COVID-19: “We must at all costs prevent the British variant from becoming the dominant strain”
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 characteristics, and what impact might it have on the pandemic, particularly in our country? Answers from Mircea Sofonea, associate professor of epidemiology and the 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 circumstances surrounding its emergence?
Mircea Sofonea: This variant was first detected in November, primarily in London and in southern and eastern England. It is important to note that the United Kingdom has a very proactive policy for detecting variants: with a sequencing effort nearly 50 times greater than that 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 stands out when analyzing the sequence of this variant is that it contains a significant number of mutations compared to other circulating variants: there are about twenty in total, whereas the others have an average of only about ten. Many of these mutations affect the spike protein, which the virus uses to enter and infect human cells.
By conducting phylogenetic studies, which allow us to 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, we see that it is not only present in high proportions throughout the United Kingdom and Ireland, but has also been officially detected in more than fifty countries around the world.
TC: Do we know the reasons behind 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., those that are epidemiologically equivalent to others) may encounter local conditions that favor their spread (such as large gatherings of people in an enclosed space). If such a situation arises for a variant and it triggers an outbreak, it will eventually become more prevalent than the other circulating variants. 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 carrying one (or more) mutation(s) that radically alters its ability to spread. If the people it infects are more contagious than those infected by existing variants, it is easy to see why this variant would eventually spread more quickly.
- Finally, a third possibility: a variant carrying mutations that would allow it to find a new “entry point” to infect people who were previously less susceptible.
In the case of the UK variant, the first mechanism has been ruled out by analyses conducted by our British colleagues. These analyses showed that once the variant was present in a region, its prevalence increased in a relatively predictable and consistent manner. This suggests that it is not a variant that appeared “in the right place at the right time” and took advantage of favorable conditions on the fringes of the epidemic.
It does indeed appear to spread more quickly than other circulating variants, though this is not linked to any specific local factor.
TC: In England, it appears 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 found that these age groups are overrepresented by nearly 25% among those infected with the new variant, compared to other variants.
It is important to remember, however, that the situation in England was unique when this variant began to spread: the country was under 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 in question were generally considered to be less contagious than others (even though there is not yet a clear scientific consensus on the matter).
This situation makes it difficult to distinguish between the last two scenarios: increased transmissibility or transmissibility that primarily affects younger age groups. To determine which is the case, we would need to examine what is happening in other countries, where public health measures are implemented differently (such as lockdowns with school closures).
Another possibility would be to determine whether the rise in infections among younger people observed in England corresponded to an increase in sequences of the variant. However, this would require certainty that the variant was detected consistently throughout the study period. Furthermore, the available data do not allow for a precise determination of the context of the infections.
In any case, we’ll know more in a few weeks.
TC: Do we have any idea what virological mechanisms might explain this virus’s success?
MS: They are currently under investigation. One proposed explanation is that one or more mutations affecting the spike protein increase its affinity for the 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, consequently, increased transmissibility among carriers.
It is worth noting that transmissibility can increase in two ways: either people are more contagious because they produce more viral particles, or, given the same number of viral particles, those particles are more infectious because they enter the cells of the new host more easily. If the ease of entry is increased here, is this also the case for the quantity of viral particles produced? We do not yet know.
TC: Couldn’t we also imagine that the virus causes more symptomatic forms of the illness, which we know facilitate transmission (coughing, runny nose, etc.)?
MS: At this point, there is no evidence to suggest that this is the case: to my knowledge, no study to date has shown a significant difference in the clinical manifestations of infections caused by this new variant. Overall, we are not seeing any difference in terms of severity or fatality rates, which is quite reassuring.
In this regard, we have heard and read repeatedly in recent days that a more contagious variant is more concerning than a more deadly virus. This statement should be qualified.
An increase in transmissibility becomes problematic if the hospital system is unable to handle the influx of patients. Indeed, 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, the situation is different.
In the context of an epidemic such as this one, where the reproduction number can rise as high as 3 (in the absence of public health measures), a hypothetical increase in case fatality rate of the same magnitude (approximately +50%) would actually be more concerning if the reproduction number exceeds 1.5. In fact, it would then result in a higher final death toll than a mutation affecting transmission.
(Editor’s note: Also known as the “effective R,” the reproduction number is an estimate of the average number of people an infected individual infects over the past 7 days. An effective R below 1 means the epidemic is subsiding.)
TC: In this case, what is the expected impact of this increase in transmissibility on the reproduction number?
MS: Researchers at Imperial College estimated that, for this new variant, the increase in transmission was in the range of 0.4 to 0.7 basic reproduction numbers (compared to other circulating variants).
The question is this: should we account for this increase by adding 0.4 to the epidemic’s reproduction number (in the event that this variant is indeed capable of infecting new age groups, thereby increasing its transmission rate by a “fixed” amount), or should we multiply the reproduction number by 1.4 (in the event that this virus is more contagious, but without necessarily having changed its target population)?
While this issue is not easy to resolve based on current data, it does not affect the projections for France, which currently has a reproduction number close to 1: the two scenarios are therefore roughly equivalent.
TC: What is the current status of the outbreak in our country? What do the models suggest about the potential impact of this new variant?
MS: The outbreak has not been under control in France for the past week, and we are currently seeing an increase in viral circulation, with the reproduction number rising and estimated at 1.10 (between 1.05 and 1.15) as of January 14. The spread is exponential, but slower than it was in early October, before public health measures were tightened.
This increase is naturally attributable to the Christmas Eve surge, though it was more moderate than initially feared. However, the impact of New Year’s Eve remains to be assessed, as it may have amplified the spread of the outbreak: people infected on December 24 and 25 were still contagious a week later. Such an effect on the current slowly spreading outbreak, combined with the return to school and work in January, could trigger a sharp resurgence. If this is the case, it will become apparent in the coming week.
For now, given the underreporting mentioned earlier, the UK variant does not yet appear to be widespread enough to affect the national reproduction number. But it could be a game-changer within two months.
It is important to remember that the first lockdown—effective but extremely drastic, with severe socioeconomic consequences—had brought the epidemic’s reproduction number down to 0.7. If this new variant increases the epidemic’s reproduction number from 0.4 to 0.7, we 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 must slow the spread of this variant as much as possible.
Mircea T. Sofonea, Associate Professor of Epidemiology and the Evolution of Infectious Diseases, MIVEGEC Laboratory, University of Montpellier
This article is republished from The Conversation under a Creative Commons license. Readthe original article.