COVID-19: What do we know about the Delta variant (and others)?
Like all living things, the SARS-CoV-2 virus evolves. During each infection, billions of new viral particles are produced. Among these new viruses, some carry mutations.
Samuel Alizon, Research Institute for Development (IRD) and Mircea T. Sofonea, University of Montpellier
This evolutionary process and this generation of mutants have been studied in detail. We now know that in most cases, these SARS-CoV-2 mutant viruses are either not transmitted to new hosts or are "neutral," meaning that the infections they cause are similar to those caused by non-mutant viruses (also known as "wild-type" or "historical" viruses).
But sometimes some of these mutants spread and take precedence over existing viruses. The most recent examples are called the alpha, beta, gamma, and now delta variants. They first emerged in the United Kingdom, South Africa, Brazil, and India, respectively. Why? What do we know about their properties? What do we know about their ability to evade vaccination?
What is a variant?
The variants that have been in the news for several months differ clinically and/or epidemiologically from the majority of SARS-CoV-2 coronavirus mutants. Specifically, a variant is distinguished by at least one of the following four properties:
- Its contagiousness, in other words its ability to infect more hosts;
- Its virulence, which is reflected in the severity of the symptoms developed by infected individuals;
- Its immune escape, which means that people who are already immune are less well protected (with, in the case of SARS-CoV-2, vaccine-induced immunity currently offering more robust protection than natural immunity);
- Its resistance to treatment.
In the case of COVID-19, this last point is not particularly problematic at present, as there are few treatments available. What is more, these treatments are intended for the severe stages of the infection, during which transmission is limited.
A first variant identified in spring 2020
The very first example of a SARS-CoV-2 variant, although rarely presented as such, emerged in the spring of 2020. Viruses carrying the D614G point mutation, affecting the gene that produces the spike protein (S) (which acts as a "key" for the virus to enter the cells it infects), emerged and spread. The underlying process was difficult to identify because the mutated form (carrying the G614 mutation) has a lower affinity for the ACE2 receptor than the wild type (in other words, it binds less easily), but the mutated form appears to be degraded less rapidly, which ultimately increases viral infectivity.
What is noteworthy is that this "substitution" mutation event (replacement of one amino acid—the "building blocks" of proteins—in the S protein with another) occurred independently in several lineages. This is a typical example of parallel evolution. The SARS-CoV-2 coronavirus originated in bats. Its transition to a new host is important because, from the virus's point of view, it requires adaptation to different cellular environments.
The phenomenon of natural selection comes into play here: research conducted in the early20th century revealed that the further a population is from its evolutionary optimum, the higher the selection gradient, and therefore the more likely it is that mutations conferring strong adaptation will be observed. Conversely, the closer the population is to an evolutionary optimum, the rarer these high-impact mutations are. In other words, it is not surprising to observe a strong parallel evolution at the start of the epidemic when the coronavirus found itself in a new host species.
Three variants of concern and six variants of interest
Beyond this initial example, it was mainly at the end of 2020 that three variants of concern were detected, now known as alpha (identified in the United Kingdom), beta (in South Africa), and gamma (in Brazil). All have been associated with major epidemic waves. The surprise was that these viruses carried more mutations in their genome than average.
In France, it has been estimated that the alpha variant is around 40% more contagious than the strains that were circulating previously. British data on tens of thousands of patients also indicate that this variant may be 50% more virulent.
As for the gamma and, even more so, beta variants, immunological data indicate that they are less sensitive to immunity induced by natural infection, which would explain their growth in France in April 2021.
In addition to these three variants of concern, there are at least six variants of interest identified by the World Health Organization (WHO). They are under surveillance because their genomes contain mutations found in certain variants of concern and because they are associated with episodes of rapid spread.
Assessing the danger of variants is no easy task.
It is extremely difficult to judge the dangerousness of a variant solely on the basis of its genome sequence. For example, alpha variants carrying an additional mutation (E484K) initially caused some concern. In particular, mutagenesis studies showed that mutations at position 484 (as well as at other positions in the S protein) likely allowed the virusto evade the immune response. However, it was subsequently observed that this mutation is not as problematic as when it is present in other genetic backgrounds (e.g., in the beta and gamma variants).
This phenomenon, well known to geneticists, is called epistasis: even if two mutations, A and B, are beneficial to the virus when isolated, the presence of both in a genome can be harmful. More generally, the expression of a gene can be strongly modulated by the expression of other genes, in which case knowing that a point mutation exists is not enough to deduce its biological effect.
The delta variant provided a second example illustrating the difficulty of anticipating the epidemiological consequences of mutations.
The case of the delta variant
This variant was initially detected in India, where other closely related viral lineages were being monitored because they carried a mutation at position E484.
While, as with other variants, it is difficult to trace the exact origin of the delta variant, it is suspected that its emergence may have been facilitated by the gathering of millions of people at a religious festival. It should be remembered that the more infections there are, the greater the number of mutants produced, and the higher the probability that a mutant will spread among the population.
Although data from India is limited, the UK's extremely detailed and transparent epidemiological monitoring, particularly its reports on variants, allows us to learn more about the characteristics of the delta variant.
It is now virtually established that this variant is more transmissible. Indeed, within households of people infected with the delta variant, there is a higher proportion of infected members. Furthermore, preliminary data from Scotland (from the same reports) indicate that infections with the delta variant could lead to more hospitalizations. Finally, the question of immune escape remains open.
With regard to vaccine immunity, no effect has been detected so far in terms of hospitalizations (protection remains around 95%), and the effect is limited when looking at reinfection (10% less protection with two doses compared to infection with the alpha variant). Natural immunity is becoming increasingly difficult to quantify as vaccination coverage progresses.
In summary, the delta variant appears to be more contagious than other known variants, but its propensity to evade immunity seems to be lower than that of the beta and gamma variants. This case illustrates the major role of epistasis and the limitations of tracking mutations one by one.
Delta variant in France: complicated detection
In France, accurate detection of the Delta variant has been difficult, as it had been for the Alpha variant, because only a small number of samples that test positive for COVID-19 are sequenced. However, screening for specific mutations in almost all positive tests has made it possible to compensate for this lack of accuracy and obtain results quickly.
Analyses of screening tests carried out up to June 8 indicated that this variant already accounted for nearly 10% of cases in the Île-de-France region in mid-June, and that it appeared to have a fairly pronounced transmission advantage over other circulating viruses.
More detailed analyses carried out using data up to June 21 showed that the delta variant had a transmission advantage of around 70% over the alpha variant in several regions of France.
The good news is that vaccination provides good protection against infection with the alpha variant (according to UK data, a 30% reduction in risk with one dose and an 80% reduction with two doses) and extremely good protection against severe forms of the disease (an 80% reduction in risk with one dose and a 95% reduction with two doses). This explains why the spread of this variant is mainly observed among younger, less vaccinated populations.
What measures should be taken?
Today, we have everything we need to prevent hospital services from becoming overwhelmed again in the near future. Vaccination is crucial, as it provides extremely effective protection against severe forms of the disease. But it is not enough, for several reasons.
On the one hand, because in order to completely relax protective measures and return to pre-2020 health measures in urban centers, more than 80% of the French population will need to be vaccinated (remember that if 95% of adults are vaccinated in France, this corresponds to 75% of the total population). On the other hand, even if the most vulnerable are likely to be protected by the fall, allowing the virus to spread widely among younger people could have a health impact that is difficult to estimate, given the high virulence of the alpha variant and the unknowns associated with long Covid.
Furthermore, although this virus rarely kills young people, current figures indicate between 1 and 6 deaths per 100,000 infections among 15-19 year olds, depending on the source. Finally, as long as SARS-CoV-2 continues to spread widely, new variants will continue to emerge and, unsurprisingly to evolutionary biologists, this virus has not become benign. On the contrary, the most contagious variants also appear to be the most virulent.
We must therefore avoid repeating the mistakes of summer 2020 and take advantage of the low incidence (less than 3,000 new infections per day as of July 1, according to our estimates) to finally unlock the resources needed to effectively implement a policy of testing, tracing (or backtracking), and isolating in the field. We must also rely on scientific arguments supporting the decisive role of aerosol transmission in order to equip enclosed spaces (particularly schools) with devices to reduce the risk of spread (ventilation, air conditioning, reduced capacity) by the start of the new school year.
Compared to last year, we now know much more about how SARS-CoV-2 spreads, and we now have a range of safe and effective vaccines. This knowledge and these tools should enable us to avoid a repeat of the dire situation we experienced last fall and winter.
Samuel Alizon, Director of Research the CNRS, Research Institute for Development (IRD) and 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. Readthe original article.