Written by Samuel Allison.
Article from the conversation
Like all living things, the SARS-CoV-2 virus evolves. During each injury it is produced 1 billion new viral particles. Among these new viruses, some carry mutations.
It was the process of evolution and this generation of mutants studied in detail. We now know that in most cases, mutated SARS-CoV-2 viruses are not transmitted to new hosts, or are neutral, i.e. the infections they cause are similar to those caused by non-mutant viruses (also known as savages or Historical).
But sometimes some of these mutations spread and take precedence over existing viruses. The most recent examples are called alpha, beta, gamma and now delta variants. It debuted in the UK, South Africa, Brazil and India, respectively. why ? What do we know about their property? What do we know about their ability to evade vaccination?
What is the alternative?
Variants reported for several months clinically and/or epidemiologically differ from the majority of SARS-CoV-2 mutations. Concretely, a variable is characterized by at least one of the following four characteristics:
- Infection, that is, its ability to infect more hosts;
- its severity, which is reflected in the severity of the symptoms that affected people develop;
- Its immune escape, which means that people who have already been vaccinated are less protected (with, in the case of SARS-CoV-2, protection is currently stronger from vaccine immunity than natural immunity);
- resistance to treatment.
In the case of Covid-19, this last point is not a big problem at the moment, because it is there Few of the treatments available. Moreover, these treatments focus on the severe stages of infection, during which transmission is limited.
The first variant is scheduled for the spring of 2020
The first example of the SARS-CoV-2 variant appeared in the spring of 2020, although it is rarely presented as such. Viruses carrying the D614G point mutation, which affects the S protein-producing gene (which serves as a “key” for the virus to enter the cells it infects) emerged and spread. The underlying process was difficult to prove, because the mutated form (carrying the G614) mutation has lower affinity for the ACE2 receptor than the wild form (in other words, binds less readily), but On the other hand, the aforementioned mutant form appears to degrade at a lower speed, which eventually leads to an increase in viral infection.
What is notable is that the ‘substitution’ mutation (the replacement of one amino acid – the “brick” of proteins – of protein S with another) occurred independently in many strains. This is a typical example of parallel evolution. The SARS-CoV-2 coronavirus comes from bats. Its transmission 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 done at the beginning of XXe The century revealed that the further away the population is from the optimum evolutionary level, the greater the gradation of selection, and therefore the more mutations conferring a strong adaptation can be observed. Conversely, the closer a population is to the optimum evolutionary level, the rarer are these high-impact mutations. In other words, the observation of a strong parallel evolution at the beginning of the epidemic when the coronavirus found itself in a new host species is not surprising.
Three variables of concern and six different types of attention
Following this first example, three particularly worrisome variants were discovered at the end of 2020, now called alpha (identified in the UK), beta (in South Africa) and gamma (in Brazil). All of them have been associated with large epidemic waves. Surprisingly, these viruses carry more mutations in their genomes than the average.
In France, the alpha variant has been roughly estimated 40% more contagious Of the breeds that were traded before. UK data covering tens of thousands of patients also suggests that the variant will have an extension 50% higher ferocity.
On the side of the gamma and . variables from the top priorities Beta-immunological data indicate that they are less sensitive to the immunity caused by natural infection, which explains this Growth in France in April 2021.
In addition to these three variables of concern, there are at least 6 different types of attention identified by the World Health Organization (WHO). They are under surveillance because their genomes contain mutations present in certain variants of concern and because they are associated with episodes of rapid spread.
Assessing the severity of variables is not an easy task
It is very difficult to judge the severity of a variant solely by its genome sequence. For example, alpha variants carrying an additional mutation (E484K) raised some concern at first. In particular, mutagenesis studies have shown that mutations at position 484 (as well as other positions of the S protein) likely allow the virus toevasion of the immune response. But it was finally noted that this mutation is not as problematic as it would be in other genetic backgrounds (eg in beta and gamma variants).
This phenomenon known to geneticists is called epistasis: even if two mutations A and B are beneficial to the virus when isolated, having both in the genome can be harmful. In general, the expression of a gene can be strongly modified by the expression of other genes, in which case knowledge of the presence of a point mutation is insufficient to infer its biological effect from it.
The delta variant provided a second example illustrating the difficulty of predicting the epidemiological consequences of mutations.
delta variable case
This variant was initially detected in India, where other closely related viral lines have been monitored because they carry 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 appearance could have been favored by gathering millions of people under Religious festival. It must be remembered that the higher the number of infections, the more mutations are produced, and the more likely the mutation will spread in the population.
Although data from India is limited, epidemiological surveillance in the UK is very detailed and transparent, including Various reports, lets us learn more about the properties of a delta variable.
It has now been roughly demonstrated that this variant is more transmissible. In fact, a greater proportion of affected extremities are located within the deltaic foci. In addition, preliminary data from Scotland (from the same reports) suggest that infection with the delta variant could lead to further hospitalizations. Finally, the question of immune escape remains open.
Regarding vaccine immunity, at present, no effect has been detected in terms of hospitalization (protection remains around 95%) and the effect is limited when looking at reinfection (10% lower protection at two doses compared to alpha variant infection). It is increasingly difficult to determine innate immunity, as vaccination coverage increases.
In summary, the delta variant appears to be more infectious than the other known variants, but its tendency to escape immunity appears to be lower than that of the beta and gamma variants. This case illustrates the key role of epistasis and the limitations of mutation monitoring one by one.
The delta variable in France: a complex detection
In France, accurate detection of the delta variant has been difficult, as it has already been for the alpha variant, because only a few samples that respond positively to the Covid-19 detection test have been sequenced. On the other hand, screening for specific mutations among almost all positive tests made it possible to compensate for this lack of accuracy and obtain results quickly.
Analyzes of screening tests carried out up to June 8 indicated that this variant already accounts for nearly 10% of cases in Ile-de-France in mid-June, and appears to have a fairly clear transmission advantage over other circulating viruses.
More detailed analyzes performed with data run up to June 21 showed that the delta variant was in France a Send advantage is about 70% over the alpha variant in several regions.
The good news is that vaccination protects well against infection of the alpha variant (according to British data, it reduces the risk by 30% with one dose and 80% with two doses) and protects very well against severe forms (reducing the risk by 80% with one dose and 95% with two doses). This explains why the prevalence of this variant is observed mainly among younger, less immunized populations.
What measures should be taken?
Today, we have all the cards on hand to prevent hospital services from being pressured again in the near future. Vaccination is crucial as it protects very effectively from severe forms. But this cannot be enough, for several reasons.
On the other hand, due to the complete relaxation of preventive measures and the return to health measures before 2020 in urban centers, more than 80% of the population of France will have to be vaccinated (remember that if 95% of adults in France are vaccinated, this corresponds to 75% of the total population). On the other hand, even if the most vulnerable are likely to be protected in the fall, allowing this virus to spread widely among the younger population may have a health impact that is difficult to estimate, given the High virulence of the alpha variant and related unknowns Covid Longs.
In addition, although this virus kills a few in the youngest, the current numbers are according to sources 1 to 6 deaths per 100,000 injuries between the ages of 15-19 years. Finally, as long as SARS-CoV-2 is widespread, new variants will continue to emerge, Not surprisingly, evolutionary biologistsThis virus has not turned into benign. On the contrary, the more contagious variants appear to be the most virulent.
So you should avoid repeating the mistakes of summer 2020, and take advantage of the low infection rate (less than 3,000 new infections per day on July 1. According to our estimates) to finally unleash the means to establish a policy for testing, tracing (or recall) and isolation in the field. It is also necessary to rely on scientific arguments that support the critical role of Aerosol transmission In order to equip enclosed spaces (especially school buildings) by the beginning of the school year with devices to reduce the risk of spread (ventilation, ventilation, reduced scales).
Compared to last year, we now know a lot more about how SARS-CoV-2 spreads, and we now have a range of safe and effective vaccines in place. This knowledge and these tools should enable us to avoid reclaiming a deteriorating situation like the one we experienced last fall and winter.
Samuel Allison, director of research at CNRS, Research Institute for Development (IRD) And the Mercia T Sofonia, Lecturer in Epidemiology and Development of Infectious Diseases, MIVEGEC Laboratory, University of Montpellier