalent to the others) find local situations that can favor their propagation (large gatherings of people in an enclosed area, for example). If such a situation arises and a variant finds itself at the origin of an outbreak, it will end up being more represented than the other variants in circulation. It's as if it were carried along by this local amplification effect, riding the wave created locally to spread throughout the population.
• The second possibility is the emergence of a variant carrying one (or more) mutations that radically alter its ability to transmit. If the people it infects are more contagious than those infected by already existing variants, it's easy to understand why this variant ends up spreading more rapidly.
• Finally, the third possibility: a variant carrying mutations that would enable it to find a new "entry point" to infect people who were previously less susceptible.

In the case of the English variant, the first mechanism is ruled out by analyses carried out by our British colleagues. They showed that once present in a territory, its frequency increased in a relatively predictable and homogeneous way. This indicates that the variant did not appear "in the right place at the right time", taking advantage of favorable conditions on the bangs of the epidemic.

It does seem to be transmitted more rapidly than other circulating variants, without this being linked to any particular local effect.

TC: In England, it would appear that the emergence of the British variant has been accompanied by a shift in infections towards younger age groups. Does this support the third scenario? Does this virus infect younger people more easily?

MS: Indeed, our colleagues at Imperial College have shown that these age groups are over-represented by almost 25% among those infected with the new variant, compared with other variants.

It should be remembered, however, that the situation in England was special when this variant began to spread: the country was confined, but schools were still open. As a result, these were the only places where significant transmission could occur. What's interesting is that the age groups concerned are normally considered to be less contagious than others (even if there's still no real scientific consensus on the subject).

This situation makes it difficult to discriminate between the last two scenarios: more contagiousness or contagiousness targeting younger classes. To be able to decide, we would need to check what is happening in other countries, where sanitary measures are applied differently (confinement with closed schools, for example).

Another possibility would be to check whether the increase in infection among younger people observed in England corresponded with the increase in sequences of the variant. For this, however, we would need to be certain that the detection of the variant was homogeneous over the period studied. Furthermore, the available data do not allow us to establish the precise context of contamination.

In any case, we'll know more in a few weeks.

TC: Do you have any idea of the virological mechanisms behind this virus's success?

MS: These are currently under investigation. One explanation put forward is that one or more mutations affecting the Spike protein increase its affinity for ACE2 receptors located on the surface of airway cells that the virus infects, facilitating entry of this variant. The result is greater infectivity of viral particles, and hence increased contagiousness in carriers.

Remember that contagiousness can be increased in two ways: either people are more contagious because they produce more viral particles, or, given the same quantity of viral particles, they are more infectious because they enter the new host's cells more easily. If the ease of entry is increased here, is this also the case for the quantity of viral particle production? We don't yet know.

TC: Couldn't we also imagine that the virus favors more symptomatic forms, which we know encourage transmission (coughing, runny nose...)?

MS: For the moment, there's nothing to indicate that this is the case: to my knowledge, no study to date has shown a significant difference in the clinical manifestations of infections with this new variant. Overall, there is no difference in terms of severity or lethality, which is reassuring.

On this subject, we've heard and read several times in recent days that a more contagious variant is more worrying than a more lethal virus. This statement needs to be qualified.

An increase in transmissibility is problematic if the hospital system proves unable to absorb the influx of patients. Indeed, the more easily the virus is transmitted, the higher the peak hospital stress. However, if we are able to cope with the wave of hospitalizations, or if we are interested in the longer-term consequences of the epidemic, things are different.

In the context of an epidemic such as this, where the number of replicates can be as high as 3 (in the absence of sanitary measures), a hypothetical increase in lethality of the same magnitude (around +50%) would in fact be more worrying if the number of replicates exceeded 1.5. This would result in a higher final mortality than a mutation affecting transmission.

(editor's note: also known as "effective R", the reproduction number is an estimate, over the last 7 days, of the average number of individuals contaminated by an infected person. An effective R of less than 1 means that the epidemic is declining).

TC: What impact is this increase in transmissibility expected to have on the number of reproductions?

MS: Researchers at Imperial College estimated that in the case of this new variant, the increase in transmission was in the order of 0.4 to 0.7 reproduction number units (compared with other circulating variants).

The question is: should this increase be taken into account by adding 0.4 to the epidemic's reproduction number (in the case where this variant is indeed capable of infecting new age groups, thereby "lumpily" increasing its transmission), or should this reproduction number be multiplied by 1.4 (in the case where this virus is more contagious, but has not necessarily changed its target)?

While this point is not easy to decide on the basis of current data, it does not constrain the projections for France, which currently has a reproduction rate close to 1: the two scenarios are therefore roughly equivalent.

TC: How is the epidemic progressing in our country? What do the models say about the possible effect of this new variant?

MS: The epidemic has been out of control in France for a week now, and we are currently witnessing an increase in the level of viral circulation, with a growing number of reproductions estimated at 1.10 (between 1.05 and 1.15) as of January 14. The spread is exponential, but slower than in early October, before health measures were stepped up.

This increase is naturally explained by the effect of Christmas Eve, although more moderate than initially feared. But the effect of New Year's Eve, which may have had an amplifying effect on the epidemic, remains to be seen: people infected on December 24 and 25 were contagious a week later. Such an effect on the current, slow-growing epidemic, combined with that of the return to school and work in January, could trigger a sharp rebound. If this is the case, it will be measurable over the coming week.

For the time being, taking into account the under-detection mentioned above, the English variant does not yet seem to be present enough to affect the said breeding numbers at national level. But it could change all that in just two months.

It should be remembered that the first containment, which was effective but extremely drastic, with heavy socio-economic consequences, reduced the epidemic's reproduction rate to 0.7. If this new variant increases the epidemic's reproduction number from 0.4 to 0.7, we can see not only that control of the epidemic is lost, but that even extremely costly and stringent measures such as those implemented during the first wave will no longer be effective. This is why we need to slow down the progression of this variant as much as possible.

Mircea T. Sofonea, Senior Lecturer in Epidemiology and Evolution of Infectious Diseases, MIVEGEC Laboratory, University of Montpellier

This article is republished from The Conversation under a Creative Commons license. Read theoriginal article.