COVID-19: "We must absolutely prevent the English variant from becoming dominant."
The B.1.1.7 variant of the SARS-CoV-2 coronavirus, previously designated VUI202012/01 (for Variant Under Investigation), is under close surveillance. When did it emerge, what do we know about its specific characteristics, and what could its impact be on the epidemic, particularly in our country? Mircea Sofonea, senior lecturer in epidemiology and infectious disease evolution at the University of Montpellier, provides the answers.
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 and in the south and east of England. It should be noted that the United Kingdom has a very proactive policy on detecting variants: with sequencing efforts nearly 50 times greater than those of France, it is the European country that provides the largest amount of SARS-CoV-2 coronavirus variant sequence data to the GISAID database.
What is striking when analyzing the sequence of this variant is that it contains a significant number of mutations compared to other variants in circulation: there are about 20 in total, while the others have an average of only about 10. Many of these mutations affect the spike protein, which the virus uses to enter and infect human cells.
By conducting phylogenetic studies, which track the evolution of the coronavirus over time, we can trace the emergence of this variant back to September in southeastern England. Five months later, it is not only present in high proportions throughout the United Kingdom and Ireland, but has also been officially detected in more than 50 countries around the world.
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. When an epidemic is stable or growing slightly, new neutral variants (i.e., epidemiologically equivalent to others) may find local conditions that favor their spread (e.g., large gatherings of people in enclosed spaces). If such a situation arises for a variant and it ends up causing an outbreak, it will eventually become more prevalent than the other variants in circulation. It is as if it were carried by this local amplification effect, riding the wave created locally to spread throughout the population.
- The second possibility is that a variant emerges that carries one (or more) mutation(s) that radically changes its ability to spread. If the people it infects are more contagious than those infected by existing variants, it is easy to understand how this variant could end up spreading more quickly.
- 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 has been ruled out by analyses carried out by our British colleagues. These have shown that once present in a territory, its frequency has increased in a relatively predictable and consistent manner. This situation indicates that this is not a variant that appeared "in the right place at the right time" and benefited from favorable conditions on the margins of the epidemic.
It appears to spread more quickly 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 toward 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 highlighted an overrepresentation of nearly 25% of these age groups among those infected with the new variant, compared to other variants.
However, it should be remembered that the situation in England was unique when this variant began to spread: the country was in lockdown, but schools were still open. As a result, these were the only places where significant transmission could occur. What is striking is that the age groups concerned were considered to be less contagious than others (although there is still no real scientific consensus on the subject).
This situation makes it difficult to distinguish between the last two scenarios: increased contagiousness or contagiousness targeting younger age groups. In order to decide, it would be necessary to examine what is happening in other countries, where health measures are applied differently (lockdown with schools closed, for example).
Another possibility would be to check whether the increase in infections among younger people observed in England corresponded with the increase in sequences of the variant. But to do so, we would need to be certain that detection of the variant was consistent throughout the period studied. Furthermore, the available data do not allow us to establish precisely the context of the infections.
In any case, we will know more in a few weeks.
TC: Do we have any idea of the virological mechanisms that might explain the success of this virus?
MS: They are currently being investigated. 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 the airway cells that the virus infects, facilitating the entry of this variant. This results in greater infectivity of the viral particles and therefore increased contagiousness of carriers.
It should be noted that contagiousness can be increased in two ways: either people are more contagious because they produce more viral particles, or, with the same amount of viral particles, these particles are more infectious because they enter the cells of the new host more easily. If the ease of entry is increased, is the quantity of viral particles produced also increased? We do not yet know.
TC: Couldn't we also imagine that the virus promotes more symptomatic forms, which we know encourage transmission (coughing, runny nose, etc.)?
MS: At present, there is no evidence to suggest that this is the case: to my knowledge, no studies to date have shown any significant difference in the clinical manifestations of infections caused by this new variant. Overall, there is no difference in terms of severity or lethality, which is quite reassuring.
On this subject, we have heard and read repeatedly 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 when the hospital system is unable to cope with the influx of patients. The more easily the virus spreads, the greater the strain on hospitals. However, if we are able to cope with the wave of hospitalizations or if we focus on the longer-term consequences of the epidemic, things are different.
In the context of an epidemic such as this one, where the reproduction number can rise to 3 (in the absence of health measures), a hypothetical increase in lethality that is quantitatively equivalent (approximately +50%) would in fact be more concerning if this reproduction number exceeds 1.5. This is because it would then result in a higher final mortality rate than a mutation affecting transmission.
(editor's note: also known as "effective R," the reproduction number is an estimate, over the last seven days, of the average number of individuals infected by one infected person. An effective R below 1 means that the epidemic is declining).
TC: In this case, what is the expected impact of this increase in transmissibility on the reproduction number?
MS: Researchers at Imperial College have estimated that in the case of this new variant, the increase in transmission is in the range of 0.4 to 0.7 reproduction number units (compared to other circulating variants).
The question that arises is: should this increase be taken into account by adding 0.4 to the reproduction number of the epidemic (in the event that this variant is indeed capable of infecting new age groups, allowing it to increase its transmission "across the board") or should this reproduction number be multiplied by 1.4 (in the event that this virus is more contagious, but without necessarily changing its target)?
While this point is not easy to decide based on current data, it does not constrain projections for France, which currently has a reproduction number close to 1: the two scenarios are therefore approximately equivalent.
TC: What is the current status of the epidemic in our country? What do the models say about the possible effect of this new variant?
MS: The epidemic has not been under control in France for a week, and we are currently seeing an increase in viral circulation, with a growing reproduction number estimated at 1.10 (between 1.05 and 1.15) as of January 14. The spread is exponential, but slower than at the beginning of October, before health measures were tightened.
This increase can naturally be explained by the effect of Christmas Eve, although it was more moderate than initially feared. However, the impact of New Year's Eve, which may have amplified the epidemic, remains to be estimated: people infected on December 24 and 25 were contagious a week later. Such an effect on the current slowly progressing epidemic, combined with the return to school and work in January, could trigger a sharp rebound. If this is the case, it will be measurable in the coming week.
For now, taking into account the aforementioned under-detection, the English variant does not yet seem to be present in sufficient numbers to affect the reproduction number at the national level. But that could change in two months.
It should be remembered that the first lockdown, which was effective but extremely drastic, with serious socio-economic consequences, had reduced the reproduction number of the epidemic to 0.7. If this new variant increases the reproduction number of the epidemic from 0.4 to 0.7, we can see that not only is control of the epidemic lost, but even extremely costly and stringent measures such as those put in place during the first wave will no longer be effective. This is why the spread of this variant must be slowed down as much as possible.
Mircea T. Sofonea, Associate Professor of Epidemiology and Evolution of Infectious Diseases, MIVEGEC Laboratory, University of Montpellier
This article is republished from The Conversation under a Creative Commons license. Readthe original article.