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 are produced billion new virus particles. Among these new viruses, some are carriers of mutations.

This process of evolution and this generation of mutants were studied in detail. We now know that in the majority of cases, these mutant SARS-CoV-2 viruses are either not transmitted to new hosts, or "neutral", that is to say that the infections they cause are similar. those caused by non-mutant viruses (also called "wild" or "historical").

But sometimes some of these mutants spread and take precedence over existing viruses. The most recent examples are variant names Alpha, Beta, Gamma, and now Delta. They first emerged in the UK, South Africa, Brazil or India respectively. Why ? What do we know about their properties? What do we know about their ability to escape vaccination?

What is a variant?

The variants that have been talked about for several months differ clinically and / or epidemiologically from the majority of mutants of the SARS-CoV-2 coronavirus. Concretely, 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 symptoms developed by infected people;
  • Its immune escape, which means that people who are already immune are less well protected (with, in the case of SARS-CoV-2, protection for the moment more robust from vaccine immunity than from natural immunity);
  • Its resistance to treatment.

In the case of Covid-19, this last point is not very problematic for the moment, because there is few treatments available. What is more, these treatments focus on the severe phases 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 it is rarely presented as such, emerged in the spring of 2020. Viruses carrying the D614G point mutation, affecting the gene producing the spike protein (S) (which serves as a "key" for the virus to enter the cells it infects) have emerged and spread. The underlying process was difficult to demonstrate, because the mutated form (carrying the G614 mutation) has a lower affinity for the ACE2 receptor than the wild form (in other words, it binds less easily), But said mutated form, on the other hand, seems to be degraded less quickly, which ultimately increases viral infectivity.

What is notable is that this “substitution” mutation event (replacement of one amino acid - the “bricks” constituting the proteins - of protein S by another) occurred independently in several lines. This is a typical example of parallel evolution. The SARS-CoV-2 coronavirus comes from bats. Its transition to a new host is important because, from the point of view of the virus, it requires adaptation to different cellular environments.

The phenomenon of natural selection intervenes here: work carried out at the beginning of the XXe century have revealed that the further a population is from its evolutionary optimum, the higher the selection gradient, and therefore the more possible it is to observe mutations conferring a strong adaptation. Conversely, the closer the population is to an evolutionary optimum, the rarer these mutations with great effect are. In other words, observing a strong parallel evolution at the start of the epidemic when the coronavirus found itself in a new host species is not so surprising.

Three variants of concern and six variants of interest

Beyond this first example, it was especially at the end of 2020 that three worrying variants were detected, now called 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 to find that these viruses carried more mutations in their genome than the average.

In France, the alpha variant was estimated to be approximately 40% more contagious than the lineages that circulated before. British data covering tens of thousands of patients also indicate that variant would have a 50% higher virulence.

On the side of gamma variants and a fortiori beta, 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 6 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.

Evaluating the dangerousness of variants is no easy task

It is extremely difficult to judge the dangerousness of a variant only via the sequence of its genome of its genome. For example, alpha variants carrying an additional mutation (E484K) initially raised some concern. In particular, mutagenesis studies have shown that mutations at position 484 (as well as other positions of the S protein) likely allow the virus toevade the immune response. But it was finally observed that this mutation is not as problematic as when it is present in other genetic backgrounds (for example in beta and gamma variants).

This phenomenon well known to geneticists is called epistasis: even if two mutations A and B are beneficial for the virus when they are isolated, the presence of both in a genome can prove to be deleterious. More generally, the expression of a gene can be strongly modulated by the expression of other genes, in which case the knowledge that there is a point mutation is insufficient to deduce its biological effect therefrom.

The delta variant provided a second example illustrating the difficulty in anticipating the epidemiological consequences of mutations.

The case of the delta variant

This variant was initially detected in India, where other closely related viral lines were monitored because they carried a mutation at position E484.

If, as for the other variants, it is difficult to trace the exact origin of the delta variant, it is suspected, on the other hand, that its emergence could have been favored by the gathering of millions of people within the framework of a religious festival. It should be remembered that the more infections there are, the higher the number of mutants produced, and the higher the probability that a mutant will spread in the population.

Although data from India is limited, the UK's extremely detailed and transparent epidemiological monitoring, including its variant reports, allows us to learn more about the characteristics of the delta variant.

It is now almost established that this variant is more transmissible. In fact, within the foci of people infected with the delta variant, there is a greater proportion of infected limbs. In addition, 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.

Regarding vaccine immunity, for the moment no effect has been detected in terms of hospitalizations (protection remains around 95%) and the effect is limited when looking at reinfection (less 10% protection at two doses relative to alpha variant infection). Natural immunity is increasingly difficult to quantify, as vaccination coverage increases.

In summary, the delta variant therefore appears to be more contagious than the other known variants, but its propensity to escape immunity seems less than that of the beta and gamma variants. This case illustrates the major role of epistasis and the limits of monitoring mutations one by one.

Delta variant in France: complicated detection

In France, the fine detection of the delta variant was difficult, as it had already been for the alpha variant, because only a small number of samples responding positive to a Covid-19 detection test are sequenced. On the other hand, screening for particular mutations among almost all of the positive tests made it possible to compensate for this lack of precision and to obtain results quickly.

Analyzes of screening tests carried out up to June 8 indicated that this variant already represented nearly 10% of cases in Île-de-France in mid-June, and that it seemed to have a fairly pronounced transmission advantage compared to other circulating viruses.

The more detailed analyzes carried out with data running up to June 21 showed that the delta variant had in France a transmission advantage of around 70% over the alpha variant in several regions.

The good news is that vaccination protects well against alpha variant infection (according to British data, 30% reduction in risk with one dose and 80% with two doses) and protects extremely well against severe forms (reduction risk of 80% with one dose and 95% with two doses). This explains why the propagation of this variant is observed mainly within younger populations, less vaccinated.

What measures to take?

Today, we have all the cards in hand to prevent the hospital services from being under pressure again in the near future. Vaccination is crucial because it protects extremely effectively against severe forms. But it cannot be enough, for several reasons.

On the one hand, because to completely relax protective measures and return to pre-2020 health measures in urban centers, more than 80% of the French population will have 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 will probably be protected in the fall, allowing this virus to circulate massively among the youngest could have a health impact that is difficult to estimate, given the high virulence of the alpha variant and unknowns related to Long Covid.

In addition, although this virus kills little in the youngest, the current figures indicate according to the sources of 1 to 6 deaths per 100.000 infections in 15-19 year olds. Finally, as long as SARS-CoV-2 spreads widely, new variants will continue to emerge and, no surprise to evolutionary biologists, this virus has not turned benign. On the contrary, the most contagious variants also seem 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 new contaminations per day on July 000 according to our estimates) to finally unlock the means to really set up a policy of testing, tracing (or retrotracing) and isolating in the field. It is also necessary to rely on the scientific arguments supporting the determining role of aerosol transmission in order to equip closed places (especially school structures) by the start of the school year with devices to reduce the risk of propagation (ventilation, ventilation, reduced gauges).

Compared to last year, we now know a lot more about how SARS-CoV-2 is spread, and we now have a range of safe and effective vaccines. This knowledge and these tools should enable us to avoid reliving a situation as degraded as the one we suffered during last fall and winter.

Samuel alizon, Research Director at CNRS, Research Institute for Development (IRD) et Mircea T. Sofonea, Lecturer in epidemiology and evolution of infectious diseases, MIVEGEC laboratory, University of Montpellier

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

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